Cardiovascular Implantable Electronic Device Infections: Compiling the Evidence

Disclosure: None.
Pub Date: Monday, January 4, 2010
Author: Muhammad R. Sohail, MD

Baddour LM, Epstein AE, Erickson CC, et al; on behalf of the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Lifelong Congenital Heart Disease and Heart Health in the Young; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; and the Interdisciplinary Council on Quality of Care and Outcomes Research. Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the American Heart Association. Circulation 2010. Published online before print January 4, 2010. 10.1161/CIRCULATIONAHA.109.192665.

The last two decades have witnessed a dramatic rise in implantation of cardiovascular implantable electronic devices (CIED) for management of numerous life-threatening cardiac rhythm disorders as well as nonarrhythmic conditions such as heart failure and chronotropic incompetence. This surge in device placement was fueled by advances in device manufacturing and programming coupled with safer implantation techniques and a number of randomized clinical trials demonstrating superiority of implanted cardiac devices over pharmacologic therapy alone.[1] One recent survey indicated that there was almost a 50% increase in the rate of CIED (including permanent pacemakers [PPMs] and implantable cardioverter-defibrillators [ICDs]) implantation between 1991 and 2003.[2] Unfortunately, escalation in device implantation has been accompanied by a disproportionate rise in the rate of CIED infections.[3,4] This disturbing trend led to several investigations exploring the epidemiology, pathogenesis, risk factors, and optimal management strategies for these complicated and potentially life-threatening infections.[5] An updated scientific statement from American Heart Association (AHA), published online ahead of print on January 4, 2010 in Circulation [6], reviews the current state of knowledge regarding CIED infections and provide guidance to clinicians on evidence-based management of CIED infections. These recommendations are rated and categorized based on strength of the scientific evidence and risk-benefit ratio.

Risk factors for CIED infection were the subject of some recently published investigations.[7,8] Perhaps the most studied and validated risk factor for device infection is the lack of perioperative antibiotic prophylaxis.[9,10] An earlier meta-analysis of randomized trials demonstrated a protective effect of antimicrobial administration at the time of CIED implantation.[10] A subsequent case-control study of clinical predictors associated with PPM infection mirrored these findings.[8] However, despite mounting evidence, many centers have failed to achieve 100% adherence to antibiotic prophylaxis and some uncertainty has lingered on regarding efficacy of this practice. For skeptics, a recent prospective, randomized, double-blinded, placebo-controlled, clinical trial [9] should provide definitive evidence regarding the protective effect of antibiotic prophylaxis before CIED implantation. In this study, a single dose of cefazolin preoperatively resulted in an estimated 80% drop in the adjusted 6-month risk of CIED infection. The rate of device infection was 0.64% for 314 patients in the cefazolin group compared with 3.28% in 335 patients in the control cohort (p = 0.016). Authors of the scientific statement have recognized the strength of evidence for primary prophylaxis of CIED infection by classifying it as a Class IA recommendation. However, the panel has acknowledged that there are no good data to support the beneficial effect of secondary prophylaxis in patients with implanted devices, and this practice is discouraged.

The impact of device features, implantation conditions, and host-related factors on subsequent risk of CIED infection have also been evaluated in a number of recent studies.[7,8,11-13] However, investigators in these studies have either concentrated on PPM alone [8] or combined cases of PPMs and ICDs in a single category.[7,11] Considering that recent epidemiologic investigations have demonstrated a considerably higher rate for ICD infection as compared with that for PPMs [2,3], future studies should analyze risk factors for ICD infection as a separate group. Whether cardiac resynchronization therapy devices constitute a third group that deserves specific attention is currently being discussed.

The diagnosis of CIED infection is more obvious in patients with inflammatory findings at generator pocket consistent with infection. In contrast, a diagnosis of CIED infection is difficult when there is blood stream infection, but no other discernible clinical or echocardiographic evidence of CIED involvement. This is particularly true in cases of Staphylococcus aureus bacteremia (SAB) in which CIED infection may be present in up to 50% of cases.[14,15] Authors of the current AHA statement recommend removal of CIED in such cases if a patient has no other identifiable source of SAB, has persistent bacteremia for >24 hours, if the infected device is an ICD, and if SAB manifests within 3 months of device implantation. However, these recommendations are based on smaller case series, and larger prospective studies are needed to optimally define the subgroup of SAB patients who have CIED infection but no pocket site or echocardiographic features of infection. Hopefully, ongoing investigations, such as Multicenter Electrophysiologic Device Infection Cohort that is being funded by the AHA, will help explicate the optimal management of patients with SAB and an implanted cardiac device. Novel data presented at the most recent Scientific Sessions of AHA [16] suggest that CIED infection in patients with coagulase-negative staphylococcal bacteremia appears to be analogous to SAB. Interestingly, the likelihood of underlying device infection was higher if coagulase-negative staphylococcal bacteremia was acquired in the community setting as compared with that nosocomial acquisition. Lastly, CIED infections in patients with gram-negative bacteremia and no ostensible evidence of device infection are uncommon.[17]

Perhaps the most valuable aspect of these guidelines for practicing clinicians are the recommendations for management of CIED infections. Although a subject of debate in the past, a consensus has emerged that infected devices need to be fully explanted even if the infection is ostensibly limited to the generator pocket.[18] The statement also incorporates detailed guidelines regarding the use of echocardiography and optimal duration of antimicrobial therapy for different clinical manifestations of CIED infection. In addition, the expert panel has reviewed germane data regarding the association between the size of the lead vegetation and the risk of pulmonary embolization. In general, data from our institution [18,19] and others [20] suggest that most transvenous leads can be removed percutaneously irrespective of the diameter of the lead vegetation. Although fragments of lead vegetations frequently embolize to lungs during percutaneous removal, clinical repercussions of such events are rare.[19]

What is the optimal waiting period following infected device extraction before implanting a replacement device? Authors of the scientific statement have emphasized, and rightly so, the need to assess the necessity of ongoing CIED therapy before a new device is implanted. It is important to recognize that up to one-third of these patients may not require a replacement device.[18] As a general rule, a replacement device can be implanted once adequate debridement of an infected generator pocket has been achieved and repeat blood cultures after removal of infected device are negative for 72 hours.[5] Although some centers have successfully performed same-day reimplantation for cases in which infection is limited to the generator pocket and admission blood cultures are negative.[21,22] The AHA panel has advocated a more conservative approach outlined above. More data are needed before same-day reimplantation can be endorsed as a well-accepted alternative to standard practice of waiting for 48 to 72 hours before implanting a new device.

In conclusion, the writing group of the new CIED infections guidelines [6] should be congratulated for providing a thorough and systemic review of the published literature with cogent and practical advice to clinicians for management of CIED infections. The audience for the guidelines is broad and includes electrophysiologists, general cardiologists, surgeons, infectious diseases physicians, internists, and allied health staff involved in providing care for patients with CIED. Although these guidelines will serve to bring some practitioners up-to-speed with the current evidence regarding CIED infections, they will also encourage others to follow a more standardized approach to their often complex management. Considering the number of unanswered questions and several ongoing investigations regarding the topic of CIED infections, the guidelines will likely require subsequent revision in the not too distant future; I am confident that the AHA’s Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease will be ready for the task.

1. Epstein AE, Dimarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for device-based therapy of cardiac rhythm abnormalities. Heart Rhythm 2008;5(6):e1-62.
2. Voigt A, Shalaby A, Saba S. Rising rates of cardiac rhythm management device infections in the United States: 1996 through 2003. J Am Coll Cardiol 2006;48(3):590-591.
3. Uslan DZ, Sohail MR, St Sauver JL, et al. Permanent pacemaker and implantable cardioverter defibrillator infection: a population-based study. Arch Intern Med 2007;167(7):669-675.
4. Cabell CH, Heidenreich PA, Chu VH, et al. Increasing rates of cardiac device infections among Medicare beneficiaries: 1990-1999. Am Heart J 2004;147(4):582-586.
5. Sohail MR, Wilson WR, Baddour LM. Infections of nonvalvular cardiovascular devices. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases, Vol. I. Philadelphia: Churchill Livingstone/Elsevier, 2010:1127-1142.
6. Baddour LM. Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the American Heart Association, endorsed by the Heart Rhythm Society. Circulation 2010 (in press).
7. Klug D, Balde M, Pavin D, et al. Risk factors related to infections of implanted pacemakers and cardioverter-defibrillators: results of a large prospective study. Circulation 2007;116(12):1349-1355.
8. Sohail MR, Uslan DZ, Khan AH, et al. Risk factor analysis of permanent pacemaker infection. Clin Infect Dis 2007;45(2):166-173.
9. de Oliveira JC, Martinelli M, Nishioka SA, et al. Efficacy of antibiotic prophylaxis before the implantation of pacemakers and cardioverter-defibrillators: results of a large, prospective, randomized, double-blinded, placebo-controlled trial. Circ Arrhythm Electrophysiol 2009;2(1):29-34.
10. Da Costa A, Kirkorian G, Cucherat M, et al. Antibiotic prophylaxis for permanent pacemaker implantation: a meta-analysis. Circulation 1998;97(18):1796-1801.
11. Bloom H, Heeke B, Leon A, et al. Renal insufficiency and the risk of infection from pacemaker or defibrillator surgery. Pacing Clin Electrophysiol 2006;29(2):142-145.
12. Al-Khatib SM, Lucas FL, Jollis JG, et al. The relation between patients’ outcomes and the volume of cardioverter-defibrillator implantation procedures performed by physicians treating Medicare beneficiaries. J Am Coll Cardiol 2005;46(8):1536-1540.
13. Lekkerkerker JC, van Nieuwkoop C, Trines SA, et al. Risk factors and time delay associated with cardiac device infections: Leiden device registry. Heart (British Cardiac Society) 2009;95(9):715-720.
14. Uslan DZ, Dowsley TF, Sohail MR, et al. Cardiovascular implantable electronic device infection in patients with Staphylococcus aureus bacteremia. Pacing Clin Electrophysiol 2009 Sep 30 [Epub ahead of print].
15. Chamis AL, Peterson GE, Cabell CH, et al. Staphylococcus aureus bacteremia in patients with permanent pacemakers or implantable cardioverter-defibrillators. Circulation 2001;104(9):1029-1033.
16. Madhavan M, Sohail MR, Friedman PA, et al. Abstract 2490: Cardiovascular implantable electronic device infection in patients with non-Staphylococcus aureus gram-positive coccal bacteremia. Circulation 2009;120(18_MeetingAbstracts):S648-c-9.
17. Uslan DZ, Sohail MR, Friedman PA, et al. Frequency of permanent pacemaker or implantable cardioverter-defibrillator infection in patients with gram-negative bacteremia. Clin Infect Dis 2006;43(6):731-736.
18. Sohail MR, Uslan DZ, Khan AH, et al. Management and outcome of permanent pacemaker and implantable cardioverter-defibrillator infections. J Am Coll Cardiol 2007;49(18):1851-1859.
19. Sohail MR, Uslan DZ, Khan AH, et al. Infective endocarditis complicating permanent pacemaker and implantable cardioverter-defibrillator infection. Mayo Clin Proc 2008;83(1):46-53.
20. Field ME, Jones SO, Epstein LM. How to select patients for lead extraction. Heart Rhythm 2007;4(7):978-985.
21. Nandyala R, Parsonnet V. One stage side-to-side replacement of infected pulse generators and leads. Pacing Clin Electrophysiol 2006;29(4):393-396.
22. Kim SS, Philips B, Smelley M, et al. Abstract 2491: Same-day device reimplantation following cardiovascular implantable electronic device extraction for isolated pocket infection. Circulation 2009;120(18_MeetingAbstracts):S649.

-- The opinions expressed in this commentary are not necessarily those of the editors or of the American Heart Association --