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Recognise risk factors and presentation features of cardiac implantable electronic device (CIED) device infection.
Formulate a diagnostic and management plan for patients with suspected CIED infection.
Provide an overview of device removal surgery and antimicrobial therapy for patients with CIED infections.
As our population ages with the increasing prevalence of comorbidities, and indication for cardiac implantable electronic devices (CIED) expand for treatment of heart failure, bradyarrhythmias and sudden cardiac death prevention, there is a simultaneous increase in associated device infections.1 The incidence of CIED infections is around 1% to 2% among reported observational and registry studies.2 3 These device infections are associated with significant morbidity, increased long-term mortality and associated healthcare costs.4 Rates of CIED infection are higher with device replacement or upgrade procedure and thoracotomy implants.5 There are several known factors associated with increased risk of CIED infection (box 1). In particular, the risk of infection is higher among patients undergoing defibrillator and cardiac resynchronisation therapy (CRT) device implants compared patients with simple pacemaker implants.6 Adequate skin preparation, strict aseptic technique, preprocedural antibiotic prophylaxis, periprocedural anticoagulant therapy management, meticulous surgical technique and a robust quality control programme is necessary for the prevention of infections. With the introduction of leadless pacemakers and subcutaneous implantable defibrillators, management of CIED infections continues to evolve.7 8 Professional society documents continue to provide guidance on prevention, diagnosis and treatment of CIED infections.9–11 In this review article, we attempt to provide an overview of prevention, diagnosis and management of CIED infections to the practising cardiologist.
Risk factors associated with CIED infection. CIED, cardiac implantable electronic device; CRT, cardiac resynchronisation therapy; ICD, implantable cardioverter defibrillator.
Chronic obstructive pulmonary disease.
Presence of central venous access/temporary pacing catheter.
Prior device infection.
Lack of antibiotic prophylaxis.
Need for reintervention.
Duration of the procedure.
Experience of the operator.
Need for temporary pacing catheter.
No of leads.
Type of device (CRT vs ICD vs pacemaker).
Location of the pocket.
Abdominal location great risk than pectoral location.
Diagnosing CIED infection
Clinical signs of CIED infection include swelling, redness, pain, erosion and discharge at the device site. Patients with an advanced stage of infection can present with fever, chills, rigours, hypotension due to sepsis and may have associated end-organ dysfunction. The presence of erythema surrounding the generator-pocket site with pain or discomfort, device erosion with lead or generator exposure makes the diagnosis of CIED relatively simple and straightforward.9 The diagnosis becomes a challenge when these signs and symptoms are absent (figure 1). Further diagnostic dilemmas include patients with bacteraemia with a CIED without generator-pocket erythema or pain, and those with transoesophageal echocardiography (TEE) evidence of a mass on an intracardiac lead without fevers ± bacteraemia. Keloids, hypertrophic scars and non-healing incision due to suture material allergy provide additional challenges on making a diagnosis.
If there is suspicion a patient has a CIED infection, the American Heart Association (AHA) recommends obtaining at least two sets of blood cultures before the initiation of antibiotic therapy, multispecialty evaluation by infectious diseases specialist and cardiologists, and perform a TEE for evidence of lead vegetation and valvular endocarditis.9 Evidence of CIED infection on TEE is a mass adherent to the device lead. However, TEE cannot distinguish thrombus versus vegetation and failure to visualise a lead mass does not exclude CIED infection.9 Needle aspiration of a pocket in a patient with haematoma or suspected infection must be avoided, as it can introduce microbes into the pocket and is associated with adverse outcomes.
A wide range of microorganisms have been shown to cause CIED infections including Gram-positive and Gram-negative bacteria, mycobacteria and fungi. Coagulase-negative staphylococci and Staphylococcus aureus are the most common causes of CIED infection as they possess several adherence factors and biofilm formation which allow for microbial attachment to the device and provide protection from antibiotic therapy preventing its eradication of infection with antibiotics alone.12 13 Antibiotics directed against the infecting microorganism are imperative to treat CIED infections appropriately. There are a variety of methods to identify the microorganism-infected CIEDs with variable rates of success which include swab cultures of the pocket and device, a tissue culture of the pocket and lead-tip cultures. During CIED removal, it is recommended to obtain tissue culture of the generator-pocket and device lead tip and perform Gram stain and culture.9 Pocket tissue cultures have been shown to be more effective than pocket swab cultures for microorganism detection.14 Multiple studies have also examined the usefulness of sonication to increase the sensitivities pocket swab, device swab and tissue cultures in patients with CIED infections.15 16
The use of alternative imaging modalities to aid in the diagnosis of CIED infections have been increasingly studied. When the diagnosis of CIED infection remains uncertain after a physical examination, blood cultures and TEE, and a high suspicion for infection remains, these alternative images should be considered. Fluoro-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) has been shown to be useful in early CIED infection and also differentiating between CIED infection and recent postimplant changes.17 18 In a systematic review by Juneau et al,19 the pooled sensitivity of 18F-FDG PET/CT for the diagnosis of CIED infection was 87% and pooled specificity was 94%. The use of 99mTc-hexamethypropylene amine oxime-labelled autologous white blood cell (99mTc-HMPAO-WBC) single-photon emission CT/CT (SPECT/CT) has also been examined in suspected CIED infections. The sensitivity of 99mTc-HMPAO-WBC SPECT/CT was 94% for detection and localisation of CIED infections and reliably excluded CIED infection during a febrile episode and sepsis with 95% negative predictive value.20 These imaging modalities are helpful particularly in complex cases where the diagnosis is not readily determined by physical examination, blood cultures and TEE. Limitations of these tests include the high costs and lack of reimbursement by the Centers for Medicare and Medicaid Services especially with PET/CT imaging, lack of availability at some centres and time-consuming.
Not uncommonly, patients with a CIED infection may present with bacteraemia and no signs or symptoms of infection at the generator-pocket site. Moreover, haematogeneous seeding of the CIED may occur from a remote source of infection. However, not all patients with a CIED and bacteraemia have an underlying CIED infection and thus, DeSimone and Sohail11 21 proposed an algorithm to assist in clinical decision-making based on several factors including the type of microorganism identified on blood cultures, duration and source of bacteraemia, type of CIED and number of device-related procedures (figure 2). Misdiagnosis of CIED infection impacts patient morbidity and mortality, while removal of a non-infected device results in unnecessary risk and costs associated with device removal and replacement.
Management of CIED infection
Superficial infection at the generator-pocket site without device involvement can be treated with 7–10 days of oral antibiotic therapy with antistaphylococci activity.9 In all other scenarios where infection involves the device, removal of the entire system is recommended as relapse rates are high in cases of hardware retention.9 12 Empiric antibiotic therapy should target staphylococcal species particularly vancomycin, until identification susceptibility testing of the infecting pathogen.
Blood cultures should be obtained following complete device removal, and the duration of therapy is based on the causative organism, the presence and duration of bloodstream infection, and associated complications such as valvular endocarditis, septic thrombophlebitis or osteomyelitis.12 For generator-pocket site infection, antibiotic therapy should be 10–14 days, while patients with bloodstream infections should have at least 14 days of antibiotic therapy, and for those with a complicated infection, duration of therapy should be 4–6 weeks.9 12 Adequate debridement and control of infection should be achieved at all sites before reimplantion of a new device and re-evaluation for continued need of the device by an electrophysiologist should be performed before new device placement.12
CIED device removal
Complete CIED removal encompasses removal of the pulse generator and the connecting leads to the myocardium. Fibrotic anchoring of the leads to the vasculature and the myocardium makes lead removal often a challenging task. The process of lead removal without the use of any specialised tools is called as lead explant procedure. Lead extraction is the removal of a lead implanted over a year or use of specialised tools to provide additional tensile support (locking stylets) and to break adhesions (mechanical, radiofrequency or laser energy) during the procedure.11 Multiple venous access sites are commonly used during the procedure for applying traction and counter traction. Several factors related to patient, lead and operator associated with adverse outcomes from the procedure are listed in box 2. Lead extraction procedures should be performed in facilities with imaging (transoesophageal echocardiography), haemodynamic monitoring and emergency backup cardiac surgery for resuscitation and repair of tears (figure 3). The risk of major complication including death is under 2%. After the hardware is removed, the pocket is debrided to remove non-viable tissue (figures 4 and 5). A drain or a vacuum-assisted device is commonly paced to aide wound healing. The wound is eventually let to heal by primary or secondary intention. A continuous quality improvement programme and a team approach are essential for optimal outcomes following device extraction procedures. Recent advances including deploying a superior vena cava (SVC) occlusion balloon were shown to improve operative mortality from the extraction procedure.22
Factors associated with adverse procedural outcomes following lead extraction
Lower body mass index.
Haematological derangements like anaemia, thrombocytopaenia and coagulopathy.
Reduced ejection fraction and advanced heart failure.
Prior cardiac surgery.
Dual coil defibrillation leads.
Coils without backfill that allow ingrowth of scar tissue.
Passive fixation compared with active fixation mechanism.
Certain lead designs.
Operator volume and outcomes.
Cohesive team dynamics.
The optimal timing of reimplantation of a new CIED after removal of an infected CIED is unknown. The replacement device should not be ipsilateral to the extraction site.9 In cases where the infection involved the pocket generator or lead erosion, reimplantation could be considered when blood cultures remain negative for 72 hours, and adequate debridement is achieved. If initial blood cultures were positive and no evidence of valve vegetation, reimplantation could be considered if repeat blood cultures are negative for 72 hours. If there is evidence of valve vegetation on TEE, then reimplantation of the device can be considered after 14 days of first negative blood cultures.9 12
There is a subset of patients with multiple comorbidities or other problems that preclude removal of an infected CIED and consideration of long-term suppressive antibiotic therapy should be provided under the discretion of an infectious diseases specialist.12 A 10-year retrospective study at the Mayo Clinic described a group of 48 patients with a retained infected CIED and placed on chronic antibiotic suppression. Tan et al 12 reported at 1 month after hospitalisation, 25% of patients had died and of those who survived, 18% relapsed within 1 year.
Technological advances over time have resulted in miniaturisation of CIED. Although techniques have been described, the optimal management of intravascular portions of an infected miniaturised CIED system (leadless pacemakers) is currently not well defined.23 Embolism a right-sided mobile echogenic mass to the pulmonary vasculature or paradoxical embolism through a patent foramen ovale to the cerebral circulation may result in undesirable consequences.24 Mobile fibrotic sleeves are often seen after lead extractions are referred to as ‘ghosts’.25 The optimal management of epicardial leads in CIED infection needs to be evaluated.26 Most immunocompetent patients tolerate leaving leads in the epicardial space without any dire consequences. Retained suture sleeves and lead fragments are a source of recurrent bacteraemia, and every attempt should be made for complete removal of intravascular hardware in CIED infection. Hybrid approaches (surgical and percutaneous), alternate approaches involving lateral thoracotomy or minimally invasive surgery, mediastinoscopy for vascular tear monitoring should be considered in high-risk patients. Occasionally in very high-risk patients, surgical debridement of the pocket with antibiotic infusion through a closed irrigation system should be considered.
CIED infections are associated with significant morbidity and mortality. A team-based approach is essential for appropriate diagnosis, management and follow up for optimal outcome. Prevention of CIED infections is paramount, and once infection develops, targeted antibiotic therapy and complete device removal are key features of patient management.
Cardiac implantable electronic device (CIED) infections are increasing over time and are associated with significant morbidity, mortality and health care expenses.
Complete CIED system removal is necessary for adequate treatment of infection. Lead extraction performed by an experienced team is associated with low rate of adverse events.
CIED infection management encompasses the continuum of prevention, accurate diagnosis of infection, management of infection along with the safe removal of the entire system, reimplantation and ongoing risk modification.
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Contributors DCD: drafting of the manuscript. MRS: review and Critique. SKM: review and overall content guarantor.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors
Competing interests None declared.
Provenance and peer review Commissioned; externally peer reviewed.
Patient consent for publication Not required.
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