**4. Clinical manifestation and diagnosis**

It is important to consider tachycardia-induced cardiomyopathy in all cases as a possible cause of systolic dysfunction and manifest heart failure, especially in patients with a new or wors‐ ened ventricular systolic dysfunction or in cases with their uncertain duration in which persistent tachycardia is found simultaneously. Since contractile dysfunction and structural changes may persist even weeks after the rhythm/rate correction, tachycardia-induced cardiomyopathy should be considered as a probable reason of ventricular dysfunction and dilatation in any patient presenting with dilated cardiomyopathy pattern, despite that the initial rhythm is not pathological or the heart rate is well controlled.

**3.5. Course of the changes over time and their reversibility**

82 Abnormal Heart Rhythms

[33, 46], that requires longer time for its resolution.

function during the last evaluation [60].

**4. Clinical manifestation and diagnosis**

Experimental studies demonstrate that changes of hemodynamics with the reduction of cardiac output or altered systemic arterial pressure occur already in the first 24 hours of rapid pacing [32]. When continued, fast cardiac pacing then induces an elevation of ventricular filling pressures, pulmonary artery pressure and a decrease of systemic arterial pressure that reach certain plateau after one week, while cardiac output, volumes and ejection fraction deteriorate

Cessation of tachycardia results in a resolution of these changes: in the first 48 hours after termination of cardiac pacing, a significant improvement of cardiac output, systemic vascular resistance, mean arterial pressure and filling pressures are present [39]. Left-ventricular ejection fraction also improves dramatically and normalizes within 1–2 weeks [39]. All hemodynamic variables normalize within the horizon of four weeks after tachycardia inter‐ ruption, but diastolic dysfunction remains detectable even after the first month period. Importantly, elevated end-diastolic and end-systolic volumes are still present after twelve weeks of pacing discontinuation, which is consistent with substantial ventricular remodeling

Although the hallmark of tachycardia-induced cardiomyopathy is an improvement or even normalization of cardiac function and size with the resulting disappearance of heart failure symptoms after cessation of tachycardia or rate control achievement, there is growing evidence that the ultrastructural abnormalities of the myocardium and residual contractility dysfunc‐ tion may persist. This has already been suggested in the experimental studies [53b], but similar conclusions have also been made in clinical observational reports [60, 61]. In one of these studies, ventricular function has been assessed using specle tracking and contrast-enhanced MRI with ventricular T1 mapping used as an index of diffuse fibrosis. Although the ejection fraction normalized three months after a successful ablation of initial tachycardia already, it has been possible to detect a somewhat greater indexed end-diastolic and end-systolic volume of the left ventricle in patients with tachycardia-induced cardiomyopathy as compared to healthy controls. Moreover, patients with previous tachycardia-induced cardiomyopathy have demonstrated reduced global left-ventricular corrected T1 time that implies a diffuse fibrosis [61]. In addition, another study [60] suggests that tachycardia tends to recur in some patients initially diagnosed with tachycardia-induced cardiomyopathy pattern and this recurrence of arrhythmia leads to a new decline of systolic ventricular function. Moreover, sudden death may occur in some of these patients despite normal or almost normal systolic

It is important to consider tachycardia-induced cardiomyopathy in all cases as a possible cause of systolic dysfunction and manifest heart failure, especially in patients with a new or wors‐ ened ventricular systolic dysfunction or in cases with their uncertain duration in which persistent tachycardia is found simultaneously. Since contractile dysfunction and structural

continually for 3–5 weeks with the final end-stage heart failure development [35, 45].

Generally, persistent tachycardia (i.e. tachycardia lasting usually weeks or months) predis‐ poses an individual to ventricular dysfunction and dilatation development, regardless of the rhythm disturbance characteristics. However, the resulting degree of systolic dysfunction and heart dilatation, the rate of their progression and the reversibility of hemodynamic and structural abnormalities after rhythm/rate correction are partially dependent on the heart rate, type and duration of the tachycardia and also on the concomitant presence of other heart diseases. In addition, there is growing evidence that irregularity of the rhythm alone may contribute to these changes manifestation and that it may also affect the rate and the extent of their resolution after rhythm correction.

**Heart rate** is apparently one of the most important factors. Tachycardia-induced cardiomy‐ opathy is rate dependent: tachycardias with higher rates manifest themselves usually earlier than those with slower rates [31, 62]. In an experimental setting, pacing at slower rate or for a shorter time usually yields a lesser degree of left-ventricular systolic dysfunction [39, 63]. However, some observational studies imply that tachycardia-induced cardiomyopathy may be found more often in patients with a slower heart rate than in those with a higher rate. This was reported in retrospective observational studies that included patients referred to cathe‐ terization ablation of focal atrial tachycardia [15, 16]. Tachycardia-induced cardiomyopathy was present in 9–19% of these cases, more frequently in patients with heart rate of less than 120 bpm. Possible explanation for this finding may include the fact that faster tachycardia is associated with early symptom manifestation in form of palpitation, whereas tachycardias with lower heart rate are better tolerated by the patient, so the remodeling and signs of heart failure have enough time to develop before the patient visits a doctor.

How fast does the tachycardia have to be to induce tachycardia-induced cardiomyopathy is still not clear. Basically, any rhythm with the rate exceeding 100 bpm for a longer period of time may lead to this pathology. In this context, it is important to note that heart rate (especially in atrial fibrillation) may vary significantly as a result of physical or mental activity, i.e. patients may show well-controlled heart rate at rest that increases abnormally during minimal exercise. Therefore, Holter ECG monitoring may be useful to identify such behavior and to raise suspicion of tachycardic origin of an observed ventricular dysfunction. Cut-offs for adequate rate control have been derived from atrial fibrillation patients. They generally vary with age, but heart rate ranging between 60 and 80 bpm at rest and 90–115 bpm during a moderate exercise are usually considered as adequate (so-called strict rate control) [64]. These target rates are sometimes difficult to achieve, however. A lenient rate control strategy [65] aiming at resting heart rate <110 bpm seems to have similar long-term results as the strict rate control of atrial fibrillation and is thus preferred nowadays.

In the experimental model, persistent **ventricular tachyarrhythmias induce** generally **more significant ventricular dysfunction** than supraventricular tachycardias [38].

Tachycardia-induced cardiomyopathy may develop in a variable time-horizon since the tachycardia onset (even after many months). Together with heart rate and type of the arrhyth‐ mia, the **tachycardia duration** is responsible for the severity and reversibility of ventricular systolic dysfunction [31] as it has been discussed earlier.

Tachycardia-induced cardiomyopathy can be present as either sole pathology or it **may accompany another heart disease**. It means that the presence of other structural heart disease does not exclude concurrent presence of tachycardia-induced cardiomyopathy. In these cases, tachycardia may worsen the pre-existing ventricular dysfunction and dilatation [12]. The degree of a ventricular dysfunction is then usually inadequate to the severity of the underlying heart disease (i.e. atherosclerotic changes of the coronary arteries). Tachycardia-induced cardiomyopathy is highly probable especially in patients with recently normal systolic function of the ventricles and in those with an improvement of dysfunction after the achieve‐ ment of an adequate rate/rhythm control.

Another factor which appears to contribute to tachycardia-induced cardiomyopathy is the **irregularity** of a rhythm. It is based not only on the observations that frequent ectopic supraventricular or ventricular beats are able to induce the pattern of reversible dilated cardiomyopathy [9, 22, 24], but also on studies on rate control in atrial fibrillation [66], which demonstrate that the irregularity of a fast rhythm may worsen cardiac function whereas it does not cause any significant hemodynamic worsening if the heart rate of the irregular rhythm falls generally within a normal range.

Assessment of a patient with suspected tachycardia-induced cardiomyopathy includes a detailed history and physical examination with the subsequent laboratory and imaging tests to state the diagnosis and severity of the disease.

### **4.1. Symptoms and signs**

The manifestation of tachycardia-induced cardiomyopathy is various. The most common symptoms include palpitations and signs of heart failure. Palpitations resulting from either high rate or irregularity of the arrhythmia are often the dominant complaint of a patient with fast tachycardia. These patients thus often consult a doctor early in search of intervention and cardiomyopathy pattern then does not have enough time to develop. On the other hand, symptoms and signs of a heart failure may predominate in those patients who do not feel palpitation and are not aware of a rhythm disturbance. In such patients, decreased exercise capacity, fatigue or congestion may be the main complaint.

Due to the fact that acuteness of the symptoms forces a patient with rapid heart rate to seek medical help shortly after the arrhythmia onset, some scholars hypothesize that tachycardiainduced cardiomyopathy is present rather in patients with slower arrhythmias. Some clinical observations support such conclusions [15, 16]: The first retrospective observational study [16] included a sample of 331 patients without structural heart diseases who underwent ablation of atrial tachycardia. Tachycardia-induced cardiomyopathy was present in 9% of them and affected rather younger patients (mean age 39 vs. 51 years), more often males (60% versus 38%) with incessant or very frequent paroxysmal tachycardia (100% vs. 20%) with a slower heart rate (120 bpm vs. 149 bpm), than arrhythmias that have not been associated with ventricular dysfunction. Similar findings have been reported also in children with persistent atrial tachycardias [15]: atrial tachycardia originating within the atrial appendage was more often associated with slower heart rate (<120 bpm) at examination, asymptomatic course (75% versus 25%) and higher prevalence of tachycardia-induced cardiomyopathy as compared to atrial tachycardia of other origins.

In all other aspects, tachycardia-induced cardiomyopathy resembles other forms of dilated cardiomyopathy: symptoms and signs of heart failure, their severity as well as neurohumoral activation are principally similar.

#### **4.2. Diagnosis**

Tachycardia-induced cardiomyopathy may develop in a variable time-horizon since the tachycardia onset (even after many months). Together with heart rate and type of the arrhyth‐ mia, the **tachycardia duration** is responsible for the severity and reversibility of ventricular

Tachycardia-induced cardiomyopathy can be present as either sole pathology or it **may accompany another heart disease**. It means that the presence of other structural heart disease does not exclude concurrent presence of tachycardia-induced cardiomyopathy. In these cases, tachycardia may worsen the pre-existing ventricular dysfunction and dilatation [12]. The degree of a ventricular dysfunction is then usually inadequate to the severity of the underlying heart disease (i.e. atherosclerotic changes of the coronary arteries). Tachycardia-induced cardiomyopathy is highly probable especially in patients with recently normal systolic function of the ventricles and in those with an improvement of dysfunction after the achieve‐

Another factor which appears to contribute to tachycardia-induced cardiomyopathy is the **irregularity** of a rhythm. It is based not only on the observations that frequent ectopic supraventricular or ventricular beats are able to induce the pattern of reversible dilated cardiomyopathy [9, 22, 24], but also on studies on rate control in atrial fibrillation [66], which demonstrate that the irregularity of a fast rhythm may worsen cardiac function whereas it does not cause any significant hemodynamic worsening if the heart rate of the irregular rhythm

Assessment of a patient with suspected tachycardia-induced cardiomyopathy includes a detailed history and physical examination with the subsequent laboratory and imaging tests

The manifestation of tachycardia-induced cardiomyopathy is various. The most common symptoms include palpitations and signs of heart failure. Palpitations resulting from either high rate or irregularity of the arrhythmia are often the dominant complaint of a patient with fast tachycardia. These patients thus often consult a doctor early in search of intervention and cardiomyopathy pattern then does not have enough time to develop. On the other hand, symptoms and signs of a heart failure may predominate in those patients who do not feel palpitation and are not aware of a rhythm disturbance. In such patients, decreased exercise

Due to the fact that acuteness of the symptoms forces a patient with rapid heart rate to seek medical help shortly after the arrhythmia onset, some scholars hypothesize that tachycardiainduced cardiomyopathy is present rather in patients with slower arrhythmias. Some clinical observations support such conclusions [15, 16]: The first retrospective observational study [16] included a sample of 331 patients without structural heart diseases who underwent ablation of atrial tachycardia. Tachycardia-induced cardiomyopathy was present in 9% of them and affected rather younger patients (mean age 39 vs. 51 years), more often males (60% versus 38%) with incessant or very frequent paroxysmal tachycardia (100% vs. 20%) with a slower heart

systolic dysfunction [31] as it has been discussed earlier.

ment of an adequate rate/rhythm control.

84 Abnormal Heart Rhythms

falls generally within a normal range.

**4.1. Symptoms and signs**

to state the diagnosis and severity of the disease.

capacity, fatigue or congestion may be the main complaint.

As soon as tachycardia-induced cardiomyopathy is suspected, tests that aim to confirm the diagnosis take place.

All patients should have **12-lead ECG** to document basic heart rhythm and its rate at patient presentation. Especially in cases with persistent atrial tachycardia, it is helpful to compare recent ECG tracing with an older one (if available) to distinguish whether the current P wave morphology corresponds with the documented sinus rhythm morphology or if it is rather suggestive for atrial focus. Since the heart rate may change over time, due to mental or physical activity, patients with suspected tachycardia-induced cardiomyopathy should undergo **continuous ECG monitoring** for at least 24 hours (ambulatory Holter ECG monitoring or inpatient telemetry). If uncertainty regarding the underlying rhythm persists, electrophysiologic testing should be considered.

Besides arrhythmia detection, the presence of left-ventricular dysfunction with/without ventricular dilatation should be documented. With this regard, **transthoracic echocardiogra‐ phy** represents a gold standard. Morphological findings are principally similar as in the dilated cardiomyopathy of other origins and differentiation between tachycardia-induced cardiomy‐ opathy and other forms of dilated cardiomyopathy is generally not possible based on the echocardiographic pattern only, although left-ventricular end-diastolic diameter tends to be usually smaller in cases of tachycardia-induced cardiomyopathy [67].

Despite that the patient presents with tachyarrhythmia, other reasons of dilated cardiomyop‐ athy pattern should be therefore considered as soon as the ventricular dysfunction and dilatation is documented at any imaging modality. Adult patients are thus often indicated to coronary angiography to exclude the most common substrate of ventricular dysfunction, i.e. a significant underlying coronary artery disease. History of alcohol intake, drug abuse, cancer and its treatment, thyreopathy or other metabolic or congenital disease should be searched for further.

A single-center experience suggests that also **serial NT-pro BNP** measurement may be useful to distinguish between tachycardia-induced cardiomyopathy and cardiomyopathies due to structural heart disease [68]. This study included patients who presented with supraventric‐ ular tachycardia and reduced left-ventricular ejection fraction <40% and underwent cardio‐ version. The NT-pro BNP level has initially been elevated in all patients. After a successful cardioversion, NT-pro BNP has decreased in virtually all patients, but the decrease has been quicker in tachycardia-induced cardiopmyopathy patients. Therefore, the ratio between the baseline NT-pro BNP and NT-pro BNP after one week following cardioversion ≥ 2.3 has had 90% sensitivity, 95% specificity and 90% accuracy to predict tachycardia-induced origin of ventricular dysfunction based on these authors.
