Editor’s Note: This article is based on Athan E, Chu VH, Tattevin P, et al. Clinical Characteristics and Outcome of Infective Endocarditis Involving Implantable Cardiac Devices. JAMA 2012; 307:1727-1735.

Background

Over 4 million patients underwent permanent pacemaker or implantable cardioverter-defibrillator (ICD) implantation between 1993 and 2008. During this period there was a 210% increase in the incidence of cardiac device infection, a costly, morbid, and sometimes lethal complication of device implantation. Cardiac device infective endocarditis (CDIE) occurs in about 10-20% of cardiac device infections and is a frequently severe complication that follows the initial skin contamination, generally at the time of implant, and ensuing subcutaneous pocket infection. The severity and frequent complexity of managing CDIE prompted this study, which assessed characteristics and outcome of CDIE, particularly in the context of health care-associated infection.

Methods

Data for this study were extracted from the International Collaboration of Endocarditis-Prospective Cohort Study (ICE-PCS), a Duke Clinical Research Institute project which enrolled 3284 patients from 61 centers worldwide between 2000 and 2006.¹ Possible or definite infective endocarditis based on modified Duke criteria² was required for inclusion in ICE-PCS. In their analysis, Athan et al.³ assigned a diagnosis of CDIE only to patients with a first episode of definite infective endocarditis who had echocardiography-confirmed valvular or lead vegetations, culture- or histology-confirmed bacterial infection of a vegetation or device lead, or who met Duke criteria for infective endocarditis and had a cardiac implantable device. In-hospital and one-year mortality were the principal outcomes of interest.

Results

Among 2760 total patients with definite infective endocarditis, 177 (6.4%) were diagnosed with CDIE. These included 152 (85.9%) patients with a permanent pacemaker, 21 (11.9%) with an ICD, and 4 (2.3%) with an unspecified device. Positive blood cultures were seen in 149 (84.2%) patients. Staphlococcus aureus was found in 35.0%, and coagulase-negative staphlococci were found in 31.6%. Echocardiography-confirmed vegetations of any kind were seen in 159 patients (89.8%), and vegetations on a cardiac device lead were seen in 135 patients (76.3%). Concurrent valve infection was seen in 66 (37.3%) patients, with an overwhelming predominance of tricuspid valve infections (65%), but also mitral (26%) and aortic involvement (9%). One case of pulmonic valve infection was noted. The presence of valve involvement in CDIE increased the likelihood of in-hospital mortality by an odds ratio of 3.31.

In 141 of these 177 patients (79.7%), system removal (i.e., extracting the device and leads) was performed. The in-hospital mortality rate of CDIE patients in this study was 12.8% when the system was removed and 23.5% when it was not. The size of the study, however, was too small to demonstrate a definitive association between system extraction and in-hospital mortality reduction. A clear mortality difference, however, was observed at one year. Removal of the lead and generator during the index hospitalization in patients with CDIE was associated with a 52% reduction in relative risk of mortality at one year compared to treatment without hardware removal. Even when hardware was removed, the presence of valve infection at the initial hospitalization worsened survival compared to the absence of valve infection.

Particular attention in this study was given to health care-associated CDIE, defined as infective endocarditis occurring in a patient who was hospitalized for more than 48 hours before signs or symptoms of endocarditis emerged (nosocomial health care-associated infection) or if such signs or symptoms developed in patients with significant health care interventions outside a hospital and before any hospitalization (non-nosocomial health care-associated infection). Among the 177 CDIE patients in this study, 81 (45.8%) were found to have health care-associated infection, which were associated with intravascular access and hemodialysis.

Finally, comparisons were made between patients with CDIE and those followed in ICE-PCS who had staphylococcal endocarditis but no implantable cardiac device. CDIE patients were more likely to be older, diabetic, male, and have a delayed presentation. They also had less in-hospital mortality (18.6%) compared to patients without cardiac devices who had native-valve (22.4%) or prosthetic-valve (31.3%) endocarditis due to staphylococcus.

Discussion

The risk of infection with implantable cardiac devices is clearly understood by practitioners, and it is among the principal hazards articulated to patients during the informed consent process for device implantation. With increasing numbers of device implants worldwide, the number of cardiac device infections continues to grow. This study highlighted particular concerns when simple cardiac device infection progresses to the more serious CDIE.

The source material for the work is a widely cited registry, the ICE-PCS database, which provided a valuable means to deepen understanding of a significant clinical problem within the limits of an observational retrospective study. A feature of ICD-PCS which may limit its applicability is the fact that participation in the registry was voluntary, so it may not reflect a true population sample. In addition, many data points were simply not available, including details on the timing and method of cardiac device system removal when this intervention was performed.

Nonetheless, this study corroborated previous, broadly reported observations, including staphylococcal infection being the predominant type of CDIE,^4,5 poorer outcomes when infections were health care-associated,⁶ and the critical importance of device system extraction in reducing mortality in cardiac device infections, particularly CDIE.⁷ One unique finding in this study was that patients with CDIE, including the subset with health care-associated CDIE, exhibited a higher prevalence of infection with methicillin-resistant Staphlococcus aureus (MRSA). Broad use of first-generation cephalosporins for prophylaxis at the time of implant was suggested as a practice that might merit reconsideration in light of these data.

CDIE is a significant risk of implantable device therapy, and this study underscores the need for attentiveness to this complication and to the relevant measures that can be taken, including optimal skin preparation pre-procedure, correct dosing and administration of antibiotic prophylaxis, and great caution when subjecting a post-device implantation patient to any further invasive, especially intravascular, procedure.

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References

1. Cabell CH, Abrutyn E, et al. Progress toward a global understanding of infective endocarditis: early lessons from the International Collaboration on Endocarditis investigation. Infect Dis Clin North Am 2002; 16:255-272.
2. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000; 30:633-638.
3. Athan E, Chu VH, Tattevin P, et al. Clinical Characteristics and Outcome of Infective Endocarditis Involving Implantable Cardiac Devices. JAMA 2012; 307:1727-1735.
4. Sohail MR, Uslan DZ, et al. Management and outcome of permanent pacemaker and implantable cardioverter-defibrillator infections. J Am Coll Cardiol 2007; 49:1851-1859.
5. Duval X, S Selton-Suty C, Alla F, et al. Endocarditis in patients with a permanent pacemaker: a 1-year epidemiological survey on infective endocarditis due to valvular and/or pacemaker infection. Clin Infect Dis 2004; 39:68-74.
6. Fowler VG Jr, Miro JM, et al. Staphylococcus aureus endocarditis: a consequence of medical progress. JAMA 2005; 293:3012-3021.
7. Baddour LM, Epstein AE, Erickson CC, et al. Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the American Heart Association. Circulation 2010; 121:458-477.

Keywords: Defibrillators, Implantable, Endocarditis, Endocarditis, Bacterial, Pacemaker, Artificial

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