**2. Technology and terminology**

Cardiac device management involves many technical details. For those less familiar with these procedures, we recommend the supplementary appendix of a recent review [7]. In addition to an outline of the generators, leads, and materials used in CIEDs, it also describes the normal step-by-step procedures of implanting, revising, and removing CIEDs. Abbreviations are both abundant and inevitable in this field and are summarized at the end of this chapter.

#### **3. Definition and categorization of CIED infection**

There are no universally agreed definitions of CIED infection. Previously used definitions have varied, but common starting points have been the site or sites of infection on one hand and the signs of probable infection on the other [8, 9]. One common and theoretically simple distinction is between local device infection and infection also affecting the blood stream, leads, and/or cardiac valves. However, in clinical practice, it is sometimes difficult to differentiate between these categories [5]. The lack of a golden standard calls for a clear presentation of used criteria. Our proposed classification, summarized below, is a synthesis of earlier studies, recommendations, and guidelines [7, 10, 11].

In short, we suggest six different categories relevant when CIED infection is considered. These are presented in **Table 1**, besides basic strategies for device and antibiotic management. The first of three categories involving the generator pocket is not a definite infection but rather early post-implantation inflammation. These superficial signs of wound inflammation are expected to wear off shortly, when suspected causes such as sutures or dressing are removed. However, as they also can be an early sign of infection, close observation is recommended.

Actual infections can be categorized as complicated or uncomplicated pocket infection based on whether they also involve blood stream infection. Echocardiography and the modified Duke criteria can be used to classify more extensive infections: suspected or definite lead infection (CIED-LI), and CIED-associated infective endocarditis affecting the heart valves (CIED-IE) [12]. A large proportion of patients end up as "possible CIED-LI". Diagnosing a definite and isolated CIED-LI



*\*Clinical systemic signs of infection include rigors, fever, embolic phenomena, and improvement after treatment. \*\*In some guidelines, device erosion is described as an entity of its own, as this always means that the system will be infected, regardless of symptoms.* 

*\*\*\*Consider day 1 as the first day of appropriate antimicrobials unless persistently bacteremic on therapy.* 

#### **Table 1.**

*Adopted from Sanoe et al. [7].* 

is difficult, but possible and would require a structurally normal tricuspid valve that remains normal after device extraction and no findings suspicious of pocket infection. Cases with occult bacteremia and neither proof of CIED infection nor alternative sources of infection, resolving after CIED extraction, are reasonable to title probable CIED infection. It may take time and sometimes also device removal before a definite diagnosis is established. However, the proposed categories may be relevant before that, as a way to structure early management. Clinical systemic signs of infection include rigors, fever, embolic phenomena, and improvement after treatment.

### **4. Epidemiology**

 The last decades have seen a steady increase in the number of patients with CIEDs [13–15]. Originally made up mostly of pacemaker implants, the continuing increase today is largely due to rising implantation rates of ICD and CRT devices [16]. Using current evidence to determine the true incidence of CIED infection is hard, as there is no uniform or mandatory reporting, no universal definition of how to classify the disease and many differences between studies regarding the time frame for measured incidence. Reviews of the literature suggest an overall incidence of CIED infection of 0.5–2.2%, based on different follow up periods from 6 weeks to 11 years [7]. Some studies instead report incidence per 1000 device years. Three large registry studies of pacemaker and ICD patients report 1.8-3.1 per 1000 device years [17–19].

*Cardiac Implantable Electronic Device-Related Infections DOI: http://dx.doi.org/10.5772/intechopen.86395* 

As new surgical procedures mature, implantation volumes increase, and the operating staff becomes more skilled, it is often reasonable to expect that the incidence of complications will decrease [20]. For CIED infections however, the opposite has been the case. Despite the variations in reported incidence and technique of reporting incidence, there are consistent results from several long-term registry studies showing increasing infection rates over time [9, 13, 18, 20–22]. These studies display not only the well-known trend of increasing implantation rate, accentuated by wider indications for ICD treatment, but also an unproportional increase in CIED infections. Furthermore, they report higher incidence of infection for ICDs and CRT compared to pacemakers and for device revisions (such as upgrades or replacements) compared to *de novo* implantations [23, 24].

 A clarifying example is a study of US discharge registries 1993–2008; during the 16-year study, implantation of pacemakers increased by 45% and ICDs by 504% and the total increase in all CIED implantation was 96%. The incidence of CIED infection increased by 210% to 2.41% between 1993 and 2008. The rate of infection was fairly constant up to 2004 when a marked increase occurred. The study revealed a parallel increase in four comorbidities (renal failure, heart failure, diabetes, and respiratory failure) among the patients starting in 2004 [13]. This shift also coincided fairly close in time with the introduction of new, broader indications for ICD treatment.

This resulted in speculations about comorbidities, together with the risks of more complex devices, explaining the increase in CIED infections [13]. As neither the aging population with more comorbidities nor the wider indications for ICDs are temporary phenomena, a conclusion has been that this has set the stage for further increases in CIED infection rates, making the study of risk factors more relevant than ever [14].

### **5. Predictors for CIED infection**

Device-related infections are the result of an interaction between different types of risk factors—related to the patient, the implantation procedure, the microbe, or the device itself [11]. These factors predispose to device infection by either increasing the risk of generator or lead contamination at the time of implantation or increasing the risk of bacteremia from a distant source with hematogenous seeding of device leads [25]. Establishing risk factors is central for prevention and numerous risk factors have been identified (**Table 2**). The evidence supporting these factors varies and their combined effect is not easily quantifiable.

#### **5.1 Risk factors related to patient, device, and procedure**

A systematic review concluded that the three most consistently identified risk factors were the number of prior procedures, their complexity, and lack of antimicrobial prophylaxis [7]. The importance of antibiotic prophylaxis has also been showed in randomized controlled trials [11].

 In a meta-analysis of 60 studies (180,000 patients), the most significant patient-related risk factors were diabetes mellitus, end-stage renal disease, chronic obstructive pulmonary disease, corticosteroid use, previous device infection, renal insufficiency, malignancy, and congestive heart failure. Other significant risk factors were symptomatic heart failure, preprocedural fever, anticoagulant drug use, heparin bridging, and chronic skin disorders. Procedural risk factors identified were postoperative hematoma, reintervention for lead dislodgement, device revision/ replacement, lack of antibiotic prophylaxis, temporary pacing before the procedure, generator exchange, and inexperienced operator (<100 procedures). Significant


Postoperative wound infection

#### **Table 2.**

*Risk factors for CIED infection [7, 11, 14, 25].* 

device-related risk factors were abdominal generator pocket, presence of epicardial leads, and positioning of two or more leads [26].

 Although this meta-analysis did not show higher infection risks for ICDs compared to pacemakers, there are numerous other studies indicating such a risk, and a generally higher risk with more complex devices including CRT [18, 27–29]. Even though it is hard to exactly quantify the difference in risk of infection with an ICD or CRT compared to a pacemaker, it is clear that more complex devices should be regarded as a risk factor [11].

Several risk factors are linked to the reopening of the device pocket, for example during upgrades, which increases the risk of introducing bacteria—highlighting problems with today's frequent upgrades and recalls.

Several summaries of known risk factors attribute age as a risk factor [11, 25, 30]. However, it is not certain that it is a fully independent factor and some studies show contradicting results, for example, the meta-analysis mentioned above [17, 26]. As old age has been consistently associated to more co-morbidities and more complex devices, we have chosen to list "old age and comorbidities" as a risk factor [11]. There are also uncertainties regarding male sex that has been listed as a risk factor of infection in a few studies [7]. Reopening of the pocket is linked to several risk factors.

#### **5.2 Microbe-related risk factors**

Studies point to a risk of CIED infection as high as 35–45% when *Staphylococcus aureus* (*S. aureus*) is found in blood cultures [8, 29], 30% with other Gram-positive cocci [31], and 6% with blood cultures with Gram-negative bacteria [32]. Hence, the finding of either *S. aureus* or other Gram-positive cocci in blood cultures is in itself a substantial risk factor for CIED infection [7].
