Clinical Indications for Therapeutic Cardiac Devices

*Ida Åberg, Gustav Mattsson and Peter Magnusson*

#### **Abstract**

Both technology and clinical indications have changed since the first cardiac devices. Choosing the right therapy, or abstaining from it, is the key to good clinical management. Pacemakers effectively reduce symptoms of bradycardia, prevent syncope in patients with sick sinus syndrome, and reduce mortality in high-degree atrioventricular block. Cardiac resynchronization therapy improves symptoms and survival in heart failure patients with reduced ejection fraction and ventricular dyssynchrony. Implantable cardioverter defibrillators terminate life-threatening ventricular arrhythmias and are indicated for the prevention of sudden cardiac death, either as secondary prevention in survivors of ventricular fibrillation or ventricular tachycardia with hemodynamic compromise or as primary prevention due to heart failure with reduced ejection fraction or other miscellaneous diseases. More recently, leadless pacemakers and subcutaneous implantable cardioverter defibrillators have been developed as alternatives in specific conditions.

**Keywords:** bradycardia, cardiac devices, cardiac resynchronization therapy, heart failure, implantable cardioverter defibrillator, indication, pacemaker, sudden cardiac death

#### **1. Introduction**

"Those who suffer from frequent and strong faints without any manifest cause die suddenly", Hippocrates stated more than 2000 years ago [1]. This is likely a description of arrhythmia-related death, which nowadays often is avoidable due to the improvements in diagnostics and treatment the world has seen since antiquity.

The majority of patients receiving a pacemaker today are above the age of 65, owing to increasing problems with impulse generation and conduction with age [2]. With the world population getting older, the prevalence of permanent pacemakers will likely continue to rise [3]. This chapter aims to present a concise description of current guidelines regarding the indications for cardiac devices, including pacemakers, cardiac resynchronization therapy (CRT), and implantable cardioverter defibrillators (ICD) (**Figure 1**).

#### **Figure 1.**

*Cardiac devices. From the top: older pacemaker, dual-chamber implantable cardioverter defibrillator, cardiac resynchronization therapy-defibrillator, dual-chamber pacemaker, single-chamber pacemaker, and leadless pacemaker.*

#### **2. Pacemaker therapy**

The medical properties of electricity have been known for some time. The physicians of ancient Rome treated acute gout with electric sea creatures. Alexander von Humboldt tested the theory of electrical conduction in biological tissue on himself. The first artificial pacemaker, powered by a hand-cranked motor, was invented by Albert Hyman in 1932. The first patient to receive an implantable pacemaker, Arne Larsson, had to wait until 1958, when he underwent the procedure at the Karolinska

**11**

*Clinical Indications for Therapeutic Cardiac Devices DOI: http://dx.doi.org/10.5772/intechopen.82463*

**2.1 Etiology**

**2.2 Pacing mode**

**2.3 Rate response**

**2.4 Pacemaker syndrome**

**2.5 Mode switch**

ing which results in mode-switch.

**2.6 Indications for permanent pacing**

the engineer Rune Elmqvist who developed the system [1].

variations of respiratory rate and tidal volume [7].

University Hospital in Stockholm. He outlived both the surgeon Åke Senning and

The most common etiology of bradycardia leading to pacemaker implantation is conduction tissue fibrosis, but there are several others etiologies responsible for slow heart rates according to data from registers, for example the Swedish pacemaker registry [4]. Some of these are reversible, such as infection/inflammation, metabolic conditions, and medications while others are congenital such as third-degree atrioventricular (AV) block associated with maternal systemic lupus erythematosus [5].

A code of four to five letters is used to describe the pacing mode. The first letter indicates where pacing occurs (where A stands for atrium, V for ventricle, and D for dual); the second describes which chamber is sensed. In the third position, the letters I (inhibit), T (trigger), or D (dual) are used to describe in which way the device responds to sensed events. An R in the fourth position means that rate response (increased pacing rate during physical exertion) is active. Finally, a fifth letter is occasionally used to describe where multicenter pacing is employed (A, V, or D) [6].

The purpose of rate response is to increase the heart rate in response to altered demand, and there are different solutions available to achieve this. Activity sensors are widely used; one example is the accelerometer that identifies postural changes and movement. Minute ventilation sensors can change the heart rate according to

The pacemaker syndrome is a condition brought on by the loss of AV synchrony caused by ventricular pacing. There are no specific diagnostic criteria, but symptoms include orthopnea, dyspnea upon exertion, orthostatic hypotension, and syncope. The mode selection trial (MOST), a prospective study of patients with sick sinus syndrome (SSS) randomized to VVIR or DDDR pacing, concluded that the incidence of pacemaker syndrome was 19.7% at 4 years after implantation. The incidence of pacemaker syndrome varies between less than 2 and 83% in multiple studies [8].

This is crucial in patients with paroxysmal atrial tachyarrhythmias. The cut-off for mode-switch is based on sensing of electrical activity of an atrial lead and is programmable, typically 180 beats per minute. Atrial flutter activity is sometimes hidden in the so-called post-ventricular blanking period and often requires reprogramming. Furthermore, nonphysiological electrical activity may lead to oversens-

In bradycardia caused by reversible etiologies, permanent pacing is not warranted, and temporary pacing should instead be considered. Generally, once

University Hospital in Stockholm. He outlived both the surgeon Åke Senning and the engineer Rune Elmqvist who developed the system [1].

#### **2.1 Etiology**

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

**10**

**Figure 1.**

*pacemaker.*

**2. Pacemaker therapy**

The medical properties of electricity have been known for some time. The physicians of ancient Rome treated acute gout with electric sea creatures. Alexander von Humboldt tested the theory of electrical conduction in biological tissue on himself. The first artificial pacemaker, powered by a hand-cranked motor, was invented by Albert Hyman in 1932. The first patient to receive an implantable pacemaker, Arne Larsson, had to wait until 1958, when he underwent the procedure at the Karolinska

*Cardiac devices. From the top: older pacemaker, dual-chamber implantable cardioverter defibrillator, cardiac resynchronization therapy-defibrillator, dual-chamber pacemaker, single-chamber pacemaker, and leadless* 

The most common etiology of bradycardia leading to pacemaker implantation is conduction tissue fibrosis, but there are several others etiologies responsible for slow heart rates according to data from registers, for example the Swedish pacemaker registry [4]. Some of these are reversible, such as infection/inflammation, metabolic conditions, and medications while others are congenital such as third-degree atrioventricular (AV) block associated with maternal systemic lupus erythematosus [5].

#### **2.2 Pacing mode**

A code of four to five letters is used to describe the pacing mode. The first letter indicates where pacing occurs (where A stands for atrium, V for ventricle, and D for dual); the second describes which chamber is sensed. In the third position, the letters I (inhibit), T (trigger), or D (dual) are used to describe in which way the device responds to sensed events. An R in the fourth position means that rate response (increased pacing rate during physical exertion) is active. Finally, a fifth letter is occasionally used to describe where multicenter pacing is employed (A, V, or D) [6].

#### **2.3 Rate response**

The purpose of rate response is to increase the heart rate in response to altered demand, and there are different solutions available to achieve this. Activity sensors are widely used; one example is the accelerometer that identifies postural changes and movement. Minute ventilation sensors can change the heart rate according to variations of respiratory rate and tidal volume [7].

#### **2.4 Pacemaker syndrome**

The pacemaker syndrome is a condition brought on by the loss of AV synchrony caused by ventricular pacing. There are no specific diagnostic criteria, but symptoms include orthopnea, dyspnea upon exertion, orthostatic hypotension, and syncope. The mode selection trial (MOST), a prospective study of patients with sick sinus syndrome (SSS) randomized to VVIR or DDDR pacing, concluded that the incidence of pacemaker syndrome was 19.7% at 4 years after implantation. The incidence of pacemaker syndrome varies between less than 2 and 83% in multiple studies [8].

#### **2.5 Mode switch**

This is crucial in patients with paroxysmal atrial tachyarrhythmias. The cut-off for mode-switch is based on sensing of electrical activity of an atrial lead and is programmable, typically 180 beats per minute. Atrial flutter activity is sometimes hidden in the so-called post-ventricular blanking period and often requires reprogramming. Furthermore, nonphysiological electrical activity may lead to oversensing which results in mode-switch.

#### **2.6 Indications for permanent pacing**

In bradycardia caused by reversible etiologies, permanent pacing is not warranted, and temporary pacing should instead be considered. Generally, once

reversible causes for bradycardia are excluded, the indication for pacing is based on the severity of bradycardia rather than its etiology [9]. It should be noted though that symptomatic sinus bradycardia as a result of medical therapy is an indication for permanent pacing if there are no alternative treatment options [10].

#### *2.6.1 Sinus node dysfunction*

Persistent sinus bradycardia, chronotropic incompetence, and sinus arrest can all be seen in sinus node disease (SND), a condition that primarily affects the elderly [10]. When diagnosing chronotropic incompetence (the inability to increase the heart rate as a response to activity or other demands), the fact that heart rate is affected by aging, medication, and physical conditioning must be taken into account. Exercise testing is the basis for diagnosis [11]. It is important to separate physiological bradycardia from inappropriate bradycardia, since sinus bradycardia in trained athletes is normal and not an indication for pacemaker therapy [10].

#### *2.6.1.1 Persistent bradycardia*

In patients with SND, pacing has not been proven to prolong survival and is therefore used to relieve symptoms. Symptoms of bradycardia include impaired tolerance to exercise, symptoms of heart failure (HF), syncope, and more subtle symptoms like dizziness and forgetfulness. Untreated patients with SSS, however, are commonly affected by systemic thromboembolism [9]. A significant reduction in stroke and atrial fibrillation (AF) among these patients has been seen with AAI or DDD compared with VVI. The DANPACE trial shows that the incidence of paroxysmal AF is higher with AAIR pacing than DDDR, and there is a two-fold increase in the risk of re-operation [12]. In the Canadian Trial of Physiologic Pacing (CTOPP) where physiologic pacing (dual-chamber or atrial) was compared to ventricular pacing in patients with symptomatic bradycardia, a reduction in the risk of AF was seen for patients who received dual-chamber pacing. No significant reduction in the risk of stroke, death, or hospitalization for HF in the first 3 years after implantation was seen with dual-chamber pacing, but the risk of perioperative complications was significantly higher in this group [13]. The MOST trial compared ventricular- to dualchamber pacing in patients with SSS, and no reduction in stroke with dual-chamber pacing was observed. However, a reduction of AF, signs and symptoms of HF, and a slight improvement in quality of life was seen [14]. Between 0.6 and 1.9% of all patients with SND develop AV block every year, which can of course be a problem when AAIR is used [9]. Rate response should be considered (class IIa recommendation) in people with SND and chronotropic incompetence according to the guidelines of the European Society of Cardiology (ESC). The indication is strengthened in those who are young and physically active. There is evidence for improvement in quality of life and exercise capacity with VVIR compared to VVI. When it comes to comparing DDD with DDDR there have been inconsistent results [9]. In extrinsic (functional, induced by for example drugs or high vagal tone) bradycardia, the prognosis is benign, and pacing is only indicated to prevent recurrent syncope [9].

#### *2.6.1.2 Intermittent bradycardia*

Documented symptomatic bradycardia due to sinoatrial block or sinus arrest in patients with intrinsic SND (including the brady-tachy form) is a class I recommendation for pacemaker therapy by the ESC [9]. When there is no documented correlation between symptoms and electrocardiography (ECG), people with intrinsic sinus node dysfunction may still be candidates for cardiac pacing if they have

**13**

*Clinical Indications for Therapeutic Cardiac Devices DOI: http://dx.doi.org/10.5772/intechopen.82463*

of pacemaker syndrome [9].

*2.6.2 Atrioventricular block*

*2.6.2.1 Persistent bradycardia*

experienced syncope and there are documented asymptomatic ventricular pauses of more than 3 seconds. This does not apply to young, well-trained, or medicated persons and during sleep. Alternative explanations such as hypotension should be ruled out before deciding on pacemaker therapy [9]. The recommendations regarding pacing mode for permanent bradycardia apply for intermittent bradycardia as well, based on the fact that there are not enough studies including only patients with intermittent bradycardia. Dual-chamber pacing is preferred to reduce the risk

Pacing improves survival in people with AV block (third-degree and seconddegree type 2), as well as prevents recurrence of syncope. There are no randomized controlled trials (RCTs), but observational studies from the beginning of the pacemaker era suggest this. One study describes a one-year mortality of about 50% in patients with complete AV block [15]. Therefore, pacemaker therapy is recommended by the ESC in these patients, even if they are asymptomatic [9]. Permanent pacing is controversial in second-degree type 1 AV block; although not if it is symptomatic or the conduction delay is situated at intra- or infra-His levels, in these cases pacing should be considered (class of recommendation IIa). If the QRS complex is

Studies have shown that above one quarter of people with VVI develop pacemaker syndrome. Dual-chamber pacing reduces the risk of these symptoms. Since they require an additional lead and have longer implantation times and a higher risk of complications, dual-chamber devices are more expensive. When the risk of AF and pacemaker syndrome is taken into account, the cost difference is small over a five-year period. Since there is no reduction in morbidity or mortality with dualchamber pacing compared to ventricular pacing, the choice should be made on an individual basis where increased risk of complications and cost is considered [9]. The United Kingdom Pacing and Cardiovascular Events (UKPACE) trial compared dual-chamber pacing to ventricular pacing in elderly patients with high grade AV block and found that pacing mode does not affect survival, and in contrast with the CTOPP trial, no reduction in AF in dual-chamber compared to ventricular pacing was seen. Fixed-rate single-chamber pacing was associated with an increased risk of stroke, transient ischemic attack, and thromboembolism compared with dualchamber pacing, but there was no difference between the rate-adaptive single-

In permanent AF and AV block, the ESC recommendation (class I recommenda-

Correlations between symptoms and ECG are not as important in intrinsic third- or second-degree AV block as it is in SSS. The ESC states that cardiac pacing is indicated in people suffering from intrinsic intermittent AV block, regardless of

In patients with syncope, the presence of bundle branch block (BBB) suggests that the cause may be complete heart block. In spite of this, less than half of patients with

documentation of correlation between symptoms and ECG findings [9].

wide, development of complete AV block is more likely [9].

chamber and dual-chamber groups [16].

*2.6.3 Suspected (undocumented) bradycardia*

*2.6.2.2 Intermittent bradycardia*

tion) is ventricular pacing with rate response [9].

#### *Clinical Indications for Therapeutic Cardiac Devices DOI: http://dx.doi.org/10.5772/intechopen.82463*

experienced syncope and there are documented asymptomatic ventricular pauses of more than 3 seconds. This does not apply to young, well-trained, or medicated persons and during sleep. Alternative explanations such as hypotension should be ruled out before deciding on pacemaker therapy [9]. The recommendations regarding pacing mode for permanent bradycardia apply for intermittent bradycardia as well, based on the fact that there are not enough studies including only patients with intermittent bradycardia. Dual-chamber pacing is preferred to reduce the risk of pacemaker syndrome [9].

#### *2.6.2 Atrioventricular block*

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

*2.6.1 Sinus node dysfunction*

*2.6.1.1 Persistent bradycardia*

*2.6.1.2 Intermittent bradycardia*

reversible causes for bradycardia are excluded, the indication for pacing is based on the severity of bradycardia rather than its etiology [9]. It should be noted though that symptomatic sinus bradycardia as a result of medical therapy is an indication

Persistent sinus bradycardia, chronotropic incompetence, and sinus arrest can all be seen in sinus node disease (SND), a condition that primarily affects the elderly [10]. When diagnosing chronotropic incompetence (the inability to increase the heart rate as a response to activity or other demands), the fact that heart rate is affected by aging, medication, and physical conditioning must be taken into account. Exercise testing is the basis for diagnosis [11]. It is important to separate physiological bradycardia from inappropriate bradycardia, since sinus bradycardia in trained athletes is normal and not an indication for pacemaker therapy [10].

In patients with SND, pacing has not been proven to prolong survival and is therefore used to relieve symptoms. Symptoms of bradycardia include impaired tolerance to exercise, symptoms of heart failure (HF), syncope, and more subtle symptoms like dizziness and forgetfulness. Untreated patients with SSS, however, are commonly affected by systemic thromboembolism [9]. A significant reduction in stroke and atrial fibrillation (AF) among these patients has been seen with AAI or DDD compared with VVI. The DANPACE trial shows that the incidence of paroxysmal AF is higher with AAIR pacing than DDDR, and there is a two-fold increase in the risk of re-operation [12]. In the Canadian Trial of Physiologic Pacing (CTOPP) where physiologic pacing (dual-chamber or atrial) was compared to ventricular pacing in patients with symptomatic bradycardia, a reduction in the risk of AF was seen for patients who received dual-chamber pacing. No significant reduction in the risk of stroke, death, or hospitalization for HF in the first 3 years after implantation was seen with dual-chamber pacing, but the risk of perioperative complications was significantly higher in this group [13]. The MOST trial compared ventricular- to dualchamber pacing in patients with SSS, and no reduction in stroke with dual-chamber pacing was observed. However, a reduction of AF, signs and symptoms of HF, and a slight improvement in quality of life was seen [14]. Between 0.6 and 1.9% of all patients with SND develop AV block every year, which can of course be a problem when AAIR is used [9]. Rate response should be considered (class IIa recommendation) in people with SND and chronotropic incompetence according to the guidelines of the European Society of Cardiology (ESC). The indication is strengthened in those who are young and physically active. There is evidence for improvement in quality of life and exercise capacity with VVIR compared to VVI. When it comes to comparing DDD with DDDR there have been inconsistent results [9]. In extrinsic (functional, induced by for example drugs or high vagal tone) bradycardia, the prognosis is benign, and pacing is only indicated to prevent recurrent syncope [9].

Documented symptomatic bradycardia due to sinoatrial block or sinus arrest in patients with intrinsic SND (including the brady-tachy form) is a class I recommendation for pacemaker therapy by the ESC [9]. When there is no documented correlation between symptoms and electrocardiography (ECG), people with intrinsic sinus node dysfunction may still be candidates for cardiac pacing if they have

for permanent pacing if there are no alternative treatment options [10].

**12**

#### *2.6.2.1 Persistent bradycardia*

Pacing improves survival in people with AV block (third-degree and seconddegree type 2), as well as prevents recurrence of syncope. There are no randomized controlled trials (RCTs), but observational studies from the beginning of the pacemaker era suggest this. One study describes a one-year mortality of about 50% in patients with complete AV block [15]. Therefore, pacemaker therapy is recommended by the ESC in these patients, even if they are asymptomatic [9]. Permanent pacing is controversial in second-degree type 1 AV block; although not if it is symptomatic or the conduction delay is situated at intra- or infra-His levels, in these cases pacing should be considered (class of recommendation IIa). If the QRS complex is wide, development of complete AV block is more likely [9].

Studies have shown that above one quarter of people with VVI develop pacemaker syndrome. Dual-chamber pacing reduces the risk of these symptoms. Since they require an additional lead and have longer implantation times and a higher risk of complications, dual-chamber devices are more expensive. When the risk of AF and pacemaker syndrome is taken into account, the cost difference is small over a five-year period. Since there is no reduction in morbidity or mortality with dualchamber pacing compared to ventricular pacing, the choice should be made on an individual basis where increased risk of complications and cost is considered [9]. The United Kingdom Pacing and Cardiovascular Events (UKPACE) trial compared dual-chamber pacing to ventricular pacing in elderly patients with high grade AV block and found that pacing mode does not affect survival, and in contrast with the CTOPP trial, no reduction in AF in dual-chamber compared to ventricular pacing was seen. Fixed-rate single-chamber pacing was associated with an increased risk of stroke, transient ischemic attack, and thromboembolism compared with dualchamber pacing, but there was no difference between the rate-adaptive singlechamber and dual-chamber groups [16].

In permanent AF and AV block, the ESC recommendation (class I recommendation) is ventricular pacing with rate response [9].

#### *2.6.2.2 Intermittent bradycardia*

Correlations between symptoms and ECG are not as important in intrinsic third- or second-degree AV block as it is in SSS. The ESC states that cardiac pacing is indicated in people suffering from intrinsic intermittent AV block, regardless of documentation of correlation between symptoms and ECG findings [9].

#### *2.6.3 Suspected (undocumented) bradycardia*

In patients with syncope, the presence of bundle branch block (BBB) suggests that the cause may be complete heart block. In spite of this, less than half of patients with

BBB and syncope are diagnosed with cardiac syncope. According to the ISSUE 1 study and the Bradycardia detection in Bundle Branch Block (B4) study [17] (that included patients with normal or preserved systolic function), it is safe to wait until the correct diagnosis is made before starting cardiac pacing [9]. ICD or CRT-D should be considered in patients with syncope who have BBB and HF, previous myocardial infarction, or ejection fraction (EF) ≤ 35%. This is because a high incidence of total and sudden cardiac death (SCD) has been observed in patients with BBB, and mostly those with HF, previous myocardial infarction, or low EF [9]. In patients with BBB who have experienced syncope but have normal EF, an electrophysiological study should be considered. If this study is abnormal, pacing is a class I recommendation in the ESC guidelines [9]. If the electrophysiological study is normal, an insertable cardiac monitor should be considered since EPS cannot rule out intermittent or paroxysmal AV block [9].

Cardiac pacing is generally indicated in alternating BBB (block involving all three fascicles on successive ECGs) since it is known to progress toward AV block fast, even if there is no history of syncope [9]. Asymptomatic BBB is not an indication for pacemaker therapy. In some cases though, patients with unexplained syncope and BBB are candidates for pacemaker therapy, especially old people with unpredictable syncope [9].

#### *2.6.4 Carotid sinus syncope*

Carotid sinus syncope is defined as a drop in blood pressure of 50 mmHg or asystole of more than 3 s as a result of carotid sinus massage [9]. Dual-chamber pacing is indicated when asystole of 6 s and syncope follows carotid sinus massage (to be performed for a full 10 s, supine and erect), and the patient has recurrent and unpredictable syncope [9].

#### *2.6.5 Tilt-induced vasovagal syncope*

Tilt-induced vasovagal syncope often affects young people and is in itself a benign condition. When deciding whether to implant a pacemaker, this must be taken into consideration [9]. Pacing may be considered (class IIb recommendation according to ESC) in these patients if they suffer from recurrent and unpredictable episodes, are older than 40 years, and have a documented cardio-inhibitory reflex, but only after other therapies have failed [9]. As with carotid sinus syncope, dualchamber pacing is recommended [9].

#### **2.7 Indications for pacing in specific conditions**

#### *2.7.1 Pacing in acute myocardial infarction*

Primary angioplasty and thrombolytic therapy have led to a decrease in AV block associated with acute myocardial infarction, but it still occurs and when it does, mortality is high [10]. When advanced second- or third-degree AV block is seen with left bundle branch block (LBBB) or when right bundle branch block occurs with left anterior or posterior fascicular block, the prognosis is particularly bad [10]. Intraventricular conduction delays develop as a result of extensive damage to the myocardium, meaning greater injury to the heart than an isolated electrical problem [10]. If the AV block is expected to be temporary, permanent pacemaker therapy should be avoided [10]. AV block associated with acute myocardial infarction resolves spontaneously in 2–7 days in most cases [9]. Permanent AV pacing is recommended by the American Heart Association (AHA) in persistent and

**15**

*Clinical Indications for Therapeutic Cardiac Devices DOI: http://dx.doi.org/10.5772/intechopen.82463*

tion are the same as those for AV block of other etiologies [9].

weeks before deciding on pacemaker therapy [9].

*2.7.4 Pacing in hypertrophic cardiomyopathy*

*2.7.3 Pacing in children and in congenital heart disease*

*heart transplantation*

*2.7.2 Pacing after cardiac surgery, transcatheter aortic valve implantation, and* 

Both AV block and SND may appear as complications after cardiac interventions, and if they persist, permanent pacing must be considered. An observation time of up to 7 days is recommended before implanting a permanent pacemaker in high degree or complete AV block following cardiac surgery or transcatheter aortic valve implantation. A shorter observation time can be used in case of complete AV block with a low escape rhythm, where resolution is not likely. SND as a result of cardiac surgery or heart transplantation should be observed from 5 days up to some

When implanting a pacemaker in a young person, several considerations have to be made. For one, they will have the pacemaker for a whole lifetime, increasing the risk of experiencing complications sometime during this period. They usually have higher activity levels than adults, and because of this and the fact that they grow the risk of stress on the device and electrode dislodgement is increased. The presence of right to left-shunt is a contraindication for endocardial leads; hence, epicardial pacing is used instead in this congenital defect. Small body size and the absence of transvenous access are other reasons why epicardial pacing is often preferred in children. Second-degree type 2 and third-degree AV block are indications (class I according to ESC) for pacemaker therapy in children who are symptomatic or if any of the following risk factors are present: ventricular dysfunction, prolonged QTc interval, complex ventricular ectopy, wide QRS complex escape rhythm, slow ventricular rate (<50 beats per minute, ventricular pauses more than three times the cycle length of the underlying rhythm) with or without symptoms. For children without any risk factors, the ESC states that pacing may be considered in highdegree and complete AV block, adding that opinions regarding the benefit of pacing differ. Pacemaker therapy is indicated for children with SND if they are symptomatic and there is a clear correlation between symptoms and bradycardia. The decision to implant a pacemaker in a child should be made after discussion with pediatric cardiologists, and it is recommended that it is done in a specialized center [9].

Patients who have symptoms because of left ventricular outflow tract obstruc-

tion can be treated medically, surgically, with septal alcohol ablation, and

symptomatic second- or third-degree AV block following acute myocardial infarction. Persistent second-degree AV block in the His-Purkinje system associated with alternating bundle branch block also constitutes an indication for permanent ventricular pacing, as well as third-degree AV block within or below the His-Purkinje system following ST elevation myocardial infarction. In the case of associated bundle branch block, permanent ventricular pacing is indicated in transient advanced second-degree and third-degree infra-nodal AV block according to AHA, whereas ESC states that there is no evidence that pacing improves outcomes in these patients [9, 10]. Permanent AV pacing may be considered in the case of persistent second-degree or third-degree AV block at the AV node level, even if there are no symptoms, according to the AHA [10]. According to the ESC, the recommendations for pacemaker therapy in permanent AV block following acute myocardial infarc*Clinical Indications for Therapeutic Cardiac Devices DOI: http://dx.doi.org/10.5772/intechopen.82463*

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

BBB and syncope are diagnosed with cardiac syncope. According to the ISSUE 1 study and the Bradycardia detection in Bundle Branch Block (B4) study [17] (that included patients with normal or preserved systolic function), it is safe to wait until the correct diagnosis is made before starting cardiac pacing [9]. ICD or CRT-D should be considered in patients with syncope who have BBB and HF, previous myocardial infarction, or ejection fraction (EF) ≤ 35%. This is because a high incidence of total and sudden cardiac death (SCD) has been observed in patients with BBB, and mostly those with HF, previous myocardial infarction, or low EF [9]. In patients with BBB who have experienced syncope but have normal EF, an electrophysiological study should be considered. If this study is abnormal, pacing is a class I recommendation in the ESC guidelines [9]. If the electrophysiological study is normal, an insertable cardiac monitor should be considered since EPS cannot rule out intermittent or paroxysmal AV

Cardiac pacing is generally indicated in alternating BBB (block involving all three fascicles on successive ECGs) since it is known to progress toward AV block fast, even if there is no history of syncope [9]. Asymptomatic BBB is not an indication for pacemaker therapy. In some cases though, patients with unexplained syncope and BBB are candidates for pacemaker therapy, especially old people with

Carotid sinus syncope is defined as a drop in blood pressure of 50 mmHg or asystole of more than 3 s as a result of carotid sinus massage [9]. Dual-chamber pacing is indicated when asystole of 6 s and syncope follows carotid sinus massage (to be performed for a full 10 s, supine and erect), and the patient has recurrent and

Tilt-induced vasovagal syncope often affects young people and is in itself a benign condition. When deciding whether to implant a pacemaker, this must be taken into consideration [9]. Pacing may be considered (class IIb recommendation according to ESC) in these patients if they suffer from recurrent and unpredictable episodes, are older than 40 years, and have a documented cardio-inhibitory reflex, but only after other therapies have failed [9]. As with carotid sinus syncope, dual-

Primary angioplasty and thrombolytic therapy have led to a decrease in AV block

associated with acute myocardial infarction, but it still occurs and when it does, mortality is high [10]. When advanced second- or third-degree AV block is seen with left bundle branch block (LBBB) or when right bundle branch block occurs with left anterior or posterior fascicular block, the prognosis is particularly bad [10]. Intraventricular conduction delays develop as a result of extensive damage to the myocardium, meaning greater injury to the heart than an isolated electrical problem [10]. If the AV block is expected to be temporary, permanent pacemaker therapy should be avoided [10]. AV block associated with acute myocardial infarction resolves spontaneously in 2–7 days in most cases [9]. Permanent AV pacing is recommended by the American Heart Association (AHA) in persistent and

**14**

block [9].

unpredictable syncope [9].

*2.6.4 Carotid sinus syncope*

unpredictable syncope [9].

*2.6.5 Tilt-induced vasovagal syncope*

chamber pacing is recommended [9].

*2.7.1 Pacing in acute myocardial infarction*

**2.7 Indications for pacing in specific conditions**

symptomatic second- or third-degree AV block following acute myocardial infarction. Persistent second-degree AV block in the His-Purkinje system associated with alternating bundle branch block also constitutes an indication for permanent ventricular pacing, as well as third-degree AV block within or below the His-Purkinje system following ST elevation myocardial infarction. In the case of associated bundle branch block, permanent ventricular pacing is indicated in transient advanced second-degree and third-degree infra-nodal AV block according to AHA, whereas ESC states that there is no evidence that pacing improves outcomes in these patients [9, 10]. Permanent AV pacing may be considered in the case of persistent second-degree or third-degree AV block at the AV node level, even if there are no symptoms, according to the AHA [10]. According to the ESC, the recommendations for pacemaker therapy in permanent AV block following acute myocardial infarction are the same as those for AV block of other etiologies [9].

#### *2.7.2 Pacing after cardiac surgery, transcatheter aortic valve implantation, and heart transplantation*

Both AV block and SND may appear as complications after cardiac interventions, and if they persist, permanent pacing must be considered. An observation time of up to 7 days is recommended before implanting a permanent pacemaker in high degree or complete AV block following cardiac surgery or transcatheter aortic valve implantation. A shorter observation time can be used in case of complete AV block with a low escape rhythm, where resolution is not likely. SND as a result of cardiac surgery or heart transplantation should be observed from 5 days up to some weeks before deciding on pacemaker therapy [9].

#### *2.7.3 Pacing in children and in congenital heart disease*

When implanting a pacemaker in a young person, several considerations have to be made. For one, they will have the pacemaker for a whole lifetime, increasing the risk of experiencing complications sometime during this period. They usually have higher activity levels than adults, and because of this and the fact that they grow the risk of stress on the device and electrode dislodgement is increased. The presence of right to left-shunt is a contraindication for endocardial leads; hence, epicardial pacing is used instead in this congenital defect. Small body size and the absence of transvenous access are other reasons why epicardial pacing is often preferred in children. Second-degree type 2 and third-degree AV block are indications (class I according to ESC) for pacemaker therapy in children who are symptomatic or if any of the following risk factors are present: ventricular dysfunction, prolonged QTc interval, complex ventricular ectopy, wide QRS complex escape rhythm, slow ventricular rate (<50 beats per minute, ventricular pauses more than three times the cycle length of the underlying rhythm) with or without symptoms. For children without any risk factors, the ESC states that pacing may be considered in highdegree and complete AV block, adding that opinions regarding the benefit of pacing differ. Pacemaker therapy is indicated for children with SND if they are symptomatic and there is a clear correlation between symptoms and bradycardia. The decision to implant a pacemaker in a child should be made after discussion with pediatric cardiologists, and it is recommended that it is done in a specialized center [9].

#### *2.7.4 Pacing in hypertrophic cardiomyopathy*

Patients who have symptoms because of left ventricular outflow tract obstruction can be treated medically, surgically, with septal alcohol ablation, and

sequential AV pacing [9]. Sequential AV pacing is an alternative when myectomy or septal alcohol ablation are contraindicated or when the risk of AV block after these procedures is considered high [9].

#### *2.7.5 Pacing in pregnancy*

Complete heart block with a slow escape rhythm with wide QRS complexes should be treated with pacemaker implantation during pregnancy, using echoguidance or electro-anatomic navigation to avoid fluoroscopy. The procedure is safe, especially when the fetus is beyond 8 weeks of gestation. In case of stable, junctional escape rhythm with narrow complexes, pacemaker implantation can be delayed until after delivery [9].

#### *2.7.6 Leadless pacemakers*

Malfunction of the electrodes is the most common cause of surgical pacemaker revision. Pocket hematoma and erosion are other complications associated with pacemaker implantation [18]. There are currently two self-contained leadless pacemaker systems available: Nanostim™ and Micra™. Nanostim™ has been evaluated in the prospective nonrandomized study LEADLESS, and the complication-free rate compares favorably with traditional pacemaker systems [18]. As for Micra™, the risk of major complications in the first 12 months after implantation was 48% lower compared to historical control patients with transvenous systems [19]. Currently, solely the VVI-mode is available via leadless pacemaker systems. Considering this, the higher cost and the fact that there is not much experience outside clinical trials with these systems yet, use of leadless pacemakers should for now be reserved for when VVI-mode is indicated and transvenous leads are unfeasible or undesirable.

#### **2.8 Emergency temporary pacing**

Bradycardia can be a life-threatening condition where immediate action is crucial. When the hemodynamics is affected resulting in symptoms of acute HF, ischemic chest pain, or signs of shock, the first step is to administer atropine intravenously. If atropine is not effective or appropriate, a continuous infusion with beta-adrenergic agonists such as isoproterenol, dopamine, or epinephrine is sometimes needed to uphold an adequate pulse until pacemaker therapy can be initiated. Another alternative is transcutaneous pacing, which can be used while waiting for implantation of a temporary transvenous- or permanent pacemaker [20]. The pads are preferably attached with anterior-posterior placement and are then connected to the defibrillator/monitor [21]. Transcutaneous pacing can be performed on a conscious patient, but sedation is preferred [21, 22]. During transcutaneous pacing, the patient must be monitored closely with ECG and with regard to hemodynamic stability [9]. Seeing that there are a number of risks associated with temporary transvenous pacing (for example, accidental extraction of the pacemaker lead by the patient, risk of infection, and thromboembolic events), the ESC recommends avoiding this treatment if possible, and otherwise keeping the treatment time as brief as possible [9].

#### **3. The implantable cardioverter defibrillator**

The first patient to receive an ICD was a woman who had survived repeated episodes of ventricular fibrillation (VF) and continued to experience arrhythmias

**17**

*Clinical Indications for Therapeutic Cardiac Devices DOI: http://dx.doi.org/10.5772/intechopen.82463*

**3.2 Cardioversion and antitachycardia pacing**

tion of SCD due to VT/VF [25].

**3.3 Indications for ICD**

*3.3.1 Secondary prevention*

**3.1 Etiology**

refractory to medical therapy [23]. This was at The Johns Hopkins Hospital in the US in 1980, after extensive work by Michel Mirowski and his colleagues. After the death of his mentor, who suffered from recurrent ventricular tachyarrhythmias, Mirowski's goal was to create a device that could monitor the heart rhythm and administer a defibrillating shock to treat life-threatening tachyarrhythmias [24]. Today the ICD is the treatment of choice for both primary and secondary preven-

Every year, cardiovascular diseases cause around 17 million deaths worldwide, of which SCD makes up approximately 25% [25]. The vast majority of these deaths are due to ventricular tachyarrhythmias. According to epidemiological data, 80% of the fatal arrhythmias occur as a consequence of structural coronary artery abnormalities. Dilated- and hypertrophic cardiomyopathies are the second most common reasons for SCD [26]. Among the young, channelopathies, cardiomyopathies, myocarditis, and drug-induced arrhythmias are more common, while coronary artery disease, valvular heart diseases, and HF predominate in older individuals [25].

Cardioversion implies that shock delivery is synchronized with the QRS complex

In patients with high risk of SCD, ICD therapy prevents SCD and prolongs life (given that life expectancy is not for other reasons less than 1–2 years) [25]. Both patients who have experienced previous ventricular arrhythmias and those who are

In patients who have survived an episode of documented VF or VT that is not hemodynamically tolerated, ICD is a class I recommendation according to the ESC, provided that there are no reversible causes and that the expected survival with good functional status is at least 1 year [25]. Recurrent sustained VT (not including the first 48 hours after myocardial infarction) in patients who are treated

with optimal medical therapy and have a normal left ventricular EF (LVEF) should be considered for ICD therapy (class IIa recommendation). Survival must be expected for at least a year with good functional status [25]. Three trials have studied the effect of ICD compared to medical treatment as secondary prevention in patients who have survived VF or sustained VT: the antiarrhythmics vs.

to avoid inducing VF by delivering a shock during the refractory period of the cardiac cycle, and it is recommended for the treatment of several supraventricular arrhythmias and monomorphic ventricular tachycardia (VT) with pulses. It should not be used to treat VF or pulseless or polymorphic VT, since these arrhythmias require unsynchronized high-energy doses, also known as defibrillation [27]. Antitachycardia pacing is an alternative way to terminate monomorphic ventricular arrhythmias; it can reduce the number of shocks and is generally tolerated well since it is rarely noticed by the patient. The mechanism is that a short sequence of pacemaker pulses (typically 8–12), with a rate slightly faster than the detected tachycardia, is delivered as a response to ventricular arrhythmia. The success rate

varies but has in some cohorts been shown to exceed 90% [28].

at increased risk of future arrhythmia can be protected by ICD therapy.

refractory to medical therapy [23]. This was at The Johns Hopkins Hospital in the US in 1980, after extensive work by Michel Mirowski and his colleagues. After the death of his mentor, who suffered from recurrent ventricular tachyarrhythmias, Mirowski's goal was to create a device that could monitor the heart rhythm and administer a defibrillating shock to treat life-threatening tachyarrhythmias [24]. Today the ICD is the treatment of choice for both primary and secondary prevention of SCD due to VT/VF [25].

#### **3.1 Etiology**

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

procedures is considered high [9].

delayed until after delivery [9].

**2.8 Emergency temporary pacing**

*2.7.6 Leadless pacemakers*

*2.7.5 Pacing in pregnancy*

sequential AV pacing [9]. Sequential AV pacing is an alternative when myectomy or septal alcohol ablation are contraindicated or when the risk of AV block after these

Complete heart block with a slow escape rhythm with wide QRS complexes should be treated with pacemaker implantation during pregnancy, using echoguidance or electro-anatomic navigation to avoid fluoroscopy. The procedure is safe, especially when the fetus is beyond 8 weeks of gestation. In case of stable, junctional escape rhythm with narrow complexes, pacemaker implantation can be

Malfunction of the electrodes is the most common cause of surgical pacemaker revision. Pocket hematoma and erosion are other complications associated with pacemaker implantation [18]. There are currently two self-contained leadless pacemaker systems available: Nanostim™ and Micra™. Nanostim™ has been evaluated in the prospective nonrandomized study LEADLESS, and the complication-free rate compares favorably with traditional pacemaker systems [18]. As for Micra™, the risk of major complications in the first 12 months after implantation was 48% lower compared to historical control patients with transvenous systems [19]. Currently, solely the VVI-mode is available via leadless pacemaker systems. Considering this, the higher cost and the fact that there is not much experience outside clinical trials with these systems yet, use of leadless pacemakers should for now be reserved for when VVI-mode is indicated and transvenous leads are unfeasible or undesirable.

Bradycardia can be a life-threatening condition where immediate action is crucial. When the hemodynamics is affected resulting in symptoms of acute HF, ischemic chest pain, or signs of shock, the first step is to administer atropine intravenously. If atropine is not effective or appropriate, a continuous infusion with beta-adrenergic agonists such as isoproterenol, dopamine, or epinephrine is sometimes needed to uphold an adequate pulse until pacemaker therapy can be initiated. Another alternative is transcutaneous pacing, which can be used while waiting for implantation of a temporary transvenous- or permanent pacemaker [20]. The pads are preferably attached with anterior-posterior placement and are then connected to the defibrillator/monitor [21]. Transcutaneous pacing can be performed on a conscious patient, but sedation is preferred [21, 22]. During transcutaneous pacing, the patient must be monitored closely with ECG and with regard to hemodynamic stability [9]. Seeing that there are a number of risks associated with temporary transvenous pacing (for example, accidental extraction of the pacemaker lead by the patient, risk of infection, and thromboembolic events), the ESC recommends avoiding this treatment if possible, and otherwise keeping the treatment time as

The first patient to receive an ICD was a woman who had survived repeated episodes of ventricular fibrillation (VF) and continued to experience arrhythmias

**16**

brief as possible [9].

**3. The implantable cardioverter defibrillator**

Every year, cardiovascular diseases cause around 17 million deaths worldwide, of which SCD makes up approximately 25% [25]. The vast majority of these deaths are due to ventricular tachyarrhythmias. According to epidemiological data, 80% of the fatal arrhythmias occur as a consequence of structural coronary artery abnormalities. Dilated- and hypertrophic cardiomyopathies are the second most common reasons for SCD [26]. Among the young, channelopathies, cardiomyopathies, myocarditis, and drug-induced arrhythmias are more common, while coronary artery disease, valvular heart diseases, and HF predominate in older individuals [25].

#### **3.2 Cardioversion and antitachycardia pacing**

Cardioversion implies that shock delivery is synchronized with the QRS complex to avoid inducing VF by delivering a shock during the refractory period of the cardiac cycle, and it is recommended for the treatment of several supraventricular arrhythmias and monomorphic ventricular tachycardia (VT) with pulses. It should not be used to treat VF or pulseless or polymorphic VT, since these arrhythmias require unsynchronized high-energy doses, also known as defibrillation [27]. Antitachycardia pacing is an alternative way to terminate monomorphic ventricular arrhythmias; it can reduce the number of shocks and is generally tolerated well since it is rarely noticed by the patient. The mechanism is that a short sequence of pacemaker pulses (typically 8–12), with a rate slightly faster than the detected tachycardia, is delivered as a response to ventricular arrhythmia. The success rate varies but has in some cohorts been shown to exceed 90% [28].

#### **3.3 Indications for ICD**

In patients with high risk of SCD, ICD therapy prevents SCD and prolongs life (given that life expectancy is not for other reasons less than 1–2 years) [25]. Both patients who have experienced previous ventricular arrhythmias and those who are at increased risk of future arrhythmia can be protected by ICD therapy.

#### *3.3.1 Secondary prevention*

In patients who have survived an episode of documented VF or VT that is not hemodynamically tolerated, ICD is a class I recommendation according to the ESC, provided that there are no reversible causes and that the expected survival with good functional status is at least 1 year [25]. Recurrent sustained VT (not including the first 48 hours after myocardial infarction) in patients who are treated with optimal medical therapy and have a normal left ventricular EF (LVEF) should be considered for ICD therapy (class IIa recommendation). Survival must be expected for at least a year with good functional status [25]. Three trials have studied the effect of ICD compared to medical treatment as secondary prevention in patients who have survived VF or sustained VT: the antiarrhythmics vs.

implantable defibrillator (AVID) study (patients with VT had syncope or serious cardiac symptoms and an LVEF of 40% or less) [29], the Cardiac Arrest Study Hamburg (CASH) (patients were survivors of cardiac arrest secondary to documented ventricular arrhythmias) [30], and the Canadian Implantable Defibrillator Study (CIDS) (patients with VT had syncope or cardiac symptoms and an LVEF of 35% or less; patients with unmonitored syncope and subsequent documentation of VT were also included) [31]. The AVID study showed an increase in overall survival in the ICD group. In the CASH study, the reduction in all-cause mortality in the ICD group did not reach statistical significance but there was a 61% reduction in SCD. The reduction in all-cause mortality and SCD seen in the ICD group in the CIDS study was not statistically significant. A meta-analysis of these three trials concluded that there is a 28% reduction in total mortality with ICD therapy compared to amiodarone, mainly due to a 50% reduction in arrhythmic mortality [32]. In the following sections, current guidelines regarding secondary prevention in specific circumstances are addressed.

#### *3.3.1.1 Acute coronary syndromes*

Approximately 6% of patients with acute coronary syndrome experience VT/VF within 48 hours after the first symptoms, the majority during or before reperfusion therapy [25, 33]*.* As stated above, ICD is recommended after an episode of VF or hemodynamically compromising VT, unless the episode occurred within 48 hours of myocardial infarction, in a patient who receives optimal medical treatment [25].

#### *3.3.1.2 Cardiomyopathies*

In patients with hypertrophic cardiomyopathy, dilated cardiomyopathy, left ventricular noncompaction cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy, ICD therapy is indicated after a survived episode of cardiac arrest due to VT/VF, or in patients who have experienced syncope or hemodynamic compromise because of spontaneous sustained VT—in accordance with the guidelines in general [25]. When it comes to arrhythmogenic right ventricular cardiomyopathy, the ESC suggests that ICD should be considered (class IIa) in patients who have experienced hemodynamically well tolerated sustained VT as well. For patients with light-chain amyloidosis or hereditary transthyretin-associated amyloidosis who have had a sustained VT with hemodynamic impact, and have a life expectancy of more than a year with good functional status, ICD should be considered. This recommendation is upgraded to a class I (is recommended) regarding restrictive cardiomyopathy [25].

#### *3.3.1.3 Hereditary primary arrhythmia syndromes*

ICD therapy and beta-blockers are recommended for patients with long QT syndrome and previous cardiac arrest and should be considered in these patients if they have experienced syncope or VT while on an adequate dose of beta-blockers [25]. In catecholaminergic polymorphic VT, ICD as an addition to beta-blockers is recommended after a survived cardiac arrest, recurrent syncope, or polymorphic/bidirectional VT during treatment with optimal medical therapy [25]. In short QT syndrome and Brugada syndrome, ICD is recommended for patients who have survived a cardiac arrest or those who have experienced documented spontaneous sustained VT [25]. In Brugada syndrome, an ICD may be indicated in primary prevention, especially when syncope is likely due to an arrhythmic event [34].

**19**

*Clinical Indications for Therapeutic Cardiac Devices DOI: http://dx.doi.org/10.5772/intechopen.82463*

high and the wait is often a year or more [25].

*3.3.2.2 Acute coronary syndromes*

*3.3.2.3 Cardiomyopathies*

In the Sudden Cardiac Death in Heart Failure (SCD-HeFT) trial a decrease in the overall mortality of 23% was seen in patients with both ischemic and nonischemic HF in New York Heart Association (NYHA) functional class II and III and an LVEF of 35% or less who received an ICD [35]. An LVEF of 35% or less and symptomatic HF (NYHA II-III) after 3 months of optimal medication is a class I indication for ICD therapy according to the ESC (provided that the expected survival with good functional status is at least 1 year) [25]. More recently, the DANISH trial randomized patients with symptomatic HF (LVEF of 35% or less) of nonischemic origin to ICD therapy or usual clinical care, and found no overall survival benefit with ICD therapy, although the risk of SCD was halved [36]. However, all-cause mortality was significantly reduced by ICD in patients younger than 59 years old. There is currently no indication for ICD therapy in patients with HF in NYHA class IV, unless they are listed for heart transplantation since their risk of SCD is generally

In 1996, results from the MADIT trial were published, showing that in patients

with a prior myocardial infarction, NYHA class I-III, LVEF of less than 35%, a documented asymptomatic nonsustained VT, and nonsuppressible VT on an electrophysiological study, prophylactic ICD therapy leads to improved survival [37]. The MADIT-II trial enrolled patients with reduced left ventricular function (LVEF 30% or less) after myocardial infarction and found that the patients who received ICD therapy had a 31% decrease in all-cause mortality [38]. LVEF should be assessed before discharge from the hospital in all patients with acute coronary syndrome, and re-assessed 6–12 weeks later, to evaluate whether or not primary prevention ICD implantation is indicated. As in nonischemic etiology with LVEF of 35% or lower, symptomatic HF (NYHA class II-III), expected survival with good functional status for at least 1 year, and optimal medical therapy for at least 3 months, ICD therapy is recommended (class I recommendation) by the ESC. At least 6 weeks must have passed since the myocardial infarction before deciding on ICD therapy [25]. The use of an ICD as prophylaxis in patients with a recent myocardial infarction (6–40 days previously) does not reduce the overall mortality; a reduction in SCD was offset by an increase in nonarrhythmic death [39]. Hence, ICD implantation within 40 days of acute myocardial infarction as primary prevention of SCD is generally not indicated but it may be considered in specific cases: preexisting impairment in LVEF, incomplete revascularization, and arrhythmia that

occurs more than 48 hours after acute myocardial infarction [25].

The DEFINITE trial studied patients with nonischemic dilated cardiomyopathy with an EF of less than 36% and premature ventricular complexes or nonsustained VT, and found that ICD implantation significantly reduced the risk of SCD [40]. The same indications for ICD therapy regarding patients with symptomatic heart failure apply to patients with dilated cardiomyopathy and left ventricular noncompaction cardiomyopathy. In addition to this, ICD should be considered in patients with dilated cardiomyopathy who have a verified disease-causing LMNA mutation (frequently seen in patients with conduction diseases) and clinical risk factors [25].

*3.3.2 Primary prevention*

*3.3.2.1 Heart failure*

#### *3.3.2 Primary prevention*

#### *3.3.2.1 Heart failure*

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

in specific circumstances are addressed.

*3.3.1.1 Acute coronary syndromes*

*3.3.1.2 Cardiomyopathies*

cardiomyopathy [25].

arrhythmic event [34].

*3.3.1.3 Hereditary primary arrhythmia syndromes*

implantable defibrillator (AVID) study (patients with VT had syncope or serious cardiac symptoms and an LVEF of 40% or less) [29], the Cardiac Arrest Study Hamburg (CASH) (patients were survivors of cardiac arrest secondary to documented ventricular arrhythmias) [30], and the Canadian Implantable Defibrillator Study (CIDS) (patients with VT had syncope or cardiac symptoms and an LVEF of 35% or less; patients with unmonitored syncope and subsequent documentation of VT were also included) [31]. The AVID study showed an increase in overall survival in the ICD group. In the CASH study, the reduction in all-cause mortality in the ICD group did not reach statistical significance but there was a 61% reduction in SCD. The reduction in all-cause mortality and SCD seen in the ICD group in the CIDS study was not statistically significant. A meta-analysis of these three trials concluded that there is a 28% reduction in total mortality with ICD therapy compared to amiodarone, mainly due to a 50% reduction in arrhythmic mortality [32]. In the following sections, current guidelines regarding secondary prevention

Approximately 6% of patients with acute coronary syndrome experience VT/VF within 48 hours after the first symptoms, the majority during or before reperfusion therapy [25, 33]*.* As stated above, ICD is recommended after an episode of VF or hemodynamically compromising VT, unless the episode occurred within 48 hours of myocardial infarction, in a patient who receives optimal medical treatment [25].

In patients with hypertrophic cardiomyopathy, dilated cardiomyopathy, left ventricular noncompaction cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy, ICD therapy is indicated after a survived episode of cardiac arrest due to VT/VF, or in patients who have experienced syncope or hemodynamic compromise because of spontaneous sustained VT—in accordance with the guidelines in general [25]. When it comes to arrhythmogenic right ventricular cardiomyopathy, the ESC suggests that ICD should be considered (class IIa) in patients who have experienced hemodynamically well tolerated sustained VT as well. For patients with light-chain amyloidosis or hereditary transthyretin-associated amyloidosis who have had a sustained VT with hemodynamic impact, and have a life expectancy of more than a year with good functional status, ICD should be considered. This recommendation is upgraded to a class I (is recommended) regarding restrictive

ICD therapy and beta-blockers are recommended for patients with long QT syndrome and previous cardiac arrest and should be considered in these patients if they have experienced syncope or VT while on an adequate dose of beta-blockers [25]. In catecholaminergic polymorphic VT, ICD as an addition to beta-blockers is recommended after a survived cardiac arrest, recurrent syncope, or polymorphic/bidirectional VT during treatment with optimal medical therapy [25]. In short QT syndrome and Brugada syndrome, ICD is recommended for patients who have survived a cardiac arrest or those who have experienced documented spontaneous sustained VT [25]. In Brugada syndrome, an ICD may be indicated in primary prevention, especially when syncope is likely due to an

**18**

In the Sudden Cardiac Death in Heart Failure (SCD-HeFT) trial a decrease in the overall mortality of 23% was seen in patients with both ischemic and nonischemic HF in New York Heart Association (NYHA) functional class II and III and an LVEF of 35% or less who received an ICD [35]. An LVEF of 35% or less and symptomatic HF (NYHA II-III) after 3 months of optimal medication is a class I indication for ICD therapy according to the ESC (provided that the expected survival with good functional status is at least 1 year) [25]. More recently, the DANISH trial randomized patients with symptomatic HF (LVEF of 35% or less) of nonischemic origin to ICD therapy or usual clinical care, and found no overall survival benefit with ICD therapy, although the risk of SCD was halved [36]. However, all-cause mortality was significantly reduced by ICD in patients younger than 59 years old. There is currently no indication for ICD therapy in patients with HF in NYHA class IV, unless they are listed for heart transplantation since their risk of SCD is generally high and the wait is often a year or more [25].

#### *3.3.2.2 Acute coronary syndromes*

In 1996, results from the MADIT trial were published, showing that in patients with a prior myocardial infarction, NYHA class I-III, LVEF of less than 35%, a documented asymptomatic nonsustained VT, and nonsuppressible VT on an electrophysiological study, prophylactic ICD therapy leads to improved survival [37]. The MADIT-II trial enrolled patients with reduced left ventricular function (LVEF 30% or less) after myocardial infarction and found that the patients who received ICD therapy had a 31% decrease in all-cause mortality [38]. LVEF should be assessed before discharge from the hospital in all patients with acute coronary syndrome, and re-assessed 6–12 weeks later, to evaluate whether or not primary prevention ICD implantation is indicated. As in nonischemic etiology with LVEF of 35% or lower, symptomatic HF (NYHA class II-III), expected survival with good functional status for at least 1 year, and optimal medical therapy for at least 3 months, ICD therapy is recommended (class I recommendation) by the ESC. At least 6 weeks must have passed since the myocardial infarction before deciding on ICD therapy [25]. The use of an ICD as prophylaxis in patients with a recent myocardial infarction (6–40 days previously) does not reduce the overall mortality; a reduction in SCD was offset by an increase in nonarrhythmic death [39]. Hence, ICD implantation within 40 days of acute myocardial infarction as primary prevention of SCD is generally not indicated but it may be considered in specific cases: preexisting impairment in LVEF, incomplete revascularization, and arrhythmia that occurs more than 48 hours after acute myocardial infarction [25].

#### *3.3.2.3 Cardiomyopathies*

The DEFINITE trial studied patients with nonischemic dilated cardiomyopathy with an EF of less than 36% and premature ventricular complexes or nonsustained VT, and found that ICD implantation significantly reduced the risk of SCD [40]. The same indications for ICD therapy regarding patients with symptomatic heart failure apply to patients with dilated cardiomyopathy and left ventricular noncompaction cardiomyopathy. In addition to this, ICD should be considered in patients with dilated cardiomyopathy who have a verified disease-causing LMNA mutation (frequently seen in patients with conduction diseases) and clinical risk factors [25]. Regarding primary prevention in HCM, a calculator that estimates the 5-year risk of SCD (HCM Risk-SCD) is recommended by the ESC to evaluate the need for ICD therapy in patients aged 16 or older. Based on the risk score, the class of recommendation regarding ICD therapy varies [25]. When it comes to primary prophylactic ICD in patients with arrhythmogenic right ventricular cardiomyopathy, the ESC suggests that ICD should be considered in patients who have experienced unexplained syncope. ICD may be considered in patients with arrhythmogenic right ventricular cardiomyopathy who have at least one risk factor for ventricular arrhythmias, including family history of premature SCD and extensive right ventricular disease. The risks of ICD therapy should be taken into account when considering it as primary prophylactic therapy [25]. Finally, ICD therapy should be considered in patients with Chagas disease (a cardiomyopathy caused by the parasite Trypanosoma cruzi) who have an EF of less than 40% [25].

#### *3.3.2.4 Hereditary primary arrhythmia syndromes*

In patients with long QT syndrome, ICD may be considered (as a complement to beta-blockers) in patients who are asymptomatic carriers of a pathogenic *KCNH2*- or *SCN5A*-mutation (high-risk genetic profiles) and have a QTc of more than 500 ms [25]. An ICD may be considered as primary prevention in short QT syndrome, if there is a family history of SCD and evidence of shortened QT in some of these patients. The available data is too scarce for any specific recommendations to be made regarding this. As for Brugada syndrome, primary prevention with an ICD should be considered in patients with a spontaneous type I ECG pattern and suspected arrhythmic syncope in their medical history, and may be considered in patients who develop VF during programmed ventricular stimulation [25].

#### *3.3.2.5 Pediatric patients*

A number of different etiologies are responsible for the risk of SCD in children: channelopathies, cardiomyopathies, and congenital heart disease. The same guidelines for when ICD is indicated apply to both adults and children, with the exception of dilated cardiomyopathy and advanced dysfunction of the left ventricle since the incidence of SCD is low in this group [25].

#### **3.4 The subcutaneous ICD**

This system is placed completely outside the thoracic cavity, eliminating problems with vascular access and transvenous leads. Subcutaneous ICD therapy is not appropriate for patients with bradycardia that requires pacing, for those who have indications for CRT or for those who need antitachycardia pacing. When these patients are excluded, subcutaneous defibrillators should be considered as an alternative to transvenous defibrillators (class IIa recommendation) in patients with an ICD indication [25]. According to the ESC, subcutaneous ICD could be considered (class IIb recommendation) as an alternative to transvenous defibrillators when there are difficulties with venous access, after ICD removal secondary to infection or in young patients who will require long-term ICD therapy [25].

#### **3.5 The wearable cardioverter defibrillator**

As the name suggests, this defibrillator is entirely external; defibrillator, leads and electrode pads are attached to a wearable vest. It may be considered for adult patients with reduced LVEF who are waiting for a more permanent solution (cardiac

**21**

*Clinical Indications for Therapeutic Cardiac Devices DOI: http://dx.doi.org/10.5772/intechopen.82463*

**3.6 Contraindications and considerations**

**3.7 Health-related quality of life**

further studies are needed [45].

**4.1 Cardiac dyssynchrony**

**4. Cardiac resynchronization therapy**

transplantation, transvenous implant) or those who are at a temporary risk of SCD,

All through the European guidelines concerning ICD indications, it is emphasized that the expected survival with good functional status should be at least 1 year for ICD to be an option. As mentioned before, symptomatic HF with NYHA class IV is considered a contraindication, unless the patient is waiting for heart transplantation. VT or VF due to reversible causes should not be treated with ICD [25]. Psychiatric illness that might be aggravated due to ICD implantation is sometimes considered a contraindication [42], although it is not mentioned as such in the ESC guidelines. Up to a fifth of terminally ill patients with an ICD experience shocks in the last weeks of life, and deactivation of the ICD should be considered when the patient's condition worsens. This issue should be discussed before implantation and as the illness progresses [25]. A magnet placed over the ICD will deactivate tachyarrhythmia therapies, and this stops inappropriate defibrillations or unnecessary defibrillations at the end of life.

In its guidelines, the ESC emphasizes the importance of discussing healthrelated quality of life issues with the patient before ICD implantation and during progression of the disease, by making it a class I recommendation. In addition to this, they recommend that patients who experience inappropriate shocks are assessed psychologically and treated for any distress [25]. Depression and anxiety are common in ICD patients; one systematic review reports anxiety in 8–63% of these patients and depression in 5–41% [43]. Similar effects on quality of life have been seen in patients with ICD and with medical therapy, with impairment in quality of life associated with adverse symptoms in both groups and experience of sporadic shocks in the ICD group [44]. Some patients develop post-traumatic stress disorder, and these symptoms have been associated with nonconstructive support (information that leads to insecurity and fear) from healthcare professionals;

In around 30% of patients suffering from chronic HF, the conduction pathways are affected, leading to cardiac dyssynchrony [46]. The aim of CRT is to, as the name suggests, improve synchrony in the heart's contraction [9]. Patients eligible for this therapy are those with a wide QRS complex, HF, and impaired left ventricular function [47]. Biventricular pacing was first introduced in the early 1990s by Bakker et al. and Cazeau et al. [48, 49]. CRT with the ability to work as an ICD is termed CRT-D, whereas the term used for a CRT that solely has a pacing function is CRT-P.

The dyssynchrony that is targeted with CRT is caused by delays in electrical conduction, and the main way to identify this is by assessing the QRS duration (in particular LBBB) [50]. A prolonged QRS duration has been associated with decreased LVEF [51]. In patients with HF, prolongation of the QRS complex has been shown to be an independent predictor of increased total mortality and SCD. LBBB is related to worse survival but not sudden death [52]. Partially, the mechanism behind

as in peripartum cardiomyopathy or active myocarditis [25, 41].

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

Regarding primary prevention in HCM, a calculator that estimates the 5-year risk of SCD (HCM Risk-SCD) is recommended by the ESC to evaluate the need for ICD therapy in patients aged 16 or older. Based on the risk score, the class of recommendation regarding ICD therapy varies [25]. When it comes to primary prophylactic ICD in patients with arrhythmogenic right ventricular cardiomyopathy, the ESC suggests that ICD should be considered in patients who have experienced unexplained syncope. ICD may be considered in patients with arrhythmogenic right ventricular cardiomyopathy who have at least one risk factor for ventricular arrhythmias, including family history of premature SCD and extensive right ventricular disease. The risks of ICD therapy should be taken into account when considering it as primary prophylactic therapy [25]. Finally, ICD therapy should be considered in patients with Chagas disease (a cardiomyopathy caused by the

parasite Trypanosoma cruzi) who have an EF of less than 40% [25].

In patients with long QT syndrome, ICD may be considered (as a complement to beta-blockers) in patients who are asymptomatic carriers of a pathogenic *KCNH2*- or *SCN5A*-mutation (high-risk genetic profiles) and have a QTc of more than 500 ms [25]. An ICD may be considered as primary prevention in short QT syndrome, if there is a family history of SCD and evidence of shortened QT in some of these patients. The available data is too scarce for any specific recommendations to be made regarding this. As for Brugada syndrome, primary prevention with an ICD should be considered in patients with a spontaneous type I ECG pattern and suspected arrhythmic syncope in their medical history, and may be considered in patients who develop VF during programmed ventricular stimulation [25].

A number of different etiologies are responsible for the risk of SCD in children:

This system is placed completely outside the thoracic cavity, eliminating problems with vascular access and transvenous leads. Subcutaneous ICD therapy is not appropriate for patients with bradycardia that requires pacing, for those who have indications for CRT or for those who need antitachycardia pacing. When these patients are excluded, subcutaneous defibrillators should be considered as an alternative to transvenous defibrillators (class IIa recommendation) in patients with an ICD indication [25]. According to the ESC, subcutaneous ICD could be considered (class IIb recommendation) as an alternative to transvenous defibrillators when there are difficulties with venous access, after ICD removal secondary to infection

As the name suggests, this defibrillator is entirely external; defibrillator, leads and electrode pads are attached to a wearable vest. It may be considered for adult patients with reduced LVEF who are waiting for a more permanent solution (cardiac

channelopathies, cardiomyopathies, and congenital heart disease. The same guidelines for when ICD is indicated apply to both adults and children, with the exception of dilated cardiomyopathy and advanced dysfunction of the left ven-

tricle since the incidence of SCD is low in this group [25].

or in young patients who will require long-term ICD therapy [25].

**3.5 The wearable cardioverter defibrillator**

*3.3.2.4 Hereditary primary arrhythmia syndromes*

*3.3.2.5 Pediatric patients*

**3.4 The subcutaneous ICD**

**20**

transplantation, transvenous implant) or those who are at a temporary risk of SCD, as in peripartum cardiomyopathy or active myocarditis [25, 41].

#### **3.6 Contraindications and considerations**

All through the European guidelines concerning ICD indications, it is emphasized that the expected survival with good functional status should be at least 1 year for ICD to be an option. As mentioned before, symptomatic HF with NYHA class IV is considered a contraindication, unless the patient is waiting for heart transplantation. VT or VF due to reversible causes should not be treated with ICD [25]. Psychiatric illness that might be aggravated due to ICD implantation is sometimes considered a contraindication [42], although it is not mentioned as such in the ESC guidelines. Up to a fifth of terminally ill patients with an ICD experience shocks in the last weeks of life, and deactivation of the ICD should be considered when the patient's condition worsens. This issue should be discussed before implantation and as the illness progresses [25]. A magnet placed over the ICD will deactivate tachyarrhythmia therapies, and this stops inappropriate defibrillations or unnecessary defibrillations at the end of life.

#### **3.7 Health-related quality of life**

In its guidelines, the ESC emphasizes the importance of discussing healthrelated quality of life issues with the patient before ICD implantation and during progression of the disease, by making it a class I recommendation. In addition to this, they recommend that patients who experience inappropriate shocks are assessed psychologically and treated for any distress [25]. Depression and anxiety are common in ICD patients; one systematic review reports anxiety in 8–63% of these patients and depression in 5–41% [43]. Similar effects on quality of life have been seen in patients with ICD and with medical therapy, with impairment in quality of life associated with adverse symptoms in both groups and experience of sporadic shocks in the ICD group [44]. Some patients develop post-traumatic stress disorder, and these symptoms have been associated with nonconstructive support (information that leads to insecurity and fear) from healthcare professionals; further studies are needed [45].

#### **4. Cardiac resynchronization therapy**

In around 30% of patients suffering from chronic HF, the conduction pathways are affected, leading to cardiac dyssynchrony [46]. The aim of CRT is to, as the name suggests, improve synchrony in the heart's contraction [9]. Patients eligible for this therapy are those with a wide QRS complex, HF, and impaired left ventricular function [47]. Biventricular pacing was first introduced in the early 1990s by Bakker et al. and Cazeau et al. [48, 49]. CRT with the ability to work as an ICD is termed CRT-D, whereas the term used for a CRT that solely has a pacing function is CRT-P.

#### **4.1 Cardiac dyssynchrony**

The dyssynchrony that is targeted with CRT is caused by delays in electrical conduction, and the main way to identify this is by assessing the QRS duration (in particular LBBB) [50]. A prolonged QRS duration has been associated with decreased LVEF [51]. In patients with HF, prolongation of the QRS complex has been shown to be an independent predictor of increased total mortality and SCD. LBBB is related to worse survival but not sudden death [52]. Partially, the mechanism behind

dyssynchrony is prolongation of the AV interval, leading to late systolic contraction which may take the place of early diastolic filling as well as cause mitral regurgitation. Furthermore, conduction delays between and in the ventricles themselves result in asynchronous contraction in the left ventricular walls with subsequent loss of cardiac efficiency [9]. Long-standing cardiac dyssynchrony can result in remodeling of the heart, causing dilation of the left ventricle, deteriorating diastolic and systolic function and worsening of HF [53].

#### **4.2 Important trials**

Several trials have been conducted in order to optimize indications for CRT. The COmparison of Medical Therapy, Pacing and Defibrillation in Heart Failure (COMPANION) trial compared optimal medical therapy, CRT-D, and CRT-P, and found that all-cause mortality and hospitalization was reduced in both CRT groups. Reduction in mortality was however only marginally significant with CRT-P, but significant in the CRT-D group [54]. In the CArdiac REsynchronization in Heart Failure (CARE-HF) trial, optimal medical therapy was compared to CRT-P, with the result that CRT-P reduced all-cause mortality and hospitalization as well as improved symptoms and quality of life [55]. Both of these trials enrolled patients in NYHA class III-IV with a QRS duration of 120 ms or more. The Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT) compared the rate of all-cause mortality and hospitalization due to HF between patients in NYHA class II or III with a QRS duration of at least 120 ms, randomized to either CRT-D or ICD, finding a reduction in the primary outcome in the CRT-D group [56].

In the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) trial, patients with HF in NYHA class I and II were randomized to CRT (with or without defibrillator) or control. The results showed an improvement in the ventricular structure and function in the CRT group and a decrease in hospitalization for HF [57]. MADIT-CRT was designed to evaluate the effect on death and HF events in patients in NYHA class I-II who received a CRT-D compared to an ICD. The risk of HF events was reduced, left ventricular volumes were reduced, and EF improved in the CRT-D group, but no significant difference in all-cause mortality was seen between the groups [58]. When the outcomes in MADIT-CRT were studied in relationship to whether or not the patient had LBBB, CRT-D led to a reduction in HF progression and a reduced risk of ventricular tachyarrhythmias in patients with LBBB while patients with non-LBBB morphology did not benefit clinically [59].

#### **4.3 General indications for CRT**

#### *4.3.1 Patients in sinus rhythm*

CRT is recommended by the ESC (class I recommendation) in patients with symptomatic HF in sinus rhythm, with a QRS duration of 130 ms or more, LBBB morphology, and an LVEF of 35% or less despite optimal medical therapy, to reduce symptoms, morbidity, and mortality [60]. CRT should be considered (class IIa recommendation) in patients who meet these criteria but do not have LBBB morphology and have a QRS duration of 150 ms or more and may be considered (class IIb recommendation) in non-LBBB morphology if the QRS duration is between 130 and 149 ms [60]. Patients with HF with reduced EF in any NYHA class who have an indication for bradycardia pacing with a high proportion of right ventricular pacing (high degree AV block, permanent AF) should receive CRT instead of a conventional pacemaker in order to reduce morbidity (class I recommendation) [60]. Lastly, patients with HF with reduced EF who already have a pacemaker or ICD and develop worsening HF

**23**

*Clinical Indications for Therapeutic Cardiac Devices DOI: http://dx.doi.org/10.5772/intechopen.82463*

considered for upgrade to CRT [60].

*4.3.2 Patients in atrial fibrillation*

(patients with AF included) [60].

CRT-D is recommended [60].

*4.3.4 Patients with indications for ICD*

last month) [9].

despite optimal medical therapy and have a high rate of ventricular pacing may be

Since AF results in irregular and often fast ventricular rates, there is a risk that biventricular pacing delivery does not work adequately in these patients, and most of the patients with AF and an intact AV node require AV junction ablation in order for biventricular pacing to work properly. When considering AV junction ablation before CRT implantation, the risk that pacemaker dependency poses must of course be taken into account [9]. In its 2013 guidelines, the ESC suggests that CRT should be considered in patients with AF who have an EF of 35% or less, are in NYHA class III-IV despite optimal medical therapy, and have a QRS duration of at least 120 ms—provided that bi-ventricular capture of as close to 100% can be achieved. In case bi-ventricular pacing is incomplete, AV junction ablation should be performed [9]. CRT is not an indication for AV junction ablation in any other situation than when it is necessary because of consistently high ventricular rates despite optimal medical therapy [60]. In addition to this, CRT should be considered in patients with reduced EF who are candidates for AV junction ablation because of uncontrolled heart rate; a QRS duration of more than 120 ms is not necessary [9]. In the slightly more recent guidelines from 2016 regarding acute and chronic HF, a QRS duration of 130 ms is the cut off for when

CRT is indicated (applies to patients in sinus rhythm as well as in AF) [60].

Right ventricular pacing might be associated with harmful effects on the cardiac function and structure; therefore, upgrading from a conventional pacemaker to CRT is recommended in patients with optimal medical therapy who have HF in NYHA class III and ambulatory class IV, EF of less than 35%, and a high percentage of right ventricular pacing [9]. It should be noted that upgrade to CRT implies a higher risk of complications compared to primary implantation [9]. In patients who have indications for bradycardia pacing and have not yet received a pacemaker, the ESC guidelines from 2013 recommend that CRT should be considered if they have a history of HF with reduced EF and an expected high rate of ventricular pacing in order to decrease the risk of worsening HF [9]. In its 2016 guidelines regarding acute and chronic HF, the ESC made CRT a class I recommendation (is recommended) in patients with HF with reduced EF regardless of NYHA class, who have an indication for ventricular pacing

Several studies, including the aforementioned RAFT and MADIT-CRT, that have compared ICD to CRT-D have found that CRT-D reduces morbidity and mortality. Therefore, when a patient is to receive an ICD, the presence of CRT indications (as mentioned) should be assessed [9]. According to the ESC guidelines, when ICD therapy is indicated in a HF patient who has a QRS complex duration between 130 and 149 ms, CRT-D should be considered. If the QRS duration is 150 ms or more,

*4.3.3 Patients with indications for bradycardia pacemakers*

Since there have been few patients included in RCTs who are in NYHA class I or IV, the evidence for CRT in these patients is inconclusive. When it comes to NYHA class IV, individual consideration should be made. The recommendations from the ESC include patients in NYHA class IV who are ambulatory (no HF hospitalizations in the

#### *Clinical Indications for Therapeutic Cardiac Devices DOI: http://dx.doi.org/10.5772/intechopen.82463*

despite optimal medical therapy and have a high rate of ventricular pacing may be considered for upgrade to CRT [60].

Since there have been few patients included in RCTs who are in NYHA class I or IV, the evidence for CRT in these patients is inconclusive. When it comes to NYHA class IV, individual consideration should be made. The recommendations from the ESC include patients in NYHA class IV who are ambulatory (no HF hospitalizations in the last month) [9].

#### *4.3.2 Patients in atrial fibrillation*

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

systolic function and worsening of HF [53].

in the primary outcome in the CRT-D group [56].

**4.3 General indications for CRT**

*4.3.1 Patients in sinus rhythm*

**4.2 Important trials**

dyssynchrony is prolongation of the AV interval, leading to late systolic contraction which may take the place of early diastolic filling as well as cause mitral regurgitation. Furthermore, conduction delays between and in the ventricles themselves result in asynchronous contraction in the left ventricular walls with subsequent loss of cardiac efficiency [9]. Long-standing cardiac dyssynchrony can result in remodeling of the heart, causing dilation of the left ventricle, deteriorating diastolic and

Several trials have been conducted in order to optimize indications for CRT. The

In the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) trial, patients with HF in NYHA class I and II were randomized to CRT (with or without defibrillator) or control. The results showed an improvement in the ventricular structure and function in the CRT group and a decrease in hospitalization for HF [57]. MADIT-CRT was designed to evaluate the effect on death and HF events in patients in NYHA class I-II who received a CRT-D compared to an ICD. The risk of HF events was reduced, left ventricular volumes were reduced, and EF improved in the CRT-D group, but no significant difference in all-cause mortality was seen between the groups [58]. When the outcomes in MADIT-CRT were studied in relationship to whether or not the patient had LBBB, CRT-D led to a reduction in HF progression and a reduced risk of ventricular tachyarrhythmias in patients with LBBB while patients with non-LBBB morphology did not benefit clinically [59].

CRT is recommended by the ESC (class I recommendation) in patients with symptomatic HF in sinus rhythm, with a QRS duration of 130 ms or more, LBBB morphology, and an LVEF of 35% or less despite optimal medical therapy, to reduce symptoms, morbidity, and mortality [60]. CRT should be considered (class IIa recommendation) in patients who meet these criteria but do not have LBBB morphology and have a QRS duration of 150 ms or more and may be considered (class IIb recommendation) in non-LBBB morphology if the QRS duration is between 130 and 149 ms [60]. Patients with HF with reduced EF in any NYHA class who have an indication for bradycardia pacing with a high proportion of right ventricular pacing (high degree AV block, permanent AF) should receive CRT instead of a conventional pacemaker in order to reduce morbidity (class I recommendation) [60]. Lastly, patients with HF with reduced EF who already have a pacemaker or ICD and develop worsening HF

COmparison of Medical Therapy, Pacing and Defibrillation in Heart Failure (COMPANION) trial compared optimal medical therapy, CRT-D, and CRT-P, and found that all-cause mortality and hospitalization was reduced in both CRT groups. Reduction in mortality was however only marginally significant with CRT-P, but significant in the CRT-D group [54]. In the CArdiac REsynchronization in Heart Failure (CARE-HF) trial, optimal medical therapy was compared to CRT-P, with the result that CRT-P reduced all-cause mortality and hospitalization as well as improved symptoms and quality of life [55]. Both of these trials enrolled patients in NYHA class III-IV with a QRS duration of 120 ms or more. The Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT) compared the rate of all-cause mortality and hospitalization due to HF between patients in NYHA class II or III with a QRS duration of at least 120 ms, randomized to either CRT-D or ICD, finding a reduction

**22**

Since AF results in irregular and often fast ventricular rates, there is a risk that biventricular pacing delivery does not work adequately in these patients, and most of the patients with AF and an intact AV node require AV junction ablation in order for biventricular pacing to work properly. When considering AV junction ablation before CRT implantation, the risk that pacemaker dependency poses must of course be taken into account [9]. In its 2013 guidelines, the ESC suggests that CRT should be considered in patients with AF who have an EF of 35% or less, are in NYHA class III-IV despite optimal medical therapy, and have a QRS duration of at least 120 ms—provided that bi-ventricular capture of as close to 100% can be achieved. In case bi-ventricular pacing is incomplete, AV junction ablation should be performed [9]. CRT is not an indication for AV junction ablation in any other situation than when it is necessary because of consistently high ventricular rates despite optimal medical therapy [60]. In addition to this, CRT should be considered in patients with reduced EF who are candidates for AV junction ablation because of uncontrolled heart rate; a QRS duration of more than 120 ms is not necessary [9]. In the slightly more recent guidelines from 2016 regarding acute and chronic HF, a QRS duration of 130 ms is the cut off for when CRT is indicated (applies to patients in sinus rhythm as well as in AF) [60].

#### *4.3.3 Patients with indications for bradycardia pacemakers*

Right ventricular pacing might be associated with harmful effects on the cardiac function and structure; therefore, upgrading from a conventional pacemaker to CRT is recommended in patients with optimal medical therapy who have HF in NYHA class III and ambulatory class IV, EF of less than 35%, and a high percentage of right ventricular pacing [9]. It should be noted that upgrade to CRT implies a higher risk of complications compared to primary implantation [9]. In patients who have indications for bradycardia pacing and have not yet received a pacemaker, the ESC guidelines from 2013 recommend that CRT should be considered if they have a history of HF with reduced EF and an expected high rate of ventricular pacing in order to decrease the risk of worsening HF [9]. In its 2016 guidelines regarding acute and chronic HF, the ESC made CRT a class I recommendation (is recommended) in patients with HF with reduced EF regardless of NYHA class, who have an indication for ventricular pacing (patients with AF included) [60].

#### *4.3.4 Patients with indications for ICD*

Several studies, including the aforementioned RAFT and MADIT-CRT, that have compared ICD to CRT-D have found that CRT-D reduces morbidity and mortality. Therefore, when a patient is to receive an ICD, the presence of CRT indications (as mentioned) should be assessed [9]. According to the ESC guidelines, when ICD therapy is indicated in a HF patient who has a QRS complex duration between 130 and 149 ms, CRT-D should be considered. If the QRS duration is 150 ms or more, CRT-D is recommended [60].

#### *4.3.5 The choice between CRT-P and CRT-D*

In order to improve prognosis, evidence points toward the use of CRT-D therapy for patients in NYHA class II and CRT-P for patients in NYHA classes III-IV [60]. There is not sufficient evidence based on RCTs for the ESC to make a specific recommendation on when to choose one over the other, but they offer some advice. In addition to patients with advanced HF, the ESC suggests CRT-P in patients with severe renal insufficiency and those who have other major comorbidities, cachexia, or frailty. CRT-D, on the other hand, is more appropriate in patients with a life expectancy of at least a year, stable HF, no comorbidities, and ischemic heart disease [9].

#### **4.4 Contraindications**

According to the Echocardiography Guided Cardiac Resynchronization Therapy (EchoCRT) study, there is a risk of increased mortality when CRT is used in patients with systolic HF and a QRS duration of less than 130 [61]; QRS of less than 130 ms is therefore considered a contraindication to CRT by the ESC [60].

#### **4.5 Cardiac contractility modulation**

Patients who lack indications for CRT but still suffer from symptomatic HF with reduced EF in spite of optimal medical therapy might be candidates for cardiac contractility modulation (CCM). It provides nonexcitatory stimulation of the ventricle in its refractory period in order to improve contractility but not cause extra systolic contractions [60].

#### **5. Future perspectives**

An interesting area of research is the attempt to build biological pacemakers. Stem cells and viral vectors have been used to introduce ion-channel genes into the heart [62]. These preclinical attempts are promising but much remains until they are ready to be considered a clinical option [63]. Nevertheless, electronic devices have been developed over decades with proven efficacy, and devastating complications are rare.

Leadless pacing provides a landmark in the development of pacemaker technology. However, it is basically limited to pacing from the right ventricle. Because most patients will benefit from AV synchronization and even additional cardiac resynchronization, efforts are made to fulfill this demand. The AV-sequential challenge could potentially be solved by a VDD mode that would rely on atrial sensing from a subcutaneous integrated ECG device. Furthermore, device systems that are able to communicate between them are being developed. The subcutaneous ICD could be combined with a leadless pacemaker, which could provide sensing/pacing in the right ventricle, including antitachycardia pacing. The ultrasound-based technology WiCS™ system for endocardial pacing of the left ventricle is another option that is currently being developed [64]. The energy is transmitted from a subcutaneous transmitter subcutaneously to a receiver in the endocardium. Leadless pacing in the right ventricular chamber combined with the left-ventricular endocardial unit and a subcutaneous pulse generator could be a possibility in the near future.

#### **6. Conclusions**

Pacemaker therapy has revolutionized the treatment of bradycardia, and with an aging population, the use of permanent pacemakers is likely to increase. SCD,

**25**

**Author details**

Stockholm, Sweden

Ida Åberg1

provided the original work is properly cited.

, Gustav Mattsson1

*Clinical Indications for Therapeutic Cardiac Devices DOI: http://dx.doi.org/10.5772/intechopen.82463*

**Conflict of interest**

a major cause of death worldwide, can now be prevented with ICD therapy. CRT reduces symptoms and risk of death in patients who have HF with reduced EF and ventricular dyssynchrony. The indications for these therapies continue to evolve as

Peter Magnusson has received lecture fees from Abbott, Bayer, Boehringer-

Ingelheim, Boston Scientific, Medtronic, MSD, Orion Pharma, and Pfizer.

new evidence emerges and novel technologies become available.

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\* and Peter Magnusson1,2

1 Centre for Research and Development, Uppsala University, Gävle, Sweden

2 Cardiology Research Unit, Department of Medicine, Karolinska Institutet,

\*Address all correspondence to: gustav.mattsson@regiongavleborg.se

*Clinical Indications for Therapeutic Cardiac Devices DOI: http://dx.doi.org/10.5772/intechopen.82463*

a major cause of death worldwide, can now be prevented with ICD therapy. CRT reduces symptoms and risk of death in patients who have HF with reduced EF and ventricular dyssynchrony. The indications for these therapies continue to evolve as new evidence emerges and novel technologies become available.

#### **Conflict of interest**

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

In order to improve prognosis, evidence points toward the use of CRT-D therapy for patients in NYHA class II and CRT-P for patients in NYHA classes III-IV [60]. There is not sufficient evidence based on RCTs for the ESC to make a specific recommendation on when to choose one over the other, but they offer some advice. In addition to patients with advanced HF, the ESC suggests CRT-P in patients with severe renal insufficiency and those who have other major comorbidities, cachexia, or frailty. CRT-D, on the other hand, is more appropriate in patients with a life expectancy of at least a year, stable HF, no comorbidities, and ischemic heart disease [9].

According to the Echocardiography Guided Cardiac Resynchronization Therapy

Patients who lack indications for CRT but still suffer from symptomatic HF with reduced EF in spite of optimal medical therapy might be candidates for cardiac contractility modulation (CCM). It provides nonexcitatory stimulation of the ventricle in its refractory period in order to improve contractility but not cause extra systolic

An interesting area of research is the attempt to build biological pacemakers. Stem cells and viral vectors have been used to introduce ion-channel genes into the heart [62]. These preclinical attempts are promising but much remains until they are ready to be considered a clinical option [63]. Nevertheless, electronic devices have been developed over decades with proven efficacy, and devastating complications are rare. Leadless pacing provides a landmark in the development of pacemaker technology. However, it is basically limited to pacing from the right ventricle. Because most patients will benefit from AV synchronization and even additional cardiac resynchronization, efforts are made to fulfill this demand. The AV-sequential challenge could potentially be solved by a VDD mode that would rely on atrial sensing from a subcutaneous integrated ECG device. Furthermore, device systems that are able to communicate between them are being developed. The subcutaneous ICD could be combined with a leadless pacemaker, which could provide sensing/pacing in the right ventricle, including antitachycardia pacing. The ultrasound-based technology WiCS™ system for endocardial pacing of the left ventricle is another option that is currently being developed [64]. The energy is transmitted from a subcutaneous transmitter subcutaneously to a receiver in the endocardium. Leadless pacing in the right ventricular chamber combined with the left-ventricular endocardial unit and a subcutaneous pulse generator could be a

Pacemaker therapy has revolutionized the treatment of bradycardia, and with an aging population, the use of permanent pacemakers is likely to increase. SCD,

patients with systolic HF and a QRS duration of less than 130 [61]; QRS of less than

(EchoCRT) study, there is a risk of increased mortality when CRT is used in

130 ms is therefore considered a contraindication to CRT by the ESC [60].

*4.3.5 The choice between CRT-P and CRT-D*

**4.4 Contraindications**

contractions [60].

**5. Future perspectives**

possibility in the near future.

**6. Conclusions**

**4.5 Cardiac contractility modulation**

**24**

Peter Magnusson has received lecture fees from Abbott, Bayer, Boehringer-Ingelheim, Boston Scientific, Medtronic, MSD, Orion Pharma, and Pfizer.

### **Author details**

Ida Åberg1 , Gustav Mattsson1 \* and Peter Magnusson1,2

1 Centre for Research and Development, Uppsala University, Gävle, Sweden

2 Cardiology Research Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden

\*Address all correspondence to: gustav.mattsson@regiongavleborg.se

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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[16] Toff WD, Camm AJ, Skehan JD. Single-chamber versus dualchamber pacing for high-grade atrioventricular block. The New England Journal of Medicine.

[17] Moya A, García-Civera R, Croci F, Menozzi C, Brugada J, Ammirati F, et al. Diagnosis, management, and outcomes of patients with syncope and bundle branch block. European Heart Journal.

[18] Reddy VY, Knops RE, Sperzel J, Miller MA, Petru J, Simon J, et al. Permanent leadless cardiac pacing: Results of the LEADLESS trial. Circulation. 2014;**129**(14):1466-1471

[19] Duray GZ et al. Long-term

performance of a transcatheter pacing system: 12-month results from the Micra Transcatheter Pacing Study. Heart Rhythm. 2017;**14**(5):702-709

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et al. Part 8: Adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;**122**:S729-S767

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2016;**34**(11):2090-2093

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The New England Journal of Medicine. 2002;**346**(24):1854-1862

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[16] Toff WD, Camm AJ, Skehan JD. Single-chamber versus dualchamber pacing for high-grade atrioventricular block. The New England Journal of Medicine. 2005;**353**(2):145-155

[17] Moya A, García-Civera R, Croci F, Menozzi C, Brugada J, Ammirati F, et al. Diagnosis, management, and outcomes of patients with syncope and bundle branch block. European Heart Journal. 2011;**32**(12):1535-1541

[18] Reddy VY, Knops RE, Sperzel J, Miller MA, Petru J, Simon J, et al. Permanent leadless cardiac pacing: Results of the LEADLESS trial. Circulation. 2014;**129**(14):1466-1471

[19] Duray GZ et al. Long-term performance of a transcatheter pacing system: 12-month results from the Micra Transcatheter Pacing Study. Heart Rhythm. 2017;**14**(5):702-709

[20] Neumar RW, Otto CW, Link MS, Kronick SL, Shuster M, Callaway CW, et al. Part 8: Adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;**122**:S729-S767

[21] Bektas F, Soyuncu S. The efficacy of transcutaneous cardiac pacing in ED. The American Journal of Emergency Medicine. 2016;**34**(11):2090-2093

[22] Gammage MD. Temporary cardiac pacing. Heart. 2000;**83**(6):715-720

[23] Mirowski M, Reid PR, Mower MM, Watkins L, Gott VL, Schauble JF, et al.

Termination of malignant ventricular arrhythmias with an implanted automatic defibrillator in human beings. The New England Journal of Medicine. 1980;**303**(6):322-324

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[29] The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients

**26**

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

Breithardt OA, et al. 2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy: The task force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Europace.

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KA, Estes NA III, Freedman RA, Gettes LS, et al. 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: A report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Journal of the American College of Cardiology.

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cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators. The New England Journal of Medicine.

[14] Lamas GA, Lee KL, Sweeney MO, Silverman R, Leon A, Yee R, et al. Ventricular pacing or dual-chamber pacing for sinus-node dysfunction.

[12] Nielsen JC, Thomsen PE, Højberg S, Møller M, Vesterlund T, Dalsgaard D, et al. A comparison of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome. European Heart

[1] Aquilina O. A brief history of cardiac pacing. Images in Paediatric Cardiology.

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[30] Kuck KH, Cappato R, Rüppel R. Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest: The Cardiac Arrest Study Hamburg (CASH). Circulation. 2000;**102**(7):748-754

[31] Connolly SJ, Gent M, Roberts RS, Dorian P, Roy D, Sheldon RS, et al. Canadian implantable defibrillator study (CIDS): A randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation. 2000;**101**(11):1297-1302

[32] Connolly SJ, Hallstrom AP, Cappato R, Schron EB, Kuck KH, Zipes DP, et al. Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials. AVID, CASH and CIDS studies. Antiarrhythmics vs Implantable Defibrillator study. Cardiac Arrest Study Hamburg. Canadian Implantable Defibrillator Study. European Heart Journal. 2000;**21**(24):2071-2078

[33] Mehta RH, Yu J, Piccini JP, Tcheng JE, Farkouh ME, Reiffel J, et al. Prognostic significance of postprocedural sustained ventricular tachycardia or fibrillation in patients undergoing primary percutaneous coronary intervention (from the HORIZONS-AMI Trial). The American Journal of Cardiology. 2012;**109**(6):805-812

[34] Brugada J, Campuzano O, Arbelo E, Sarquella-Brugada G, Brugada R. Present status of Brugada syndrome: JACC state-of-the-art review. Journal of the American College of Cardiology. 2018;**72**(9):1046-1059

[35] Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, et al. Amiodarone or an implantable cardioverter–defibrillator for congestive heart failure. New England Journal of Medicine. 2005;**352**(3):225-237

[36] Køber L, Thune JJ, Nielsen JC, Haarbo J, Vidbæk L, Korup E, et al. Defibrillator implantation in patients with nonischemic systolic heart failure. The New England Journal of Medicine. 2016;**375**(13):1221-1230

[37] Moss AJ, Hall WJ, Cannom DS, Daubert JP, Higgins SL, Klein H, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. The New England Journal of Medicine. 1996;**335**(26):1933-1940

[38] Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. The New England Journal of Medicine. 2002;**346**(12):877-883

[39] Hohnloser SH, Kuck KH, Dorian P, Roberts RS, Hampton JR, Hatala R, et al. Prophylactic use of an implantable cardioverter–defibrillator after acute myocardial infarction. The New England Journal of Medicine. 2004;**351**(24):2481-2488

[40] Kadish A, Dyer A, Daubert JP, Quigg R, Estes NA, Anderson KP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. The New England Journal of Medicine. 2004;**350**(21):2151-2158

[41] Reek S, Burri H, Roberts PR, Perings C, Epstein AE, Klein HU, et al. The wearable cardioverterdefibrillator: Current technology and evolving indications. Europace. 2017;**19**(3):335-345

[42] DiMarco JP. Implantable cardioverter–defibrillators. The New England Journal of Medicine. 2003;**349**(19):1836-1847

**29**

1974-1979

*Clinical Indications for Therapeutic Cardiac Devices DOI: http://dx.doi.org/10.5772/intechopen.82463*

> [51] Murkofsky RL, Dangas G, Diamond JA, Mehta D, Schaffer A, Ambrose JA. A prolonged QRS duration on surface electrocardiogram is a specific indicator of left ventricular dysfunction [see comment]. Journal of the American College of Cardiology. 1998;**32**(2):476-482

[52] Iuliano S, Fisher SG, Karasik PE, Fletcher RD, Singh SN. QRS duration and mortality in patients with congestive heart failure. American Heart Journal. 2002;**143**(6):1085-1091

[53] Jaffe LM, Morin DP. Cardiac resynchronization therapy: History, present status, and future directions. The Ochsner Journal.

[54] Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. The New England Journal of Medicine.

2014;**14**(4):596-607

2004;**350**(21):2140-2150

2005;**352**(15):1539-1549

2010;**363**(25):2385-2395

2008;**52**(23):1834-1843

[56] Tang AS, Wells GA, Talajic M, Arnold MO, Sheldon R, Connolly S, et al. Cardiac-resynchronization therapy for mild-to-moderate heart failure. The New England Journal of Medicine.

[57] Linde C, Abraham WT, Gold MR, St John Sutton M, Ghio S, Daubert C, et al. Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. Journal of the American College of Cardiology.

[55] Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. The New England Journal of Medicine.

[43] Magyar-Russell G, Thombs BD, Cai JX, Baveja T, Kuhl EA, Singh PP, et al. The prevalence of anxiety and depression in adults with implantable cardioverter defibrillators: A systematic review. Journal of Psychosomatic Research. 2011;**71**(4):223-231

[44] Schron EB, Exner DV, Jenkins LS, Steinberg JS, Cook JR, Kutalek SP, et al. Quality of life in the antiarrhythmics versus implantable defibrillators trial: Impact of therapy and influence of adverse symptoms and defibrillator shocks. Circulation. 2002;**105**(5):589-594

[45] Morken IM, Bru E, Norekvål TM, Larsen AI, Idsoe T, Karlsen B, et al. Perceived support from healthcare professionals, shock anxiety and post-traumatic stress in implantable cardioverter defibrillator recipients.

[46] Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, et al. Cardiac resynchronization in chronic heart failure. The New England Journal of Medicine. 2002;**346**(24):1845-1853

[47] Leyva F, Nisam S, Auricchio A. 20 years of cardiac resynchronization therapy. Journal of the American College of Cardiology. 2014;**64**(10):1047-1058

[48] Bakker PF, Meijburg HW, de Vries JW, Mower MM, Thomas AC, Hull ML, et al. Biventricular pacing in end-stage heart failure improves functional capacity and left ventricular function. Journal of Interventional Cardiac Electrophysiology. 2000;**4**(2):395-404

[49] Cazeau S, Ritter P, Bakdach S, Lazarus A, Limousin M, Henao L, et al. Four chamber pacing in dilated cardiomyopathy. Pacing and Clinical Electrophysiology. 1994;**17**(11 Pt 2):

[50] Kass DA. Cardiac resynchronization therapy. Journal of Cardiovascular Electrophysiology. 2005;**16**(s1):S35-S41

Journal of Clinical Nursing. 2014;**23**(3-4):450-460

*Clinical Indications for Therapeutic Cardiac Devices DOI: http://dx.doi.org/10.5772/intechopen.82463*

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

cardioverter–defibrillator for congestive heart failure. New England Journal of Medicine. 2005;**352**(3):225-237

[36] Køber L, Thune JJ, Nielsen JC, Haarbo J, Vidbæk L, Korup E, et al. Defibrillator implantation in patients with nonischemic systolic heart failure. The New England Journal of Medicine.

[37] Moss AJ, Hall WJ, Cannom DS, Daubert JP, Higgins SL, Klein H, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. The New England Journal of Medicine. 1996;**335**(26):1933-1940

[38] Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. The New England Journal of Medicine.

[39] Hohnloser SH, Kuck KH, Dorian P, Roberts RS, Hampton JR, Hatala R, et al. Prophylactic use of an implantable

cardioverter–defibrillator after acute myocardial infarction. The New England Journal of Medicine.

[40] Kadish A, Dyer A, Daubert JP, Quigg R, Estes NA, Anderson KP, et al. Prophylactic defibrillator implantation in patients with

nonischemic dilated cardiomyopathy. The New England Journal of Medicine.

[41] Reek S, Burri H, Roberts PR, Perings C, Epstein AE, Klein HU, et al. The wearable cardioverterdefibrillator: Current technology and evolving indications. Europace.

2004;**351**(24):2481-2488

2004;**350**(21):2151-2158

2017;**19**(3):335-345

[42] DiMarco JP. Implantable cardioverter–defibrillators. The New England Journal of Medicine.

2003;**349**(19):1836-1847

2002;**346**(12):877-883

2016;**375**(13):1221-1230

resuscitated from near-fatal ventricular arrhythmias. The New England Journal of Medicine. 1997;**337**(22):1576-1583

[30] Kuck KH, Cappato R, Rüppel R.

[31] Connolly SJ, Gent M, Roberts RS, Dorian P, Roy D, Sheldon RS, et al. Canadian implantable defibrillator study (CIDS): A randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation.

[32] Connolly SJ, Hallstrom AP, Cappato R, Schron EB, Kuck KH, Zipes DP, et al. Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials. AVID, CASH and CIDS studies. Antiarrhythmics vs Implantable Defibrillator study. Cardiac Arrest Study Hamburg. Canadian Implantable Defibrillator Study. European Heart Journal.

[33] Mehta RH, Yu J, Piccini JP, Tcheng

[34] Brugada J, Campuzano O, Arbelo E, Sarquella-Brugada G, Brugada R. Present status of Brugada syndrome: JACC state-of-the-art review. Journal of the American College of Cardiology.

Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest: The Cardiac Arrest Study Hamburg (CASH). Circulation. 2000;**102**(7):748-754

2000;**101**(11):1297-1302

2000;**21**(24):2071-2078

JE, Farkouh ME, Reiffel J, et al. Prognostic significance of postprocedural sustained ventricular tachycardia or fibrillation in patients undergoing primary percutaneous coronary intervention (from the HORIZONS-AMI Trial). The American Journal of Cardiology.

2012;**109**(6):805-812

2018;**72**(9):1046-1059

[35] Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, et al. Amiodarone or an implantable

**28**

[43] Magyar-Russell G, Thombs BD, Cai JX, Baveja T, Kuhl EA, Singh PP, et al. The prevalence of anxiety and depression in adults with implantable cardioverter defibrillators: A systematic review. Journal of Psychosomatic Research. 2011;**71**(4):223-231

[44] Schron EB, Exner DV, Jenkins LS, Steinberg JS, Cook JR, Kutalek SP, et al. Quality of life in the antiarrhythmics versus implantable defibrillators trial: Impact of therapy and influence of adverse symptoms and defibrillator shocks. Circulation. 2002;**105**(5):589-594

[45] Morken IM, Bru E, Norekvål TM, Larsen AI, Idsoe T, Karlsen B, et al. Perceived support from healthcare professionals, shock anxiety and post-traumatic stress in implantable cardioverter defibrillator recipients. Journal of Clinical Nursing. 2014;**23**(3-4):450-460

[46] Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, et al. Cardiac resynchronization in chronic heart failure. The New England Journal of Medicine. 2002;**346**(24):1845-1853

[47] Leyva F, Nisam S, Auricchio A. 20 years of cardiac resynchronization therapy. Journal of the American College of Cardiology. 2014;**64**(10):1047-1058

[48] Bakker PF, Meijburg HW, de Vries JW, Mower MM, Thomas AC, Hull ML, et al. Biventricular pacing in end-stage heart failure improves functional capacity and left ventricular function. Journal of Interventional Cardiac Electrophysiology. 2000;**4**(2):395-404

[49] Cazeau S, Ritter P, Bakdach S, Lazarus A, Limousin M, Henao L, et al. Four chamber pacing in dilated cardiomyopathy. Pacing and Clinical Electrophysiology. 1994;**17**(11 Pt 2): 1974-1979

[50] Kass DA. Cardiac resynchronization therapy. Journal of Cardiovascular Electrophysiology. 2005;**16**(s1):S35-S41

[51] Murkofsky RL, Dangas G, Diamond JA, Mehta D, Schaffer A, Ambrose JA. A prolonged QRS duration on surface electrocardiogram is a specific indicator of left ventricular dysfunction [see comment]. Journal of the American College of Cardiology. 1998;**32**(2):476-482

[52] Iuliano S, Fisher SG, Karasik PE, Fletcher RD, Singh SN. QRS duration and mortality in patients with congestive heart failure. American Heart Journal. 2002;**143**(6):1085-1091

[53] Jaffe LM, Morin DP. Cardiac resynchronization therapy: History, present status, and future directions. The Ochsner Journal. 2014;**14**(4):596-607

[54] Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. The New England Journal of Medicine. 2004;**350**(21):2140-2150

[55] Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. The New England Journal of Medicine. 2005;**352**(15):1539-1549

[56] Tang AS, Wells GA, Talajic M, Arnold MO, Sheldon R, Connolly S, et al. Cardiac-resynchronization therapy for mild-to-moderate heart failure. The New England Journal of Medicine. 2010;**363**(25):2385-2395

[57] Linde C, Abraham WT, Gold MR, St John Sutton M, Ghio S, Daubert C, et al. Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. Journal of the American College of Cardiology. 2008;**52**(23):1834-1843

[58] Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. The New England Journal of Medicine. 2009;**361**(14):1329-1338

[59] Zareba W, Klein H, Cygankiewicz I, Hall WJ, McNitt S, Brown M, et al. Effectiveness of cardiac resynchronization therapy by QRS morphology in the multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT). Circulation. 2011;**123**(10):1061-1072

[60] Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: The task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal. 2016;**37**(27):2129-2200

[61] Ruschitzka F, Abraham WT, Singh JP, Bax JJ, Borer JS, Brugada J, et al. Cardiac-resynchronization therapy in heart failure with a narrow QRS complex. The New England Journal of Medicine. 2013;**369**(15):1395-1405

[62] Rosen MR. Gene therapy and biological pacing. The New England Journal of Medicine. 2014;**371**(12):1158-1159

[63] Rosen MR, Robinson RB, Brink PR, Cohen IS. The road to biological pacing. Nature Reviews. Cardiology. 2011;**8**(11):656-666

[64] Sperzel J, Burri H, Gras D, Tjong FV, Knops RE, Hindricks G, et al. State of the art of leadless pacing. Europace. 2015;**17**(10):1508-1513

**31**

respectively).

**Chapter 3**

**Abstract**

The Subcutaneous Implantable

*Peter Magnusson, Joseph V. Pergolizzi and Jo Ann LeQuang*

The subcutaneous ICD (S-ICD) represents an important advancement in defibrillation therapy that obviates the need for a transvenous lead, the most frequent complication with transvenous devices. The S-ICD has been shown similarly safe and effective as transvenous ICD therapy, but the two devices are not interchangeable. The S-ICD is only suitable for patients who do not require bradycardia or antitachycardia pacing functionality. In patients with underlying diseases associated with polymorphic ventricular tachycardia and a long life expectancy, an S-ICD may be the preferred choice. Moreover, it is advantageous in the situation of increased risk of endocarditis, i.e., previous device system infection and immunosuppression, including hemodialysis. In patients with abnormal vascular access and/or right-sided heart structural abnormalities, it may be the only option. The S-ICD is bulkier, the battery longevity is shorter, and the device cost is higher, even though remote follow-up is possible. A two- or three-incision implant procedure has been described with a lateral placement of the device and a single subcutaneous lead. The rate of inappropriate therapy for both S-ICD and transvenous systems is similar, but S-ICD inappropriate shocks are more frequently attributable to oversensing, which

**Keywords:** lead complications, subcutaneous ICD, sudden cardiac death, S-ICD,

The subcutaneous implantable cardioverter defibrillator (S-ICD) offers an alternative rescue device for sudden cardiac death in the form of an implantable device that can offer defibrillation therapy without the need for a transvenous lead. Lead failure is the most frequent source of complication requiring surgical revision. Approximately 20% of transvenous leads fail within 10 years and extraction may lead to devastating complications, including death [1–5]. The S-ICD differs from conventional transvenous ICD systems in other important ways: an S-ICD requires no transvenous leads (the most frequent source of device complications) but S-ICDs do not offer bradycardia pacing, antitachycardia pacing, cardiac resynchronization, plus they have limited programmability. Approved in Europe in 2009, the S-ICD system (SQ-RX 1010, Boston Scientific, Natick, Massachusetts, USA) consists of a pulse generator and a tripolar defibrillation lead, both of which are implanted subcutaneously. In terms of size, weight, and footprint, the S-ICD device is larger and heavier than a conventional transvenous ICD (approximately 130 vs. 60 g,

Cardioverter-Defibrillator

can often be resolved with sensing adjustments.

transvenous ICD, T-wave oversensing

**1. Introduction**

#### **Chapter 3**

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

[58] Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. The New England Journal of Medicine.

[59] Zareba W, Klein H, Cygankiewicz I,

[60] Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: The task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal.

[61] Ruschitzka F, Abraham WT, Singh JP, Bax JJ, Borer JS, Brugada J, et al. Cardiac-resynchronization therapy in heart failure with a narrow QRS complex. The New England Journal of Medicine. 2013;**369**(15):1395-1405

[63] Rosen MR, Robinson RB, Brink PR,

[64] Sperzel J, Burri H, Gras D, Tjong FV, Knops RE, Hindricks G, et al. State of the art of leadless pacing. Europace.

Cohen IS. The road to biological pacing. Nature Reviews. Cardiology.

2011;**8**(11):656-666

2015;**17**(10):1508-1513

2009;**361**(14):1329-1338

2011;**123**(10):1061-1072

2016;**37**(27):2129-2200

[62] Rosen MR. Gene therapy and biological pacing. The New England Journal of Medicine. 2014;**371**(12):1158-1159

Hall WJ, McNitt S, Brown M, et al. Effectiveness of cardiac resynchronization therapy by QRS morphology in the multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT). Circulation.

**30**

## The Subcutaneous Implantable Cardioverter-Defibrillator

*Peter Magnusson, Joseph V. Pergolizzi and Jo Ann LeQuang*

#### **Abstract**

The subcutaneous ICD (S-ICD) represents an important advancement in defibrillation therapy that obviates the need for a transvenous lead, the most frequent complication with transvenous devices. The S-ICD has been shown similarly safe and effective as transvenous ICD therapy, but the two devices are not interchangeable. The S-ICD is only suitable for patients who do not require bradycardia or antitachycardia pacing functionality. In patients with underlying diseases associated with polymorphic ventricular tachycardia and a long life expectancy, an S-ICD may be the preferred choice. Moreover, it is advantageous in the situation of increased risk of endocarditis, i.e., previous device system infection and immunosuppression, including hemodialysis. In patients with abnormal vascular access and/or right-sided heart structural abnormalities, it may be the only option. The S-ICD is bulkier, the battery longevity is shorter, and the device cost is higher, even though remote follow-up is possible. A two- or three-incision implant procedure has been described with a lateral placement of the device and a single subcutaneous lead. The rate of inappropriate therapy for both S-ICD and transvenous systems is similar, but S-ICD inappropriate shocks are more frequently attributable to oversensing, which can often be resolved with sensing adjustments.

**Keywords:** lead complications, subcutaneous ICD, sudden cardiac death, S-ICD, transvenous ICD, T-wave oversensing

#### **1. Introduction**

The subcutaneous implantable cardioverter defibrillator (S-ICD) offers an alternative rescue device for sudden cardiac death in the form of an implantable device that can offer defibrillation therapy without the need for a transvenous lead. Lead failure is the most frequent source of complication requiring surgical revision. Approximately 20% of transvenous leads fail within 10 years and extraction may lead to devastating complications, including death [1–5]. The S-ICD differs from conventional transvenous ICD systems in other important ways: an S-ICD requires no transvenous leads (the most frequent source of device complications) but S-ICDs do not offer bradycardia pacing, antitachycardia pacing, cardiac resynchronization, plus they have limited programmability. Approved in Europe in 2009, the S-ICD system (SQ-RX 1010, Boston Scientific, Natick, Massachusetts, USA) consists of a pulse generator and a tripolar defibrillation lead, both of which are implanted subcutaneously. In terms of size, weight, and footprint, the S-ICD device is larger and heavier than a conventional transvenous ICD (approximately 130 vs. 60 g, respectively).

S-ICDs are indicated for primary and secondary prevention but are seen as particularly useful for primary-prevention patients with a long life expectancy. The selection of an S-ICD system over a transvenous ICD may be based on a variety of factors. Transvenous ICD patients who experience device-related complications, such as lead problems, may be revised to an S-ICD device. In a German multicenter study, 25% of S-ICD patients had a previous transvenous system explanted because of device complications [6].

#### **2. Implant techniques and considerations**

The S-ICD system is composed of a tripolar parasternal lead, positioned to the left (about 1–2 cm) and parallel to the sternal midline; this lead plugs into the pulse generator, which is implanted over the fifth to sixth rib and positioned submuscularly between the midaxillarly and anterior axillary lines. The lead has three electrodes, two of which sense only. The defibrillation electrode is positioned between the two sensing electrodes. The sensing vector is created from the sensing electrode to the can, with the device automatically selecting the better electrode for the vector to assure optimal sensing. Device implantation may require minimal (to verify final position) to no fluoroscopy, as much of the technique relies on anatomical landmarks [7]. See **Figure 1**.

A three-incision technique (plus pocket formation) was originally pioneered for S-ICD implantation, and a newer two-incision approach has been described in the literature [8]. The two-incision approach creates an intermuscular pocket for the pulse generator rather than a subcutaneous pocket by incising the inframammary crease at the anterior border of the latissimus dorsi, allowing the generator to fit between the two muscles. Then a small incision at the xiphoid process (in the same direction as pocket incision) allows an electrode insertion device to tunnel the lead in place [8, 9]. In a study of 36 patients, the two-incision approach was found to be safe and effective and it may produce superior cosmetic results compared to the three-incision approach [9]. See **Figure 2**.

#### **Figure 1.**

*The S-ICD device is implanted over the fifth to sixth rib and to the side; the parasternal lead senses the subcutaneous ECG and automatically determines which of two sensing vectors to use (top or bottom electrode to can). (Artwork by Todd Cooper, courtesy of Jo Ann LeQuang).*

**33**

**Figure 2.**

*patient.).*

sary for S-ICD patients has been challenged.

*The Subcutaneous Implantable Cardioverter-Defibrillator DOI: http://dx.doi.org/10.5772/10.5772/intechopen.80859*

The time required for device implantation has been recently reported as an average of 68 ± 20 minutes which includes intraoperative defibrillation threshold (DT) testing [10]. DT testing is of decreasing importance with transvenous ICDs but remains a much-discussed topic for S-ICD systems. Guidelines still recommend DT testing during S-ICD implantation, even though it is often used without intraoperative testing based on generalized findings from transvenous systems [11–13]. In a study of 98 S-ICD patients, 25% of patients failed to convert their induced arrhythmia with the first intraoperative 65 joule shock, necessitating further

*Lateral view of a patient with an implanted S-ICD. (Courtesy of Dr. Peter Magnusson with permission of* 

therapy delivery and/or external defibrillation. In this study, 24/25 patients could be successfully defibrillated following either reversal of shocking polarity or lead reposition although the desired 10 joules safety margin could not be achieved in 4/24 of these patients [14]. This suggests the importance of perioperative DT testing. However, 100% of patients could be converted from defibrillation with an internal 80 joule shock [14]. In a subsequent study of 110 consecutive S-ICD patients, 50% (n = 55) did not undergo defibrillation testing at implant for any of several reasons (including patient condition, age, and physician preference). In this group, 11% had episodes of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) necessitating therapy delivery and all of them were effectively converted with the first 80 joule shock [15]. Ventricular tachycardia is a rhythm disorder originating in the heart's lower chambers that has a rate of at least 100 beats per minute; ventricular fibrillation is a much faster, chaotic heart rhythm that causes the heart to quiver rather than pump effectively. Thus, the notion that DT testing at implant is neces-

S-ICD implantation may be carried out under local anesthesia [16], conscious sedation, or general anesthesia (64.1% of U.S. implants of S-ICD systems [17]. The rate of complications at implant is low and the most commonly reported

*The Subcutaneous Implantable Cardioverter-Defibrillator DOI: http://dx.doi.org/10.5772/10.5772/intechopen.80859*

#### **Figure 2.**

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

**2. Implant techniques and considerations**

three-incision approach [9]. See **Figure 2**.

*can). (Artwork by Todd Cooper, courtesy of Jo Ann LeQuang).*

of device complications [6].

See **Figure 1**.

S-ICDs are indicated for primary and secondary prevention but are seen as particularly useful for primary-prevention patients with a long life expectancy. The selection of an S-ICD system over a transvenous ICD may be based on a variety of factors. Transvenous ICD patients who experience device-related complications, such as lead problems, may be revised to an S-ICD device. In a German multicenter study, 25% of S-ICD patients had a previous transvenous system explanted because

The S-ICD system is composed of a tripolar parasternal lead, positioned to the left (about 1–2 cm) and parallel to the sternal midline; this lead plugs into the pulse generator, which is implanted over the fifth to sixth rib and positioned submuscularly between the midaxillarly and anterior axillary lines. The lead has three electrodes, two of which sense only. The defibrillation electrode is positioned between the two sensing electrodes. The sensing vector is created from the sensing electrode to the can, with the device automatically selecting the better electrode for the vector to assure optimal sensing. Device implantation may require minimal (to verify final position) to no fluoroscopy, as much of the technique relies on anatomical landmarks [7].

A three-incision technique (plus pocket formation) was originally pioneered for S-ICD implantation, and a newer two-incision approach has been described in the literature [8]. The two-incision approach creates an intermuscular pocket for the pulse generator rather than a subcutaneous pocket by incising the inframammary crease at the anterior border of the latissimus dorsi, allowing the generator to fit between the two muscles. Then a small incision at the xiphoid process (in the same direction as pocket incision) allows an electrode insertion device to tunnel the lead in place [8, 9]. In a study of 36 patients, the two-incision approach was found to be safe and effective and it may produce superior cosmetic results compared to the

*The S-ICD device is implanted over the fifth to sixth rib and to the side; the parasternal lead senses the subcutaneous ECG and automatically determines which of two sensing vectors to use (top or bottom electrode to* 

**32**

**Figure 1.**

*Lateral view of a patient with an implanted S-ICD. (Courtesy of Dr. Peter Magnusson with permission of patient.).*

The time required for device implantation has been recently reported as an average of 68 ± 20 minutes which includes intraoperative defibrillation threshold (DT) testing [10]. DT testing is of decreasing importance with transvenous ICDs but remains a much-discussed topic for S-ICD systems. Guidelines still recommend DT testing during S-ICD implantation, even though it is often used without intraoperative testing based on generalized findings from transvenous systems [11–13]. In a study of 98 S-ICD patients, 25% of patients failed to convert their induced arrhythmia with the first intraoperative 65 joule shock, necessitating further therapy delivery and/or external defibrillation. In this study, 24/25 patients could be successfully defibrillated following either reversal of shocking polarity or lead reposition although the desired 10 joules safety margin could not be achieved in 4/24 of these patients [14]. This suggests the importance of perioperative DT testing. However, 100% of patients could be converted from defibrillation with an internal 80 joule shock [14]. In a subsequent study of 110 consecutive S-ICD patients, 50% (n = 55) did not undergo defibrillation testing at implant for any of several reasons (including patient condition, age, and physician preference). In this group, 11% had episodes of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) necessitating therapy delivery and all of them were effectively converted with the first 80 joule shock [15]. Ventricular tachycardia is a rhythm disorder originating in the heart's lower chambers that has a rate of at least 100 beats per minute; ventricular fibrillation is a much faster, chaotic heart rhythm that causes the heart to quiver rather than pump effectively. Thus, the notion that DT testing at implant is necessary for S-ICD patients has been challenged.

S-ICD implantation may be carried out under local anesthesia [16], conscious sedation, or general anesthesia (64.1% of U.S. implants of S-ICD systems [17]. The rate of complications at implant is low and the most commonly reported

complication is infection (1.8%) [18]. By dispensing with the transvenous leads, the S-ICD system avoids periprocedural and complications associated with conventional transvenous defibrillation leads, i.e. pericardial effusion, pneumothorax, accidental arterial puncture, nerve plexus injury, and tricuspid valve damage [19].

#### **3. Safety and efficacy of S-ICDs**

S-ICDs appear to have similar rates of infection and other complications as transvenous systems and to be similarly effective in rescuing patients from sudden cardiac death, but there are important distinctions between the two systems.

#### **3.1 Safety**

In a retrospective study of 1160 patients who received an implantable defibrillator (either transvenous system or S-ICD) at two centers in the Netherlands, patients were analyzed using propensity matching to yield 140 matched patient pairs. The rates of complications, infection, and inappropriate therapy were statistically similar between groups, but S-ICD patients had significantly fewer lead-related complications than the transvenous group (0.8 vs. 11.5%, p = 0.030) and more non-lead-related complications (9.9 vs. 2.2%, p = 0.047) [20]. The most frequently reported S-ICD complication involved device sensing.(20) Pooled data from the Investigational Device Exemption (IDE) and postmarket registry EFFORTLESS (n = 882) found S-ICD-related complications occurred at a rate of 11.1% at 3 years, but with no lead failures, S-ICD-related endocarditis, or bacteremia [21]. An IDE allows a device that is the subject of a clinical study to be used to collect data about safety and effectiveness that may be later used to submit to the U.S. Food and Drug Administration (FDA). Device-related complications were more frequent with transvenous systems when compared to S-ICD devices in a propensity-matched case–control study of 69 S-ICD and 69 transvenous ICD patients followed for a mean of 31 ± 19 or 32 ± 21 months, respectively. About 29% of transvenous ICD patients experienced a device-related complication compared to 6% of S-ICD patients, reducing the risk of complications for S-ICD patients by 70%; transvenous lead problems were the most frequently reported complication in the former group [22].

In the largest study of S-ICD patients (n = 3717) to date, complications were low at 1.2% overall. The most frequently reported complications were cardiac arrest (0.4%), hematoma (0.3%), death (0.3%), lead dislodgement (0.1%), myocardial infarction (0.1%), and hemothorax (<0.1%) [23]. Device revision during index hospitalization was infrequent (0.1%) [23]. Infections occur at roughly similar rates with S-ICD and transvenous systems but with the important distinction that S-ICD infections may sometimes be resolved with conservative therapy (course of antibiotics with device left in place), whereas most transvenous ICD infections necessitate the extraction of the device and the transvenous leads. In a survey from the U.K. reporting on data from 111 S-ICD patients, 11/111 (10%) of patients experienced infection, of whom 6 could be successfully treated conservatively without device extraction [24]. The EFFORTLESS registry (n = 472) reported a 4% rate of documented or suspected infections and complication-free rates at 30 and 360 days were 97 and 94%, respectively [25].

Once implanted, the S-ICD device delivers a nonprogrammable, high-energy rescue shock (80 joules) to the thorax compared to shocks of 45 joules to the heart administered by conventional transvenous systems. Notably the S-ICD delivers a 65 joule shock during implant testing. Therapy delivery differs markedly between S-ICD and transvenous systems in terms of the amount of energy delivered, location

**35**

*The Subcutaneous Implantable Cardioverter-Defibrillator DOI: http://dx.doi.org/10.5772/10.5772/intechopen.80859*

**4. Inappropriate shocks with S-ICDs**

therapy delivery was 13.1% [21].

**3.2 Efficacy**

of shocking vectors, and potential for damage to surrounding tissue or the heart. In a porcine study, the mean time to therapy delivery was significantly longer with an S-ICD than a transvenous system (19 vs. 9 seconds, p = 0.001) but the S-ICD shocks were associated with less elevation of cardiac biomarkers. The longer time to therapy may be advantageous in that device patients often experience short runs of nonsustained VT. On the other hand, S-ICD shocks were associated with more skeletal muscle injuries than transvenous device shocks owing to the energy patterns resulting from the device placement but the clinical relevance of this is likely negligible [26].

Effective shock therapy is often defined as conversion of an episode of VT/ VF within five shocks, differing from effective first-shock therapy which occurs when the initial shock converts the arrhythmia. In a study of 79 S-ICD patients at a tertiary center, 7.6% of patients experienced at least one appropriate shock for a ventricular tachyarrhythmia during the follow-up period (mean 12.8 ± 13.7 months) [27]. In a multicenter study from Germany (n = 40), shock efficacy was 96.4% [95% confidence interval (CI), 12.8–100%] and first-shock efficacy was 57.9% (95% CI, 35.6–77.4%) [6]. In an effort to analyze S-ICD efficacy in a large group of diverse patients, data from the Investigation Device Exemption (IDE) clinical study and the EFFORTLESS post-market registry were pooled to provide information about 882 patients followed for 651 ± 345 days. About 59 patients experienced therapy delivery for 111 spontaneous VT/VF episodes with first-shock efficacy in 90.1% of events and shock efficacy (termination with five or fewer shocks) in 98.2% of patients [21]. In the EFFORTLESS registry (n = 472), first-shock efficacy in discrete episodes of VT/VF was 88% and shock efficacy within five shocks was 100% [25].

Inappropriate shock describes therapy delivery to treat an episode which the device inappropriately detects as a ventricular tachyarrhythmia. Inappropriate shocks have been recognized as a significant clinical challenge with transvenous systems as well as S-ICDs. In a tertiary care center study of 79 S-ICD patients, inappropriate shock occurred in 8.9% (n = 7) of patients, attributable to T-wave oversensing, atrial tachyarrhythmia with rapid atrioventricular conduction, external interference and/or baseline oversensing due to lead movement [27]. T-wave oversensing occurs when the device inappropriately senses ventricular repolarizations (the T-waves on the electrocardiograph) counting them as ventricular events, leading to double counting of the intrinsic ventricular rate. In a multicenter German study (n = 40) with a median follow-up of 229 days, four patients (10%) experienced 21 arrhythmic episodes resulting in 28 therapy deliveries. Four of these episodes were inappropriately identified by the device as ventricular tachyarrhythmias, with the result that two patients received inappropriate shocks. This results in a rate of 10% inappropriately detected ventricular tachycardia and 5% delivery of inappropriate therapy [6]. In a study using pooled data from the IDE and EFFORTLESS post-market registry (n = 882), the three-year rate for inappropriate

It does not appear there are statistically more cases of inappropriate therapy in S-ICD patients compared to transvenous ICD patients. A propensity-matched study (69 patients with a transvenous ICD and 69 with an S-ICD) found the rate of inappropriate shocks was 9% in the transvenous and 3% in the S-ICD groups but this was not statistically significant (p = 0.49) [22]. In a study of 54 S-ICD patients in a

of shocking vectors, and potential for damage to surrounding tissue or the heart. In a porcine study, the mean time to therapy delivery was significantly longer with an S-ICD than a transvenous system (19 vs. 9 seconds, p = 0.001) but the S-ICD shocks were associated with less elevation of cardiac biomarkers. The longer time to therapy may be advantageous in that device patients often experience short runs of nonsustained VT. On the other hand, S-ICD shocks were associated with more skeletal muscle injuries than transvenous device shocks owing to the energy patterns resulting from the device placement but the clinical relevance of this is likely negligible [26].

#### **3.2 Efficacy**

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

**3. Safety and efficacy of S-ICDs**

**3.1 Safety**

complication is infection (1.8%) [18]. By dispensing with the transvenous leads, the S-ICD system avoids periprocedural and complications associated with conventional transvenous defibrillation leads, i.e. pericardial effusion, pneumothorax, accidental arterial puncture, nerve plexus injury, and tricuspid valve damage [19].

S-ICDs appear to have similar rates of infection and other complications as transvenous systems and to be similarly effective in rescuing patients from sudden cardiac death, but there are important distinctions between the two systems.

In a retrospective study of 1160 patients who received an implantable defibrillator (either transvenous system or S-ICD) at two centers in the Netherlands, patients were analyzed using propensity matching to yield 140 matched patient pairs. The rates of complications, infection, and inappropriate therapy were statistically similar between groups, but S-ICD patients had significantly fewer lead-related complications than the transvenous group (0.8 vs. 11.5%, p = 0.030) and more non-lead-related complications (9.9 vs. 2.2%, p = 0.047) [20]. The most frequently reported S-ICD complication involved device sensing.(20) Pooled data from the Investigational Device Exemption (IDE) and postmarket registry EFFORTLESS (n = 882) found S-ICD-related complications occurred at a rate of 11.1% at 3 years, but with no lead failures, S-ICD-related endocarditis, or bacteremia [21]. An IDE allows a device that is the subject of a clinical study to be used to collect data about safety and effectiveness that may be later used to submit to the U.S. Food and Drug Administration (FDA). Device-related complications were more frequent with transvenous systems when compared to S-ICD devices in a propensity-matched case–control study of 69 S-ICD and 69 transvenous ICD patients followed for a mean of 31 ± 19 or 32 ± 21 months, respectively. About 29% of transvenous ICD patients experienced a device-related complication compared to 6% of S-ICD patients, reducing the risk of complications for S-ICD patients by 70%; transvenous lead problems

were the most frequently reported complication in the former group [22].

In the largest study of S-ICD patients (n = 3717) to date, complications were low at 1.2% overall. The most frequently reported complications were cardiac arrest (0.4%), hematoma (0.3%), death (0.3%), lead dislodgement (0.1%), myocardial infarction (0.1%), and hemothorax (<0.1%) [23]. Device revision during index hospitalization was infrequent (0.1%) [23]. Infections occur at roughly similar rates with S-ICD and transvenous systems but with the important distinction that S-ICD infections may sometimes be resolved with conservative therapy (course of antibiotics with device left in place), whereas most transvenous ICD infections necessitate the extraction of the device and the transvenous leads. In a survey from the U.K. reporting on data from 111 S-ICD patients, 11/111 (10%) of patients experienced infection, of whom 6 could be successfully treated conservatively without device extraction [24]. The EFFORTLESS registry (n = 472) reported a 4% rate of documented or suspected infections and complication-free rates at 30 and 360 days

Once implanted, the S-ICD device delivers a nonprogrammable, high-energy rescue shock (80 joules) to the thorax compared to shocks of 45 joules to the heart administered by conventional transvenous systems. Notably the S-ICD delivers a 65 joule shock during implant testing. Therapy delivery differs markedly between S-ICD and transvenous systems in terms of the amount of energy delivered, location

**34**

were 97 and 94%, respectively [25].

Effective shock therapy is often defined as conversion of an episode of VT/ VF within five shocks, differing from effective first-shock therapy which occurs when the initial shock converts the arrhythmia. In a study of 79 S-ICD patients at a tertiary center, 7.6% of patients experienced at least one appropriate shock for a ventricular tachyarrhythmia during the follow-up period (mean 12.8 ± 13.7 months) [27]. In a multicenter study from Germany (n = 40), shock efficacy was 96.4% [95% confidence interval (CI), 12.8–100%] and first-shock efficacy was 57.9% (95% CI, 35.6–77.4%) [6]. In an effort to analyze S-ICD efficacy in a large group of diverse patients, data from the Investigation Device Exemption (IDE) clinical study and the EFFORTLESS post-market registry were pooled to provide information about 882 patients followed for 651 ± 345 days. About 59 patients experienced therapy delivery for 111 spontaneous VT/VF episodes with first-shock efficacy in 90.1% of events and shock efficacy (termination with five or fewer shocks) in 98.2% of patients [21]. In the EFFORTLESS registry (n = 472), first-shock efficacy in discrete episodes of VT/VF was 88% and shock efficacy within five shocks was 100% [25].

### **4. Inappropriate shocks with S-ICDs**

Inappropriate shock describes therapy delivery to treat an episode which the device inappropriately detects as a ventricular tachyarrhythmia. Inappropriate shocks have been recognized as a significant clinical challenge with transvenous systems as well as S-ICDs. In a tertiary care center study of 79 S-ICD patients, inappropriate shock occurred in 8.9% (n = 7) of patients, attributable to T-wave oversensing, atrial tachyarrhythmia with rapid atrioventricular conduction, external interference and/or baseline oversensing due to lead movement [27]. T-wave oversensing occurs when the device inappropriately senses ventricular repolarizations (the T-waves on the electrocardiograph) counting them as ventricular events, leading to double counting of the intrinsic ventricular rate. In a multicenter German study (n = 40) with a median follow-up of 229 days, four patients (10%) experienced 21 arrhythmic episodes resulting in 28 therapy deliveries. Four of these episodes were inappropriately identified by the device as ventricular tachyarrhythmias, with the result that two patients received inappropriate shocks. This results in a rate of 10% inappropriately detected ventricular tachycardia and 5% delivery of inappropriate therapy [6]. In a study using pooled data from the IDE and EFFORTLESS post-market registry (n = 882), the three-year rate for inappropriate therapy delivery was 13.1% [21].

It does not appear there are statistically more cases of inappropriate therapy in S-ICD patients compared to transvenous ICD patients. A propensity-matched study (69 patients with a transvenous ICD and 69 with an S-ICD) found the rate of inappropriate shocks was 9% in the transvenous and 3% in the S-ICD groups but this was not statistically significant (p = 0.49) [22]. In a study of 54 S-ICD patients in a

real-world prospective registry, the one-year rate for inappropriate therapy delivery was 17%, most of whom had single-zone programming [10].

Inappropriate shocks with S-ICDs may be minimized. Most of them are caused by T-wave oversensing. In a survey from the U.K. (n = 111 implanted patients covered), 24 appropriate shocks were delivered in 12% of the patients (n = 13) and 51 inappropriate shocks were delivered in 15% of the patients (n = 17), of which 80% could be traced to T-wave oversensing [24]. In the EFFORTLESS registry (n = 472), there was a 7% rate of inappropriate therapy delivery in 360 days, mainly due to oversensing [25]. The main causes of inappropriate therapy delivery have been reported to be supraventricular tachycardia (SVT) at a rate above the discrimination zone, T-wave oversensing, other types of oversensing (e.g. interference), SVT discrimination errors, and low-amplitude signals [21]. Inappropriate therapy delivery due to T-wave oversensing can often be remedied by adjusting the sensing vector or adding another discrimination zone (dual-zone programming) [10].

Certain patients may be at elevated risk for inappropriate shock. A single-center study of 18 hypertrophic cardiomyopathy (HCM) patients implanted with an S-ICD system and followed for a mean 31.7 ± 15.4 months concluded that HCM patients may be at elevated risk for T-wave oversensing which could lead to inappropriate therapy delivery. In this study, 39% of these HCM patients had T-wave oversensing and 22% of the study population (n = 4) experienced inappropriate therapy delivery [28]. An evaluation of 581 S-ICD patients found that inappropriate shocks caused by oversensing occurred in 8.3% of S-ICD patients and patients with HCM and/or a history of atrial fibrillation were at elevated risk for inappropriate therapy [29]. There is a paucity of data on the use of S-ICD devices in HCM patients, but a small study of 27 HCM patients screened for possible S-ICD therapy found 85% (n = 23) were deemed appropriate candidates and 15 had the device implanted [30]. At implant testing, all patients were successfully defibrillated with a 65 joules shock and most induced arrhythmias were terminated with a 50 joules shock (12/15). After the median follow-up period of 17.5 months (range 3–35 months), there were no appropriate shocks and one inappropriate shock, attributed to oversensing caused when the QRS amplitude was reduced while the patient bent forward. In this particular high-risk patient group of HCM patients without a pacing indication, the S-ICD was effective at detecting and terminating tachyarrhythmias [30].

#### **5. Mortality**

The mortality risk with S-ICD implantation is low, but merits scrutiny. On the one hand, S-ICD implantation is generally associated with fewer risks than transvenous ICD implantation in that no transvenous leads are required. On the other hand, patient selection for S-ICD may favor more high-risk patients (such as those with a prior infection, renal failure, comorbid conditions such as diabetes) but also includes many younger and generally fitter patients. Overall, mortality data from S-ICD studies appears favorable. In a pooled analysis combining IDE data and EFFORTLESS registry information, the one-year and two-year mortality rates were 1.6 and 3.2%, respectively [21]. In a study of real-world use of S-ICDs in 54 primary- and secondary-prevention patients, mortality at the mean follow-up duration of 2.6 ± 1.9 years was 11% but no patient died of sudden cardiac arrest [10]. In a six-month study comparing 91 S-ICD and 182 single-chamber transvenous ICD patients, mortality rates were similar although the S-ICD patients had more severe pre-existing illness at implant [31]. It may be that the similar mortality rates between transvenous and S-ICD populations reflects the patient populations rather than the implantation procedure or device characteristics [23].

**37**

*The Subcutaneous Implantable Cardioverter-Defibrillator DOI: http://dx.doi.org/10.5772/10.5772/intechopen.80859*

pharmacological therapy may be added [32].

**7. Primary and secondary prevention**

ming appears advantageous.

vs. 5.0%, p = 0.0004) [18].

The S-ICD device was designed to be a streamlined system with fewer than 10 programmable features (transvenous ICDs have over 100 programmable features) and to perform in a largely automated fashion in terms of device function. The recent introduction of dual-zone programming to S-ICDs added a degree of programmability and reduced inappropriate shock [32]. Arrhythmia detection in the S-ICD relies on a system of template matching, based on waveform morphology of the subcutaneous ECG obtained at implant [33]. Oversensing and sensing-related problems are the most frequently reported problems but are being addressed in terms of device design and programmability. T-wave oversensing occurs when the device incorrectly identifies a T-wave as a QRS complex and counts it as a native ventricular beat, which leads to double-counting the rate. The use of dual-zone device programming has reduced the incidence of inappropriate therapy as a result of double-counting caused by T-wave oversensing [34]. T-wave inversions and QRS complexes that are overly large or very small may be particularly vulnerable to sensing anomalies. Reprogramming the sensing vector or therapy zones may be helpful in such instances [35, 36]. In a propensity-matched study comparing transvenous ICDs to S-ICDs, there were three inappropriate shocks in the S-ICD group, all of which were due to T-wave oversensing in sinus rhythm and all of which could be eliminated with adjustment of the sensing vector [22]. Furthermore, it has been observed with increasing operator experience and better programming techniques, sensing problems have been reduced [21]. In a study using pooled data from the IDE and EFFORTLESS registry, the rate of inappropriate therapy associated with oversensing was <1% [21]. When inappropriate shock occurs, the stored electrograms will likely help identify the cause. If lead malposition is suspected, a chest X-ray may be appropriate. In case of oversensing, the sensing vector may be optimized, device programming may be revised to add a second detection zone, or

SVT discrimination likewise relies on template-matching (which is similar to transvenous systems) but the S-ICD may be able to accomplish this with a higher degree of resolution than transvenous ICDs [33]. The use of dual-zone program-

Primary- and secondary-prevention patients represent two distinct patient populations who may be treated with S-ICD therapy, although S-ICDs seem particularly well suited for primary-prevention patients. Secondary-prevention patients have a lower rate of comorbid conditions and significantly higher left-ventricular ejection fractions (LVEF) than primary-prevention patients (48 vs. 36%, p < 0.0001), while primary-prevention patients had a higher incidence of heart failure and were more likely to have had a transvenous ICD implanted before the S-ICD. Primary-prevention patients also have a higher rate of ischemic cardiomyopathy (41 vs. 33%) and nonischemic cardiomyopathy (28 vs. 12%) [18]. S-ICDs have been shown to be effective for both primary- and secondary-prevention patients. In a study of 856 S-ICD patients (mean follow-up 644 days), there were no significant differences between primary- and secondary-prevention populations in the rates of effective arrhythmia conversions, inappropriate therapy, mortality or complications although appropriate therapy delivery was delivered to significantly more secondary-prevention than primary prevention patients (11.9

**6. Troubleshooting S-ICDs**

#### **6. Troubleshooting S-ICDs**

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

was 17%, most of whom had single-zone programming [10].

real-world prospective registry, the one-year rate for inappropriate therapy delivery

Inappropriate shocks with S-ICDs may be minimized. Most of them are caused

Certain patients may be at elevated risk for inappropriate shock. A single-center study of 18 hypertrophic cardiomyopathy (HCM) patients implanted with an S-ICD system and followed for a mean 31.7 ± 15.4 months concluded that HCM patients may be at elevated risk for T-wave oversensing which could lead to inappropriate therapy delivery. In this study, 39% of these HCM patients had T-wave oversensing and 22% of the study population (n = 4) experienced inappropriate therapy delivery [28]. An evaluation of 581 S-ICD patients found that inappropriate shocks caused by oversensing occurred in 8.3% of S-ICD patients and patients with HCM and/or a history of atrial fibrillation were at elevated risk for inappropriate therapy [29]. There is a paucity of data on the use of S-ICD devices in HCM patients, but a small study of 27 HCM patients screened for possible S-ICD therapy found 85% (n = 23) were deemed appropriate candidates and 15 had the device implanted [30]. At implant testing, all patients were successfully defibrillated with a 65 joules shock and most induced arrhythmias were terminated with a 50 joules shock (12/15). After the median follow-up period of 17.5 months (range 3–35 months), there were no appropriate shocks and one inappropriate shock, attributed to oversensing caused when the QRS amplitude was reduced while the patient bent forward. In this particular high-risk patient group of HCM patients without a pacing indication, the

S-ICD was effective at detecting and terminating tachyarrhythmias [30].

than the implantation procedure or device characteristics [23].

The mortality risk with S-ICD implantation is low, but merits scrutiny. On the one hand, S-ICD implantation is generally associated with fewer risks than transvenous ICD implantation in that no transvenous leads are required. On the other hand, patient selection for S-ICD may favor more high-risk patients (such as those with a prior infection, renal failure, comorbid conditions such as diabetes) but also includes many younger and generally fitter patients. Overall, mortality data from S-ICD studies appears favorable. In a pooled analysis combining IDE data and EFFORTLESS registry information, the one-year and two-year mortality rates were 1.6 and 3.2%, respectively [21]. In a study of real-world use of S-ICDs in 54 primary- and secondary-prevention patients, mortality at the mean follow-up duration of 2.6 ± 1.9 years was 11% but no patient died of sudden cardiac arrest [10]. In a six-month study comparing 91 S-ICD and 182 single-chamber transvenous ICD patients, mortality rates were similar although the S-ICD patients had more severe pre-existing illness at implant [31]. It may be that the similar mortality rates between transvenous and S-ICD populations reflects the patient populations rather

by T-wave oversensing. In a survey from the U.K. (n = 111 implanted patients covered), 24 appropriate shocks were delivered in 12% of the patients (n = 13) and 51 inappropriate shocks were delivered in 15% of the patients (n = 17), of which 80% could be traced to T-wave oversensing [24]. In the EFFORTLESS registry (n = 472), there was a 7% rate of inappropriate therapy delivery in 360 days, mainly due to oversensing [25]. The main causes of inappropriate therapy delivery have been reported to be supraventricular tachycardia (SVT) at a rate above the discrimination zone, T-wave oversensing, other types of oversensing (e.g. interference), SVT discrimination errors, and low-amplitude signals [21]. Inappropriate therapy delivery due to T-wave oversensing can often be remedied by adjusting the sensing vector or adding another discrimination zone (dual-zone programming) [10].

**36**

**5. Mortality**

The S-ICD device was designed to be a streamlined system with fewer than 10 programmable features (transvenous ICDs have over 100 programmable features) and to perform in a largely automated fashion in terms of device function. The recent introduction of dual-zone programming to S-ICDs added a degree of programmability and reduced inappropriate shock [32]. Arrhythmia detection in the S-ICD relies on a system of template matching, based on waveform morphology of the subcutaneous ECG obtained at implant [33]. Oversensing and sensing-related problems are the most frequently reported problems but are being addressed in terms of device design and programmability. T-wave oversensing occurs when the device incorrectly identifies a T-wave as a QRS complex and counts it as a native ventricular beat, which leads to double-counting the rate. The use of dual-zone device programming has reduced the incidence of inappropriate therapy as a result of double-counting caused by T-wave oversensing [34]. T-wave inversions and QRS complexes that are overly large or very small may be particularly vulnerable to sensing anomalies. Reprogramming the sensing vector or therapy zones may be helpful in such instances [35, 36]. In a propensity-matched study comparing transvenous ICDs to S-ICDs, there were three inappropriate shocks in the S-ICD group, all of which were due to T-wave oversensing in sinus rhythm and all of which could be eliminated with adjustment of the sensing vector [22]. Furthermore, it has been observed with increasing operator experience and better programming techniques, sensing problems have been reduced [21]. In a study using pooled data from the IDE and EFFORTLESS registry, the rate of inappropriate therapy associated with oversensing was <1% [21]. When inappropriate shock occurs, the stored electrograms will likely help identify the cause. If lead malposition is suspected, a chest X-ray may be appropriate. In case of oversensing, the sensing vector may be optimized, device programming may be revised to add a second detection zone, or pharmacological therapy may be added [32].

SVT discrimination likewise relies on template-matching (which is similar to transvenous systems) but the S-ICD may be able to accomplish this with a higher degree of resolution than transvenous ICDs [33]. The use of dual-zone programming appears advantageous.

#### **7. Primary and secondary prevention**

Primary- and secondary-prevention patients represent two distinct patient populations who may be treated with S-ICD therapy, although S-ICDs seem particularly well suited for primary-prevention patients. Secondary-prevention patients have a lower rate of comorbid conditions and significantly higher left-ventricular ejection fractions (LVEF) than primary-prevention patients (48 vs. 36%, p < 0.0001), while primary-prevention patients had a higher incidence of heart failure and were more likely to have had a transvenous ICD implanted before the S-ICD. Primary-prevention patients also have a higher rate of ischemic cardiomyopathy (41 vs. 33%) and nonischemic cardiomyopathy (28 vs. 12%) [18]. S-ICDs have been shown to be effective for both primary- and secondary-prevention patients. In a study of 856 S-ICD patients (mean follow-up 644 days), there were no significant differences between primary- and secondary-prevention populations in the rates of effective arrhythmia conversions, inappropriate therapy, mortality or complications although appropriate therapy delivery was delivered to significantly more secondary-prevention than primary prevention patients (11.9 vs. 5.0%, p = 0.0004) [18].

The freedom from any appropriate therapy delivery was 88.4% among primaryprevention patients with an LVEF ≤35 and 96.2% among primary-prevention patients with an LVEF >35%. The freedom from any appropriate therapy delivery among secondary-prevention patients was 92.1% [18]. Spontaneous conversion to sinus rhythm was more frequent among primary-prevention patients (about 48% of all ventricular tachyarrhythmias) compared to secondary-prevention patients (31%) [18]. However, the rates of inappropriate therapy delivery and complications were similar for both primary- and secondary-prevention patients [18].

#### **8. The optimal candidates for S-ICD**

S-ICD systems are indicated for patients who require rescue defibrillation but do not need bradycardia pacing support and would not benefit from antitachycardia pacing or cardiac resynchronization therapy. This includes primary- and secondaryprevention patients. By avoiding transvenous leads, the S-ICD is particularly appropriate for patients with occluded veins or limited venous access (who are not suitable candidates for transvenous systems) and the S-ICD may be beneficial for younger, fitter, and active patients. The generator position of the S-ICD patient may make it easier and safer for strong, fit patients to resume active lifestyles without jeopardizing lead position.

Despite the fact that S-ICD devices are larger than transvenous systems, their lateral placement may result in more pleasing esthetic results than a conventional transvenous ICD. Young device patients likely will have a lifetime of device therapy, resulting over time in much hardware in their vasculature; the S-ICD thus presents an advantage in that regard. It appears that S-ICDs are implanted in a younger patient population; a survey of multiple U.K. hospitals (n = 111 patients) found the median patient age was 33 (range 10–87 years) [24]. The mean age of patients in the EFFORTLESS registry was 49 ± 18 years (range 9–88 years) [25]. Younger patients with cardiomyopathy or channelopathy often have a high rate of complications with conventional transvenous ICDs [37] and it has been thought they may be better served with an S-ICD device [9].

In a multicenter case–control study, it was found that 59.4% of S-ICD patients were primary-prevention and the main underlying cardiac conditions were dilated cardiomyopathy (36.2%), ischemic cardiomyopathy (15.9%), and HCM (14.5%) [38]. In particular, these patients have been considered challenging to treat with a conventional transvenous ICD in that they may have an erratic electrical substrate in the heart and increased left-ventricular mass, which could contribute to an elevated DT. First-shock efficacy rates of up to 88% are promising in light of these challenges [25]. In a study of 50 hypertrophic cardiomyopathy patients implanted with S-ICDs, 96% of patients could be induced to an arrhythmia at implant and of the 73 episodes of VF induced, 98% were successfully converted with 65 joules from the S-ICD during DT testing. One patient in this study (2%) required rescue external defibrillation [39]. The patient who failed internal defibrillation had a body mass index of 36 and was successfully converted by an 80 joules shock with reversed polarity from the S-ICD [39].

#### **9. Current guidelines**

#### **9.1 Indications**

The most recent guidelines to address S-ICD were published by the American Heart Association, the American College of Cardiology, and the Heart Rhythm

**39**

*The Subcutaneous Implantable Cardioverter-Defibrillator DOI: http://dx.doi.org/10.5772/10.5772/intechopen.80859*

(Class of Recommendation III, level of evidence B) [40].

need long-term ICD therapy [41].

cally selects the optimal sensing vector [11].

**9.2 Pre-implant testing**

**9.3 Programming**

mable 80 joules of energy [11].

**10. Future directions**

optimize clinical workflow.

Society in 2017 [40]. The An S-ICD is indicated (Class of Recommendation 1, level of evidence B) for patients who meet indication criteria for a transvenous ICD but who have inadequate vascular access or are at high risk of infection and for whom there is no anticipated need for bradycardia or antitachycardia pacing. Further, implantation of an S-ICD is deemed reasonable for patients with an ICD indication for whom there is no anticipated need for bradycardia or antitachycardia pacing (Class of Recommendation IIa, level of evidence B). An S-ICD is contraindicated in a patient who is indicated for bradycardia pacing, antitachycardia pacing for termination of ventricular tachyarrhythmias, and/or cardiac resynchronization therapy

The European Society of Cardiology guidelines from 2015 report that S-ICDs are effective in preventing sudden cardiac death and the device is recommended as an alternative to transvenous ICDs in patients who are indicated for defibrillation but not pacing support, cardiac resynchronization therapy, or antitachycardia pacing (Class IIa, Level C). Moreover, the S-ICD was considered to be a useful alternative for patients in whom venous access was difficult or for patients who had a transvenous system explanted because of an infection or for young patients expected to

Those considered for S-ICD therapy should be screened with a modified version of the three-channel surface electrocardiogram (ECG) set up to represent the sensing vectors of the S-ICD. With the patient both standing and supine, the ratio of R-wave to T-wave should be established and signal quality evaluated. If any of the three vectors does not result in satisfactory sensing, the S-ICD should not be implanted. Once the actual device is implanted in the patient, the system automati-

The S-ICD may be programmed to detect arrhythmias using a single- or dualzone configuration. In the dual-zone configuration, a lower cutoff rate defines what might be called a "conditional shock zone" to which a discrimination algorithm is applied so that therapy is withheld if the rhythm might be deemed supraventricular in origin or non-arrhythmic oversensing. This discrimination zone relies on a form of template matching. Above that rate, a cutoff establishes the "shock zone" which delivers a shock based on the rate criterion alone. When the capacitors charge in anticipation of shock delivery, a confirmation algorithm assures the persistence of the arrhythmia prior to sending the shock. Shocks are delivered at the nonprogram-

The evolution of the S-ICD adds an important new device into the armamentarium for rescuing patients from sudden cardiac death. To further improve S-ICD technology, size reduction, increased battery longevity, and improved T-wave rejection will be needed. In the near future, improvement in sensing function might eliminate the need for a separate screening ECG prior to implant, which could

Improved battery technology is particularly important as the S-ICD is often used in patients with a relatively long life expectancy. Leadless pacemaker systems that

#### *The Subcutaneous Implantable Cardioverter-Defibrillator DOI: http://dx.doi.org/10.5772/10.5772/intechopen.80859*

Society in 2017 [40]. The An S-ICD is indicated (Class of Recommendation 1, level of evidence B) for patients who meet indication criteria for a transvenous ICD but who have inadequate vascular access or are at high risk of infection and for whom there is no anticipated need for bradycardia or antitachycardia pacing. Further, implantation of an S-ICD is deemed reasonable for patients with an ICD indication for whom there is no anticipated need for bradycardia or antitachycardia pacing (Class of Recommendation IIa, level of evidence B). An S-ICD is contraindicated in a patient who is indicated for bradycardia pacing, antitachycardia pacing for termination of ventricular tachyarrhythmias, and/or cardiac resynchronization therapy (Class of Recommendation III, level of evidence B) [40].

The European Society of Cardiology guidelines from 2015 report that S-ICDs are effective in preventing sudden cardiac death and the device is recommended as an alternative to transvenous ICDs in patients who are indicated for defibrillation but not pacing support, cardiac resynchronization therapy, or antitachycardia pacing (Class IIa, Level C). Moreover, the S-ICD was considered to be a useful alternative for patients in whom venous access was difficult or for patients who had a transvenous system explanted because of an infection or for young patients expected to need long-term ICD therapy [41].

#### **9.2 Pre-implant testing**

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

**8. The optimal candidates for S-ICD**

jeopardizing lead position.

served with an S-ICD device [9].

**9. Current guidelines**

**9.1 Indications**

The freedom from any appropriate therapy delivery was 88.4% among primary-

S-ICD systems are indicated for patients who require rescue defibrillation but do not need bradycardia pacing support and would not benefit from antitachycardia pacing or cardiac resynchronization therapy. This includes primary- and secondaryprevention patients. By avoiding transvenous leads, the S-ICD is particularly appropriate for patients with occluded veins or limited venous access (who are not suitable candidates for transvenous systems) and the S-ICD may be beneficial for younger, fitter, and active patients. The generator position of the S-ICD patient may make it easier and safer for strong, fit patients to resume active lifestyles without

Despite the fact that S-ICD devices are larger than transvenous systems, their lateral placement may result in more pleasing esthetic results than a conventional transvenous ICD. Young device patients likely will have a lifetime of device therapy, resulting over time in much hardware in their vasculature; the S-ICD thus presents an advantage in that regard. It appears that S-ICDs are implanted in a younger patient population; a survey of multiple U.K. hospitals (n = 111 patients) found the median patient age was 33 (range 10–87 years) [24]. The mean age of patients in the EFFORTLESS registry was 49 ± 18 years (range 9–88 years) [25]. Younger patients with cardiomyopathy or channelopathy often have a high rate of complications with conventional transvenous ICDs [37] and it has been thought they may be better

In a multicenter case–control study, it was found that 59.4% of S-ICD patients were primary-prevention and the main underlying cardiac conditions were dilated cardiomyopathy (36.2%), ischemic cardiomyopathy (15.9%), and HCM (14.5%) [38]. In particular, these patients have been considered challenging to treat with a conventional transvenous ICD in that they may have an erratic electrical substrate in the heart and increased left-ventricular mass, which could contribute to an elevated DT. First-shock efficacy rates of up to 88% are promising in light of these challenges [25]. In a study of 50 hypertrophic cardiomyopathy patients implanted with S-ICDs, 96% of patients could be induced to an arrhythmia at implant and of the 73 episodes of VF induced, 98% were successfully converted with 65 joules from the S-ICD during DT testing. One patient in this study (2%) required rescue external defibrillation [39]. The patient who failed internal defibrillation had a body mass index of 36 and was successfully converted by an 80 joules shock with reversed polarity from the S-ICD [39].

The most recent guidelines to address S-ICD were published by the American Heart Association, the American College of Cardiology, and the Heart Rhythm

prevention patients with an LVEF ≤35 and 96.2% among primary-prevention patients with an LVEF >35%. The freedom from any appropriate therapy delivery among secondary-prevention patients was 92.1% [18]. Spontaneous conversion to sinus rhythm was more frequent among primary-prevention patients (about 48% of all ventricular tachyarrhythmias) compared to secondary-prevention patients (31%) [18]. However, the rates of inappropriate therapy delivery and complications

were similar for both primary- and secondary-prevention patients [18].

**38**

Those considered for S-ICD therapy should be screened with a modified version of the three-channel surface electrocardiogram (ECG) set up to represent the sensing vectors of the S-ICD. With the patient both standing and supine, the ratio of R-wave to T-wave should be established and signal quality evaluated. If any of the three vectors does not result in satisfactory sensing, the S-ICD should not be implanted. Once the actual device is implanted in the patient, the system automatically selects the optimal sensing vector [11].

#### **9.3 Programming**

The S-ICD may be programmed to detect arrhythmias using a single- or dualzone configuration. In the dual-zone configuration, a lower cutoff rate defines what might be called a "conditional shock zone" to which a discrimination algorithm is applied so that therapy is withheld if the rhythm might be deemed supraventricular in origin or non-arrhythmic oversensing. This discrimination zone relies on a form of template matching. Above that rate, a cutoff establishes the "shock zone" which delivers a shock based on the rate criterion alone. When the capacitors charge in anticipation of shock delivery, a confirmation algorithm assures the persistence of the arrhythmia prior to sending the shock. Shocks are delivered at the nonprogrammable 80 joules of energy [11].

#### **10. Future directions**

The evolution of the S-ICD adds an important new device into the armamentarium for rescuing patients from sudden cardiac death. To further improve S-ICD technology, size reduction, increased battery longevity, and improved T-wave rejection will be needed. In the near future, improvement in sensing function might eliminate the need for a separate screening ECG prior to implant, which could optimize clinical workflow.

Improved battery technology is particularly important as the S-ICD is often used in patients with a relatively long life expectancy. Leadless pacemaker systems that

might work together with an S-ICD are in development which would allow for bradycardia pacing support, antitachycardia pacing and a subcutaneous defibrillator without transvenous leads [32]. The development of a leadless epicardial pacemaker might allow for left-atrial and left-ventricular pacing function to be integrated to the S-ICD. Taken altogether, these improvements could make the S-ICD the preferred device in the vast majority of cases for rescue from sudden cardiac death.

#### **11. Conclusion**

The subcutaneous implantable cardioverter defibrillator (S-ICD) offers an alternative to transvenous ICDs but the two systems should not be considered interchangeable. The S-ICD is appropriate for patients who require only rescue defibrillation (primary or secondary prevention) but does not offer bradycardia pacing, antitachycardia pacing, overdrive pacing, or cardiac resynchronization therapy. S-ICD devices may be appropriate in patients who have occluded vasculature or device infection with a transvenous system. Effectiveness, rate of infections, and survival rates are similar for both devices although, in general, S-ICDs may be implanted in patients with more serious underlying conditions such as end-stage renal disease or advanced diabetes. Infections with S-ICDs are more likely to be effectively treated with a conservative course of antibiotic therapy and no device extraction. Inappropriate shocks occur at similar rates with both systems but are more likely caused by oversensing in the S-ICD. A main advantage of S-ICDs over transvenous systems is the elimination of the transvenous defibrillation lead which may be considered the Achilles heel of the transvenous system, having a 10-year complication rate of 25%. It is likely that considerable advances in ICD therapy will occur in the next decade as the S-ICD systems are further refined.

**41**

**Author details**

Stockholm, Sweden

Sweden

provided the original work is properly cited.

Peter Magnusson1,2, Joseph V. Pergolizzi3

3 Native Cardio, Inc., Naples, Florida, USA

4 NEMA Research Inc., Naples, Florida, USA

\*Address all correspondence to: joann@leqmedical.com

*The Subcutaneous Implantable Cardioverter-Defibrillator DOI: http://dx.doi.org/10.5772/10.5772/intechopen.80859*

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

1 Cardiology Research Unit, Department of Medicine, Karolinska Institute,

2 Centre for Research and Development, Uppsala University/Region Gävleborg,

and Jo Ann LeQuang4

\*

#### **Conflict of interest**

The authors have no conflicts of interest to declare.

*The Subcutaneous Implantable Cardioverter-Defibrillator DOI: http://dx.doi.org/10.5772/10.5772/intechopen.80859*

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

**11. Conclusion**

**Conflict of interest**

might work together with an S-ICD are in development which would allow for bradycardia pacing support, antitachycardia pacing and a subcutaneous defibrillator without transvenous leads [32]. The development of a leadless epicardial pacemaker might allow for left-atrial and left-ventricular pacing function to be integrated to the S-ICD. Taken altogether, these improvements could make the S-ICD the preferred device in the vast majority of cases for rescue from sudden cardiac death.

The subcutaneous implantable cardioverter defibrillator (S-ICD) offers an alternative to transvenous ICDs but the two systems should not be considered interchangeable. The S-ICD is appropriate for patients who require only rescue defibrillation (primary or secondary prevention) but does not offer bradycardia pacing, antitachycardia pacing, overdrive pacing, or cardiac resynchronization therapy. S-ICD devices may be appropriate in patients who have occluded vasculature or device infection with a transvenous system. Effectiveness, rate of infections, and survival rates are similar for both devices although, in general, S-ICDs may be implanted in patients with more serious underlying conditions such as end-stage renal disease or advanced diabetes. Infections with S-ICDs are more likely to be effectively treated with a conservative course of antibiotic therapy and no device extraction. Inappropriate shocks occur at similar rates with both systems but are more likely caused by oversensing in the S-ICD. A main advantage of S-ICDs over transvenous systems is the elimination of the transvenous defibrillation lead which may be considered the Achilles heel of the transvenous system, having a 10-year complication rate of 25%. It is likely that considerable advances in ICD therapy will

occur in the next decade as the S-ICD systems are further refined.

The authors have no conflicts of interest to declare.

**40**

#### **Author details**

Peter Magnusson1,2, Joseph V. Pergolizzi3 and Jo Ann LeQuang4 \*

1 Cardiology Research Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden

2 Centre for Research and Development, Uppsala University/Region Gävleborg, Sweden

3 Native Cardio, Inc., Naples, Florida, USA

4 NEMA Research Inc., Naples, Florida, USA

\*Address all correspondence to: joann@leqmedical.com

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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S01410-6736

JAHA.115.003181

*The Subcutaneous Implantable Cardioverter-Defibrillator DOI: http://dx.doi.org/10.5772/10.5772/intechopen.80859*

[13] Healey JS, Hohnloser SH, Glikson M, Neuzner J, Mabo P, Vinolas X, et al. Cardioverter defibrillator implantation without induction of ventricular fibrillation: A single-blind, noninferiority, randomised controlled trial (SIMPLE). Lancet. 2015;**385**(14):785, 61903-791, 61906. DOI: 10.1016/ S01410-6736

[14] Frommeyer G, Zumhagen S, Dechering DG, Larbig R, Bettin M, Loher A, et al. Intraoperative defibrillation testing of subcutaneous implantable Cardioverter-defibrillator systems–A Simple issue. Journal of the American Heart Association. 2016;**5**:e003181. DOI: 10.1161/ JAHA.115.003181

[15] Miller MA, Palaniswamy C, Dukkipati SR, Balulad S, Smietana J, Vigdor A, et al. Subcutaneous implantable cardioverter-defibrillator implantation without defibrillation testing. Journal of the American College of Cardiology. 2017;**69**:3118-3119. DOI: 10.1016/j.jacc.2017.04.037

[16] Dabiri Abkenari L, Theuns D, Valk S, Van Belle Y, de Groot N, Haitsma D, et al. Clinical experience with a novel subcutaenous implantable defibrillator system in a single center. Clinical Research in Cardiology: Official Journal of the German Cardiac Society. 2011;**100**:737-744. DOI: 10.1007/00392-011-0303-6

[17] Gold MR, Aasbo JD, El-Chami MF, Niebauer M, Herre J, Prutkin JM, et al. Subcutaneous implantable cardioverter-defibrillator post-approval study: Clinical characteristics and perioperative results. Heart Rhythm: The Official Journal of the Heart Rhythm Society. 2017;**14**:1456-1463. DOI: 10.1016/j.hrthm.2017.05.016

[18] Boersma LV, Barr CS, Burke MC, Leon AR, Theuns DA, Herre JM, et al. Performance of the subcutaneous implantable cardioverter-defibrillator in patients with a primary prevention indication with and without a reduced ejection fraction versus patients with a secondary prevention indication. Heart Rhythm: The Official Journal of the Heart Rhythm Society. 2017;**14**:367-375. DOI: 10.1016/j.hrthmj.2016.11.025

[19] Olde Nordkamp LRA, Conte G, Rosenmoller B, Warnaars JLF, Tan HL, Caputo ML, et al. Brugada syndrome and the subcutaneous implantable cardioverter-defibrillator. Journal of the American College of Cardiology. 2016;**68**:665-666. DOI: 10.1016/j. jacc.2016.05.058

[20] Brouwer TF, Yilmaz D, Lindeboom R, Buiten MS, Olde Nordkamp LR, Schalij MJ, et al. Long-term clinical outcomes of subcutaneous versus transvenous implantable defibrillator therapy. Journal of the American College of Cardiology. 2016;**68**:2047- 2055. DOI: 10.1016/j.jacc.2016.08.044

[21] Burke MC, Gold MR, Knight BP, Barr CS, Theuns DA, Boersma LV, et al. Safety and efficacy of the totally subcutaneous implantable defibrillator: 2-year results from a pooled analysis of the IDE study and EFFORTLESS registry. Journal of the American College of Cardiology. 2015;**65**:1605-1615. DOI: 10.1016/j. jacc.2015.02.047

[22] Honarbakhsh S, Providencia R, Srinivasan N, Ahsan S, Lowe M, Rowland E, et al. A propensity matched case-control study comparing efficacy, safety and costs of the subcutaneous vs. transvenous implantable cardioverter defibrillator. International Journal of Cardiology. 2017;**228**:280-285. DOI: 10.1016/j.ijcard.2016.11.017

[23] Friedman DJ, Parzynski CS, Varosy PD, Prutkin JM, Patton KK, Mithani A, et al. Trends and in-hospital outcomes associated with adoption of the subcutaneous implantable cardioverter defibrillator in the United States. JAMA

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[8] Winter J, Siekiera M, Shin DI, Meyer C, Kropil P, Clahsen H, et al. Intermuscular technique for implantation of the subcutaneous implantable cardioverter defibrillator:

Long-term performance and

complications. Europace. 2017;**19**:2036- 2041. DOI: 10.1093/europace/euw297

[9] Migliore F, Allocca G, Calzolari V, Crosato M, Facchin D, Daleffe E, et al. Intermuscular two-incision technique for subcutaneous implantable Cardioverter defibrillator implantation: Results from a multicenter registry. Pacing and Clinical Electrophysiology: PACE. 2017;**40**:278-285. DOI: 10.1111/

[10] Mesquita J, Cavaco D, Ferreira A, Lopes N, Santos PG, Carvalho MS, et al. Effectiveness of subcutaneous implantable cardioverter-defibrillators and determinants of inappropriate shock delivery. International Journal of Cardiology. 2017;**232**:176-180. DOI:

[11] Wilkoff BL, Fauchier L, Stiles MK, Morillo CA, Al-Khatib SM, Almendral J, et al. 2015 HRS/EHRA/APHRS/ SOLAECE expert consensus statement on optimal implantable cardioverterdefibrillator programming and testing. Europace. 2016;**18**:159-183. DOI:

[12] Bansch D, Bonnemeier H, Brandt J, Bode F, Svendsen JH, Taborsky M, et al. Intra-operative defibrillation testing and clinical shock efficacy in patients with implantable cardioverter-defibrillators:

The NORDIC ICD randomized clinical trial. European Heart Journal. 2015;**36**:2500-2507. DOI: 10.1093/

eurheartj/ehv292

10.1016/jicard.2017.01.034

10.1093/europace/euv411

NEJMoa0909545

pace.12987

[1] Kleemann T, Becker T, Doenges K, Vater M, Senges J, Schneider S, et al. Annual rate of transvenous

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[6] Aydin A, Hartel FW, Schluter M, Butter C, Kobe J, Seifert M, et al. Shock efficacy of subcutaneous implantable cardioverter-defibrillator for prevention of sudden cardiac death. Circulation. Arrhythmia and Electrophysiology. 2012;**5**:913-919. DOI: 10.1161/

[7] Bardy GH, Smith WM, Hood MA, Crozier IG, Melton IC, Jordaens L, et al. An entirely subcutaneous

Cardiology. 2016;**1**:900-911. DOI: 10.1001/jamacardio.2016.2782

[24] Jarman JW, Todd DM. United Kingdom national experience of entirely subcutaneous implantable cardioverterdefibrillator technology: Important lessons to learn. Europace. 2013;**15**:1158- 1165. DOI: 10.1093/europace/eut016

[25] Lambiase PD, Barr C, Theuns DA, Knops R, Neuzil P, Johansen JB, et al. Worldwide experience with a totally subcutaneous implantable defibrillator: Early results from the EFFORTLESS S-ICD registry. European Heart Journal. 2014;**35**:1657-1665. DOI: 10.1093/ eurheartj/ehu112

[26] Garcia R, Inal S, Favreau F, Jayle C, Hauet T, Bruneval P, et al. Subcutaneous cardioverter defibrillator has longer time to therapy but is less cardiotoxic than transvenous cardioverter defibrillator. Study carried out in a preclinical porcine model. Europace. 2018;**20**:873-879. DOI: 10.1093/ europaceeux074

[27] Khazen C, Magnusson P, Flandorfer J, Schukro C. The subcutaneous implantable cardioverter-defibrillator: A tertiary center experience. Cardiology Journal. 2 May 2018. DOI: 10.5603/ CJ.a2018.0050. [Epub ahead of print]

[28] Frommeyer G, Dechering DG, Zumhagen S, Loher A, Kobe J, Eckardt L, et al. Long-term follow-up of subcutaneous ICD systems in patients with hypertrophic cardiomyopathy: A single-center experience. Clinical Research in Cardiology: Official Journal of the German Cardiac Society. 2016;**105**:89-93. DOI: 10.1007/ s00392-015-0901-9

[29] Olde Nordkamp LR, Brouwer TF, Barr C, Theuns DA, Boersma LV, Johansen JB, et al. Inappropriate shocks in the subcutaneous ICD: Incidence, predictors and management. International Journal of Cardiology.

2015;**195**:126-133. DOI: 10.1016/j. ijcard.2015.015.135

[30] Weinstock J, Bader YH, Maron MS, Rowin EJ, Link MS. Subcutaneous implantable cardioverter defibrillator in patients with hypertrophic cardiomyopathy: An initial experience. Journal of the American Heart Association. 2016;**5**:piie002488. DOI: 10.1161/JAHA.115.002488

[31] Mithani AA, Kath H, Hunter K, Andriulli J, Ortman M, Field J, et al. Characteristics and early clinical outcomes of patients undergoing totally subcutaneous vs. transvenous single chamber implantable cardioverter defibrillator placement. Europace. 2018;**20**:308-314. DOI: 10.1093/ europace/eux026

[32] McLeod CJ, Boersma L, Okamura H, Friedman PA. The subcutaneous implantable cardioverter defibrillator: State-of-the-art review. European Heart Journal. 2017;**38**:247-257. DOI: 10.1093/ eurheartj/ehv507

[33] De Maria E, Olaru A, Cappelli S. The entirely subcutaneous defibrillator (s-icd): State of the art and selection of the ideal candidate. Current Cardiology Reviews. 2015;**11**:180-186. DOI: 10.2174/ 157403X10666140827094126

[34] Weiss R, Knight BP, Gold MR, Leon AR, Herre JM, Hood M, et al. Safety and efficacy of a totally subcutaneous implantablecardioverter defibrillator. Circulation. 2013;**128**:944-953. DOI: 10.1161/ CIRCULATIONAHA.113.003042

[35] Gold MR, Theuns DA, Knight BP, Sturdivant JL, Sanghera R, Ellenbogen KA, et al. Head-to-head comparison of arrhythmia discrimination performance of subcutaneous and transvenous ICD arrhythmia detection algorithms: The START study. Journal of Cardiovascular Electrophysiology. 2012;**23**:359-366. DOI: 10.1111/j.1540-8167.2011.02199

**45**

*The Subcutaneous Implantable Cardioverter-Defibrillator DOI: http://dx.doi.org/10.5772/10.5772/intechopen.80859*

> hrthm.2017.10.035. [Epub ahead of print] No abstract available. PMID:

[41] Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, et al. ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). European Heart Journal. 2015;**36**:2793- 2867. DOI: 10.1093/eurheartj/ehv316

29097320

[36] Kooiman KM, Knops RE, Olde Nordkamp L, Wilde AA, de Groot JR. Inappropriate subcutaneous implantable cardioverter-defibrillator shocks due to T-wave oversensing can be prevented: Implications for management. Heart Rhythm: The Official Journal of the Heart Rhythm Society. 2014;**11**:426- 434. DOI: 10.1016/j.hrthm.2013.12.007

[37] Migliore F, Silvano M, Zorzi A, Bertaglia E, Siciliano M, Leoni L, et al. Implantable cardioverter defibrillator therapy in young patients with

[38] Kobe J, Reinke F, Meyer C, Shin DI, Martens E, Kaab S, et al. Implantation and follow-up of totally subcutaneous versus conventional implantable cardioverter-defibrillators: A multicenter case-control study. Heart Rhythm: The official Journal of the Heart Rhythm Society. 2013;**10**:29-36. DOI: 10.1016/j.hrthm.2012.09.126

[39] Maurizi N, Tanini I, Olivotto I, Amendola E, Limongelli G, Losi MA, et al. Effectiveness of subcutaneous implantable cardioverter-defibrillator testing in patients with hypertrophic cardiomyopathy. International Journal of Cardiology. 2017;**231**:115-119. DOI:

[40] Al-Khatib SM, Stevenson WG, Ackerman MJ, Gillis AM, Bryant WJ, et al. AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: Executive summary: A report of the American College of Cardiology/ American Heart Association task force on clinical practice guidelines and the Heart Rhythm Society. Heart Rhythm: The Official Journal of the Heart Rhythm Society. 30 Oct 2017. pii: **S1547- 5271**(17);31249-31253. DOI: 10.1016/j.

10.1016/j.ijcard.2016.12.187

cardiomyopathies and channelopathies: A single Italian Centre experience. Journal of Cardiovascular Medicine (Hagerstown, Md). 2016;**17**:485-493. DOI: 10.2459/JCM.0000000000000395 *The Subcutaneous Implantable Cardioverter-Defibrillator DOI: http://dx.doi.org/10.5772/10.5772/intechopen.80859*

[36] Kooiman KM, Knops RE, Olde Nordkamp L, Wilde AA, de Groot JR. Inappropriate subcutaneous implantable cardioverter-defibrillator shocks due to T-wave oversensing can be prevented: Implications for management. Heart Rhythm: The Official Journal of the Heart Rhythm Society. 2014;**11**:426- 434. DOI: 10.1016/j.hrthm.2013.12.007

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

2015;**195**:126-133. DOI: 10.1016/j.

[30] Weinstock J, Bader YH, Maron MS, Rowin EJ, Link MS. Subcutaneous implantable cardioverter defibrillator

cardiomyopathy: An initial experience.

[31] Mithani AA, Kath H, Hunter K, Andriulli J, Ortman M, Field J, et al. Characteristics and early clinical outcomes of patients undergoing totally subcutaneous vs. transvenous single chamber implantable cardioverter defibrillator placement. Europace. 2018;**20**:308-314. DOI: 10.1093/

[32] McLeod CJ, Boersma L, Okamura H, Friedman PA. The subcutaneous implantable cardioverter defibrillator: State-of-the-art review. European Heart Journal. 2017;**38**:247-257. DOI: 10.1093/

[33] De Maria E, Olaru A, Cappelli S. The entirely subcutaneous defibrillator (s-icd): State of the art and selection of the ideal candidate. Current Cardiology Reviews. 2015;**11**:180-186. DOI: 10.2174/

157403X10666140827094126

[34] Weiss R, Knight BP, Gold MR, Leon AR, Herre JM, Hood M, et al. Safety and efficacy of a totally subcutaneous implantablecardioverter defibrillator. Circulation. 2013;**128**:944-953. DOI: 10.1161/ CIRCULATIONAHA.113.003042

[35] Gold MR, Theuns DA, Knight BP, Sturdivant JL, Sanghera R, Ellenbogen KA, et al. Head-to-head comparison of arrhythmia discrimination performance of subcutaneous and transvenous ICD arrhythmia detection algorithms: The START study. Journal of Cardiovascular Electrophysiology. 2012;**23**:359-366. DOI: 10.1111/j.1540-8167.2011.02199

in patients with hypertrophic

Journal of the American Heart Association. 2016;**5**:piie002488. DOI:

10.1161/JAHA.115.002488

europace/eux026

eurheartj/ehv507

ijcard.2015.015.135

Cardiology. 2016;**1**:900-911. DOI: 10.1001/jamacardio.2016.2782

[24] Jarman JW, Todd DM. United Kingdom national experience of entirely subcutaneous implantable cardioverterdefibrillator technology: Important lessons to learn. Europace. 2013;**15**:1158- 1165. DOI: 10.1093/europace/eut016

[25] Lambiase PD, Barr C, Theuns DA, Knops R, Neuzil P, Johansen JB, et al. Worldwide experience with a totally subcutaneous implantable defibrillator: Early results from the EFFORTLESS S-ICD registry. European Heart Journal. 2014;**35**:1657-1665. DOI: 10.1093/

[26] Garcia R, Inal S, Favreau F, Jayle C, Hauet T, Bruneval P, et al. Subcutaneous cardioverter defibrillator has longer time to therapy but is less cardiotoxic than transvenous cardioverter defibrillator. Study carried out in a preclinical porcine model. Europace. 2018;**20**:873-879. DOI: 10.1093/

[27] Khazen C, Magnusson P, Flandorfer

J, Schukro C. The subcutaneous implantable cardioverter-defibrillator: A tertiary center experience. Cardiology Journal. 2 May 2018. DOI: 10.5603/ CJ.a2018.0050. [Epub ahead of print]

[28] Frommeyer G, Dechering DG, Zumhagen S, Loher A, Kobe J, Eckardt L, et al. Long-term follow-up of subcutaneous ICD systems in patients with hypertrophic cardiomyopathy: A single-center experience. Clinical Research in Cardiology: Official Journal of the German Cardiac Society. 2016;**105**:89-93. DOI: 10.1007/

[29] Olde Nordkamp LR, Brouwer TF, Barr C, Theuns DA, Boersma LV, Johansen JB, et al. Inappropriate shocks in the subcutaneous ICD: Incidence, predictors and management. International Journal of Cardiology.

eurheartj/ehu112

europaceeux074

s00392-015-0901-9

**44**

[37] Migliore F, Silvano M, Zorzi A, Bertaglia E, Siciliano M, Leoni L, et al. Implantable cardioverter defibrillator therapy in young patients with cardiomyopathies and channelopathies: A single Italian Centre experience. Journal of Cardiovascular Medicine (Hagerstown, Md). 2016;**17**:485-493. DOI: 10.2459/JCM.0000000000000395

[38] Kobe J, Reinke F, Meyer C, Shin DI, Martens E, Kaab S, et al. Implantation and follow-up of totally subcutaneous versus conventional implantable cardioverter-defibrillators: A multicenter case-control study. Heart Rhythm: The official Journal of the Heart Rhythm Society. 2013;**10**:29-36. DOI: 10.1016/j.hrthm.2012.09.126

[39] Maurizi N, Tanini I, Olivotto I, Amendola E, Limongelli G, Losi MA, et al. Effectiveness of subcutaneous implantable cardioverter-defibrillator testing in patients with hypertrophic cardiomyopathy. International Journal of Cardiology. 2017;**231**:115-119. DOI: 10.1016/j.ijcard.2016.12.187

[40] Al-Khatib SM, Stevenson WG, Ackerman MJ, Gillis AM, Bryant WJ, et al. AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: Executive summary: A report of the American College of Cardiology/ American Heart Association task force on clinical practice guidelines and the Heart Rhythm Society. Heart Rhythm: The Official Journal of the Heart Rhythm Society. 30 Oct 2017. pii: **S1547- 5271**(17);31249-31253. DOI: 10.1016/j.

hrthm.2017.10.035. [Epub ahead of print] No abstract available. PMID: 29097320

[41] Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, et al. ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). European Heart Journal. 2015;**36**:2793- 2867. DOI: 10.1093/eurheartj/ehv316

**47**

**Chapter 4**

**Abstract**

(formerly St. Jude Medical).

cardiac rhythm management.

**1. Introduction**

Nanostim™ pacemaker, transcatheter pacemaker

Leadless Pacemakers

*Peter Magnusson, Joseph V. Pergolizzi Jr and Jo Ann LeQuang*

Leadless or transcatheter pacemakers have recently been introduced to market

with important benefits and some limitations. Implanted entirely within the right ventricle, these devices eliminate the need for transvenous pacing leads and pacemaker pockets and thus reduce the risk of infections and lead-related problems. Currently, they offer only VVI/R pacing and they cannot provide atrial sensing, antitachycardia pacing, or AV synchrony. They offer a number of features (such as rate response) and electrogram storage, albeit more limited than in a transvenous system. Real-world clinical data are needed to better comment on projected battery life, which manufacturers suggest will be at least equivalent to transvenous devices. Extracting an implanted leadless pacemaker remains a challenge, although proprietary snare and removal systems are available. However, a leadless pacemaker at end of service may be programmed to OOO and left in place; a revised device may be implanted adjacent. These innovative new devices may have important uses in special populations. Initial data on implant success and adverse events are favorable. Currently, there are two leadless pacemakers available: the Micra™ device by Medtronic and the Nanostim™ device by Abbott

**Keywords:** LEADLESS clinical study, leadless pacemaker, Micra™ pacemaker,

The most vulnerable portion of the implantable cardiac pacemaker system is the transvenous lead(s), which can dislodge, fracture, experience insulation breach, and may lead to a host of adverse events including perforation, venous occlusion, tricuspid regurgitation, oversensing (with inappropriate device function), and infection. The innovation of a leadless pacemaker offers pacing support through a catheter-delivered device that is situated entirely within the right ventricle. A leadless pacemaker eliminates the need for both a pacemaker pocket and transvenous access. Its main limitations are lack of atrial pacing and sensing capabilities and the inability to provide antitachycardia pacing. For patients who require solely single-chamber ventricular pacing (VVI/R), the leadless pacemaker offers an important new option. Growing experience with these leadless devices shows great promise and expanding applications, even though real-world clinical experience is limited. The Spanish Pacemaker Registry reported about 1.6% leadless pacemakers out of all 12,697 reported devices by 2016 [1]. Despite this slow uptake, leadless pacing systems may be an important "disrupting technology" in

## **Chapter 4** Leadless Pacemakers

*Peter Magnusson, Joseph V. Pergolizzi Jr and Jo Ann LeQuang*

### **Abstract**

Leadless or transcatheter pacemakers have recently been introduced to market with important benefits and some limitations. Implanted entirely within the right ventricle, these devices eliminate the need for transvenous pacing leads and pacemaker pockets and thus reduce the risk of infections and lead-related problems. Currently, they offer only VVI/R pacing and they cannot provide atrial sensing, antitachycardia pacing, or AV synchrony. They offer a number of features (such as rate response) and electrogram storage, albeit more limited than in a transvenous system. Real-world clinical data are needed to better comment on projected battery life, which manufacturers suggest will be at least equivalent to transvenous devices. Extracting an implanted leadless pacemaker remains a challenge, although proprietary snare and removal systems are available. However, a leadless pacemaker at end of service may be programmed to OOO and left in place; a revised device may be implanted adjacent. These innovative new devices may have important uses in special populations. Initial data on implant success and adverse events are favorable. Currently, there are two leadless pacemakers available: the Micra™ device by Medtronic and the Nanostim™ device by Abbott (formerly St. Jude Medical).

**Keywords:** LEADLESS clinical study, leadless pacemaker, Micra™ pacemaker, Nanostim™ pacemaker, transcatheter pacemaker

#### **1. Introduction**

The most vulnerable portion of the implantable cardiac pacemaker system is the transvenous lead(s), which can dislodge, fracture, experience insulation breach, and may lead to a host of adverse events including perforation, venous occlusion, tricuspid regurgitation, oversensing (with inappropriate device function), and infection. The innovation of a leadless pacemaker offers pacing support through a catheter-delivered device that is situated entirely within the right ventricle. A leadless pacemaker eliminates the need for both a pacemaker pocket and transvenous access. Its main limitations are lack of atrial pacing and sensing capabilities and the inability to provide antitachycardia pacing. For patients who require solely single-chamber ventricular pacing (VVI/R), the leadless pacemaker offers an important new option. Growing experience with these leadless devices shows great promise and expanding applications, even though real-world clinical experience is limited. The Spanish Pacemaker Registry reported about 1.6% leadless pacemakers out of all 12,697 reported devices by 2016 [1]. Despite this slow uptake, leadless pacing systems may be an important "disrupting technology" in cardiac rhythm management.

#### **2. Device description**

There are currently two commercially available leadless pacemakers, which are designed to reside entirely within the right ventricle, affixed to the ventricular septum either mid-way or near the apex (see **Figure 1**). These devices are manufactured by two of the leading pacemaker companies in the world: Medtronic makes the Micra™ leadless pacemaker and Abbott (formerly St. Jude Medical) the Nanostim™ leadless pacemaker. The devices are cylindrical, attach directly to right ventricular septum, and have pacing and sensing electrodes that adhere to the myocardium with a retrieval loop on the other end of the device to facilitate extraction.

Leadless pacemakers are capable of pacing in the VVI mode with the programmable option of rate response (VVIR). The Medtronic device contains a lithium-silver-vanadium-oxide/carbon monofluoride battery (120 mAh), while the Abbott device utilizes a lithium carbon monofluoride battery with 248 mAh [2]. Both devices weigh about 2 g; the Abbott device (Nanostim™) is longer and thinner (42 mm in length and 5.99 mm diameter), while the Medtronic device (Micra™) is shorter and thicker (25.9 and, 6.7 mm) [2]. The Abbott device is secured via an active-fixation type helix mechanism, while the Medtronic device relies on passive fixation with nitinol tines [3]. Battery longevity in leadless pacemakers is estimated to be about 12–14 years. The Abbott (Nanostim™) leadless pacemaker was the subject of a global alert in late 2016 because of premature battery depletion that could result in loss of output and telemetry. The battery is a proprietary lithium-carbon monofluoride cell. Of 1423 Nanostim™ implantations around the world, 34 batteries failed (about 2%), but without any associated patient injury [4].

Leadless pacemakers at present cannot offer dual-chamber pacing modes or antitachycardia pacing; thus, they are only appropriate for patients who require VVI/ VVIR or VOO/VOOR pacing. Electrogram storage is possible but there is limited device memory compared to transvenous pacemaker systems [5].

#### **Figure 1.**

*The leadless pacemaker is implanted via a catheter into the right ventricle and affixed near the apex or midway on the right-ventricular septum where the operator attains acceptable electrical measurements (capture threshold, R-wave amplitude, and pacing impedance). The integral pacing and sensing electrodes in the device eliminate the need for transvenous pacing leads (illustration by Todd Cooper).*

**49**

*Leadless Pacemakers*

manual pressure [7].

perioperative waiting period.

*DOI: http://dx.doi.org/10.5772/intechopen.83546*

Leadless pacemakers are typically implanted via right or left femoral venous access into the septal wall of the right ventricle, although a right internal jugular vein approach has been described in the literature [6]. Right femoral access is preferred as the femoral iliac system nothing is less sharply angled on this side at the point where it joins the inferior vena cava [7]. The outer delivery sheath needed to deliver the pacemaker may have a diameter of 27 French (9 mm), which can be accommodated at implant by using a step-up sequence of dilators. Ultrasound with or without micropuncture has been recommended to avoid accidental arterial puncture or suboptimal sites of femoral puncture. As delivery sheaths may be large caliber, a poorly positioned puncture may make hemostasis challenging at the point when the sheath is withdrawn [7]. The proprietary delivery catheter is deflectable and advances with the device via the superior or inferior vena cava into the right atrium, over the tricuspid valve, and then into the right ventricle. The delivery catheter releases the device, which is affixed by active- or passive-fixation mechanisms to the endocardium [7]. Fluoroscopy may be used to confirm appropriate position. On radiography, the implanted devices look like a small cylinder (about the size and shape of a triple-A battery) [8]. Appropriate position is confirmed with acceptable electrical measurements generally defined as capture threshold ≤1.0 V at 0.24–0.4 ms, R-wave >6 mV, and impedance >500 Ω. The introducer sheath is then detached and removed and hemostasis achieved by a closure device, sutures, or

Unlike pacing thresholds with transvenous systems, which tend to gradually rise weeks after implant, the capture threshold for a leadless device may be expected to decrease somewhat about 30 min after implant and then stabilize. In two cases reports, threshold values in for a leadless pacemaker (Nanostim™) decreased markedly during the perioperative period. In one case, the pacing threshold was >6.5 V, the initial R-wave was >12.0 mV, and impedance was 1830 Ω. Rather than reposition the system, it was decided to wait for 30 min, at which time the pacing threshold was 2.25 V at 0.4 ms and impedance dropped to 1520 Ω. The same report described another case in which the pacing threshold was >6.5 V and impedance was 1330 Ω, but after allowing 25 min to elapse, the capture threshold decreased to 2.0 V at 0.4 ms and impedance was measured the next day at 800 Ω [9]. In fact, thresholds continued to improve in both cases the day after implant. It has been speculated that acute injury caused by the extension of the active-fixation helix being screwed into the myocardium might cause an increase in threshold that attenuates rapidly [9]. Thus, it may not always be necessary to reposition the device during implant in order to obtain adequate thresholds; instead, it requires a

As with other implanted devices, operator experience may help reduce adverse events at implant. In an analysis of all patients implanted with a leadless pacemaker (Nanostim™) in the LEADLESS and LEADLESS II clinical trials (n = 1439), 6.4% of patients experienced a serious adverse device effect (SADE) in the first 30 days after implant, but SADE rates dropped significantly from 7.4 to 4.5% (p = 0.038), once the operator had more than 10 implants. Over time, the need for device repositioning likewise decreased with operator experience, from the first quartile (26.8%) to the fourth quartile (14.8%), p < 0.001 [10]. This suggests that there is a learning curve for leadless pacemaker implantation, not unlike that for other implantable devices, such as cardiac resynchronization therapy systems and subcutaneous implantable cardioverter defibrillators. The most frequently reported adverse events were cardiac perforation (24 events, 1.7% of patients) followed by device

dislodgement (20 events, 1.4%) and tamponade (18 events, 1.3%) [10].

**3. Implantation techniques**

### **3. Implantation techniques**

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

There are currently two commercially available leadless pacemakers, which are designed to reside entirely within the right ventricle, affixed to the ventricular septum either mid-way or near the apex (see **Figure 1**). These devices are manufactured by two of the leading pacemaker companies in the world: Medtronic makes the Micra™ leadless pacemaker and Abbott (formerly St. Jude Medical) the Nanostim™ leadless pacemaker. The devices are cylindrical, attach directly to right ventricular septum, and have pacing and sensing electrodes that adhere to the myocardium with a retrieval loop on the other end of the device to

Leadless pacemakers are capable of pacing in the VVI mode with the programmable option of rate response (VVIR). The Medtronic device contains a lithium-silver-vanadium-oxide/carbon monofluoride battery (120 mAh), while the Abbott device utilizes a lithium carbon monofluoride battery with 248 mAh [2]. Both devices weigh about 2 g; the Abbott device (Nanostim™) is longer and thinner (42 mm in length and 5.99 mm diameter), while the Medtronic device (Micra™) is shorter and thicker (25.9 and, 6.7 mm) [2]. The Abbott device is secured via an active-fixation type helix mechanism, while the Medtronic device relies on passive fixation with nitinol tines [3]. Battery longevity in leadless pacemakers is estimated to be about 12–14 years. The Abbott (Nanostim™) leadless pacemaker was the subject of a global alert in late 2016 because of premature battery depletion that could result in loss of output and telemetry. The battery is a proprietary lithium-carbon monofluoride cell. Of 1423 Nanostim™ implantations around the world, 34 batteries failed (about 2%), but without any associated

Leadless pacemakers at present cannot offer dual-chamber pacing modes or antitachycardia pacing; thus, they are only appropriate for patients who require VVI/ VVIR or VOO/VOOR pacing. Electrogram storage is possible but there is limited

*The leadless pacemaker is implanted via a catheter into the right ventricle and affixed near the apex or midway on the right-ventricular septum where the operator attains acceptable electrical measurements (capture threshold, R-wave amplitude, and pacing impedance). The integral pacing and sensing electrodes in* 

*the device eliminate the need for transvenous pacing leads (illustration by Todd Cooper).*

device memory compared to transvenous pacemaker systems [5].

**2. Device description**

facilitate extraction.

patient injury [4].

**48**

**Figure 1.**

Leadless pacemakers are typically implanted via right or left femoral venous access into the septal wall of the right ventricle, although a right internal jugular vein approach has been described in the literature [6]. Right femoral access is preferred as the femoral iliac system nothing is less sharply angled on this side at the point where it joins the inferior vena cava [7]. The outer delivery sheath needed to deliver the pacemaker may have a diameter of 27 French (9 mm), which can be accommodated at implant by using a step-up sequence of dilators. Ultrasound with or without micropuncture has been recommended to avoid accidental arterial puncture or suboptimal sites of femoral puncture. As delivery sheaths may be large caliber, a poorly positioned puncture may make hemostasis challenging at the point when the sheath is withdrawn [7]. The proprietary delivery catheter is deflectable and advances with the device via the superior or inferior vena cava into the right atrium, over the tricuspid valve, and then into the right ventricle. The delivery catheter releases the device, which is affixed by active- or passive-fixation mechanisms to the endocardium [7]. Fluoroscopy may be used to confirm appropriate position. On radiography, the implanted devices look like a small cylinder (about the size and shape of a triple-A battery) [8]. Appropriate position is confirmed with acceptable electrical measurements generally defined as capture threshold ≤1.0 V at 0.24–0.4 ms, R-wave >6 mV, and impedance >500 Ω. The introducer sheath is then detached and removed and hemostasis achieved by a closure device, sutures, or manual pressure [7].

Unlike pacing thresholds with transvenous systems, which tend to gradually rise weeks after implant, the capture threshold for a leadless device may be expected to decrease somewhat about 30 min after implant and then stabilize. In two cases reports, threshold values in for a leadless pacemaker (Nanostim™) decreased markedly during the perioperative period. In one case, the pacing threshold was >6.5 V, the initial R-wave was >12.0 mV, and impedance was 1830 Ω. Rather than reposition the system, it was decided to wait for 30 min, at which time the pacing threshold was 2.25 V at 0.4 ms and impedance dropped to 1520 Ω. The same report described another case in which the pacing threshold was >6.5 V and impedance was 1330 Ω, but after allowing 25 min to elapse, the capture threshold decreased to 2.0 V at 0.4 ms and impedance was measured the next day at 800 Ω [9]. In fact, thresholds continued to improve in both cases the day after implant. It has been speculated that acute injury caused by the extension of the active-fixation helix being screwed into the myocardium might cause an increase in threshold that attenuates rapidly [9]. Thus, it may not always be necessary to reposition the device during implant in order to obtain adequate thresholds; instead, it requires a perioperative waiting period.

As with other implanted devices, operator experience may help reduce adverse events at implant. In an analysis of all patients implanted with a leadless pacemaker (Nanostim™) in the LEADLESS and LEADLESS II clinical trials (n = 1439), 6.4% of patients experienced a serious adverse device effect (SADE) in the first 30 days after implant, but SADE rates dropped significantly from 7.4 to 4.5% (p = 0.038), once the operator had more than 10 implants. Over time, the need for device repositioning likewise decreased with operator experience, from the first quartile (26.8%) to the fourth quartile (14.8%), p < 0.001 [10]. This suggests that there is a learning curve for leadless pacemaker implantation, not unlike that for other implantable devices, such as cardiac resynchronization therapy systems and subcutaneous implantable cardioverter defibrillators. The most frequently reported adverse events were cardiac perforation (24 events, 1.7% of patients) followed by device dislodgement (20 events, 1.4%) and tamponade (18 events, 1.3%) [10].

The leadless pacemaker is shipped already programmed to VVI pacing. It is sometimes helpful to switch the device to VOO during implant, for example, to better manage a pacemaker-dependent patient or if electromagnetic devices used during implant could potentially interfere with the pacemaker. A conventional transvenous pacemaker can be set to VOO mode perioperatively with simple magnet application, but this is not possible with some leadless pacemakers. Instead, the manufacturer or other expert team should be consulted in the event that the leadless pacemaker must be implanted in VOO mode [11].

Implant success rates are high with leadless devices. In the LEADLESS study (Nanostim™), the pacemaker could be implanted successfully in 95.8% of patients with a procedural time of 28.6 ± 17.8 min and fluoroscopy time of 13.9 ± 9.1 min [3]. In a study at a Polish single center, 10 patients were successfully implanted with a leadless pacemaker (Micra™), which was implanted with a mean implant duration of 82 min and mean fluoroscopy time of 3.5 min [12]. In a case series of five leadless pacemaker (Micra™) patients, the average duration of implantation procedure was 47 ± 11 min, which appeared to shorten over the series from a peak of 65 (second case) to 38 min for the last case [13]. In this case series, the mean capture threshold was 0.53 ± 0.27 V at 0.24 ms and mean R-wave was 13 ± 5.8 mV with no cases of acute dislodgement [13]. A study of 92 patients with leadless pacemakers (Micra™) at a Swiss single center found median capture thresholds at implant were 0.38 V at 0.24 ms (range 0.13–2.88 V at 0.24 ms), which remained stable throughout 1 year of follow-up [14]. In a case series of five leadless pacemaker patients (Micra™), all of the devices were successfully implanted [13]. A study of leadless pacing (Micra™) in Japan enrolled 38 patients at four sites and reported an implant success rate of 100% and the rate of freedom from major complications at 1 year was 96%. At 6 months, 98.3% had low, stable capture thresholds [15].

#### **4. Safety and efficacy**

#### **4.1 Micra™ clinical studies**

A prospective multicenter uncontrolled study enrolled 725 patients with an indication for single-chamber pacing to be implanted with a leadless pacemaker (Micra™). The primary endpoint was the percentage of patients with low, stable electrical capture thresholds at 6 months, defined as ≤2.0 V at 0.24 ms that increased ≤1.5 V from implant. The device could be successfully implanted in 719/725 patients (99.2%), and 96.0% met the primary endpoint at 6 months. At 6 months, the mean capture threshold was 0.54 V at 0.24 ms with an R-wave of 15.3 mV and 627 Ω impedance. The majority of patients (91%) had a pacing output of <1.5 V at 0.24 ms at 6 months, which implies that battery longevity should exceed 12 years [16]. A total of 28 major complications were reported in 25/725 patients, but no devices dislodged. Those complications included cardiac injuries (n = 11), complications at the puncture site in the groin (n = 5), thromboembolism (n = 2), pacing problems (n = 2), and other complications (n = 8). In total, three patients required device revision (two had elevated capture thresholds and one had pacemaker syndrome) and devices were deactivated (OOO mode) and abandoned; a transvenous pacing system was implanted. One patient had the device explanted because of transient loss of capture and a new leadless pacemaker was implanted [16].

A worldwide postapproval registry of the Micra™ device reported 99.1% rate of successful implantations in 1817 patients with a one-year major complication rate of 2.7% (95% confidence interval [CI], 2.0–3.7%), 63% lower than the rate of

**51**

*Leadless Pacemakers*

*DOI: http://dx.doi.org/10.5772/intechopen.83546*

because of ventricular tachycardia [14].

**4.2 Nanostim™ clinical trials: LEADLESS, LEADLESS II**

and deploy (94.4%) [15].

none of which required device extraction [17].

major complications for transvenous pacemaker patients (hazard ratio 0.37, 95% CI, 0.27–0.52, p < 0.001). In this study, there were three instances of device infection,

A single-center registry of 66 patients undergoing leadless pacemaker implantation (Micra™) reported that the indications in this population were third-degree atrioventricular block, sinus node dysfunction, or permanent atrial fibrillation with bradycardia (30.3, 21.2, and 45.5%, respectively). Implant success was achieved in 65/66 patients, and electrical measurements were stable over the follow-up period of 10.4 ± 6.1 months. At the last follow-up, the mean capture threshold was 0.57 ± 0.32 V, the mean R-wave was measured at 10.62 ± 4.36 mV, and the mean impedance was 580 ± 103 Ω. In this study, one patient experienced a major adverse event (loss of device function) and there were three minor adverse events [18]. A single-arm observational study based on a postapproval registry of Micra™ leadless pacemakers reported a 99.6% success rate in device implants (792/795 patients) at 96 centers in 20 countries. At 30 days after implantation, 13 major complications were reported in 12 patients (1.51% complication rate, 95% CI, 0.78– 2.62%) [19]. In a Swiss retrospective observational study of 92 Micra™ patients, the serious adverse event rate was 6.5% (n = 6), resulting in extended hospitalization for five patients and one death; three other adverse events occurred over the one-year follow-up (3.3% of patients, n = 3), resulting in revision to a conventional transvenous pacemaker in two patients and extraction of the pacemaker in the third

Physician acceptance of leadless pacing appears to be high. A study of leadless pacing (Micra™) in Japan enrolled 38 patients, and most of the implanting physicians said the leadless pacemaker was "extremely easy" or "easy" to implant (91.6%)

The prospective, single-arm, multicenter LEADLESS observational study (n = 470) evaluated the freedom from serious adverse device events at 6 months as the primary endpoint. The study had to be interrupted owing to the occurrence of cardiac perforation events that required changes in the protocol and training. In the 300 patients enrolled after the study interruption, freedom from serious adverse device events was 94.6% (95% CI, 91.0–97.2%), although 18 serious adverse device events were observed in 6.6% of patients (n = 16), the most frequent of which were perforation (1.3%), vascular complications (1.3%), and dislodgement of the device (0.3%). When all 470 patients were included (before and after the interruption), 6.6% of all patients experienced a serious adverse device-related event [20].

The LEADLESS clinical trial retrospectively evaluated safety and efficacy of the Nanostim™ leadless pacemaker over a minimum of 3 years of follow-up. A total of 33 patients (mean age 77 ± 8 years) were enrolled, of whom 31 received a leadless pacemaker [21]. Two patients could not be implanted (one procedure was aborted and the other was revised to an ICD.) At 3 years, 74% (23/31) of patients were alive and no deaths were attributable to the leadless pacemaker. Most patients (89.9%) reported freedom from serious adverse events (95% CI, 79.5–100%), and 9% experienced device-related complications, of whom two had procedure-related serious adverse events. One suffered perforation leading to tamponade and the other had inadvertent implantation of the leadless pacemaker into the left ventricle by way of a patent foramen ovale, which was successfully retrieved and a new device implanted into the right ventricle. A third complication was reported after 37 months attributed to battery malfunction and necessitating device revision, which involved the successful removal of the leadless pacemaker and replacement

#### *Leadless Pacemakers DOI: http://dx.doi.org/10.5772/intechopen.83546*

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

leadless pacemaker must be implanted in VOO mode [11].

The leadless pacemaker is shipped already programmed to VVI pacing. It is sometimes helpful to switch the device to VOO during implant, for example, to better manage a pacemaker-dependent patient or if electromagnetic devices used during implant could potentially interfere with the pacemaker. A conventional transvenous pacemaker can be set to VOO mode perioperatively with simple magnet application, but this is not possible with some leadless pacemakers. Instead, the manufacturer or other expert team should be consulted in the event that the

Implant success rates are high with leadless devices. In the LEADLESS study (Nanostim™), the pacemaker could be implanted successfully in 95.8% of patients with a procedural time of 28.6 ± 17.8 min and fluoroscopy time of 13.9 ± 9.1 min [3]. In a study at a Polish single center, 10 patients were successfully implanted with a leadless pacemaker (Micra™), which was implanted with a mean implant duration of 82 min and mean fluoroscopy time of 3.5 min [12]. In a case series of five leadless pacemaker (Micra™) patients, the average duration of implantation procedure was 47 ± 11 min, which appeared to shorten over the series from a peak of 65 (second case) to 38 min for the last case [13]. In this case series, the mean capture threshold was 0.53 ± 0.27 V at 0.24 ms and mean R-wave was 13 ± 5.8 mV with no cases of acute dislodgement [13]. A study of 92 patients with leadless pacemakers (Micra™) at a Swiss single center found median capture thresholds at implant were 0.38 V at 0.24 ms (range 0.13–2.88 V at 0.24 ms), which remained stable throughout 1 year of follow-up [14]. In a case series of five leadless pacemaker patients (Micra™), all of the devices were successfully implanted [13]. A study of leadless pacing (Micra™) in Japan enrolled 38 patients at four sites and reported an implant success rate of 100% and the rate of freedom from major complications at 1 year was 96%. At 6 months, 98.3% had low, stable capture

A prospective multicenter uncontrolled study enrolled 725 patients with an indication for single-chamber pacing to be implanted with a leadless pacemaker (Micra™). The primary endpoint was the percentage of patients with low, stable electrical capture thresholds at 6 months, defined as ≤2.0 V at 0.24 ms that increased ≤1.5 V from implant. The device could be successfully implanted in 719/725 patients (99.2%), and 96.0% met the primary endpoint at 6 months. At 6 months, the mean capture threshold was 0.54 V at 0.24 ms with an R-wave of 15.3 mV and 627 Ω impedance. The majority of patients (91%) had a pacing output of <1.5 V at 0.24 ms at 6 months, which implies that battery longevity should exceed 12 years [16]. A total of 28 major complications were reported in 25/725 patients, but no devices dislodged. Those complications included cardiac injuries (n = 11), complications at the puncture site in the groin (n = 5), thromboembolism (n = 2), pacing problems (n = 2), and other complications (n = 8). In total, three patients required device revision (two had elevated capture thresholds and one had pacemaker syndrome) and devices were deactivated (OOO mode) and abandoned; a transvenous pacing system was implanted. One patient had the device explanted because of transient loss of

A worldwide postapproval registry of the Micra™ device reported 99.1% rate of successful implantations in 1817 patients with a one-year major complication rate of 2.7% (95% confidence interval [CI], 2.0–3.7%), 63% lower than the rate of

capture and a new leadless pacemaker was implanted [16].

**50**

thresholds [15].

**4. Safety and efficacy**

**4.1 Micra™ clinical studies**

major complications for transvenous pacemaker patients (hazard ratio 0.37, 95% CI, 0.27–0.52, p < 0.001). In this study, there were three instances of device infection, none of which required device extraction [17].

A single-center registry of 66 patients undergoing leadless pacemaker implantation (Micra™) reported that the indications in this population were third-degree atrioventricular block, sinus node dysfunction, or permanent atrial fibrillation with bradycardia (30.3, 21.2, and 45.5%, respectively). Implant success was achieved in 65/66 patients, and electrical measurements were stable over the follow-up period of 10.4 ± 6.1 months. At the last follow-up, the mean capture threshold was 0.57 ± 0.32 V, the mean R-wave was measured at 10.62 ± 4.36 mV, and the mean impedance was 580 ± 103 Ω. In this study, one patient experienced a major adverse event (loss of device function) and there were three minor adverse events [18].

A single-arm observational study based on a postapproval registry of Micra™ leadless pacemakers reported a 99.6% success rate in device implants (792/795 patients) at 96 centers in 20 countries. At 30 days after implantation, 13 major complications were reported in 12 patients (1.51% complication rate, 95% CI, 0.78– 2.62%) [19]. In a Swiss retrospective observational study of 92 Micra™ patients, the serious adverse event rate was 6.5% (n = 6), resulting in extended hospitalization for five patients and one death; three other adverse events occurred over the one-year follow-up (3.3% of patients, n = 3), resulting in revision to a conventional transvenous pacemaker in two patients and extraction of the pacemaker in the third because of ventricular tachycardia [14].

Physician acceptance of leadless pacing appears to be high. A study of leadless pacing (Micra™) in Japan enrolled 38 patients, and most of the implanting physicians said the leadless pacemaker was "extremely easy" or "easy" to implant (91.6%) and deploy (94.4%) [15].

#### **4.2 Nanostim™ clinical trials: LEADLESS, LEADLESS II**

The prospective, single-arm, multicenter LEADLESS observational study (n = 470) evaluated the freedom from serious adverse device events at 6 months as the primary endpoint. The study had to be interrupted owing to the occurrence of cardiac perforation events that required changes in the protocol and training. In the 300 patients enrolled after the study interruption, freedom from serious adverse device events was 94.6% (95% CI, 91.0–97.2%), although 18 serious adverse device events were observed in 6.6% of patients (n = 16), the most frequent of which were perforation (1.3%), vascular complications (1.3%), and dislodgement of the device (0.3%). When all 470 patients were included (before and after the interruption), 6.6% of all patients experienced a serious adverse device-related event [20].

The LEADLESS clinical trial retrospectively evaluated safety and efficacy of the Nanostim™ leadless pacemaker over a minimum of 3 years of follow-up. A total of 33 patients (mean age 77 ± 8 years) were enrolled, of whom 31 received a leadless pacemaker [21]. Two patients could not be implanted (one procedure was aborted and the other was revised to an ICD.) At 3 years, 74% (23/31) of patients were alive and no deaths were attributable to the leadless pacemaker. Most patients (89.9%) reported freedom from serious adverse events (95% CI, 79.5–100%), and 9% experienced device-related complications, of whom two had procedure-related serious adverse events. One suffered perforation leading to tamponade and the other had inadvertent implantation of the leadless pacemaker into the left ventricle by way of a patent foramen ovale, which was successfully retrieved and a new device implanted into the right ventricle. A third complication was reported after 37 months attributed to battery malfunction and necessitating device revision, which involved the successful removal of the leadless pacemaker and replacement

with a new one. Up to 35 months, the electrical parameters of the leadless pacemakers were appropriate [21]. A retrospective assessment of 31 of the 33 patients from the LEADLESS study was conducted to evaluate the complication rates, device performance, and rate response features at 1 year. No pacemaker-related adverse events occurred from 3 months postimplant to 12 months. At 12 months, the mean pacing threshold was 0.43 ± 0.30 V at 0.4 ms, the mean R-wave was 10.3 ± 2.2 mV, and 61% had rate response features activated, of whom adequate results were achieved by all [22].

The LEADLESS II study is a premarket, nonrandomized, prospective, multicenter study of 526 patients with a leadless pacemaker (Nanostim™) who were followed for safety and efficacy for 6 months [3]. Inclusion criterion was a singlechamber ventricular pacing indication (which included patients with persistent or permanent atrial fibrillation). The primary efficacy outcome was achievement of a therapeutic capture threshold (defined as ≤2.0 V at 0.4 ms) and appropriate sensing (≥5.0 mV R-wave or an R-wave that exceeded the R-wave value at implant). By an intention-to-treat analysis, 90.0% of patients in the primary cohort achieved this at implant. At 12 months, the mean capture threshold was 0.58 ± 0.31 V at 0.4 ms and the mean R-wave was 9.2 ± 2.9 mV. At 12 months, the mean percentage of ventricular pacing was 51.6 ± 39.1%. The primary safety outcome was freedom from devicerelated adverse events in the first 6 months after implant, which was achieved by 93.3% of patients. Over 6 months, a total of 22 serious adverse events related to the device occurred in 20 patients (6.7%) in the primary cohort. In the total cohort, the rate of serious adverse events related to the device was 6.5%. Devices migrated from the heart into the pulmonary artery or right femoral vein in four and two patients, respectively, and all devices were successfully retrieved percutaneously [3]. The majority of patients did not require revision to reposition the pacemaker (70.2%), but 4.4% of patients required two or more attempts to reposition the device. The mean duration of hospital stay was 1.1 ± 1.7 days (range 0–33) [3]. Over the course of the study, 28 patients died (5.3%) but no deaths were related to the device.

The LEADLESS II patient cohort (n = 718) was compared retrospectively to 1436 transvenous pacemaker patients (historical data) with the results that leadless pacemaker patients had fewer complications (hazard ratio 0.44, 95% CI, 0.23–0.60, p < 0.001) broken down as short-term complications (5.8 vs. 9.4%, p = 0.01) and mid-term complications (0.56 vs. 4.9%, p < 0.001). Specifically, leadless pacemaker patients had more pericardial effusions (1.53 vs. 0.35%, p = 0.005), but similar rates of vascular events (1.11 vs. 0.42%, p = 0.085), dislodgements (0.97 vs. 1.39%, p = 0.54), and generator complications (0.70 vs. 0.28%, p = 0.17). Leadless pacemaker patients had no cases of thoracic trauma compared to 3.27% of transvenous patients [23].

In October 2016, an advisory was issued for the Nanostim™ device regarding premature battery depletion [24]. A prospective, observational, single-center study was conducted in Germany with patients implanted early (up until April 2014) or late (starting December 2015 and thereafter). The cohort included 14 consecutive patients (77 ± 9 years, 57% male) with a mean follow-up of 29.5 ± 11.5 months (range 11.9–44.6 months). Most were "early" patients (n = 9, 64%) implanted before the implantation suspension and five were implanted "late" (36%). From data obtained at the last follow-up, 57% had permanent atrial fibrillation with complete heart block, 21% were considered pacemaker dependent, and 36% had a mean regular escape rhythm of 37 ± 2 beats per minute (bpm). Almost half of the patients had signs of battery malfunction (43%, n = 6), all of whom had "early" implants. Using the Kaplan-Meier method, the mean time calculated from implant to device failure was 39.0 months (standard error 1.85 months, 95% CI, 35.4–42.7 months). Device parameters fell within the normal range for all patients (100%) at the last follow-up before battery malfunction was detected. Devices

**53**

*Leadless Pacemakers*

was longer [24].

systems [25].

**4.4 Other safety issues**

*DOI: http://dx.doi.org/10.5772/intechopen.83546*

**4.3 Meta-analyses and comparative studies**

myocardium at the site of implantation [27].

device utilizes blood temperature for its rate response [2].

patients at 12 months, 42% at 24 months, and 39% at 36 months [21].

**5. Leadless pacemaker features**

**5.1 Rate response**

were explanted and analysis showed reduced electrolytes in the lithium carbon monofluoride battery, which caused high internal battery resistance, reducing the available current for device function. While a report from 2016 showed Nanostim™ battery malfunction occurred at a global rate of 2.4%, the rate at this particular institution was much higher, possibly owing to the fact that the observation period

In a meta-analysis of lead and device dislodgement (n = 18 studies, 17,321 patients) involving conventional transvenous pacemakers and leadless pacemakers (both Micra™ and Nanostim™), the weighted mean incidence of lead dislodgement in transvenous devices was 1.71%. Atrial leads had a higher dislodgement rate than ventricular leads (odds ratio 3.56, 95% CI, 1.96–6.70). The dislodgement rate for leadless devices was reported in three studies (n = 2116) and was 0, 0.13, and 1.0%, respectively, showing an overall lower dislodgement rate than conventional

In a propensity score-matched study, 440 pacemaker patients were matched based on whether they had a leadless system (n = 220) or a transvenous system (n = 220). The complication rate at 800 days of follow-up was significantly lower in

Ventricular arrhythmias after the implantation of a leadless pacemaker should be considered as potential side effect secondary to leadless pacemaker implantation. A case report in the literature describes a patient who experienced short episodes of polymorphic ventricular tachycardia (VT) in the perioperative period and high ventricular rates with short-long-short runs of polymorphic VT induced by premature ventricular contractions. The system was extracted successfully, revised with a new device of the same type successfully implanted at a different position in the right ventricle, and the VT resolved. The pro-arrhythmic effect of the leadless pacemaker remains to be elucidated, but it may involve the irritation of the right-ventricular

Both commercially available systems offer rate response. The Micra™ device utilizes a programmable accelerometer that works on three axes. Rate response is set up based on three activity vectors. The accelerometer can be programmed following a five-minute exercise test, which should be conducted before hospital discharge and then at an in-clinic visit later. While Vector 1 can be programmed as the nominal setting, an early study in 51 patients (278 tests, 818 vector measurements) found the manual selection of a vector produced better results than opting for the default Vector 1 setting. In initial testing, Vector 1 was found to be adequate in 74.5% of patients but in in-clinic testing, Vector 1 was adequate for 64.7%, while Vector 3 was adequate in 68.6% (and Vector 2 was adequate in 51.0%) [28]. The Nanostim™

In the LEADLESS clinical trial (n = 31), rate response was turned on in 61% of

the leadless pacemaker group (0.9 vs. 4.7%, 95% CI, p = 0.02) [26].

#### *Leadless Pacemakers DOI: http://dx.doi.org/10.5772/intechopen.83546*

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

achieved by all [22].

with a new one. Up to 35 months, the electrical parameters of the leadless pacemakers were appropriate [21]. A retrospective assessment of 31 of the 33 patients from the LEADLESS study was conducted to evaluate the complication rates, device performance, and rate response features at 1 year. No pacemaker-related adverse events occurred from 3 months postimplant to 12 months. At 12 months, the mean pacing threshold was 0.43 ± 0.30 V at 0.4 ms, the mean R-wave was 10.3 ± 2.2 mV, and 61% had rate response features activated, of whom adequate results were

The LEADLESS II study is a premarket, nonrandomized, prospective, multicenter study of 526 patients with a leadless pacemaker (Nanostim™) who were followed for safety and efficacy for 6 months [3]. Inclusion criterion was a singlechamber ventricular pacing indication (which included patients with persistent or permanent atrial fibrillation). The primary efficacy outcome was achievement of a therapeutic capture threshold (defined as ≤2.0 V at 0.4 ms) and appropriate sensing (≥5.0 mV R-wave or an R-wave that exceeded the R-wave value at implant). By an intention-to-treat analysis, 90.0% of patients in the primary cohort achieved this at implant. At 12 months, the mean capture threshold was 0.58 ± 0.31 V at 0.4 ms and the mean R-wave was 9.2 ± 2.9 mV. At 12 months, the mean percentage of ventricular pacing was 51.6 ± 39.1%. The primary safety outcome was freedom from devicerelated adverse events in the first 6 months after implant, which was achieved by 93.3% of patients. Over 6 months, a total of 22 serious adverse events related to the device occurred in 20 patients (6.7%) in the primary cohort. In the total cohort, the rate of serious adverse events related to the device was 6.5%. Devices migrated from the heart into the pulmonary artery or right femoral vein in four and two patients, respectively, and all devices were successfully retrieved percutaneously [3]. The majority of patients did not require revision to reposition the pacemaker (70.2%), but 4.4% of patients required two or more attempts to reposition the device. The mean duration of hospital stay was 1.1 ± 1.7 days (range 0–33) [3]. Over the course of the study, 28 patients died (5.3%) but no deaths were related to the device. The LEADLESS II patient cohort (n = 718) was compared retrospectively to 1436 transvenous pacemaker patients (historical data) with the results that leadless pacemaker patients had fewer complications (hazard ratio 0.44, 95% CI, 0.23–0.60, p < 0.001) broken down as short-term complications (5.8 vs. 9.4%, p = 0.01) and mid-term complications (0.56 vs. 4.9%, p < 0.001). Specifically, leadless pacemaker patients had more pericardial effusions (1.53 vs. 0.35%, p = 0.005), but similar rates of vascular events (1.11 vs. 0.42%, p = 0.085), dislodgements (0.97 vs. 1.39%, p = 0.54), and generator complications (0.70 vs. 0.28%, p = 0.17). Leadless pacemaker patients had no cases of thoracic trauma compared to 3.27% of transvenous patients [23]. In October 2016, an advisory was issued for the Nanostim™ device regarding premature battery depletion [24]. A prospective, observational, single-center study was conducted in Germany with patients implanted early (up until April 2014) or late (starting December 2015 and thereafter). The cohort included 14 consecutive patients (77 ± 9 years, 57% male) with a mean follow-up of 29.5 ± 11.5 months (range 11.9–44.6 months). Most were "early" patients (n = 9, 64%) implanted before the implantation suspension and five were implanted "late" (36%). From data obtained at the last follow-up, 57% had permanent atrial fibrillation with complete heart block, 21% were considered pacemaker dependent, and 36% had a mean regular escape rhythm of 37 ± 2 beats per minute (bpm). Almost half of the patients had signs of battery malfunction (43%, n = 6), all of whom had "early" implants. Using the Kaplan-Meier method, the mean time calculated from implant to device failure was 39.0 months (standard error 1.85 months, 95% CI, 35.4–42.7 months). Device parameters fell within the normal range for all patients (100%) at the last follow-up before battery malfunction was detected. Devices

**52**

were explanted and analysis showed reduced electrolytes in the lithium carbon monofluoride battery, which caused high internal battery resistance, reducing the available current for device function. While a report from 2016 showed Nanostim™ battery malfunction occurred at a global rate of 2.4%, the rate at this particular institution was much higher, possibly owing to the fact that the observation period was longer [24].

#### **4.3 Meta-analyses and comparative studies**

In a meta-analysis of lead and device dislodgement (n = 18 studies, 17,321 patients) involving conventional transvenous pacemakers and leadless pacemakers (both Micra™ and Nanostim™), the weighted mean incidence of lead dislodgement in transvenous devices was 1.71%. Atrial leads had a higher dislodgement rate than ventricular leads (odds ratio 3.56, 95% CI, 1.96–6.70). The dislodgement rate for leadless devices was reported in three studies (n = 2116) and was 0, 0.13, and 1.0%, respectively, showing an overall lower dislodgement rate than conventional systems [25].

In a propensity score-matched study, 440 pacemaker patients were matched based on whether they had a leadless system (n = 220) or a transvenous system (n = 220). The complication rate at 800 days of follow-up was significantly lower in the leadless pacemaker group (0.9 vs. 4.7%, 95% CI, p = 0.02) [26].

#### **4.4 Other safety issues**

Ventricular arrhythmias after the implantation of a leadless pacemaker should be considered as potential side effect secondary to leadless pacemaker implantation. A case report in the literature describes a patient who experienced short episodes of polymorphic ventricular tachycardia (VT) in the perioperative period and high ventricular rates with short-long-short runs of polymorphic VT induced by premature ventricular contractions. The system was extracted successfully, revised with a new device of the same type successfully implanted at a different position in the right ventricle, and the VT resolved. The pro-arrhythmic effect of the leadless pacemaker remains to be elucidated, but it may involve the irritation of the right-ventricular myocardium at the site of implantation [27].

#### **5. Leadless pacemaker features**

#### **5.1 Rate response**

Both commercially available systems offer rate response. The Micra™ device utilizes a programmable accelerometer that works on three axes. Rate response is set up based on three activity vectors. The accelerometer can be programmed following a five-minute exercise test, which should be conducted before hospital discharge and then at an in-clinic visit later. While Vector 1 can be programmed as the nominal setting, an early study in 51 patients (278 tests, 818 vector measurements) found the manual selection of a vector produced better results than opting for the default Vector 1 setting. In initial testing, Vector 1 was found to be adequate in 74.5% of patients but in in-clinic testing, Vector 1 was adequate for 64.7%, while Vector 3 was adequate in 68.6% (and Vector 2 was adequate in 51.0%) [28]. The Nanostim™ device utilizes blood temperature for its rate response [2].

In the LEADLESS clinical trial (n = 31), rate response was turned on in 61% of patients at 12 months, 42% at 24 months, and 39% at 36 months [21].

#### **5.2 Capture management**

The Micra™ leadless pacemaker offers a capture management system, while the Nanostim™ does not.

#### **5.3 Magnet mode**

Application of a magnet over the implant site of a conventional transvenous pacemaker will cause it to behave in highly specific ways (for example, asynchronous fixed-rate pacing) in response in a function known as magnet mode. The Micra™ device does not offer magnet mode, but the Nanostim™ will pace at 100 bpm for eight beats and then go to asynchronous pacing at 90 bpm (or 65 bpm if the device is at the elective replacement indicator) [5].

#### **5.4 Magnetic resonance imaging compatibility**

The MIMICRY study (Monocenter Investigation Micra™ MRI Study) examined magnetic resonance imaging (MRI) compatibility in 15 leadless pacemaker patients undergoing either a 1.5 Tesla (T) or 3.0 T cardiac MRI scan; one patient was excluded from the study because severe claustrophobia precluded an MRI. Device parameters remained stable during the MRI and over the one and three-month observation points nothing showed MRI scans were safe and feasible [29]. In an *ex vivo* study using porcine hearts, leadless pacemakers were implanted in the heart (100% success rate) and then MRI conducted to assess artifacts. In most of the MRI sequences, the right ventricle and septal area near the device showed some degree of artifact, which might compromise utility, but the rest of the myocardium was free of artifacts. The leadless-pacemaker-created artifact had the shape of a shamrock and was brighter in the 3 T scans than the 1.5 T images [30].

#### **5.5 Compatibility with external electrical cardioversion**

A case report describes an 85-year-old woman with bradycardia and atrial fibrillation who received a leadless pacemaker (Micra™) and underwent external electrical cardioversion with three shocks at 100, 200, and 360 J. The three cardioversion shocks had no observable effect on the implanted leadless pacemaker [31].

#### **6. Device retrieval**

To date, there is limited experience with normal, expected end-of-life device revision. Revision may be accomplished by retrieving the old device and implanting a new one, or by simply inactivating the exhausted device and adding a new device nearby. In theory at least, device retrieval seems preferable, in that it limits the amount of hardware in the body and might reduce long-term complications or device-device interference [32]. Successful acute and chronic device retrievals have been reported in the literature. A study on human cadaver hearts has demonstrated that it is feasible to simply implant a new leadless pacemaker without removing the old one [33]. Successful device extraction in a porcine model was reported using a single-loop retrieval snare and a superior vena cava approach [34].

In a study of Micra™ pacemaker revisions, 989 implants were analyzed and compared to 2667 control patients with a transvenous ventricular single-chamber pacemaker. The actuarial rate for device revision at 24 months following implant was 1.4% for leadless pacemakers (11 revisions in 10 patients) compared to 5.3%

**55**

*Leadless Pacemakers*

*DOI: http://dx.doi.org/10.5772/intechopen.83546*

with no procedure-related adverse events [37].

in the transvenous pacemaker group (123 revisions in 117 patients), that is, 75% lower for leadless pacemakers (95% CI, 53–87%, p < 0.001). The main reasons for extracting a leadless device were a need for a different device therapy, pacemaker syndrome, and prosthetic valve endocarditis. No leadless pacemaker was extracted because of device dislodgement or device-related infection. In seven cases, the device was deactivated and abandoned; in three cases, the device was extracted percutaneously; and in one case, the device was removed during aortic valve surgery.

In a retrospective study of 40 successful retrievals of leadless pacemakers (Micra™), 73% (n = 29) consented to supplying procedural details to a research study by Afzal and colleagues. This largest retrieval study to date differentiated between "immediate retrievals" (n = 11) in which the original device was retrieved perioperatively and "delayed retrieval" (n = 18) in which the retrieval involved a new procedure at a later date. The median duration between implant and retrieval in the delayed retrieval group was 46 days (range 1–95 days). The most commonly reported reasons for leadless pacemaker retrieval were elevated pacing threshold upon tether removal (immediate retrieval) and elevated threshold, endovascular infection, or need to switch to transvenous system (delayed retrieval) [36]. The mean duration for a retrieval procedure was 63.11 ± 56 min with a mean fluoroscopy exposure of 16.7 ± 9.8 min. Retrieval was accomplished using a snaring system deployed via a delivery catheter or steerable sheath. No serious complications were reported [36]. In the LEADLESS II trial, the implantable device was retrieved successfully and without complications in seven patients at 160 ± 180 days (median 100 days, 1–413 range). Of these patients, three were implanted with a new leadless pacemaker, two were implanted with a conventional transvenous pacing system, and two patients were implanted with a cardiac resynchronization therapy (CRT) device for heart failure. In a study composed of leadless pacemaker patients who required leadless pacemaker removal from three other multicenter studies, 5/5 patients who required acute extraction (within 6 weeks of implant) and 10/11 of patients who required chronic extraction (≥6 weeks after implant) experienced successful device retrieval

Acute explantation of the leadless device was reported in the literature when the device migrated into the pulmonary artery a few days after implantation in a 34-year-old patient with infective endocarditis. A single-loop snare guided by a steerable sheath was used to retrieve the migrated device, and a second leadless pacemaker was successfully implanted with no further complications [38]. A case report describes a 62-year-old pacemaker patient who had a leadless pacemaker implanted (to replace an infected transvenous system) and then revised with a second leadless pacemaker because of failure to capture at maximum output settings. The procedure was conducted by implanting the new leadless pacemaker into the patient, assuring its proper function, and then extracting the original underperforming leadless device using a triple-loop snare system [39]. A singlecenter case series reported extraction of leadless pacemakers (Nanostim™) in three cases with 100% success rate and fluoroscopic exposure times of 12, 16, and 19 min. Each extraction was preceded by a transesophageal 3D echocardiogram to assess the device's mobility with the heart and possible endothelialization. Retrieval was carried out using the proprietary catheter system from the manufacturer [40].

A novel extraction technique using a cryoballoon steerable sheath together with a snare was reported for the successful retrieval of a leadless pacemaker (Micra™), which was securely positioned in the patient but had an unusual subacute rise in pacing threshold [41]. The pacemaker was first implanted at the right-ventricular apex, but pacing thresholds were too high there (1.63 V at 0.24 ms), so the device was repositioned to a site on the right-ventricular septum with acceptable thresholds

Overall, 64% of deactivated leadless pacemakers were left *in situ* [35].

#### *Leadless Pacemakers DOI: http://dx.doi.org/10.5772/intechopen.83546*

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

if the device is at the elective replacement indicator) [5].

and was brighter in the 3 T scans than the 1.5 T images [30].

**5.5 Compatibility with external electrical cardioversion**

**5.4 Magnetic resonance imaging compatibility**

The Micra™ leadless pacemaker offers a capture management system, while the

Application of a magnet over the implant site of a conventional transvenous pacemaker will cause it to behave in highly specific ways (for example, asynchronous fixed-rate pacing) in response in a function known as magnet mode. The Micra™ device does not offer magnet mode, but the Nanostim™ will pace at 100 bpm for eight beats and then go to asynchronous pacing at 90 bpm (or 65 bpm

The MIMICRY study (Monocenter Investigation Micra™ MRI Study) examined magnetic resonance imaging (MRI) compatibility in 15 leadless pacemaker patients undergoing either a 1.5 Tesla (T) or 3.0 T cardiac MRI scan; one patient was excluded from the study because severe claustrophobia precluded an MRI. Device parameters remained stable during the MRI and over the one and three-month observation points nothing showed MRI scans were safe and feasible [29]. In an *ex vivo* study using porcine hearts, leadless pacemakers were implanted in the heart (100% success rate) and then MRI conducted to assess artifacts. In most of the MRI sequences, the right ventricle and septal area near the device showed some degree of artifact, which might compromise utility, but the rest of the myocardium was free of artifacts. The leadless-pacemaker-created artifact had the shape of a shamrock

A case report describes an 85-year-old woman with bradycardia and atrial fibrillation who received a leadless pacemaker (Micra™) and underwent external electrical cardioversion with three shocks at 100, 200, and 360 J. The three cardioversion

To date, there is limited experience with normal, expected end-of-life device revision. Revision may be accomplished by retrieving the old device and implanting a new one, or by simply inactivating the exhausted device and adding a new device nearby. In theory at least, device retrieval seems preferable, in that it limits the amount of hardware in the body and might reduce long-term complications or device-device interference [32]. Successful acute and chronic device retrievals have been reported in the literature. A study on human cadaver hearts has demonstrated that it is feasible to simply implant a new leadless pacemaker without removing the old one [33]. Successful device extraction in a porcine model was reported using a

In a study of Micra™ pacemaker revisions, 989 implants were analyzed and compared to 2667 control patients with a transvenous ventricular single-chamber pacemaker. The actuarial rate for device revision at 24 months following implant was 1.4% for leadless pacemakers (11 revisions in 10 patients) compared to 5.3%

shocks had no observable effect on the implanted leadless pacemaker [31].

single-loop retrieval snare and a superior vena cava approach [34].

**5.2 Capture management**

Nanostim™ does not.

**6. Device retrieval**

**5.3 Magnet mode**

**54**

in the transvenous pacemaker group (123 revisions in 117 patients), that is, 75% lower for leadless pacemakers (95% CI, 53–87%, p < 0.001). The main reasons for extracting a leadless device were a need for a different device therapy, pacemaker syndrome, and prosthetic valve endocarditis. No leadless pacemaker was extracted because of device dislodgement or device-related infection. In seven cases, the device was deactivated and abandoned; in three cases, the device was extracted percutaneously; and in one case, the device was removed during aortic valve surgery. Overall, 64% of deactivated leadless pacemakers were left *in situ* [35].

In a retrospective study of 40 successful retrievals of leadless pacemakers (Micra™), 73% (n = 29) consented to supplying procedural details to a research study by Afzal and colleagues. This largest retrieval study to date differentiated between "immediate retrievals" (n = 11) in which the original device was retrieved perioperatively and "delayed retrieval" (n = 18) in which the retrieval involved a new procedure at a later date. The median duration between implant and retrieval in the delayed retrieval group was 46 days (range 1–95 days). The most commonly reported reasons for leadless pacemaker retrieval were elevated pacing threshold upon tether removal (immediate retrieval) and elevated threshold, endovascular infection, or need to switch to transvenous system (delayed retrieval) [36]. The mean duration for a retrieval procedure was 63.11 ± 56 min with a mean fluoroscopy exposure of 16.7 ± 9.8 min. Retrieval was accomplished using a snaring system deployed via a delivery catheter or steerable sheath. No serious complications were reported [36].

In the LEADLESS II trial, the implantable device was retrieved successfully and without complications in seven patients at 160 ± 180 days (median 100 days, 1–413 range). Of these patients, three were implanted with a new leadless pacemaker, two were implanted with a conventional transvenous pacing system, and two patients were implanted with a cardiac resynchronization therapy (CRT) device for heart failure. In a study composed of leadless pacemaker patients who required leadless pacemaker removal from three other multicenter studies, 5/5 patients who required acute extraction (within 6 weeks of implant) and 10/11 of patients who required chronic extraction (≥6 weeks after implant) experienced successful device retrieval with no procedure-related adverse events [37].

Acute explantation of the leadless device was reported in the literature when the device migrated into the pulmonary artery a few days after implantation in a 34-year-old patient with infective endocarditis. A single-loop snare guided by a steerable sheath was used to retrieve the migrated device, and a second leadless pacemaker was successfully implanted with no further complications [38]. A case report describes a 62-year-old pacemaker patient who had a leadless pacemaker implanted (to replace an infected transvenous system) and then revised with a second leadless pacemaker because of failure to capture at maximum output settings. The procedure was conducted by implanting the new leadless pacemaker into the patient, assuring its proper function, and then extracting the original underperforming leadless device using a triple-loop snare system [39]. A singlecenter case series reported extraction of leadless pacemakers (Nanostim™) in three cases with 100% success rate and fluoroscopic exposure times of 12, 16, and 19 min. Each extraction was preceded by a transesophageal 3D echocardiogram to assess the device's mobility with the heart and possible endothelialization. Retrieval was carried out using the proprietary catheter system from the manufacturer [40].

A novel extraction technique using a cryoballoon steerable sheath together with a snare was reported for the successful retrieval of a leadless pacemaker (Micra™), which was securely positioned in the patient but had an unusual subacute rise in pacing threshold [41]. The pacemaker was first implanted at the right-ventricular apex, but pacing thresholds were too high there (1.63 V at 0.24 ms), so the device was repositioned to a site on the right-ventricular septum with acceptable thresholds (0.75 V at 0.24 ms). The threshold increased unexpectedly over the next 30 min to 2.2 V at 0.24 ms with no radiographic proof of dislodgement. Using a 15 French steerable cryoballoon sheath in an introducer to the right atrium, the sheath could be navigated over the tricuspid valve and into the right ventricle. A 7 French 20 mm snare was then introduced into the steerable sheath. The retrieval loop on the leadless pacemaker was successfully snared and could be extracted along with the introducer and sheath. No blood clot or visible defect was found on the extracted device. A second leadless pacemaker was implanted at the mid-septum of the right ventricle with good electrical measurements (capture threshold 0.5 V at 0.24 ms), which remained stable over 30 minutes. At 1 month, the patient has a capture threshold of 0.62 V at 0.24 ms, an R-wave of 8.6 mV, and impedance of 600 Ω [41].

Of 1423 leadless Nanostim™ pacemakers implanted around the world, there were 34 reported cases of premature battery depletion with a 90.4% successful retrieval rate even though these were chronic implants (battery depletion occurred at 2.9 ± 0.4 years). Of the seven patients in whom retrieval was not possible, most cases were caused by an inaccessible or otherwise nonfunctional retrieval loop on the device [4].

#### **7. Quality of life**

In a study of health-related quality of life using the Short-Form 36 (SF-36) questionnaire at baseline, 3 months, and 12 months in 720 Micra™ patients, all domains improved significantly at 3 and 12 months compared to baseline values and 96% were "satisfied" or "very satisfied" with the aesthetic appearance of the system, 91% with their recovery, and 74% with their current activity level [42]. Leadless pacemakers were associated with fewer restrictions on activity than leadless pacemakers in a survey of 720 patients [42].

In a study of leadless pacemaker (Micra™) patients, some national differences emerged. In this study, 35 Japanese patients were reviewed compared to 658 similar patients outside of Japan. Fewer Japanese-only patients compared to outside-Japan patients were "very satisfied" or "satisfied" with their recovery (74.3 vs. 91.8%, p = 0.002), but those who reported themselves "very satisfied" or "satisfied" with the device's cosmetic appearance were similar (91.4 Japanese vs. 96.2% outside Japan). All implants in the Japanese patients were successful [15].

#### **8. Guidelines**

Leadless pacemakers are indicated for patients with symptomatic bradycardia requiring single-chamber ventricular bradycardia pacing support; persistent atrial tachyarrhythmias in such patients are not a contraindication for leadless pacing. In fact, many patients who receive a leadless pacemaker have persistent or permanent atrial fibrillation with slow ventricular response.

The role of leadless pacemakers following removal of an infected conventional transvenous pacing system is debated. Since a leadless device requires no pocket formation and has no transvenous leads, it would appear to be suitable for a revision system for appropriate patients. In a study of patients who required device replacement after a conventional pacemaker system was infected (n = 17), patients were implanted with a Nanostim™ (n = 11) or Micra™ (n = 6) device [43]. In six patients, the leadless pacemaker was implanted within a week or less while in 11 patients, the leadless pacemakers was implanted after at least 1 week. In all patients, there was no infection over the course of a mean follow-up of 16 ± 12 months. This patient population included seven patients with a history of recurrent device infections

**57**

*Leadless Pacemakers*

*DOI: http://dx.doi.org/10.5772/intechopen.83546*

pacing mode during implant [5].

benefits from leadless pacemakers.

**9.1 Limited or occluded venous access**

**9. Special populations**

infection with a conventional pacemaker [43].

(mean follow-up of 20 ± 14 months). This study suggests that a leadless pacemaker may be a viable revision pacing system for selected patients who experienced device

The French Working Group on Cardiac Pacing and Electrophysiology of the French Society of Cardiology has issued specific guidelines on leadless pacing [44]. Currently, the indication for leadless pacing is a patient indicated for VVIR pacing and the patient's life, as well as device service life must be taken into account as device retrieval may not always be possible. They consider that leadless devices should be implanted only in centers that also perform cardiac surgery, because of the higher incidence of tamponade, vascular complications, perforations caused by large-diameter sheaths, or other complications associated with leadless pacemakers [44].

It has been recommended that anesthesiologists familiarize themselves with all implantable device technologies, including leadless pacemakers [5]. A challenge to these devices is that interrogation software may not be readily available and that implantation should be coordinated with device manufacturer representatives or cardiologists, for example, if the device should be programmed to an asynchronous

In 64% of patients enrolled in one of the pivotal trials for leadless pacemakers (Micra™), the pacing indication was managing persistent or permanent atrial fibrillation with slow ventricular response [16]. In that pivotal trial, only 6% of patients had a clear-cut medical reason that limited or contraindicated them from a transvenous system. However, there are many emerging groups who may derive

Leadless pacemakers may be an important alternative to conventional devices in patients with thromboses, venous obstruction, tortuous or abnormal venous anatomy, superior vena cava syndrome, or other conditions may be contraindicated for a conventional transvenous pacemaker. A case report describes a patient with thirddegree atrioventricular (AV) block who experienced an occlusive thrombosis of the superior vena cava and had her conventional VDD transvenous pacemaker replaced with a leadless device [45]. Limited venous access as an anatomical challenge may be overcome with a leadless pacemaker as in a case study of a bradycardic hemodialysis patient who suffered from skin erosion in the chest area due to radiation treatments for esophageal carcinoma. The leadless pacemaker was implanted successfully, but the patient developed ventricular tachyarrhythmias, necessitating the implantation of a subcutaneous implantable cardioverter-defibrillator. At 1 month, both devices

were performing adequately with no device-device interactions [46].

**9.2 Pacemaker-dependent patients transitioned to leadless pacing**

tion due to his immunocompromised condition [47].

A 72-year-old man with a thrombosed venous stent, renal failure, and myelodysplastic syndrome presented with second-degree AV block. A leadless pacemaker was preferred (Micra™) because of limited venous access and a high risk of infec-

When it is necessary to extract transvenous leads in a pacemaker-dependent patient, a common approach is to utilize a temporary pacemaker with activefixation lead as a bridge to a contralateral pacemaker implantation. A case report

#### *Leadless Pacemakers DOI: http://dx.doi.org/10.5772/intechopen.83546*

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

(0.75 V at 0.24 ms). The threshold increased unexpectedly over the next 30 min to 2.2 V at 0.24 ms with no radiographic proof of dislodgement. Using a 15 French steerable cryoballoon sheath in an introducer to the right atrium, the sheath could be navigated over the tricuspid valve and into the right ventricle. A 7 French 20 mm snare was then introduced into the steerable sheath. The retrieval loop on the leadless pacemaker was successfully snared and could be extracted along with the introducer and sheath. No blood clot or visible defect was found on the extracted device. A second leadless pacemaker was implanted at the mid-septum of the right ventricle with good electrical measurements (capture threshold 0.5 V at 0.24 ms), which remained stable over 30 minutes. At 1 month, the patient has a capture threshold of

0.62 V at 0.24 ms, an R-wave of 8.6 mV, and impedance of 600 Ω [41].

inaccessible or otherwise nonfunctional retrieval loop on the device [4].

Japan). All implants in the Japanese patients were successful [15].

atrial fibrillation with slow ventricular response.

**7. Quality of life**

**8. Guidelines**

in a survey of 720 patients [42].

Of 1423 leadless Nanostim™ pacemakers implanted around the world, there were 34 reported cases of premature battery depletion with a 90.4% successful retrieval rate even though these were chronic implants (battery depletion occurred at 2.9 ± 0.4 years). Of the seven patients in whom retrieval was not possible, most cases were caused by an

In a study of health-related quality of life using the Short-Form 36 (SF-36) questionnaire at baseline, 3 months, and 12 months in 720 Micra™ patients, all domains improved significantly at 3 and 12 months compared to baseline values and 96% were "satisfied" or "very satisfied" with the aesthetic appearance of the system, 91% with their recovery, and 74% with their current activity level [42]. Leadless pacemakers were associated with fewer restrictions on activity than leadless pacemakers

In a study of leadless pacemaker (Micra™) patients, some national differences emerged. In this study, 35 Japanese patients were reviewed compared to 658 similar patients outside of Japan. Fewer Japanese-only patients compared to outside-Japan patients were "very satisfied" or "satisfied" with their recovery (74.3 vs. 91.8%, p = 0.002), but those who reported themselves "very satisfied" or "satisfied" with the device's cosmetic appearance were similar (91.4 Japanese vs. 96.2% outside

Leadless pacemakers are indicated for patients with symptomatic bradycardia requiring single-chamber ventricular bradycardia pacing support; persistent atrial tachyarrhythmias in such patients are not a contraindication for leadless pacing. In fact, many patients who receive a leadless pacemaker have persistent or permanent

The role of leadless pacemakers following removal of an infected conventional transvenous pacing system is debated. Since a leadless device requires no pocket formation and has no transvenous leads, it would appear to be suitable for a revision system for appropriate patients. In a study of patients who required device replacement after a conventional pacemaker system was infected (n = 17), patients were implanted with a Nanostim™ (n = 11) or Micra™ (n = 6) device [43]. In six patients, the leadless pacemaker was implanted within a week or less while in 11 patients, the leadless pacemakers was implanted after at least 1 week. In all patients, there was no infection over the course of a mean follow-up of 16 ± 12 months. This patient population included seven patients with a history of recurrent device infections

**56**

(mean follow-up of 20 ± 14 months). This study suggests that a leadless pacemaker may be a viable revision pacing system for selected patients who experienced device infection with a conventional pacemaker [43].

The French Working Group on Cardiac Pacing and Electrophysiology of the French Society of Cardiology has issued specific guidelines on leadless pacing [44]. Currently, the indication for leadless pacing is a patient indicated for VVIR pacing and the patient's life, as well as device service life must be taken into account as device retrieval may not always be possible. They consider that leadless devices should be implanted only in centers that also perform cardiac surgery, because of the higher incidence of tamponade, vascular complications, perforations caused by large-diameter sheaths, or other complications associated with leadless pacemakers [44].

It has been recommended that anesthesiologists familiarize themselves with all implantable device technologies, including leadless pacemakers [5]. A challenge to these devices is that interrogation software may not be readily available and that implantation should be coordinated with device manufacturer representatives or cardiologists, for example, if the device should be programmed to an asynchronous pacing mode during implant [5].

#### **9. Special populations**

In 64% of patients enrolled in one of the pivotal trials for leadless pacemakers (Micra™), the pacing indication was managing persistent or permanent atrial fibrillation with slow ventricular response [16]. In that pivotal trial, only 6% of patients had a clear-cut medical reason that limited or contraindicated them from a transvenous system. However, there are many emerging groups who may derive benefits from leadless pacemakers.

#### **9.1 Limited or occluded venous access**

Leadless pacemakers may be an important alternative to conventional devices in patients with thromboses, venous obstruction, tortuous or abnormal venous anatomy, superior vena cava syndrome, or other conditions may be contraindicated for a conventional transvenous pacemaker. A case report describes a patient with thirddegree atrioventricular (AV) block who experienced an occlusive thrombosis of the superior vena cava and had her conventional VDD transvenous pacemaker replaced with a leadless device [45]. Limited venous access as an anatomical challenge may be overcome with a leadless pacemaker as in a case study of a bradycardic hemodialysis patient who suffered from skin erosion in the chest area due to radiation treatments for esophageal carcinoma. The leadless pacemaker was implanted successfully, but the patient developed ventricular tachyarrhythmias, necessitating the implantation of a subcutaneous implantable cardioverter-defibrillator. At 1 month, both devices were performing adequately with no device-device interactions [46].

A 72-year-old man with a thrombosed venous stent, renal failure, and myelodysplastic syndrome presented with second-degree AV block. A leadless pacemaker was preferred (Micra™) because of limited venous access and a high risk of infection due to his immunocompromised condition [47].

#### **9.2 Pacemaker-dependent patients transitioned to leadless pacing**

When it is necessary to extract transvenous leads in a pacemaker-dependent patient, a common approach is to utilize a temporary pacemaker with activefixation lead as a bridge to a contralateral pacemaker implantation. A case report describes the use of a leadless pacemaker in a pacemaker-dependent patient with dextrocardia who required lead extraction following endocarditis. The implantation procedure was uneventful and the leadless pacemaker performed well with stable measurements taken 1 year postimplant [48].

#### **9.3 Transplanted hearts**

The literature reports on successful implantation of a leadless pacemaker in a transplanted heart [49].

#### **9.4 Patients with prosthetic valves**

The permanent position of a transvenous lead over the tricuspid valve may cause damage to the valve. In patients with a prosthetic tricuspid valve, locating a transvenous lead over the tricuspid valve must be considered carefully. The literature reports a case in which a 67-year-old woman with three valve replacements (an aortic mechanical valve, a mitral mechanical valve, and a tricuspid prosthesis) underwent successful implantation of a leadless pacemaker (Micra™) for high-degree AV block with permanent atrial fibrillation. She had previously had an epicardial pacemaker, which experienced lead dysfunction and transient loss of capture [50].

In a study of 23 leadless pacemaker patients (both Micra™ and Nanostim™), devices were implanted in the septal-apical area or the mid-septal region of the right ventricle. No observed changes in heart structure or heart function, such as changes to the tricuspid valve, were found. One patient in this study developed increased tricuspid valve regurgitation but without abnormal leaflet motion or any changes in annulus size, suggesting it was caused by changes in right ventricular pressure [51].

#### **9.5 Tandem subcutaneous ICD with leadless pacemaker**

It is not difficult to imagine the possibilities of combining a subcutaneous ICD (S-ICD) with a leadless pacemaker to allow for bradycardia pacing support and rescue defibrillation in a patient without the need for any transvenous leads. In an experimental study (n = 40, animal models were ovine, porcine, and canine), the dual devices were successfully implanted in 39/40 and 23 animals were followed for 90 days. Appropriate pacing was observed in 100% of animals by the leadless pacemaker, and the ICD could communicate unidirectionally with the pacemaker in 99% of cases. When triggered, the leadless pacemaker could deliver antitachycardia pacing (10 beats at 81% of the coupling interval) in 100% of attempts, while the S-ICD was able to maintain appropriate sensing [52]. While this is a preliminary animal study, it demonstrates the potential of utilizing these two leadless systems in tandem. For an S-ICD and a leadless pacemaker to work effectively together, they require the ability to communicate with each other, which, in turn, depends on the device orientation within the subject. In a canine study (n = 23), it was found that communication could occur in 100% of the implanted dogs although the median angle of the leadless pacemaker was 29°, and the median distance of the S-ICD to the leadless pacemaker was 0.8 cm. While these are not optimal values, communication was effective. A retrospective study of 72 leadless pacemaker patients found the median angle of the leadless pacemaker was 56 degrees; in a retrospective analysis of 100 S-ICD patients, the median distance between the coil and the position of the leadless pacemaker was 4.6 cm [53]. Thus, it appears that communication between devices is possible and that humans offer a better theoretical positioning opportunity for such communication than dogs.

**59**

**9.9 Small patients**

*Leadless Pacemakers*

**9.6 Dialysis patients**

rate < 20 mL/min/1.73 m2

*DOI: http://dx.doi.org/10.5772/intechopen.83546*

pacemaker following the shock remained stable [54].

**9.7 Patients with indwelling inferior vena cava filters**

pacemaker in the presence of an IVC filter.

**9.8 Left atrial appendage occluders**

embolism and recent development of AV block [57].

Dual device implantation was performed in an 81-year-old man who received an S-ICD in 2012 after explant of three transvenous ICDs due to infection [54]. At the time of S-ICD implant, the patient had no indication for bradycardia pacing, but that changed in 2015 when he developed sinus bradycardia with a daytime heart rate of about 20 bpm. Both subclavian veins were occluded, and it was decided to implant a leadless pacemaker (Micra™). The device was successfully implanted with satisfactory electrical measurements (capture threshold was 0.38 V at 0.24 ms capture threshold, the R-wave was 10.4 mV, and impedance was 640 Ω). When programmed to high outputs, the leadless pacemaker did not appear to interact with the S-ICD, even at its most sensitive settings. The patient was doing well with improved function at 4 months. At 6 months, the patient had a VT that was appropriately sensed and converted at first shock. The threshold of the leadless

For patients with chronic renal disease, a leadless pacemaker may allow preservation for central veins, necessary for permanent dialysis vascular access [55]. In patients with end-stage renal disease and the need for an implantable pacemaker, it is best to avoid transvenous leads if possible. Since kidney disease can progress rapidly, patients with a high risk for renal failure (for example, glomerular filtration

pacemakers or S-ICD systems rather than transvenous devices when possible [56].

Leadless pacemakers are contraindicated in patients with an indwelling inferior vena cava (IVC) filter, but as IVC filters become more common, the role of leadless pacemakers in this population will be explored. In some cases, an IVC filter might block passage of a catheter entering the femoral vein and routing toward the heart, but there are cases reported in the literature in which the catheter with the leadless pacemaker has been able to navigate around the indwelling IVC device. However, large studies of leadless pacemakers exclude IVC filter patients, so there is not much data on how a leadless pacemaker might be deployed in this population. A few cases in the literature suggest it is feasible, at least in selected cases, to implant a leadless

A case report in the literature describes the successful implant of a Micra™ device via a collateral branch of the right common femoral vein through a previously implanted IVC filter in a 68-year-old man with a history of pulmonary

There is a report in the literature of a dual implant of a left-atrial-appendage occluder (Watchman™, Boston Scientific, Natick, Massachusetts, USA) and a leadless pacemaker (Micra™) in a single procedure. The patient was a 73-year-old woman with persistent atrial fibrillation. Both devices were implanted via right femoral access with no complications and good results at 1 month postimplant [58].

The idea that this miniaturized pacemaker might be appropriate in smaller

patients has been explored in a few case studies. The literature reports a

); it may be helpful to consider these patients for leadless

#### *Leadless Pacemakers DOI: http://dx.doi.org/10.5772/intechopen.83546*

Dual device implantation was performed in an 81-year-old man who received an S-ICD in 2012 after explant of three transvenous ICDs due to infection [54]. At the time of S-ICD implant, the patient had no indication for bradycardia pacing, but that changed in 2015 when he developed sinus bradycardia with a daytime heart rate of about 20 bpm. Both subclavian veins were occluded, and it was decided to implant a leadless pacemaker (Micra™). The device was successfully implanted with satisfactory electrical measurements (capture threshold was 0.38 V at 0.24 ms capture threshold, the R-wave was 10.4 mV, and impedance was 640 Ω). When programmed to high outputs, the leadless pacemaker did not appear to interact with the S-ICD, even at its most sensitive settings. The patient was doing well with improved function at 4 months. At 6 months, the patient had a VT that was appropriately sensed and converted at first shock. The threshold of the leadless pacemaker following the shock remained stable [54].

#### **9.6 Dialysis patients**

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

**9.5 Tandem subcutaneous ICD with leadless pacemaker**

measurements taken 1 year postimplant [48].

**9.3 Transplanted hearts**

transplanted heart [49].

pressure [51].

**9.4 Patients with prosthetic valves**

describes the use of a leadless pacemaker in a pacemaker-dependent patient with dextrocardia who required lead extraction following endocarditis. The implantation procedure was uneventful and the leadless pacemaker performed well with stable

The literature reports on successful implantation of a leadless pacemaker in a

The permanent position of a transvenous lead over the tricuspid valve may cause damage to the valve. In patients with a prosthetic tricuspid valve, locating a transvenous lead over the tricuspid valve must be considered carefully. The literature reports a case in which a 67-year-old woman with three valve replacements (an aortic mechanical valve, a mitral mechanical valve, and a tricuspid prosthesis) underwent successful implantation of a leadless pacemaker (Micra™) for high-degree AV block with permanent atrial fibrillation. She had previously had an epicardial pacemaker, which experienced lead dysfunction and transient loss of capture [50]. In a study of 23 leadless pacemaker patients (both Micra™ and Nanostim™), devices were implanted in the septal-apical area or the mid-septal region of the right ventricle. No observed changes in heart structure or heart function, such as changes to the tricuspid valve, were found. One patient in this study developed increased tricuspid valve regurgitation but without abnormal leaflet motion or any changes in annulus size, suggesting it was caused by changes in right ventricular

It is not difficult to imagine the possibilities of combining a subcutaneous ICD (S-ICD) with a leadless pacemaker to allow for bradycardia pacing support and rescue defibrillation in a patient without the need for any transvenous leads. In an experimental study (n = 40, animal models were ovine, porcine, and canine), the dual devices were successfully implanted in 39/40 and 23 animals were followed for 90 days. Appropriate pacing was observed in 100% of animals by the leadless pacemaker, and the ICD could communicate unidirectionally with the pacemaker in 99% of cases. When triggered, the leadless pacemaker could deliver antitachycardia pacing (10 beats at 81% of the coupling interval) in 100% of attempts, while the S-ICD was able to maintain appropriate sensing [52]. While this is a preliminary animal study, it demonstrates the potential of utilizing these two leadless systems in tandem. For an S-ICD and a leadless pacemaker to work effectively together, they require the ability to communicate with each other, which, in turn, depends on the device orientation within the subject. In a canine study (n = 23), it was found that communication could occur in 100% of the implanted dogs although the median angle of the leadless pacemaker was 29°, and the median distance of the S-ICD to the leadless pacemaker was 0.8 cm. While these are not optimal values, communication was effective. A retrospective study of 72 leadless pacemaker patients found the median angle of the leadless pacemaker was 56 degrees; in a retrospective analysis of 100 S-ICD patients, the median distance between the coil and the position of the leadless pacemaker was 4.6 cm [53]. Thus, it appears that communication between devices is possible and that humans offer a better theoretical positioning opportu-

**58**

nity for such communication than dogs.

For patients with chronic renal disease, a leadless pacemaker may allow preservation for central veins, necessary for permanent dialysis vascular access [55]. In patients with end-stage renal disease and the need for an implantable pacemaker, it is best to avoid transvenous leads if possible. Since kidney disease can progress rapidly, patients with a high risk for renal failure (for example, glomerular filtration rate < 20 mL/min/1.73 m2 ); it may be helpful to consider these patients for leadless pacemakers or S-ICD systems rather than transvenous devices when possible [56].

#### **9.7 Patients with indwelling inferior vena cava filters**

Leadless pacemakers are contraindicated in patients with an indwelling inferior vena cava (IVC) filter, but as IVC filters become more common, the role of leadless pacemakers in this population will be explored. In some cases, an IVC filter might block passage of a catheter entering the femoral vein and routing toward the heart, but there are cases reported in the literature in which the catheter with the leadless pacemaker has been able to navigate around the indwelling IVC device. However, large studies of leadless pacemakers exclude IVC filter patients, so there is not much data on how a leadless pacemaker might be deployed in this population. A few cases in the literature suggest it is feasible, at least in selected cases, to implant a leadless pacemaker in the presence of an IVC filter.

A case report in the literature describes the successful implant of a Micra™ device via a collateral branch of the right common femoral vein through a previously implanted IVC filter in a 68-year-old man with a history of pulmonary embolism and recent development of AV block [57].

#### **9.8 Left atrial appendage occluders**

There is a report in the literature of a dual implant of a left-atrial-appendage occluder (Watchman™, Boston Scientific, Natick, Massachusetts, USA) and a leadless pacemaker (Micra™) in a single procedure. The patient was a 73-year-old woman with persistent atrial fibrillation. Both devices were implanted via right femoral access with no complications and good results at 1 month postimplant [58].

#### **9.9 Small patients**

The idea that this miniaturized pacemaker might be appropriate in smaller patients has been explored in a few case studies. The literature reports a

successful implantation of a leadless device (Micra™) in an 11-year-old patient with recurrent syncopal episodes and prolonged sinus pauses [59]. A 71-year-old man with achondroplastic dwarfism had a transvenous pacemaker for decades for third-degree AV block; in 2010, a pocket infection with endocarditis of the tricuspid valve necessitated the extraction of the conventional pacemaker and placement of an epicardial dual-chamber pacemaker with tunneling of leads. The patient was pacemaker dependent with permanent atrial fibrillation and developed an untreatable pocket infection. He was implanted with a leadless pacemaker (Micra™) via standard implantation technique, which was complicated by the fact that the delivery catheter was much longer than the patient's inferior limb. The device was successfully implanted and showed good electrical results. The epicardial device was then removed via a mini-thoracotomy [60]. A leadless pacemaker (Micra™) could be successfully implanted in a small-frame geriatric patient with third-degree AV block and a history of pacemaker implantations and infections [61].

#### **9.10 Vasovagal syncope**

A leadless pacemaker was successfully implanted in a 17-year-old male patient with cardioinhibitory syncope. The patient had vasovagal syncope with episodes of bradycardia and drops in arterial blood pressure. An implantable loop recorder documented a pause of 9 s, whereupon he was implanted with the leadless pacemaker [62]. Cardioinhibitory syncope may be a temporary condition.

#### **9.11 AV nodal ablation with permanent pacing**

For rate control in patients with symptomatic atrial fibrillation (AF), atrioventricular (AV) nodal ablation with subsequent pacemaker implantation (the so-called "ablate and pace" procedure) is an established course of treatment. In a multicenter observational study of 127 such patients, 60 received a leadless pacemaker and 67 a conventional transvenous pacemaker. The primary efficacy endpoint of this study was acceptable sensing thresholds (R wave ≥5.0 mV and pacing threshold ≤2.0 V at 0.4 ms). Nearly all patients (95% in leadless and 97% in conventional groups) met the primary endpoint. Five early and one late minor adverse events occurred in the leadless pacemaker group and three early adverse events occurred in the conventional pacemaker group (not statistically significantly different). Thus, it appears that leadless pacemakers may be a viable option for "ablate and pace" patients [63]. In another study in a similar population, 21 patients with permanent atrial fibrillation underwent implantation of a leadless pacemaker (Micra™) followed by AV junctional ablation; these patients were followed over 12 months with no major device-related complications. Two patients in this study died over the course of the 12 month follow-up of noncardiac causes [64]. Short- and long-term outcomes of patients undergoing a simultaneous leadless pacemaker implantation were reported from an observational study of 137 patients (mean age 77.9 ± 10.5 years) in which 19.7% (n = 37) underwent simultaneous AV nodal ablation. The complication rate was 5.5% in patients who just had leadless pacemaker insertion and 11% in those who underwent both ablation and pacemaker implant. There were no cases of device dislodgement in either group. Over the mean follow-up of 123 ± 48 days, 3.6% patients (n = 3) died, but all deaths were unrelated to cardiovascular causes. There were no significant differences between groups in terms of pacing and sensing threshold values [65].

**61**

**10. Costs**

*Leadless Pacemakers*

without complications [67].

**9.13 Congenital heart disorders**

*DOI: http://dx.doi.org/10.5772/intechopen.83546*

**9.12 Concurrent valve replacement and pacemaker implantation**

confirmed using intraoperative transesophageal echocardiography [66].

The literature reports a case in which a 91-year-old man underwent a successful transcatheter aortic valve implantation (TAVI) but experienced the not uncommon side effect of conduction disturbances. As the patient was frail and elderly, it was decided to implant a leadless pacemaker to help manage the arrhythmias rather than a transvenous system. The procedure was successful and the patient was discharged

Patients with congenital heart disorders are at an elevated risk for arrhythmias and anatomical anomalies, which may complicate venous access and device implantation. In fact, congenital heart disease patients have a rate for pacemakerrelated complications that approaches 40% compared to about 5% in the general population [68]. A case study in the literature reports on a 47-year-old female pacemaker-dependent patient with congenital heart disease who had experienced complications with a transvenous pacemaker (lead malfunction followed by occlusion of the superior vena cava and innominate veins). The transvenous lead was abandoned, and the patient was revised to an epicardial system. She presented with dizzy spells, and it was found her epicardial system was nearing end of service and had elevated thresholds. As there was no viable vascular access, it was decided to revise her pacemaker to a leadless system (Micra™). The leadless pacemaker was implanted via left femoral venous access and a steerable catheter to the right ventricular apical septal region where it was successfully positioned with good

At present, leadless pacemakers cost significantly more than a conventional transvenous device without the expense of two transvenous leads. The question of cost effectiveness in medical devices is always complicated, but it must be taken into account that even with a higher upfront cost, leadless pacemakers have substantially longer expected longevity (up to twice as long as a conventional transvenous pacemaker) and fewer complications [13]. In an online survey conducted by the European Heart Rhythm Association (EHRA) of 52 centers who participate in the EHRA Research Network, most of the 52 centers who reported said they implanted leadless pacemakers (86%) but at a small volume (82% said they implanted fewer than 30 such devices in the past 12 months). The main reasons for the low volume were device costs (91%) and lack of reimbursement for these systems (55%) [50].

electrical values (1.0 V at 0.4 ms with an R-wave of 8 mV) [69].

The literature reports on a 66-year-old female with rheumatic heart disease, permanent atrial fibrillation with slow ventricular response, and renal failure. She was admitted for mitral valve replacement and tricuspid valve repair, at which time a *de novo* pacemaker would be implanted to help manage transient AV block. It was decided to implant a leadless pacemaker (Micra™), but the sequence of these three procedures (valve replacement, valve repair, and pacemaker implantation) was not clear. The device was anchored at an adjacent septal site with measurements of 1.25 V at 0.24 ms capture threshold, R-wave of 7 mV, and impedance of 600 Ω. After this satisfactory implantation was achieved, a tricuspid ring annuloplasty was carried out successfully, and the proper position of the leadless pacemaker was

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

infections [61].

**9.10 Vasovagal syncope**

successful implantation of a leadless device (Micra™) in an 11-year-old patient with recurrent syncopal episodes and prolonged sinus pauses [59]. A 71-year-old man with achondroplastic dwarfism had a transvenous pacemaker for decades for third-degree AV block; in 2010, a pocket infection with endocarditis of the tricuspid valve necessitated the extraction of the conventional pacemaker and placement of an epicardial dual-chamber pacemaker with tunneling of leads. The patient was pacemaker dependent with permanent atrial fibrillation and developed an untreatable pocket infection. He was implanted with a leadless pacemaker (Micra™) via standard implantation technique, which was complicated by the fact that the delivery catheter was much longer than the patient's inferior limb. The device was successfully implanted and showed good electrical results. The epicardial device was then removed via a mini-thoracotomy [60]. A leadless pacemaker (Micra™) could be successfully implanted in a small-frame geriatric patient with third-degree AV block and a history of pacemaker implantations and

A leadless pacemaker was successfully implanted in a 17-year-old male patient with cardioinhibitory syncope. The patient had vasovagal syncope with episodes of bradycardia and drops in arterial blood pressure. An implantable loop recorder documented a pause of 9 s, whereupon he was implanted with the leadless pace-

For rate control in patients with symptomatic atrial fibrillation (AF), atrioventricular (AV) nodal ablation with subsequent pacemaker implantation (the so-called "ablate and pace" procedure) is an established course of treatment. In a multicenter observational study of 127 such patients, 60 received a leadless pacemaker and 67 a conventional transvenous pacemaker. The primary efficacy endpoint of this study was acceptable sensing thresholds (R wave ≥5.0 mV and pacing threshold ≤2.0 V at 0.4 ms). Nearly all patients (95% in leadless and 97% in conventional groups) met the primary endpoint. Five early and one late minor adverse events occurred in the leadless pacemaker group and three early adverse events occurred in the conventional pacemaker group (not statistically significantly different). Thus, it appears that leadless pacemakers may be a viable option for "ablate and pace" patients [63]. In another study in a similar population, 21 patients with permanent atrial fibrillation underwent implantation of a leadless pacemaker (Micra™) followed by AV junctional ablation; these patients were followed over 12 months with no major device-related complications. Two patients in this study died over the course of the 12 month follow-up of noncardiac causes [64]. Short- and long-term outcomes of patients undergoing a simultaneous leadless pacemaker implantation were reported from an observational study of 137 patients (mean age 77.9 ± 10.5 years) in which 19.7% (n = 37) underwent simultaneous AV nodal ablation. The complication rate was 5.5% in patients who just had leadless pacemaker insertion and 11% in those who underwent both ablation and pacemaker implant. There were no cases of device dislodgement in either group. Over the mean follow-up of 123 ± 48 days, 3.6% patients (n = 3) died, but all deaths were unrelated to cardiovascular causes. There were no significant differences between groups in terms of pacing and

maker [62]. Cardioinhibitory syncope may be a temporary condition.

**9.11 AV nodal ablation with permanent pacing**

**60**

sensing threshold values [65].

#### **9.12 Concurrent valve replacement and pacemaker implantation**

The literature reports on a 66-year-old female with rheumatic heart disease, permanent atrial fibrillation with slow ventricular response, and renal failure. She was admitted for mitral valve replacement and tricuspid valve repair, at which time a *de novo* pacemaker would be implanted to help manage transient AV block. It was decided to implant a leadless pacemaker (Micra™), but the sequence of these three procedures (valve replacement, valve repair, and pacemaker implantation) was not clear. The device was anchored at an adjacent septal site with measurements of 1.25 V at 0.24 ms capture threshold, R-wave of 7 mV, and impedance of 600 Ω. After this satisfactory implantation was achieved, a tricuspid ring annuloplasty was carried out successfully, and the proper position of the leadless pacemaker was confirmed using intraoperative transesophageal echocardiography [66].

The literature reports a case in which a 91-year-old man underwent a successful transcatheter aortic valve implantation (TAVI) but experienced the not uncommon side effect of conduction disturbances. As the patient was frail and elderly, it was decided to implant a leadless pacemaker to help manage the arrhythmias rather than a transvenous system. The procedure was successful and the patient was discharged without complications [67].

#### **9.13 Congenital heart disorders**

Patients with congenital heart disorders are at an elevated risk for arrhythmias and anatomical anomalies, which may complicate venous access and device implantation. In fact, congenital heart disease patients have a rate for pacemakerrelated complications that approaches 40% compared to about 5% in the general population [68]. A case study in the literature reports on a 47-year-old female pacemaker-dependent patient with congenital heart disease who had experienced complications with a transvenous pacemaker (lead malfunction followed by occlusion of the superior vena cava and innominate veins). The transvenous lead was abandoned, and the patient was revised to an epicardial system. She presented with dizzy spells, and it was found her epicardial system was nearing end of service and had elevated thresholds. As there was no viable vascular access, it was decided to revise her pacemaker to a leadless system (Micra™). The leadless pacemaker was implanted via left femoral venous access and a steerable catheter to the right ventricular apical septal region where it was successfully positioned with good electrical values (1.0 V at 0.4 ms with an R-wave of 8 mV) [69].

#### **10. Costs**

At present, leadless pacemakers cost significantly more than a conventional transvenous device without the expense of two transvenous leads. The question of cost effectiveness in medical devices is always complicated, but it must be taken into account that even with a higher upfront cost, leadless pacemakers have substantially longer expected longevity (up to twice as long as a conventional transvenous pacemaker) and fewer complications [13]. In an online survey conducted by the European Heart Rhythm Association (EHRA) of 52 centers who participate in the EHRA Research Network, most of the 52 centers who reported said they implanted leadless pacemakers (86%) but at a small volume (82% said they implanted fewer than 30 such devices in the past 12 months). The main reasons for the low volume were device costs (91%) and lack of reimbursement for these systems (55%) [50].

#### **11. Future challenges**

Currently, leadless pacing is limited to right-ventricular pacing only. The vast majority of pacemaker patients depend on AV synchronization and may even benefit from additional cardiac resynchronization for heart failure. One way to solve the AV-sequential issue is to employ VDD mode that would allow for atrial sensing; a subcutaneous ECG integrated into the circuit would be an option.

Systems that are able to communicate between devices are being developed, i.e., integration of a leadless pacemaker with an S-ICD. Ideally, this combination would offer reliable sensing/pacing in the right ventricle including antitachycardia pacing in order to terminate VT without shock therapy. Moreover, combining intracardiac signals from the leadless pacemaker with the subcutaneous ECG from the S-ICD may improve the system's ability to discriminate arrhythmias.

Another concern is handling of the device at the end of its service life. Likely, the devices will be encapsulated and could be programmed off (OOO mode), and up to three devices can reasonably be accommodated within the right ventricle [33]. However, many pacemaker patients are old with a shorter life expectancy than projected batter longevity and will only need one device.

Extraction will be necessary in the event of an infection, and the development of safe catheter-based tools would be helpful even in the situation of complete device encapsulation. More data are needed about safety of leadless pacemakers with regard to infection, device migration, and RV failure in long-term follow-up.

A leadless ultrasound-based technology used by the WiCS™ system (Wireless Cardiac Stimulation, EBR Systems) has been developed for endocardial pacing of the left ventricle [70]. The ultrasound energy is transmitted from a subcutaneous transmitter to an endocardial receiver unit in the endocardium. This device is fixed by three self-expanding nitinol tines on the device. Thus, this cardiac resynchronization therapy (CRT) system comprises three parts: the left-ventricular endocardial unit (using ultrasound for conversion of electrical energy), the subcutaneous pulse generator, and a conventional pacing device. The subcutaneously implanted pulse generator consists of a battery connected by a cable to a transmitter. The system detects right-ventricular stimulation provided by the concomitant pacemaker, CRT device, or ICD.

#### **12. Conclusion**

The technology of leadless pacing is a disruptive innovation with the potential to usher in a new era of cardiac pacing and solve problems related to the transvenous leads and pocket. The first-generation leadless pacemakers are limited to singlechamber pacing, typically VVIR pacing, but further innovations may expand that. Battery longevity is supposed to be excellent, but real-world clinical data are needed from long-term use to confirm this. The extraction of a leadless pacemaker remains a challenge. Future directions include integration of leadless pacing with S-ICDs, dual-chamber devices, and a leadless version of CRT pacing.

#### **Acknowledgements**

Todd Cooper of Coyote Studios in Los Angeles, California, provided the original illustration. The authors acknowledge editorial assistance provided by John Bisney who proofed the final manuscript. Trademarks and registered trademarks in this chapter are the property of their respective owners.

**63**

**Author details**

Stockholm, Sweden

Gävle, Sweden

*Leadless Pacemakers*

**Conflict of interest**

*DOI: http://dx.doi.org/10.5772/intechopen.83546*

The authors have no relevant conflicts to disclose.

provided the original work is properly cited.

Peter Magnusson1,2, Joseph V. Pergolizzi Jr 3

3 NEMA Research, Inc., Naples, Florida, USA

\*Address all correspondence to: joann@leqmedical.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

1 Cardiology Research Unit, Department of Medicine, Karolinska Institute,

2 Centre for Research and Development, Uppsala University/Region Gävleborg,

and Jo Ann LeQuang3

\*

*Leadless Pacemakers DOI: http://dx.doi.org/10.5772/intechopen.83546*

### **Conflict of interest**

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

Currently, leadless pacing is limited to right-ventricular pacing only. The vast majority of pacemaker patients depend on AV synchronization and may even benefit from additional cardiac resynchronization for heart failure. One way to solve the AV-sequential issue is to employ VDD mode that would allow for atrial sensing;

Systems that are able to communicate between devices are being developed, i.e., integration of a leadless pacemaker with an S-ICD. Ideally, this combination would offer reliable sensing/pacing in the right ventricle including antitachycardia pacing in order to terminate VT without shock therapy. Moreover, combining intracardiac signals from the leadless pacemaker with the subcutaneous ECG from the S-ICD

Another concern is handling of the device at the end of its service life. Likely, the devices will be encapsulated and could be programmed off (OOO mode), and up to three devices can reasonably be accommodated within the right ventricle [33]. However, many pacemaker patients are old with a shorter life expectancy than

Extraction will be necessary in the event of an infection, and the development of safe catheter-based tools would be helpful even in the situation of complete device encapsulation. More data are needed about safety of leadless pacemakers with regard to infection, device migration, and RV failure in long-term follow-up. A leadless ultrasound-based technology used by the WiCS™ system (Wireless Cardiac Stimulation, EBR Systems) has been developed for endocardial pacing of the left ventricle [70]. The ultrasound energy is transmitted from a subcutaneous transmitter to an endocardial receiver unit in the endocardium. This device is fixed by three self-expanding nitinol tines on the device. Thus, this cardiac resynchronization therapy (CRT) system comprises three parts: the left-ventricular endocardial unit (using ultrasound for conversion of electrical energy), the subcutaneous pulse generator, and a conventional pacing device. The subcutaneously implanted pulse generator consists of a battery connected by a cable to a transmitter. The system detects right-ventricular stimulation provided by the concomitant pacemaker, CRT

The technology of leadless pacing is a disruptive innovation with the potential to usher in a new era of cardiac pacing and solve problems related to the transvenous leads and pocket. The first-generation leadless pacemakers are limited to singlechamber pacing, typically VVIR pacing, but further innovations may expand that. Battery longevity is supposed to be excellent, but real-world clinical data are needed from long-term use to confirm this. The extraction of a leadless pacemaker remains a challenge. Future directions include integration of leadless pacing with S-ICDs,

Todd Cooper of Coyote Studios in Los Angeles, California, provided the original illustration. The authors acknowledge editorial assistance provided by John Bisney who proofed the final manuscript. Trademarks and registered trademarks in this

a subcutaneous ECG integrated into the circuit would be an option.

may improve the system's ability to discriminate arrhythmias.

projected batter longevity and will only need one device.

dual-chamber devices, and a leadless version of CRT pacing.

chapter are the property of their respective owners.

**11. Future challenges**

**62**

device, or ICD.

**12. Conclusion**

**Acknowledgements**

The authors have no relevant conflicts to disclose.

### **Author details**

Peter Magnusson1,2, Joseph V. Pergolizzi Jr 3 and Jo Ann LeQuang3 \*

1 Cardiology Research Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden

2 Centre for Research and Development, Uppsala University/Region Gävleborg, Gävle, Sweden

3 NEMA Research, Inc., Naples, Florida, USA

\*Address all correspondence to: joann@leqmedical.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

### **References**

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[2] Kancharla K, Deshmukh AJ, Friedman PA. Leadless pacemakers— Implant, explant and long-term safety and efficacy data. Journal of Atrial Fibrillation. 2017;**10**(2):1581

[3] Reddy VY, Exner DV, Cantillon DJ, Doshi R, Bunch TJ, Tomassoni GF, et al. Percutaneous implantation of an entirely intracardiac leadless pacemaker. The New England Journal of Medicine. 2015;**373**(12):1125-1135

[4] Lakkireddy D, Knops R, Atwater B, Neuzil P, Ip J, Gonzalez E, et al. A worldwide experience of the management of battery failures and chronic device retrieval of the Nanostim leadless pacemaker. Heart Rhythm: The Official Journal of the Heart Rhythm Society. 2017;**14**(12):1756-1763

[5] Cronin B, Essandoh MK. Update on cardiovascular implantable electronic devices for anesthesiologists. Journal of Cardiothoracic and Vascular Anesthesia. 2018;**32**(4):1871-1884

[6] Kolek MJ, Crossley GH, Ellis CR. Implantation of a MICRA leadless pacemaker via right internal jugular vein. JACC Clinical Electrophysiology. 2018;**4**(3):420-421

[7] Lloyd MS, El-Chami MF, Nilsson KR Jr, Cantillon DJ. Transcatheter/leadless pacing. Heart Rhythm: The Official Journal of the Heart Rhythm Society. 2018;**15**(4):624-628

[8] Conyers JM, Rajiah P, Ahn R, Abbara S, Saboo SS. Imaging features of leadless cardiovascular devices. Diagnostic and Interventional Radiology (Ankara, Turkey). 2018;**24**(4):203-208

[9] Kawata H, Patel PM, Banker R. Nanostim leadless pacemaker system: A longer waiting period after active fixation may reduce unnecessary repositioning. HeartRhythm Case Reports. 2018;**4**(2):63-65

[10] Tjong FVY, Beurskens NEG, Neuzil P, Defaye P, Delnoy PP, Ip J, et al. The learning curve associated with the implantation of the Nanostim leadless pacemaker. Journal of Interventional Cardiac Electrophysiology: An International Journal of Arrhythmias and Pacing. 2018;**53**(2):239-247

[11] Essandoh M. Perioperative management of the micra leadless pacemaker. Journal of Cardiothoracic and Vascular Anesthesia. 2017;**31**(6):e97-ee8

[12] Grabowski M, Michalak M, Gawalko M, Gajda S, Cacko A, Januszkiewicz L, et al. Implantation of the Micra transcatheter pacing system: Single Polish center experience with the real costs of hospitalization analysis. Cardiology Journal. 2018

[13] Shen EN, Ishihara CH, Uehara DR. Leadless pacemaker: Report of the first experience in Hawai'i. Hawai'i Journal of Medicine & Public Health: A Journal of Asia Pacific Medicine & Public Health. 2018;**77**(4):79-82

[14] Valiton V, Graf D, Pruvot E, Carroz P, Fromer M, Bisch L, et al. Leadless pacing using the transcatheter pacing system (Micra TPS) in the real world: Initial Swiss experience from the Romandie region. Europace. 2018

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[23] Cantillon DJ, Dukkipati SR, Ip JH, Exner DV, Niazi IK, Banker RS, et al. Comparative study of acute and mid-term complications with leadless and transvenous cardiac pacemakers. Heart Rhythm: The Official Journal of the Heart Rhythm Society.

[24] Richter S, Doring M, Ebert M, Bode K, Mussigbrodt A, Sommer P, et al. Battery malfunction of a leadless cardiac pacemaker: Worrisome single-center experience. Circulation.

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[28] Bari Z, Vamos M, Bogyi P, Reynolds D, Sheldon T, Fagan DH, et al. Physical activity detection in patients with intracardiac leadless pacemaker. Journal

[26] Tjong FVY, Knops RE, Udo EO, Brouwer TF, Dukkipati SR, Koruth JS, et al. Leadless pacemaker versus

Electrophysiology: PACE. 2018

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2015;**65**(15):1497-1504

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[16] Reynolds D, Duray GZ, Omar R, Soejima K, Neuzil P, Zhang S, et al. A leadless intracardiac transcatheter pacing system. The New England Journal of Medicine.

[17] El-Chami MF, Al-Samadi F, Clementy N, Garweg C, Martinez-Sande JL, Piccini JP, et al. Updated performance of the Micra transcatheter pacemaker in the real-world setting: A comparison to the investigational study and a transvenous historical control. Heart Rhythm: The Official Journal of the Heart Rhythm Society. 2018

[18] Garweg C, Ector J, Voros G, Greyling A, Vandenberk B, Foulon S, et al. Monocentric experience of leadless pacing with focus on challenging cases for conventional pacemaker. Acta Cardiologica. 2018;**73**(5):459-468

Society. 2017;**14**(9):1375-1379

Europace. 2018

[20] Sperzel J, Defaye P, Delnoy PP, Garcia Guerrero JJ, Knops RE, Tondo C, et al. Primary safety results from the LEADLESS Observational Study.

[21] Tjong FVY, Knops RE, Neuzil P, Petru J, Sediva L, Wilde AAM, et al. Midterm safety and performance of a leadless cardiac pacemaker: 3-year follow-up to the LEADLESS Trial (Nanostim Safety and Performance

Trial for a Leadless Cardiac Pacemaker System). Circulation.

2018;**137**(6):633-635

[19] Roberts PR, Clementy N, Al Samadi F, Garweg C, Martinez-Sande JL, Iacopino S, et al. A leadless pacemaker in the real-world setting: The Micra Transcatheter Pacing System Post-Approval Registry. Heart Rhythm: The Official Journal of the Heart Rhythm

#### *Leadless Pacemakers DOI: http://dx.doi.org/10.5772/intechopen.83546*

japanese patients vs. rest of the world— Results from a global clinical trial. Circulation Journal: Official Journal of the Japanese Circulation Society. 2017;**81**(11):1589-1595

[16] Reynolds D, Duray GZ, Omar R, Soejima K, Neuzil P, Zhang S, et al. A leadless intracardiac transcatheter pacing system. The New England Journal of Medicine. 2016;**374**(6):533-541

[17] El-Chami MF, Al-Samadi F, Clementy N, Garweg C, Martinez-Sande JL, Piccini JP, et al. Updated performance of the Micra transcatheter pacemaker in the real-world setting: A comparison to the investigational study and a transvenous historical control. Heart Rhythm: The Official Journal of the Heart Rhythm Society. 2018

[18] Garweg C, Ector J, Voros G, Greyling A, Vandenberk B, Foulon S, et al. Monocentric experience of leadless pacing with focus on challenging cases for conventional pacemaker. Acta Cardiologica. 2018;**73**(5):459-468

[19] Roberts PR, Clementy N, Al Samadi F, Garweg C, Martinez-Sande JL, Iacopino S, et al. A leadless pacemaker in the real-world setting: The Micra Transcatheter Pacing System Post-Approval Registry. Heart Rhythm: The Official Journal of the Heart Rhythm Society. 2017;**14**(9):1375-1379

[20] Sperzel J, Defaye P, Delnoy PP, Garcia Guerrero JJ, Knops RE, Tondo C, et al. Primary safety results from the LEADLESS Observational Study. Europace. 2018

[21] Tjong FVY, Knops RE, Neuzil P, Petru J, Sediva L, Wilde AAM, et al. Midterm safety and performance of a leadless cardiac pacemaker: 3-year follow-up to the LEADLESS Trial (Nanostim Safety and Performance Trial for a Leadless Cardiac Pacemaker System). Circulation. 2018;**137**(6):633-635

[22] Knops RE, Tjong FV, Neuzil P, Sperzel J, Miller MA, Petru J, et al. Chronic performance of a leadless cardiac pacemaker: 1-year follow-up of the LEADLESS trial. Journal of the American College of Cardiology. 2015;**65**(15):1497-1504

[23] Cantillon DJ, Dukkipati SR, Ip JH, Exner DV, Niazi IK, Banker RS, et al. Comparative study of acute and mid-term complications with leadless and transvenous cardiac pacemakers. Heart Rhythm: The Official Journal of the Heart Rhythm Society. 2018;**15**(7):1023-1030

[24] Richter S, Doring M, Ebert M, Bode K, Mussigbrodt A, Sommer P, et al. Battery malfunction of a leadless cardiac pacemaker: Worrisome single-center experience. Circulation. 2018;**137**(22):2408-2410

[25] Wang Y, Hou W, Zhou C, Yin Y, Lu S, Liu G, et al. Meta-analysis of the incidence of lead dislodgement with conventional and leadless pacemaker systems. Pacing and Clinical Electrophysiology: PACE. 2018

[26] Tjong FVY, Knops RE, Udo EO, Brouwer TF, Dukkipati SR, Koruth JS, et al. Leadless pacemaker versus transvenous single-chamber pacemaker therapy: A propensity score-matched analysis. Heart Rhythm: The Official Journal of the Heart Rhythm Society. 2018;**15**(9):1387-1393

[27] Amin AK, Billakanty SR, Chopra N, Fu EY, Nichols AJ, Kleman JM, et al. Premature ventricular contractioninduced polymorphic ventricular tachycardia after leadless pacemaker implantation: A unique adverse effect of leadless pacing. HeartRhythm Case Reports. 2018;**4**(5):180-183

[28] Bari Z, Vamos M, Bogyi P, Reynolds D, Sheldon T, Fagan DH, et al. Physical activity detection in patients with intracardiac leadless pacemaker. Journal

**64**

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

cardiovascular devices. Diagnostic and Interventional Radiology (Ankara, Turkey). 2018;**24**(4):203-208

[10] Tjong FVY, Beurskens NEG, Neuzil P, Defaye P, Delnoy PP, Ip J, et al. The learning curve associated with the implantation of the Nanostim leadless pacemaker. Journal of Interventional Cardiac Electrophysiology: An International Journal of Arrhythmias and Pacing. 2018;**53**(2):239-247

[9] Kawata H, Patel PM, Banker R. Nanostim leadless pacemaker system: A longer waiting period after active fixation may reduce unnecessary repositioning. HeartRhythm Case

Reports. 2018;**4**(2):63-65

[11] Essandoh M. Perioperative management of the micra leadless pacemaker. Journal of Cardiothoracic

[12] Grabowski M, Michalak M, Gawalko M, Gajda S, Cacko A, Januszkiewicz L, et al. Implantation of the Micra transcatheter pacing system: Single Polish center experience with the real costs of hospitalization analysis.

[13] Shen EN, Ishihara CH, Uehara DR. Leadless pacemaker: Report of the first experience in Hawai'i. Hawai'i Journal of Medicine & Public Health: A Journal of Asia Pacific Medicine & Public Health.

[14] Valiton V, Graf D, Pruvot E, Carroz P, Fromer M, Bisch L, et al. Leadless pacing using the transcatheter pacing system (Micra TPS) in the real world: Initial Swiss experience from the Romandie region. Europace. 2018

[15] Soejima K, Asano T, Ishikawa T, Kusano K, Sato T, Okamura H, et al. Performance of leadless pacemaker in

and Vascular Anesthesia. 2017;**31**(6):e97-ee8

Cardiology Journal. 2018

2018;**77**(4):79-82

[1] Cano Perez O, Pombo Jimenez M, Fidalgo Andres ML, Lorente Carreno D, Coma Samartin R. Spanish Pacemaker Registry. 14th Official Report of the Spanish Society of Cardiology Working Group on Cardiac Pacing (2016). Revista Espanola de Cardiologia (English ed). 2017;**70**(12):1083-1097

**References**

[2] Kancharla K, Deshmukh AJ, Friedman PA. Leadless pacemakers— Implant, explant and long-term safety and efficacy data. Journal of Atrial Fibrillation. 2017;**10**(2):1581

[3] Reddy VY, Exner DV, Cantillon DJ, Doshi R, Bunch TJ, Tomassoni GF, et al. Percutaneous implantation of an entirely intracardiac leadless pacemaker. The New England Journal of Medicine.

[4] Lakkireddy D, Knops R, Atwater B, Neuzil P, Ip J, Gonzalez E, et al. A worldwide experience of the management of battery failures and chronic device retrieval of the Nanostim leadless pacemaker. Heart Rhythm: The Official Journal of the Heart Rhythm Society. 2017;**14**(12):1756-1763

[5] Cronin B, Essandoh MK. Update on cardiovascular implantable electronic devices for anesthesiologists. Journal of Cardiothoracic and Vascular Anesthesia.

[6] Kolek MJ, Crossley GH, Ellis CR. Implantation of a MICRA leadless pacemaker via right internal jugular vein. JACC Clinical Electrophysiology.

[7] Lloyd MS, El-Chami MF, Nilsson KR Jr, Cantillon DJ. Transcatheter/leadless pacing. Heart Rhythm: The Official Journal of the Heart Rhythm Society.

[8] Conyers JM, Rajiah P, Ahn R, Abbara S, Saboo SS. Imaging features of leadless

2015;**373**(12):1125-1135

2018;**32**(4):1871-1884

2018;**4**(3):420-421

2018;**15**(4):624-628

of Cardiovascular Electrophysiology. 2018

[29] Blessberger H, Kiblboeck D, Reiter C, Lambert T, Kellermair J, Schmit P, et al. Monocenter Investigation Micra(R) MRI study (MIMICRY): Feasibility study of the magnetic resonance imaging compatibility of a leadless pacemaker system. Europace. 2018

[30] Edlinger C, Granitz M, Paar V, Jung C, Pfeil A, Eder S, et al. Visualization and appearance of artifacts of leadless pacemaker systems in cardiac MRI : An experimental ex vivo study. Wiener Klinische Wochenschrift. 2018;**130**(13-14):427-435

[31] Filipovic K, Bellmann B, Luker J, Steven D, Sultan A. External electrical cardioversion of persistent atrial fibrillation in a patient with a Micra Transcatheter Pacing System. Indian Pacing and Electrophysiology Journal. 2018;**18**(1):44-46

[32] Beurskens NE, Tjong FV, Knops RE. End-of-life management of leadless cardiac pacemaker therapy. Arrhythmia & Electrophysiology Review. 2017;**6**(3):129-133

[33] Omdahl P, Eggen MD, Bonner MD, Iaizzo PA, Wika K. Right ventricular anatomy can accommodate multiple micra transcatheter pacemakers. Pacing and Clinical Electrophysiology: PACE. 2016;**39**(4):393-397

[34] Vatterott PJ, Eggen MD, Mattson AR, Omdahl PK, Hilpisch KE, Iaizzo PA. Retrieval of a chronically implanted leadless pacemaker within an isolated heart using direct visualization. HeartRhythm Case Reports. 2018;**4**(5):167-169

[35] Grubman E, Ritter P, Ellis CR, Giocondo M, Augostini R, Neuzil P, et al. To retrieve, or not to retrieve: System revisions with the Micra

transcatheter pacemaker. Heart Rhythm: The Official Journal of the Heart Rhythm Society. 2017;**14**(12):1801-1806

[36] Afzal MR, Daoud EG, Cunnane R, Mulpuru SK, Koay A, Hussain A, et al. Techniques for successful early retrieval of the Micra transcatheter pacing system: A worldwide experience. Heart Rhythm: The Official Journal of the Heart Rhythm Society. 2018;**15**(6):841-846

[37] Reddy VY, Miller MA, Knops RE, Neuzil P, Defaye P, Jung W, et al. Retrieval of the leadless cardiac pacemaker: A multicenter experience. Circulation. Arrhythmia and Electrophysiology. 2016;**9**(12):pii:e004626

[38] Taborsky M, Skala T, Kocher M, Fedorco M. Extraction of a dislocated leadless pacemaker in a patient with infective endocarditis and repeated endocardial and epicardial pacing system infections. Biomedical Papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2018

[39] M RA, Dar T, Houmsse M, Augostini R, Daoud EG, Hummel J. Successful denovo implantation and explanation of an old malfunctioning micratm leadless pacemaker. Journal of Atrial Fibrillation. 2017;**10**(4):1723

[40] Gonzalez Villegas E, Al Razzo O, Silvestre Garcia J, Mesa Garcia J. Leadless pacemaker extraction from a single-center perspective. Pacing and Clinical Electrophysiology: PACE. 2018;**41**(2):101-105

[41] Chan NY, Yuen HC, Mok NS. Successful percutaneous retrieval of a leadless pacemaker due to an acute rise in pacing threshold. Indian Pacing and Electrophysiology Journal. 2017;**17**(6):186-188

[42] Tjong FVY, Beurskens NEG, de Groot JR, Waweru C, Liu S, Ritter P,

**67**

2018;**59**(1):36-39

*Leadless Pacemakers*

Electrophysiology. 2018

*DOI: http://dx.doi.org/10.5772/intechopen.83546*

after transcatheter lead extraction in complex anatomy patient. Clinical Case

[49] Martinez-Sande JL, Garcia-Seara J, Gonzalez-Melchor L, Rodriguez-Manero M, Gomez-Otero I, Gonzalez-Juanatey JR. Leadless pacemaker implantation in a transplanted heart. Revista Espanola de Cardiologia (English ed). 2018

[50] Boveda S, Lenarczyk R, Haugaa KH, Iliodromitis K, Finlay M, Lane D, et al. Use of leadless pacemakers in Europe:

Rhythm Association survey. Europace.

[51] Salaun E, Tovmassian L, Simonnet B, Giorgi R, Franceschi F, Koutbi-Franceschi L, et al. Right ventricular and tricuspid valve function in patients chronically implanted with leadless pacemakers. Europace.

[52] Tjong FVY, Brouwer TF, Koop B, Soltis B, Shuros A, Schmidt B, et al. Acute and 3-month performance of a communicating leadless antitachycardia

implantable defibrillator. JACC Clinical Electrophysiology. 2017;**3**(13):1487-1498

[53] Quast ABE, Tjong FVY, Koop BE, Wilde AAM, Knops RE, Burke MC. Device orientation of a leadless pacemaker and subcutaneous

implantable cardioverter-defibrillator in canine and human subjects and the effect on intrabody communication.

Motwani M, Zaidi AM. Totally leadless dual-device implantation for combined spontaneous ventricular tachycardia defibrillation and pacemaker function: A first report. The Canadian Journal of Cardiology. 2017;**33**(8):1066.e5-1066.e7

[55] Maradey JA, Jao GT, Vachharajani TJ. Leadless pacemaker placement

[54] Ahmed FZ, Cunnington C,

pacemaker and subcutaneous

Results of the European Heart

2018;**20**(3):555-559

2018;**20**(5):823-828

Europace. 2018

Reports. 2018;**6**(6):1106-1108

et al. Health-related quality of life impact of a transcatheter pacing system. Journal of Cardiovascular

[43] Beurskens NEG, Tjong FVY, Dasselaar KJ, Kuijt WJ, Wilde AAM, Knops RE. Leadless pacemaker implantation after explantation of infected conventional pacemaker systems: A viable solution? Heart Rhythm: The Official Journal of the

Heart Rhythm Society. 2018

[44] Defaye P, Klug D, Anselme F, Gras D, Hermida JS, Piot O, et al. Recommendations for the implantation

of leadless pacemakers from the French Working Group on Cardiac Pacing and Electrophysiology of the French Society of Cardiology. Archives of Cardiovascular Diseases.

[45] Dell'Era G, Porcellini S, Boggio E, Prenna E, Gravellone M, Varalda M, et al. Transcatheter leadless pacemaker implantation in a patient with failing transvenous pacemaker and total occlusion of superior vena cava. Journal of Cardiovascular Medicine (Hagerstown, Md). 2018;**19**(9):511-512

[46] Enomoto Y, Hashimoto H, Ishii R, Torii S, Nakamura K, Noro M, et al. Leadless pacemaker and subcutaneous implantable cardioverter defibrillator combination in a hemodialysis patient. Circulation Journal: Official Journal of the Japanese Circulation Society. 2018

[47] Sideris S, Archontakis S, Vaina S, Stroumpouli E, Koumallos N, Gatzoulis K, et al. Leadless pacing systems: A valuable alternative for patients with severe access problems. Hellenic Journal of Cardiology: HJC = Hellenike kardiologike epitheorese.

[48] De Regibus V, Pardeo A, Artale P, Petretta A, Filannino P, Iacopino S. Leadless pacemaker implantation

2018;**111**(1):53-58

#### *Leadless Pacemakers DOI: http://dx.doi.org/10.5772/intechopen.83546*

et al. Health-related quality of life impact of a transcatheter pacing system. Journal of Cardiovascular Electrophysiology. 2018

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

transcatheter pacemaker. Heart Rhythm:

[36] Afzal MR, Daoud EG, Cunnane R, Mulpuru SK, Koay A, Hussain A, et al. Techniques for successful early retrieval of the Micra transcatheter pacing system: A worldwide experience. Heart Rhythm: The Official Journal of the Heart Rhythm Society.

[37] Reddy VY, Miller MA, Knops RE,

Arrhythmia and Electrophysiology.

[38] Taborsky M, Skala T, Kocher M, Fedorco M. Extraction of a dislocated leadless pacemaker in a patient with infective endocarditis and repeated endocardial and epicardial pacing system infections. Biomedical Papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2018

[39] M RA, Dar T, Houmsse M, Augostini R, Daoud EG, Hummel J. Successful denovo implantation and explanation of an old malfunctioning micratm leadless pacemaker. Journal of Atrial Fibrillation. 2017;**10**(4):1723

[40] Gonzalez Villegas E, Al Razzo O, Silvestre Garcia J, Mesa Garcia J. Leadless pacemaker extraction from a single-center perspective. Pacing and Clinical Electrophysiology: PACE.

[41] Chan NY, Yuen HC, Mok NS. Successful percutaneous retrieval of a leadless pacemaker due to an acute rise in pacing threshold. Indian Pacing and Electrophysiology Journal.

[42] Tjong FVY, Beurskens NEG, de Groot JR, Waweru C, Liu S, Ritter P,

2018;**41**(2):101-105

2017;**17**(6):186-188

Neuzil P, Defaye P, Jung W, et al. Retrieval of the leadless cardiac pacemaker: A multicenter

experience. Circulation.

2016;**9**(12):pii:e004626

The Official Journal of the Heart Rhythm Society. 2017;**14**(12):1801-1806

2018;**15**(6):841-846

of Cardiovascular Electrophysiology.

[29] Blessberger H, Kiblboeck D, Reiter C, Lambert T, Kellermair J, Schmit P, et al. Monocenter Investigation Micra(R) MRI study (MIMICRY): Feasibility study of the magnetic resonance imaging compatibility of a leadless pacemaker system. Europace.

[30] Edlinger C, Granitz M, Paar V, Jung C, Pfeil A, Eder S, et al. Visualization and appearance of artifacts of leadless pacemaker systems in cardiac MRI : An experimental ex vivo study. Wiener Klinische Wochenschrift.

[31] Filipovic K, Bellmann B, Luker J, Steven D, Sultan A. External electrical cardioversion of persistent atrial fibrillation in a patient with a Micra Transcatheter Pacing System. Indian Pacing and Electrophysiology Journal.

[32] Beurskens NE, Tjong FV, Knops RE. End-of-life management of leadless cardiac pacemaker therapy. Arrhythmia

[33] Omdahl P, Eggen MD, Bonner MD, Iaizzo PA, Wika K. Right ventricular anatomy can accommodate multiple micra transcatheter pacemakers. Pacing and Clinical Electrophysiology: PACE.

[34] Vatterott PJ, Eggen MD, Mattson AR, Omdahl PK, Hilpisch KE, Iaizzo PA. Retrieval of a chronically implanted leadless pacemaker within an isolated heart using direct visualization. HeartRhythm Case Reports.

[35] Grubman E, Ritter P, Ellis CR, Giocondo M, Augostini R, Neuzil P, et al. To retrieve, or not to retrieve: System revisions with the Micra

& Electrophysiology Review.

2018;**130**(13-14):427-435

2018;**18**(1):44-46

2017;**6**(3):129-133

2016;**39**(4):393-397

2018;**4**(5):167-169

2018

2018

**66**

[43] Beurskens NEG, Tjong FVY, Dasselaar KJ, Kuijt WJ, Wilde AAM, Knops RE. Leadless pacemaker implantation after explantation of infected conventional pacemaker systems: A viable solution? Heart Rhythm: The Official Journal of the Heart Rhythm Society. 2018

[44] Defaye P, Klug D, Anselme F, Gras D, Hermida JS, Piot O, et al. Recommendations for the implantation of leadless pacemakers from the French Working Group on Cardiac Pacing and Electrophysiology of the French Society of Cardiology. Archives of Cardiovascular Diseases. 2018;**111**(1):53-58

[45] Dell'Era G, Porcellini S, Boggio E, Prenna E, Gravellone M, Varalda M, et al. Transcatheter leadless pacemaker implantation in a patient with failing transvenous pacemaker and total occlusion of superior vena cava. Journal of Cardiovascular Medicine (Hagerstown, Md). 2018;**19**(9):511-512

[46] Enomoto Y, Hashimoto H, Ishii R, Torii S, Nakamura K, Noro M, et al. Leadless pacemaker and subcutaneous implantable cardioverter defibrillator combination in a hemodialysis patient. Circulation Journal: Official Journal of the Japanese Circulation Society. 2018

[47] Sideris S, Archontakis S, Vaina S, Stroumpouli E, Koumallos N, Gatzoulis K, et al. Leadless pacing systems: A valuable alternative for patients with severe access problems. Hellenic Journal of Cardiology: HJC = Hellenike kardiologike epitheorese. 2018;**59**(1):36-39

[48] De Regibus V, Pardeo A, Artale P, Petretta A, Filannino P, Iacopino S. Leadless pacemaker implantation

after transcatheter lead extraction in complex anatomy patient. Clinical Case Reports. 2018;**6**(6):1106-1108

[49] Martinez-Sande JL, Garcia-Seara J, Gonzalez-Melchor L, Rodriguez-Manero M, Gomez-Otero I, Gonzalez-Juanatey JR. Leadless pacemaker implantation in a transplanted heart. Revista Espanola de Cardiologia (English ed). 2018

[50] Boveda S, Lenarczyk R, Haugaa KH, Iliodromitis K, Finlay M, Lane D, et al. Use of leadless pacemakers in Europe: Results of the European Heart Rhythm Association survey. Europace. 2018;**20**(3):555-559

[51] Salaun E, Tovmassian L, Simonnet B, Giorgi R, Franceschi F, Koutbi-Franceschi L, et al. Right ventricular and tricuspid valve function in patients chronically implanted with leadless pacemakers. Europace. 2018;**20**(5):823-828

[52] Tjong FVY, Brouwer TF, Koop B, Soltis B, Shuros A, Schmidt B, et al. Acute and 3-month performance of a communicating leadless antitachycardia pacemaker and subcutaneous implantable defibrillator. JACC Clinical Electrophysiology. 2017;**3**(13):1487-1498

[53] Quast ABE, Tjong FVY, Koop BE, Wilde AAM, Knops RE, Burke MC. Device orientation of a leadless pacemaker and subcutaneous implantable cardioverter-defibrillator in canine and human subjects and the effect on intrabody communication. Europace. 2018

[54] Ahmed FZ, Cunnington C, Motwani M, Zaidi AM. Totally leadless dual-device implantation for combined spontaneous ventricular tachycardia defibrillation and pacemaker function: A first report. The Canadian Journal of Cardiology. 2017;**33**(8):1066.e5-1066.e7

[55] Maradey JA, Jao GT, Vachharajani TJ. Leadless pacemaker placement

in a patient with chronic kidney disease: A strategy to preserve central veins. Hemodialysis International International Symposium on Home Hemodialysis. 2018

[56] Kusztal M, Nowak K. Cardiac implantable electronic device and vascular access: Strategies to overcome problems. The Journal of Vascular Access. 2018:1129729818762981

[57] Flores E, Patel M, Orme G, Su W. Successful implantation of a Micra leadless pacemaker via collateral femoral vein and inferior vena cava filter. Clinical Case Reports. 2018;**6**(3):502-505

[58] Johar S, Luqman N. Implant of a left atrial appendage occluder device (Watchman) and leadless pacing system (Micra) through the same venous access in a single sitting. BMJ Case Reports. 2018;**2018**

[59] Tejman-Yarden S, Nof E, Beinart R, Ovadia N, Goldshmit Y, Buber J, et al. Leadless pacemaker implantation in a pediatric patient with prolonged sinus pauses. Pediatric Cardiology. 2018;**39**(4):844-847

[60] Morani G, Bolzan B, Borio G, Tomasi L, Ribichini FL. Leadless pacemaker implantation in achondroplastic dwarfism and recurrent cardiac implantable electronic device infections: A case report. Europace. 2018;**20**(7):1160

[61] Tse G, Liu T, Li G, Tak Wong W, Chin Pang Chan G, Chan YS, et al. Implantation of the Micra leadless pacemaker in a patient with a low body mass index of 16. Oxford Medical Case Reports. 2017;**2017**(9):omx051

[62] De Regibus V, Moran D, Chierchia GB, Brugada P, de Asmundis C. Leadless pacing in a young patient with cardioinhibitory vasovagal syncope. Indian Pacing and Electrophysiology Journal. 2018;**18**(3):120-122

[63] Yarlagadda B, Turagam MK, Dar T, Janagam P, Veerapaneni V, Atkins D, et al. Safety and feasibility of leadless pacemaker in patients undergoing atrioventricular node ablation for atrial fibrillation. Heart Rhythm: The Official Journal of the Heart Rhythm Society. 2018;**15**(7):994-1000

[64] Okabe T, El-Chami MF, Lloyd MS, Buck B, Gornick CC, Moore JC, et al. Leadless pacemaker implantation and concurrent atrioventricular junction ablation in patients with atrial fibrillation. Pacing and Clinical Electrophysiology: PACE. 2018;**41**(5):504-510

[65] Martinez-Sande JL, Rodriguez-Manero M, Garcia-Seara J, Lago M, Gonzalez-Melchor L, Kreidieh B, et al. Acute and long-term outcomes of simultaneous atrioventricular node ablation and leadless pacemaker implantation. Pacing and Clinical Electrophysiology: PACE. 2018

[66] Marai I, Diab S, Ben-Avi R, Kachel E. Intraoperative implantation of micra leadless pacemaker during valve surgery. The Annals of Thoracic Surgery. 2018;**105**(5):e211-e2e2

[67] Shikama T, Miura M, Shirai S, Hayashi M, Morita J, Nagashima M, et al. Leadless pacemaker implantation following transcatheter aortic valve implantation using SAPIEN 3. Korean Circulation Journal. 2018;**48**(6):534-535

[68] McLeod CJ, Attenhofer Jost CH, Warnes CA, Hodge D 2nd, Hyberger L, Connolly HM, et al. Epicardial versus endocardial permanent pacing in adults with congenital heart disease. Journal of Interventional Cardiac Electrophysiology: An International Journal of Arrhythmias and Pacing. 2010;**28**(3):235-243

[69] Sanhoury M, Fassini G, Tundo F, Moltrasio M, Ribatti V, Lumia G, et al. Rescue leadless pacemaker implantation

**69**

*Leadless Pacemakers*

2015;**17**(10):1508-1513

*DOI: http://dx.doi.org/10.5772/intechopen.83546*

[70] Sperzel J, Burri H, Gras D, Tjong FV, Knops RE, Hindricks G, et al. State of the art of leadless pacing. Europace.

in a pacemaker-dependent patient with congenital heart disease and no alternative routes for pacing. Journal of Atrial Fibrillation. 2017;**9**(5):1542

*Leadless Pacemakers DOI: http://dx.doi.org/10.5772/intechopen.83546*

*Cardiac Pacing and Monitoring - New Methods, Modern Devices*

[63] Yarlagadda B, Turagam MK, Dar T, Janagam P, Veerapaneni V, Atkins D, et al. Safety and feasibility of leadless pacemaker in patients undergoing atrioventricular node ablation for atrial fibrillation. Heart Rhythm: The Official Journal of the Heart Rhythm Society.

[64] Okabe T, El-Chami MF, Lloyd MS, Buck B, Gornick CC, Moore JC, et al. Leadless pacemaker implantation and concurrent atrioventricular junction ablation in patients with atrial fibrillation. Pacing and Clinical Electrophysiology: PACE.

[65] Martinez-Sande JL, Rodriguez-Manero M, Garcia-Seara J, Lago M, Gonzalez-Melchor L, Kreidieh B, et al. Acute and long-term outcomes of simultaneous atrioventricular node ablation and leadless pacemaker implantation. Pacing and Clinical Electrophysiology: PACE. 2018

[66] Marai I, Diab S, Ben-Avi R, Kachel E. Intraoperative implantation of micra leadless pacemaker during valve surgery. The Annals of Thoracic Surgery. 2018;**105**(5):e211-e2e2

[67] Shikama T, Miura M, Shirai S, Hayashi M, Morita J, Nagashima M, et al. Leadless pacemaker implantation following transcatheter aortic valve implantation using SAPIEN 3. Korean Circulation Journal. 2018;**48**(6):534-535

[68] McLeod CJ, Attenhofer Jost CH, Warnes CA, Hodge D 2nd, Hyberger L, Connolly HM, et al. Epicardial versus endocardial permanent pacing in adults with congenital heart disease. Journal of Interventional Cardiac Electrophysiology: An International Journal of Arrhythmias and Pacing.

[69] Sanhoury M, Fassini G, Tundo F, Moltrasio M, Ribatti V, Lumia G, et al. Rescue leadless pacemaker implantation

2010;**28**(3):235-243

2018;**15**(7):994-1000

2018;**41**(5):504-510

in a patient with chronic kidney disease: A strategy to preserve central veins. Hemodialysis International International Symposium on Home

[56] Kusztal M, Nowak K. Cardiac implantable electronic device and vascular access: Strategies to overcome problems. The Journal of Vascular Access. 2018:1129729818762981

[57] Flores E, Patel M, Orme G, Su W. Successful implantation of a Micra leadless pacemaker via collateral femoral vein and inferior vena cava filter. Clinical Case Reports.

[58] Johar S, Luqman N. Implant of a left atrial appendage occluder device (Watchman) and leadless pacing system (Micra) through the same venous access in a single sitting. BMJ Case Reports.

[59] Tejman-Yarden S, Nof E, Beinart R, Ovadia N, Goldshmit Y, Buber J, et al. Leadless pacemaker implantation in a pediatric patient with prolonged sinus pauses. Pediatric Cardiology.

[60] Morani G, Bolzan B, Borio G, Tomasi L, Ribichini FL. Leadless pacemaker implantation in

achondroplastic dwarfism and recurrent cardiac implantable electronic device infections: A case report. Europace.

[61] Tse G, Liu T, Li G, Tak Wong W, Chin Pang Chan G, Chan YS, et al. Implantation of the Micra leadless pacemaker in a patient with a low body mass index of 16. Oxford Medical Case

[62] De Regibus V, Moran D, Chierchia GB, Brugada P, de Asmundis C. Leadless

Reports. 2017;**2017**(9):omx051

pacing in a young patient with cardioinhibitory vasovagal syncope. Indian Pacing and Electrophysiology

Journal. 2018;**18**(3):120-122

Hemodialysis. 2018

2018;**6**(3):502-505

2018;**39**(4):844-847

2018;**20**(7):1160

2018;**2018**

**68**

in a pacemaker-dependent patient with congenital heart disease and no alternative routes for pacing. Journal of Atrial Fibrillation. 2017;**9**(5):1542

[70] Sperzel J, Burri H, Gras D, Tjong FV, Knops RE, Hindricks G, et al. State of the art of leadless pacing. Europace. 2015;**17**(10):1508-1513

**71**

**Chapter 5**

**Abstract**

Thumb ECGs

*Hani Annabi and Jo Ann LeQuang*

patient care as well as for research into AF.

**1. Introduction**

Atrial Fibrillation and the Role of

*Peter Magnusson, Magnus Samuelsson, Joseph V. Pergolizzi Jr,* 

Atrial fibrillation (AF) may be underdiagnosed, and there is much that remains unknown about this prevalent and potentially life-threatening arrhythmia. AF epidemiology has been thwarted in part by the fact that about a third of patients with AF have no symptoms, those with symptoms may experience them intermittently or have vague symptoms, and it can be challenging to capture an episode on a 12-lead ECG, which is required for diagnosis. There are many significant knowledge gaps in our understanding of AF etiology and progression. A new user-friendly device that allows for frequent self-monitoring of the heart rhythm has been introduced. With the thumb ECG, patients can record a tracing multiple times a day. A smartphone app will soon allow them to interact with their healthcare providers about these ECG recordings. An ECG parser will allow for an algorithm-directed, rapid, automatic interpretation of these recordings with high specificity and sensitivity. This may help researchers learn more about the so-called *silent AF,* AF progression (and possible remission), and risk factors for AF. This technology holds great promise for

**Keywords:** arrhythmia, atrial fibrillation, thumb ECG, Coala heart monitor, stroke

Atrial fibrillation (AF) is the most common sustained arrhythmia and associated with a fivefold increased risk of stroke and a threefold increased risk of heart failure; thus, AF is a major cause of cardiovascular morbidity [1–3]. The European Society of Cardiology (ESC) recognizes five main types of AF: first diagnosed episode, paroxysmal, persistent, long-standing persistent, and permanent [3] (see **Table 1**). It had long been thought that *AF begets AF* and the arrhythmia followed a linear forward progression from short, infrequent, self-terminating episodes to more persistent forms of AF, but that paradigm has been challenged in that about 3% of patients seem to have paroxysmal AF that never advances to more persistent forms [4]. It is now recognized that AF may plateau, remit/relapse, and one patient can simultaneously have multiple types of AF [5]. The ESC has also identified seven clinical types of AF, as the etiology of AF may relate to any of multiple mechanisms (see **Table 2**). In addition to types and categories of AF, the arrhythmia burden is frequently used as a metric

to describe the amount of time an individual spends in AF [6].

#### **Chapter 5**
