Renal Disease in Patients Undergoing Cardiac Implantable Electronic Device Extraction for Infectious and Non-infectious Indications

DOI: 10.19102/icrm.2015.060503

¹CHRISTOPHER A. HEALY, MD and ²ROGER G. CARRILLO, MD

¹Divisions of Cardiology, University of Miami Miller School of Medicine, Miami, FL

²Division of Cardiothoracic Surgery, University of Miami Miller School of Medicine, Miami, FL

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ABSTRACT. The aim of this paper was to examine the prevalence and severity of chronic kidney disease (CKD) among patients undergoing cardiac implantable electronic device (CIED) extraction, for either infectious or noninfectious indications. We evaluated all patients who underwent CIED extraction from January 2004 to May 2013. Indications for device extraction were determined to be either infectious or non-infectious. Patients were classified into CKD Stages I–V based on the National Kidney Foundation Dialysis Outcomes Quality Initiative guidelines. One thousand and seventeen patients underwent CIED extraction, 661 for infectious indications and 356 for non-infectious indications. The prevalence and severity of CKD were as follows in the infectious and non-infectious groups, respectively: CKD Stage I, 11.2% and 17.4%; CKD Stage II, 35.4% and 42.1%; CKD Stage IIIA, 20.4% and 17.4%; CKD Stage IIIB, 11.3% and 12.1%; CKD Stage IV, 4.8% and 2.8%; and CKD Stage IV, 15.7% and 5.1%. Overall, severe renal dysfunction (≥CKD Stage IIIB) was present in 31.9% of patients in the infectious group and 19.9% of patients in the non-infectious group. A significant proportion of patients who undergo CIED extraction, including >30% of those referred for infectious indications, have advanced renal failure.

KEYWORDS. cardiac implantable electronic device, device extraction, device infection.

Dr. Carrillo has the following industry relationships: consultant for Spectranetics, Boston Scientific, Sorin, Medtronic, St. Jude Medical, and Biotronik; speaker’s bureau for Medtronic, St. Jude Medical, and Sorin; and grant/research support from St. Jude Medical and Medtronic.
Manuscript received February 25, 2015, Final version accepted March 24, 2015.

Address correspondence to: Chris Healy, Division of Cardiology, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL 33136. E-mail: healycr@gmail.com

Introduction

Cardiac implantable electronic device (CIED) leads can require extraction for numerous reasons. These reasons include infection, malfunction, pain, and venous occlusion. Perhaps the most feared of these indications is infection, because it is associated with significant morbidity and mortality.¹ Despite the routine use of sterile techniques and peri-implant antibiotics, CIED infection rates continue to rise, with a significant financial cost to the health-care system as a whole.² Much has been published with regard to the risk factors for CIED infection; impaired renal function has been shown to be an independent risk factor for CIED infection.^3–5 It has also been previously reported that patients with renal insufficiency who develop CIED infection may be at increased risk of poor outcomes.^4–6 In this study, we set out to determine the prevalence and severity of renal insufficiency in patients referred for CIED extraction for infectious and non-infectious indications and the impact this may have on extraction outcomes.

Methods

Data were prospectively gathered on 1,017 consecutive CIED patients undergoing device extraction (from January 2004 to May 2013) and included in this analysis. All patients were referred to the University of Miami Hospital, a tertiary referral center for device extraction. The majority of patients did not undergo initial device implantation at the University of Miami Hospital. Demographic characteristics and reasons for device removal were assessed, and indication for device removal was categorized as either infectious or non-infectious. Serum creatinine was measured upon hospital admission, and the estimated glomerular filtration rate (eGFR), as determined by the Modification of Diet in Renal Disease (MDRD) equation, was recorded for all patients in order to quantify the degree of chronic kidney disease (CKD). The patients were categorized into CKD stages I–V based on the National Kidney Foundation Dialysis Outcomes Quality Initiative guidelines.⁷

Institutional Review Board approval was obtained for this study. All study procedures were carried out in accordance with the Declaration of Helsinki regarding research involving human subjects. The summary statistics of continuous variables were reported as mean±standard deviation.

Infectious and non-infectious indications were determined as described in the 2009 Heart Rhythm Society guidelines on transvenous lead extraction, with infectious indication defined as the presence of at least one of the following: valvular endocarditis, lead endocarditis, pocket abscess, device erosion, skin adherence, chronic draining sinus, occult Gram-positive bacteremia, or occult Gram-negative bacteremia. The definition of major complications was also based on these guidelines.⁸

Results

A total of 1,017 consecutive patients underwent device removal between January 2004 and May 2013. Six hundred and sixty-one patients (65.0%) had their device removed because of infection. Three hundred and fifty-six patients (35.0%) had their device removed for non-infectious reasons. Demographic characteristics revealed that patients undergoing device extraction for infectious indications were more likely to have hypertension (87.8 versus 77.7%, p<0.0001), diabetes (45.8 versus 35.5%, p=0.001), and coronary artery disease (64.4 versus 50.3%, p<0.0001). Meanwhile, patients undergoing device extraction for non-infectious indications were more likely to suffer from heart failure (78.7 versus 59.6 %, p<0.0001) (Table 1).

Of the 661 patients in the infectious group and the 356 patients in the non-infectious group, 11.2% (74) and 17.4% (62) had CKD Stage I (p=0.009), 35.4% (234) and 42.1% (150) had CKD Stage II (p=0.04), 20.4% (135) and 17.4% (62) had CKD Stage IIIA (p=0.24), 11.3% (75) and 12.1% (43) had CKD Stage IIIB (p=0.73), 4.8% (32) and 2.8%¹⁰ had CKD Stage IV (p=0.09), and 15.7% (104) and 5.1% (18) had CKD Stage V (p<0.0001) (Figures 1 and 2). Overall, severe renal dysfunction (≥CKD Stage IIIB) was present in 31.9% (211) of the patients in the infectious group and 19.9% (71) of the patients in the non-infectious group (p<0.0001, Figure 3). Incomplete data on renal function were present for 1.1% (7) of the patients in the infectious group and 3.1% (11) of the patients in the non-infectious group.

Discussion

This study revealed a high prevalence of renal dysfunction among patients undergoing CIED extraction for both infectious and non-infectious indications. Advanced renal failure (presence of CKD Stages IIIB, IV, or V) was present in 31.9% and 19.9% of the patients in the infectious and non-infectious groups, respectively (Figure 3). Diabetes, hypertension, and heart failure were also quite prevalent in this study population (Table 1). As these are known risk factors for CKD, this may explain the high prevalence of CKD in these patients. This observation is important for at least two reasons.

First, multiple reports have examined the presence of renal dysfunction as a risk factor for the development of CIED infection.^3–5 It has also been shown that not only the presence but also the severity of renal dysfunction is associated with an increased risk of CIED infection.⁴ A number of previous studies have primarily focused on the presence or absence of CKD and/or end-stage renal disease (ESRD).^3,5,16 In this study, renal function was stratified by the stage of CKD. This is important because CKD stage is calculated by determining eGFR with the MDRD equation, which takes into account age, race, and gender.⁷ Patients with CKD Stages I (eGFR≥90 ml/min/1.73 m²) and II (eGFR 60–90 ml/min/1.73 m²) have relatively mild renal dysfunction. Meanwhile, patients with CKD Stage IIIB (eGFR 45–30 ml/min/1.73 m²), IV (eGFR 30–15 ml/min/1.73 m²), and V (eGFR ≤15 ml/min/1.73 m²) have more advanced renal dysfunction. It has been previously reported that the annual mortality rates for patients with stage IIIB, IV, and V CKD are as high as 15%, 20%, and 30%, respectively.⁹ It is reasonable to speculate that the significant risk of mortality associated with advanced renal dysfunction is further compounded by the presence of multiple comorbidities as well as CIED infection present in a significant number of patients referred for device extraction.

CIED infection is a serious complication in all patients, regardless of renal function, and is associated with significant morbidity and mortality.^10–12 Aggressive parenteral antibiotic therapy and complete device removal should be recommended for any patient who can tolerate the procedure.¹³ Device extraction carries serious risks, including death. However, it has been shown that a delay of device removal carries an even higher risk of mortality.¹¹

The second reason why high rates of CKD among patients undergoing CIED extraction are so important has to do with the fact that the vast majority of CIED leads travel through the central veins. This predisposes patients with CIED leads to central venous stenosis (CVS).¹⁴ CVS may not present a problem in patients who are not receiving dialysis. However, in those who require dialysis, CVS can be a life-threatening condition. In our study, 31.9% and 19.9% of patients in the infectious and non-infectious groups had advanced CKD. A significant proportion of these patients will likely have their renal dysfunction progress to the point that they will need dialysis therapy and require the creation of arteriovenous (AV) access. CVS can significantly limit options for AV access, a prerequisite for life-saving hemodialysis. In this regard, the high prevalence of renal disease in patients who require CIED therapy presents a unique problem.

Prevention of infection and CVS related to CIED therapy is challenging, and few options exist to effectively reduce rates of either of these serious complications. There have been reports of hemodialysis patients with epicardial devices developing bacteremia without resulting CIED infection.¹⁵ Epicardial systems may be an option for some patients with ESRD, because this is a group of patients in whom both CIED use and infection are on the rise.¹⁶ Epicardial systems can also be used to help prevent CVS as well. It should be noted, though, that implantation of an epicardial system requires a significantly more invasive procedure. The subcutaneous implantable cardioverter-defibrillator is also an attractive option as it may decrease rates of device infection and CVS by avoiding the central venous system altogether.

Limitations

The current study is limited by the fact that only CIED patients undergoing device removal were included, and by the retrospective nature of the study design.

Conclusion

To the best of our knowledge, this is the largest report evaluating the prevalence and severity of renal dysfunction in patients undergoing CIED extraction. It is also the first report comparing the prevalence and severity of CKD in patients undergoing CIED extraction for infectious and non-infectious indications. This analysis demonstrates that a large number of patients undergoing CIED extraction have an advanced degree of renal failure and that the prevalence is significantly higher in those patients referred for infectious indications.

References

1. Athan E, Chu VH, Tattevin P, et al. Clinical characteristics and outcome of infective endocarditis involving implantable cardiac devices. JAMA 2012;16:1727–1735. [CrossRef] [PubMed]
2. Greenspon AJ, Patel JD, Lau E, et al. 16-year trends in infection burden for pacemakers and implantable cardioverter-defibrillators in the United States 1993 to 2008. J Am Coll Cardiol 2011;10:1001–1006. [CrossRef] [PubMed]
3. Le KY, Sohail MR, Friedman PA, et al. Clinical predictors of cardiovascular implantable electronic device-related infective endocarditis. Pacing Clin Electrophysiol 2011;4:450–459. [CrossRef] [PubMed]
4. Tompkins C, McLean R, Cheng A, et al. End stage renal disease predicts complications in pacemakers and ICD implants. J Cardiovasc Electrophysiol 2011;10:1099–1104. [CrossRef] [PubMed]
5. Uslan DZ, Gleva MJ, Warren DK, et al. Cardiovascular implantable electronic device replacement infections and prevention: results from the REPLACE Registry. Pacing Clin Electrophysiol 2012;1:81–87. [CrossRef] [PubMed]
6. Habib A, Le KY, Baddour LM, et al. Predictors of mortality in patients with cardiovascular implantable electronic device infections. Am J Cardiol 2013;6:874–879. [CrossRef] [PubMed]
7. National Kidney Foundation: K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;2:S1–266. [PubMed]
8. Wilkoff BL, Love CJ, Byrd CL, et al. Transvenous lead extraction: Heart Rhythm Society expert consensus on facilities, training, indications, and patient management. Heart Rhythm 2009;7:1085–1104. [CrossRef] [PubMed]
9. Patel UD, Young EW, Ojo AO, Hayward RA. CKD progression and mortality among older patients with diabetes. Am J Kidney Dis 2005;3:406–414. [CrossRef] [PubMed]
10. Greenspon AJ, Prutkin JM, Sohail MR, et al. Timing of the most recent device procedure influences the clinical outcome of lead-associated endocarditis results of the MEDIC (Multicenter Electrophysiologic Device Infection Cohort). J Am Coll Cardiol 2012;7:681–687. [CrossRef] [PubMed]
11. Le KY, Sohail MR, Friedman PA, et al. Impact of timing of device removal on mortality in patients with cardiovascular implantable electronic device infections. Heart Rhythm 2011;11:1678–1685. [CrossRef] [PubMed]
12. Sohail MR, Uslan DZ, Khan AH, et al. Infective endocarditis complicating permanent pacemaker and implantable cardioverter-defibrillator infection. Mayo Clin Proc 2008;1:46–53. [CrossRef] [PubMed]
13. 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;3:458–477. [CrossRef] [PubMed]
14. Asif A, Salman L, Carrillo RG, et al. Patency rates for angioplasty in the treatment of pacemaker-induced central venous stenosis in hemodialysis patients: results of a multi-center study. Semin Dial 2009;6:671–676. [CrossRef] [PubMed]
15. Asif A, Carrillo R, Garisto JD, et al. Epicardial cardiac rhythm devices for dialysis patients: minimizing the risk of infection and preserving central veins. Semin Dial 2012;1:88–94. [CrossRef] [PubMed]
16. Charytan DM, Patrick AR, Liu J, et al. Trends in the use and outcomes of implantable cardioverter-defibrillators in patients undergoing dialysis in the United States. Am J Kidney Dis 2011;3:409–417. [CrossRef] [PubMed]