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Cardiac Implantable Electronic Device Removal in Patients with Left Ventricular Assist Device Associated Infections ARUN KRISHNAMOORTHY, M.D.,∗ SEAN D. POKORNEY, M.D., M.B.A.,∗ ROBERT K. LEWIS, M.D., Ph.D.,∗ JAMES P. DAUBERT, M.D.,∗ RUTH A. GREENFIELD, M.D.,∗ DONALD D. HEGLAND, M.D.,∗ CARMELO A. MILANO, M.D.,† JOSEPH G. ROGERS, M.D.,∗ JACOB N. SCHRODER, M.D.,† CHETAN B. PATEL, M.D.,∗ and JONATHAN P. PICCINI, M.D., M.H.S.∗ From the ∗ Divisions of Cardiology; and †Cardiothoracic Surgery, Duke University Medical Center, Durham, North Carolina, USA
CIED Removal in LVAD Infections. Introduction: Heart failure patients with left ventricular assist devices (LVADs) are at risk for infection. Cardiac implantable electronic devices (CIEDs) are commonly present in these patients. The course of infections in patients with an LVAD and a CIED is not well described. Methods and Results: We identified 6 patients with a durable LVAD that underwent CIED removal because of an LVAD associated infection (LVADI). Patient and infection characteristics, management strategy, and clinical outcomes are described. All 6 patients were male, and the mean age was 59.6 years (range 43–72). Four of 6 patients had an ischemic cardiomyopathy, and 3 patients were diabetic. The median creatinine clearance for patients was 40.5 mg/dL (range 19–65). Five of 6 patients had a continuous flow LVAD placed as destination therapy. Four of 6 patients had a previous LVADI managed medically before the current infection leading to CIED removal. The indication for CIED removal was a bloodstream infection in 5 of 6 patients. Three of these patients had potential vegetations identified by echocardiography on device leads. The mean implanted age of the removed leads was 62 months (range 1–179), and 1 of the 6 patients experienced a procedural complication (hematoma) from CIED removal. Four of 6 patients that underwent CIED removal for an LVADI had recurrence of infection. Five of 6 patients died during the initial presentation or from repeat presentation for infection. Conclusion: Despite CIED removal for an LVADI, recurrent infections are common and mortality remains high. (J Cardiovasc Electrophysiol, Vol. 25, pp. 1199-1205, November 2014) artificial cardiac pacing, implantable cardioverter defibrillators, infection, mechanical circulatory support Introduction Implanted medical devices have become common in heart failure patients. Cardiac implantable electronic device (CIEDs) that deliver cardiac resynchronization therapy (CRT), prevent sudden cardiac death (intracardiac defibrillators [ICDs]), and devices combining these tech-
This manuscript was processed by a guest editor. This work was supported by a generous donation from Al Tatum in support of the Duke Lead Extraction Research Program. Carmelo A. Milano reports compensation for participation on a speaker’s bureau and serving as a consultant/advisory board member for Thoratec Corporaton and HeartWare, Inc. Joseph G. Rogers reports serving as a nonpaid consultant to Thoratec Corporation. Chetan B. Patel reports consulting fees from Thoratec Corporation and HeartWare, Inc. Jonathan P. Piccini reports consulting and proctorship for Spectranetics. Other authors: No disclosures. Address for correspondence: Arun Krishnamoorthy, M.D., Division of Cardiology, Duke University Medical Center, 2301 Erwin Road, DUMC 3845, Durham, NC 27710, USA. Fax: 919-681-9842; E-mail: arun. [email protected] Manuscript received 19 January 2014; Revised manuscript received 25 April 2014; Accepted for publication 27 May 2014. doi: 10.1111/jce.12461
nologies (CRT-D) have demonstrated mortality benefits.1-8 In advanced heart failure patients failing optimal medical therapy, left ventricular assist devices (LVADs) are increasingly used as an alternative to cardiac transplantation or as a bridge until a suitable organ becomes available.9-12 Despite the advantages observed with LVAD implantation, infection can complicate LVAD therapy and leads to significant morbidity and mortality.13-15 The optimal management of an infection in the setting of an LVAD remains incompletely defined despite an improved understanding of clinical manifestations and causative microorganisms.15 Moreover, decision making in patients with LVAD associated infections (LVADIs) can be complicated by the presence of a concomitant CIED, as these devices are common in patients who progress to LVAD therapy. Guidelines for the management of an established CIED infection, in the absence of other device hardware, advise complete removal of the CIED.16 However, it is incompletely understood how CIED removal in the case of an LVADI affects the clinical course in these patients. The causative microorganism may have already seeded the LVAD and thus continue to persist on the LVAD as a source of infection. To further understand CIED removals performed for LVADIs, we identified a cohort of LVAD patients at our institution that underwent CIED removal for an infection and describe their clinical and infection characteristics, management strategy, and clinical outcomes.
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Methods Study Cohort Patients who underwent a CIED lead removal for any cause at Duke University Hospital, a tertiary care referral center, between January 1st, 2005, and February 26th, 2012, were identified (n = 528). From this cohort, 10 patients had a lead removal performed after durable LVAD implantation (patients with temporary mechanical support were excluded). Six of these patients were identified as having a CIED removed for the primary indication of an infection associated with a durable LVAD. CIED infections were defined by the 2010 American Heart Association (AHA) guidelines.16 These infections included CIED pocket infections and persistent bloodstream infections (without another obvious source) with or without echodensities noted on indwelling leads. LVADIs were defined by current International Society for Heart and Lung Transplantation criteria.7,17 Such infections did not necessarily result directly from the LVAD, but deserved special consideration because of the presence of the LVAD.7,17 In our patients these LVADIs represented a CIED pocket infection, bloodstream infections, and driveline or LVAD pocket infections. All patients in the cohort were treated with appropriate antibiotic therapy, also per guideline recommendations.16 Patient and infection characteristics, CIED and lead data, management strategy, and clinical outcomes were obtained from comprehensive chart review. The institutional review board of Duke University approved the research study. Lead Removal The lead removals described in our cohort were performed by a percutaneous-transvenous method; 1 patient did undergo both a combination of a percutaneous-transvenous and open surgical lead removal for different leads during the same procedure. Consistent with the Heart Rhythm Society (HRS) Consensus Statement, lead explanation refers to lead removal without the need for specialized equipment and performed just by traction; lead extraction refers to lead removal requiring specialized equipment such as laser sheaths.18-20 Duke Lead Extraction Protocol All patients underwent both electrophysiology and cardiothoracic surgery consultation regarding lead management. Intraoperative care included transesophageal echocardiography pre-, intra-, and postprocedurally. All patients were prepared for a possible CIED extraction and the procedures were performed in the Duke University operating room in conjunction with cardiothoracic surgery, as per the HRS 2009 Consensus Statement recommendations and our institutional protocol.20,21 All patients were prepared for possible median sternotomy. In some of the extractions either a laser sheath (Spectranetics, Colorado Springs, CO, USA) or femoral snare workstation (Cook Medical, Bloomington, IN, USA) was employed to facilitate the extraction. Results Patient Characteristics The baseline characteristics of the cohort are shown in Table 1. The mean age was 59.6 years (range 43–72), all were
male, and 4 of 6 patients had an ischemic cardiomyopathy. All but 1 of the patients had a continuous flow Heartmate II (HMII) device (Thoratec, Inc., Pleasanton, CA, USA) placed as destination therapy. The remaining patient had an extracorporeal pulsatile flow LVAD (Thoratec, Inc.) placed as a bridge to transplant. Infections and Antibiotic Management As shown in Table 2, bloodstream infections represented 5 of the 6 LVADIs leading to CIED removal, and 1 of these patients also had a concurrent driveline infection. The remaining patient had a CIED pocket infection leading to CIED removal. Of the 5 patients with bloodstream infections, 3 had lead echodensities observed on echocardiography. The causative organisms of the bloodstream infections included gram-positive cocci and nosocomial gram-negative bacilli. The time interval from LVAD implantation to CIED removal ranged from 4 days to 31 months. All patients surviving to discharge after CIED removal (n = 4) completed their guideline recommended antibiotic therapy.16 Two patients were placed on chronic antibiotic suppressive therapy due to either a history of or current LVAD driveline infection. In the patients not maintained on chronic antibiotic suppressive therapy, surveillance blood cultures were obtained for a short period after discharge. In 1 case, cultures were followed monthly for 2 months after the CIED removal. In the case of the CIED pocket infection, a single surveillance culture was obtained 1 month after discharge. There were 4 patients who had a history of a prior LVADI managed without CIED removal (if implanted at the time): driveline infection (n = 1), bloodstream infection (n = 1), bloodstream infection and driveline infection (n = 1), and bloodstream infection and LVAD pocket infection (n = 1). The microbiology of these previous LVADIs for each patient was usually not the same as that of the LVADIs leading to CIED removal (n = 3). These infections occurred at a median of 12.5 months prior to CIED removal. CIED Hardware and Procedural Management Table 3 describes the implanted CIED hardware, procedural management, and complications. All of the patients had a defibrillator and 4 of the 6 patients had a CRT-D device. The mean dwell time of the 16 removed leads was 62 ± 42 months (range 1–179). All patients were prepared for a possible lead extraction; 4 patients required laser lead extraction, whereas 2 patients only required traction. After CIED removal (traction) and reintroduction of anticoagulation for the LVAD, 1 patient developed a pocket hematoma that required surgical evacuation. Another procedure (laser sheath) was complicated by retained lead fragments at both the superior vena cava and distal ICD coils. Outcomes Patient outcomes are shown in Table 4. Despite CIED removal, 1 of 3 patients (n = 2) had early recurrence (within 5 months) of bloodstream infection. Each of these patients (patients 1 and 2) died from progressive sepsis. Patient 2 was eventually managed with an LVAD exchange; however, the patient died 1 month after this procedure. This patient had been maintained on chronic oral antibiotic suppressive therapy until the time of his recurrent infection.
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TABLE 1 Patient Characteristics Patient Age at CIED removal Gender Etiology of CM Diabetes mellitus Creatinine clearance (mL/min/1.73 m2 ) BMI (kg/m2 ) LVAD type LVAD indication
1
2
3
4
5
6
77 Male Ischemic Yes 65 25.0 HM2 DT
55 Male Nonischemic No 45 29.2 HM2 DT
47 Male Ischemic Yes 36 40.1 HM2 DT
72 Male Ischemic Yes 33 26.0 HM2 DT
43 Male Nonischemic No 19 34.7 Extracorporeal pulsatile PVAD BTT
64 Male Ischemic No 56 33.6 HM2 DT
CM = cardiomyopathy; BMI = body mass index; LVAD = left ventricular assist device; HM2 = Heartmate 2; PVAD = peripheral ventricular assist device; DT = destination therapy; BTT = bridge to transplant. TABLE 2 Infection Characteristics Patient LVADI leading to CIED removal Microorganism Echocardiogram pre CIED removal Time from LVAD implant to CIED removal Previous LVADIs before CIED removal
1
2
3
4
5
6
BSI
Driveline infection and BSI P. aerguinosa
BSI
BSI
BSI
CIED pocket infection
VRE faecium
ESBL K. pneumonia
MSSA No lead echodensity 4 days
Recurrent LVADI after CIED removal
Amp sensitive No growth Enterococcus Echodensity on RV Echodensity on RA No lead echodensity Echodensity on RA No lead echodensity lead lead lead 23 months 12 months 4 months 4 days 31 months
None
Driveline infection and BSI
Driveline infection
BSI
None
BSI
BSI
BSI
None
None
BSI and pocket infection from prior LVAD Driveline infection and BSI
LVADI = left ventricular assist device associated infection; CIED = cardiac implantable electronic device; BSI = bloodstream infection; MSSA = methicillin sensitive Staphylococcus aureus; VRE = vancomycin resistant Enterococcus; ESBL = extended spectrum beta lactamase; RA = right atrium; RV = right ventricle. TABLE 3 CIED Characteristics and Procedural Details Patient
1
Type of CIED Dual-chamber ICD removed Last generator 13 implant to CIED removal (months) Lead implant to CIED RA and RV 49, removal (months) CS 2 Removal technique Traction Procedural complications
Pocket hematoma requiring surgical evacuation
2
3
4
5
6
CRT-D
CRT-D
Single-chamber ICD
CRT-D
CRT-D
23
40
1
7
1
RV 72, RA and CS 24 Laser sheath
RA and RV 78, CS 76 Laser sheath
RV 1
None
Retained SVC and distal coil
Traction None
RV 179, RA 92, LV 46 Laser sheath and surgical removal of epicardial LV lead None
RA and RV 75, CS 70 Laser sheath None
ICD = intracardiac defibrillator; CRT-D = cardiac resynchronization therapy defibrillator; CS = coronary sinus; LV = left ventricle; SVC = superior vena cava.
In addition, 2 other patients (patients 3 and 6) had recurrent LVADIs at 1 and 2 years post CIED removal and each died soon thereafter from sepsis. Patient 3 had recurrence of infection 1 year after CIED removal despite chronic suppressive therapy for driveline infection. Patient 6 had their CIED originally removed for a CIED pocket infection. Of the 2 remaining patients, patient 5 did not have recurrence of bloodstream infection after CIED removal but died 8 days after the procedure from continued multiorgan failure. Patient 4, also with a bloodstream infection leading to removal of the CIED, remained free of infection and was alive
after 3 years of follow-up. In total, 5 of the 6 patients died of infection, either during the initial presentation or after repeat presentation for infection. Figure 1 provides a timeline of the clinical course of each patient in the cohort, including CIED implantation, all infections, approximate periods of treatment with antibiotics, CIED removal, and subsequent outcomes. Discussion In a small cohort of patients who underwent CIED removal because of an LVADI, we observed that most patients
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TABLE 4 Clinical Outcomes Patient
1
Clinical outcomes
Early recurrence of BSI
Mortality
Died 1 month after CIED removal from sepsis
2
3
4
Recurrence of BSI Single-chamber ICD after 5 months and reimplanted and LVAD exchanged recurrence of BSI after 1 year Died 1 month after Died 4 months after LVAD exchange recurrent BSI from from sepsis sepsis
had a recurrent infection despite isolated CIED removal. Our findings also show that the prognosis of patients after isolated CIED removal remained poor. The poor outcomes observed highlight the difficulties in the management and treatment of LVADIs, especially in the presence of a concomitant CIED. These findings raise the question as to whether or not concomitant CIED and LVAD removal (i.e., complete hardware removal) should be the treatment of choice for such infections. The most important finding in this descriptive cohort study is that recurrent LVADI was common. Recurrent infections were due to both persistent microorganisms as well as new pathogens. There was significant variance with respect to the time course of recurrent infection, occurring both early (within 5 months) and later. Among the 4 patients in our cohort that had recurrence of an LVADI after CIED removal, 3 of these patients had a history of a previously treated LVADI managed without CIED removal. Two of these 3 patients had a prior driveline infection of the same LVAD that was in place at the time of CIED removal, possibly suggesting colonization of the LVAD even before the onset of the LVADI leading to CIED removal. Moreover, patients with an LVADI recurrence may have had a susceptibility to developing recurrent infections with additional comorbidities and/or risk factors for infection (e.g., diabetes and renal insufficiency).5 For example, among those with diabetes, 2 of 3 of these patients had LVADI recurrence. This predisposition to developing repeat infection may also have accounted for the variance in the microorganisms found with each patient on different presentations. Chronic antibiotic suppressive therapy, as suggested by an alternative analysis, may have delayed LVADI recurrence in the 2 patients treated in this fashion.22 However, treatment with suppressive antibiotics in these 2 patients, initially begun for prior driveline infections, did not prevent multiple recurrent infections from occurring. Thus, despite both CIED removal and chronic antibiotic suppressive therapy, an LVADI recurred in these patients. Ideally, intracardiac infection is treated with complete hardware removal. Based upon the available data, it is unknown if exchange of the LVAD combined with CIED removal results in complete resolution of LVADI and improved long-term survival. Recent observations on patients with an HMII device provide some reassurance on the safety of such a procedure.23 In a cohort of over 1,000 patients with an HMII implanted over a 5-year period, 79 replacements were performed. The most common indications were for percutaneous driveline damage, device thrombosis, and infection. Seven patients (9%) had the device replaced for infection. Although these observational data demonstrated a relatively low
No recurrent infection Alive after 3-year of follow-up
5
6
No recurrence of BSI
Recurrence of driveline and BSI after 2 years
Died 8 days after CIED removal from multiorgan failure
Died 1 month after recurrent infection from sepsis
operative mortality (6.5% within 30 days) with HMII pump exchange, the procedure does require a redo median sternotomy for an infection in order to remove the outflow cannula graft and the LVAD pump. In the 1 patient in whom the LVAD was replaced for infection in our cohort (patient 6 had his LVAD repeatedly exchanged for pump failures), the procedure was ultimately unsuccessful in clearing the LVADI, and the patient died soon thereafter. In addition, a period free from implanted hardware is potentially required in order to sterilize the bloodstream and an infected thoracic space. Such an interval without the hemodynamic support provided by mechanical circulation is often not feasible. Even temporary devices may not provide the necessary support for the required length of time for resolution of the infection. At our center we assess for evidence of myocardial recovery (even partial) in every LVAD-associated complication in order to identify those patients that may tolerate LVAD removal rather than exchange. Myocardial recovery rates, however, remain low in the global experience with durable LVAD support and the likelihood that a patient with an LVADI has sustainable myocardial recovery is small.24 There are risks associated with CIED removal, including lead extraction. The risks remain high when performed for a CIED infection, as observed in patients without an LVAD.25 Two-thirds of the lead extraction procedures required the use of a laser sheath and all were performed in a hybrid operating room with surgical back up. Complications of lead extraction can include myocardial and avulsion injury or septic pulmonary emboli from lead vegetation; major complications and in-hospital mortality have been noted to be less than 2% and 1%, respectively, at centers with experience.26,27 Risk factors for lead extraction complications include the number of leads, lead dwell time, female gender, and removal of ICD leads (especially dual coil leads).28 All of our patients had an ICD lead, and the mean implanted age of the total 16 removed leads was 62 months. In our cohort, 1 patient had partial retained hardware, likely negating the potential benefits of lead removal. Another patient developed a large pocket hematoma requiring surgical evacuation after reintroduction of anticoagulation for prevention of LVAD thrombosis. As LVAD patients are almost always on chronic warfarin therapy for anticoagulation (the exception being for bleeding complications), our practice before proceeding to device extraction is to discontinue warfarin and bridge with an unfractionated heparin infusion.29 Heparin is stopped approximately 6 hours preprocedure (e.g., at midnight) and then restarted approximately 24 hours after the procedure without a bolus. Finally, the role of ICD therapy after LVAD implantation remains in evolution.30 Ventricular arrhythmias (VAs) are
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Figure 1. Patient timelines. *Black horizontal bars represent the approximate time periods antibiotics were administered. For a high quality, full color version of this figure, please see Journal of Cardiovascular Electrophysiology’s website: www.wileyonlinelibrary.com/journal/jce
common after LVAD implantation, despite improvements in cardiac output from the LVAD, and may result from the underlying substrate, right ventricular failure, or position of the inflow cannula abutting the myocardium. Patients may be able to tolerate VAs for prolonged period of time with an LVAD in place. Two recent relatively large analyses report
that though VAs are common after continuous flow LVAD implantation, ICD therapy may not provide a mortality benefit for these patients.31,32 However, alternate analyses have found that VAs post-LVAD are associated with a higher mortality and ICDs are associated with improved survival.33-35 Thus, the decision to electively replace an ICD generator or
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to implant a de novo ICD remains an unresolved question in LVAD patients. Limitations This cohort is small and is from a single institution. This is also a retrospective analysis with all of the inherent limitations. Additionally, we were unable to compare the outcomes to an LVADI cohort without CIED removal. It is important to note, though, that the intent of this analysis was to describe the natural history and outcomes associated with LVADI in the presence of CIED in situ. Finally, all but 1 of the patients in our cohort had a history of bloodstream infection. Therefore, these results may not be generalizable to patients with a localized CIED pocket infection.22 Future Directions Given the increasing number of LVADs in clinical practice and the poor outcomes evident with CIED/LVAD infections, more studies are needed to help inform best practices in the management of LVAD patients. First, clinical studies need to address whether concomitant LVAD removal should always be performed with lead extraction when a bloodstream infection is present. Second (and perhaps more importantly), more data are needed to address whether or not continued ICD therapy/implantation improves survival in patients with LVADs. Conclusions The number of LVAD implantations continues to increase; however, these devices are often complicated by infections. The management of these patients is more challenging when a CIED is present, and, despite CIED removal, LVADIs often reoccur. Recurrence is particularly frequent in cases of a bloodstream infection. Mortality remains high and the primary cause of death in these patients is subsequent or recurrent infection. The risks and benefits of CIED removal and/or LVAD exchange and optimal management strategy in LVADIs with a concomitant CIED require careful consideration and further study. References 1. Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, Kocovic DZ, Packer M, Clavell AL, Hayes DL, Ellestad M, Trupp RJ, Underwood J, Pickering F, Truex C, McAtee P, Messenger J: Cardiac resynchronization in chronic heart failure. N Engl J Med 2002;346:1845-1853. 2. Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML: Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877-883. 3. Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM: Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140-2150. 4. Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, Domanski M, Troutman C, Anderson J, Johnson G, McNulty SE, ClappChanning N, Davidson-Ray LD, Fraulo ES, Fishbein DP, Luceri RM, Ip JH: Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225-237. 5. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L: The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005;352:15391549.
6. Linde C, Abraham WT, Gold MR, St John Sutton M, Ghio S, Daubert C: Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol 2008;52:1834-1843. 7. Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP, Estes NA 3rd, Foster E, Greenberg H, Higgins SL, Pfeffer MA, Solomon SD, Wilber D, Zareba W: Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med 2009;361:13291338. 8. Tang AS, Wells GA, Talajic M, Arnold MO, Sheldon R, Connolly S, Hohnloser SH, Nichol G, Birnie DH, Sapp JL, Yee R, Healey JS, Rouleau JL: Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med 2010;363:2385-2395. 9. Kirklin JK, Naftel DC, Kormos RL, Stevenson LW, Pagani FD, Miller MA, Baldwin JT, Young JB: Fifth INTERMACS annual report: Risk factor analysis from more than 6,000 mechanical circulatory support patients. J Heart Lung Transplant 2013;32:141-156. 10. Miller LW, Pagani FD, Russell SD, John R, Boyle AJ, Aaronson KD, Conte JV, Naka Y, Mancini D, Delgado RM, MacGillivray TE, Farrar DJ, Frazier OH: Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med 2007;357:885-896. 11. Rose EA, Gelijns AC, Moskowitz AJ, Heitjan DF, Stevenson LW, Dembitsky W, Long JW, Ascheim DD, Tierney AR, Levitan RG, Watson JT, Meier P, Ronan NS, Shapiro PA, Lazar RM, Miller LW, Gupta L, Frazier OH, Desvigne-Nickens P, Oz MC, Poirier VL: Longterm use of a left ventricular assist device for end-stage heart failure. N Engl J Med 2001;345:1435-1443. 12. Slaughter MS, Rogers JG, Milano CA, Russell SD, Conte JV, Feldman D, Sun B, Tatooles AJ, Delgado RM, Long JW, Wozniak TC, Ghumman W, Farrar DJ, Frazier OH: Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med 2009;361:2241-2251. 13. Topkara VK, Kondareddy S, Malik F, Wang IW, Mann DL, Ewald GA, Moazami N: Infectious complications in patients with left ventricular assist device: Etiology and outcomes in the continuous-flow era. Ann Thorac Surg 2010;90:1270-1277. 14. Schaffer JM, Allen JG, Weiss ES, Arnaoutakis GJ, Patel ND, Russell SD, Shah AS, Conte JV: Infectious complications after pulsatile-flow and continuous-flow left ventricular assist device implantation. J Heart Lung Transplant 2011;30:164-174. 15. Nienaber JJC, Kusne S, Riaz T, Walker RC, Baddour LM, Wright AJ, Park SJ, Vikram HR, Keating MR, Arabia FA, Lahr BD, Sohail MR: Clinical manifestations and management of left ventricular assist device-associated infections. Clin Infect Dis 2013;57:1438-1448. 16. Baddour LM, Epstein AE, Erickson CC, Knight BP, Levison ME, Lockhart PB, Masoudi FA, Okum EJ, Wilson WR, Beerman LB, Bolger AF, Estes NAM, Gewitz M, Newburger JW, Schron EB, Taubert KA: Update on cardiovascular implantable electronic device infections and their management: A scientific statement from the American Heart Association. Circulation 2010;121:458-477. 17. Hannan MM, Husain S, Mattner F, Danziger-Isakov L, Drew RJ, Corey GR, Schueler S, Holman WL, Lawler LP, Gordon SM, Mahon NG, Herre JM, Gould K, Montoya JG, Padera RF, Kormos RL, Conte JV, Mooney ML: Working formulation for the standardization of definitions of infections in patients using ventricular assist devices. J Heart Lung Transplant 2011;30:375-384. 18. Love CJ: Update on indications, techniques, and complications of cardiac implantable device lead extraction. Curr Treat Options Cardiovasc Med 2012;14:565-570. 19. Mulpuru SK, Pretorius VG, Birgersdotter-Green UM: Device infections: Management and indications for lead extraction. Circulation 2013;128:1031-1038. 20. Wilkoff BL, Love CJ, Byrd CL, Bongiorni MG, Carrillo RG, Crossley GH 3rd, Epstein LM, Friedman RA, Kennergren CE, Mitkowski P, Schaerf RH, Wazni OM: Transvenous lead extraction: Heart Rhythm Society expert consensus on facilities, training, indications, and patient management: This document was endorsed by the American Heart Association (AHA). Heart Rhythm 2009;6:1085-1104. 21. Gaca JG, Lima B, Milano CA, Lin SS, Davis RD, Lowe JE, Smith PK: Laser-assisted extraction of pacemaker and defibrillator leads: The role of the cardiac surgeon. Ann Thorac Surg 2009;87:1446-1450; discussion 1450-1451. 22. Riaz T, Nienaber JJ, Baddour LM, Walker RC, Park SJ, Sohail MR: Cardiovascular implantable electronic device infections in left ventricular assist device recipients. Pacing Clin Electrophysiol 2014;37:225-230.
Krishnamoorthy et al. 23. Moazami N, Milano CA, John R, Sun B, Adamson RM, Pagani FD, Smedira N, Slaughter MS, Farrar DJ, Frazier OH: Pump replacement for left ventricular assist device failure can be done safely and is associated with low mortality. Ann Thorac Surg 2013;95:500-505. 24. Drakos SG, Kfoury AG, Stehlik J, Selzman CH, Reid BB, Terrovitis JV, Nanas JN, Li DY: Bridge to recovery: Understanding the disconnect between clinical and biological outcomes. Circulation 2012;126:230241. 25. Le HY, Sohail MR, Friedman PA, Uslan DZ, Cha SS, Hayes DL, Wilson WR, Steckelber JM, Baddour LM: Impact of timing of device removal on mortality in patients with cardiovascular implantable electronic device infections. Heart Rhythm 2011;8:1678-1685. 26. Byrd CL, Wilkoff BL, Love CJ, Sellers TD, Reiser C: Clinical study of the laser sheath for lead extraction: The total experience in the United States. Pacing Clin Electrophysiol 2002;25:804-808. 27. Wilkoff BL, Byrd CL, Love CJ, Hayes DL, Sellers TD, Schaerf R, Parsonnet V, Epstein LM, Sorrentino RA, Reiser C: Pacemaker lead extraction with the laser sheath: Results of the pacing lead extraction with the excimer sheath (PLEXES) trial. J Am Coll Cardiol 1999;33:16711676. 28. Agarwal SK, Kamireddy S, Nemec J, Voigt A, Saba S: Predictors of complications of endovascular chronic lead extractions from pacemakers and defibrillators: A single-operator experience. J Cardiovasc Electrophysiol 2009;2:171-175. 29. Suarez J, Patel CB, Felker GM, Becker R, Hernandez AF, Rogers JG: Mechanisms of bleeding and approach to patients with axial-flow left ventricular assist devices. Circ Heart Fail 2011;4:779-784.
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30. Raasch H, Jensen BC, Chang PP, Mounsey JP, Gehi AK, Chung EH, Sheridan BC, Bowen A, Katz JN: Epidemiology, management, and outcomes of sustained ventricular arrhythmias after continuous-flow left ventricular assist device implantation. Am Heart J 2012;164:373378. 31. Enriquez AD, Calenda B, Miller MA, Anyanwu AC, Pinney SP: The role of implantable cardioverter-defibrillators in patients with continuous flow left ventricular assist devices. Circ Arrhythm Electrophysiol 2013;6:668-674. 32. Garan AR, Yuzefpolskaya M, Colombo PC, Morrow JP, Te-Frey R, Dano D, Takayama H, Naka Y, Garan H, Jorde UP, Uriel N: Ventricular arrhythmias and implantable cardioverter-defibrillator therapy in patients with continuous-flow left ventricular assist devices: Need for primary prevention? J Am Coll Cardiol 2013;61:25422550. 33. Refaat MM, Tanaka T, Kormos RL, McNamara D, Teuteberg J, Winowich S, London B, Simon MA: Survival benefit of implantable cardioverter-defibrillators in left ventricular assist device-supported heart failure patients. J Card Fail 2012;18:140-145. 34. Cantillon DJ, Tarakji KG, Kumbhani DJ, Smedira NG, Starling R, Wilkoff BL: Improved survival among ventricular assist device recipients with a concomitant implantable cardioverter-defibrillator. Heart Rhythm 2010;7:466-471. 35. Brenyo A, Rao M, Koneru S, Hallinan W, Shah S, Massey HT, Chen L, Polonsky B, McNitt S, Huang DT, Goldenberg f, Aktas M: Risk for mortality for ventricular arrhythmia in ambulatory LVAD patients. J Cardiovasc Electrophysiol 2012;23:515-520.
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Cardiac Implantable Electronic Device Removal in Patients with Left Ventricular Assist Device Associated Infections ARUN KRISHNAMOORTHY, M.D.,∗ SEAN D. POKORNEY, M.D., M.B.A.,∗ ROBERT K. LEWIS, M.D., Ph.D.,∗ JAMES P. DAUBERT, M.D.,∗ RUTH A. GREENFIELD, M.D.,∗ DONALD D. HEGLAND, M.D.,∗ CARMELO A. MILANO, M.D.,† JOSEPH G. ROGERS, M.D.,∗ JACOB N. SCHRODER, M.D.,† CHETAN B. PATEL, M.D.,∗ and JONATHAN P. PICCINI, M.D., M.H.S.∗ From the ∗ Divisions of Cardiology; and †Cardiothoracic Surgery, Duke University Medical Center, Durham, North Carolina, USA
CIED Removal in LVAD Infections. Introduction: Heart failure patients with left ventricular assist devices (LVADs) are at risk for infection. Cardiac implantable electronic devices (CIEDs) are commonly present in these patients. The course of infections in patients with an LVAD and a CIED is not well described. Methods and Results: We identified 6 patients with a durable LVAD that underwent CIED removal because of an LVAD associated infection (LVADI). Patient and infection characteristics, management strategy, and clinical outcomes are described. All 6 patients were male, and the mean age was 59.6 years (range 43–72). Four of 6 patients had an ischemic cardiomyopathy, and 3 patients were diabetic. The median creatinine clearance for patients was 40.5 mg/dL (range 19–65). Five of 6 patients had a continuous flow LVAD placed as destination therapy. Four of 6 patients had a previous LVADI managed medically before the current infection leading to CIED removal. The indication for CIED removal was a bloodstream infection in 5 of 6 patients. Three of these patients had potential vegetations identified by echocardiography on device leads. The mean implanted age of the removed leads was 62 months (range 1–179), and 1 of the 6 patients experienced a procedural complication (hematoma) from CIED removal. Four of 6 patients that underwent CIED removal for an LVADI had recurrence of infection. Five of 6 patients died during the initial presentation or from repeat presentation for infection. Conclusion: Despite CIED removal for an LVADI, recurrent infections are common and mortality remains high. (J Cardiovasc Electrophysiol, Vol. 25, pp. 1199-1205, November 2014) artificial cardiac pacing, implantable cardioverter defibrillators, infection, mechanical circulatory support Introduction Implanted medical devices have become common in heart failure patients. Cardiac implantable electronic device (CIEDs) that deliver cardiac resynchronization therapy (CRT), prevent sudden cardiac death (intracardiac defibrillators [ICDs]), and devices combining these tech-
This manuscript was processed by a guest editor. This work was supported by a generous donation from Al Tatum in support of the Duke Lead Extraction Research Program. Carmelo A. Milano reports compensation for participation on a speaker’s bureau and serving as a consultant/advisory board member for Thoratec Corporaton and HeartWare, Inc. Joseph G. Rogers reports serving as a nonpaid consultant to Thoratec Corporation. Chetan B. Patel reports consulting fees from Thoratec Corporation and HeartWare, Inc. Jonathan P. Piccini reports consulting and proctorship for Spectranetics. Other authors: No disclosures. Address for correspondence: Arun Krishnamoorthy, M.D., Division of Cardiology, Duke University Medical Center, 2301 Erwin Road, DUMC 3845, Durham, NC 27710, USA. Fax: 919-681-9842; E-mail: arun. [email protected] Manuscript received 19 January 2014; Revised manuscript received 25 April 2014; Accepted for publication 27 May 2014. doi: 10.1111/jce.12461
nologies (CRT-D) have demonstrated mortality benefits.1-8 In advanced heart failure patients failing optimal medical therapy, left ventricular assist devices (LVADs) are increasingly used as an alternative to cardiac transplantation or as a bridge until a suitable organ becomes available.9-12 Despite the advantages observed with LVAD implantation, infection can complicate LVAD therapy and leads to significant morbidity and mortality.13-15 The optimal management of an infection in the setting of an LVAD remains incompletely defined despite an improved understanding of clinical manifestations and causative microorganisms.15 Moreover, decision making in patients with LVAD associated infections (LVADIs) can be complicated by the presence of a concomitant CIED, as these devices are common in patients who progress to LVAD therapy. Guidelines for the management of an established CIED infection, in the absence of other device hardware, advise complete removal of the CIED.16 However, it is incompletely understood how CIED removal in the case of an LVADI affects the clinical course in these patients. The causative microorganism may have already seeded the LVAD and thus continue to persist on the LVAD as a source of infection. To further understand CIED removals performed for LVADIs, we identified a cohort of LVAD patients at our institution that underwent CIED removal for an infection and describe their clinical and infection characteristics, management strategy, and clinical outcomes.
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Methods Study Cohort Patients who underwent a CIED lead removal for any cause at Duke University Hospital, a tertiary care referral center, between January 1st, 2005, and February 26th, 2012, were identified (n = 528). From this cohort, 10 patients had a lead removal performed after durable LVAD implantation (patients with temporary mechanical support were excluded). Six of these patients were identified as having a CIED removed for the primary indication of an infection associated with a durable LVAD. CIED infections were defined by the 2010 American Heart Association (AHA) guidelines.16 These infections included CIED pocket infections and persistent bloodstream infections (without another obvious source) with or without echodensities noted on indwelling leads. LVADIs were defined by current International Society for Heart and Lung Transplantation criteria.7,17 Such infections did not necessarily result directly from the LVAD, but deserved special consideration because of the presence of the LVAD.7,17 In our patients these LVADIs represented a CIED pocket infection, bloodstream infections, and driveline or LVAD pocket infections. All patients in the cohort were treated with appropriate antibiotic therapy, also per guideline recommendations.16 Patient and infection characteristics, CIED and lead data, management strategy, and clinical outcomes were obtained from comprehensive chart review. The institutional review board of Duke University approved the research study. Lead Removal The lead removals described in our cohort were performed by a percutaneous-transvenous method; 1 patient did undergo both a combination of a percutaneous-transvenous and open surgical lead removal for different leads during the same procedure. Consistent with the Heart Rhythm Society (HRS) Consensus Statement, lead explanation refers to lead removal without the need for specialized equipment and performed just by traction; lead extraction refers to lead removal requiring specialized equipment such as laser sheaths.18-20 Duke Lead Extraction Protocol All patients underwent both electrophysiology and cardiothoracic surgery consultation regarding lead management. Intraoperative care included transesophageal echocardiography pre-, intra-, and postprocedurally. All patients were prepared for a possible CIED extraction and the procedures were performed in the Duke University operating room in conjunction with cardiothoracic surgery, as per the HRS 2009 Consensus Statement recommendations and our institutional protocol.20,21 All patients were prepared for possible median sternotomy. In some of the extractions either a laser sheath (Spectranetics, Colorado Springs, CO, USA) or femoral snare workstation (Cook Medical, Bloomington, IN, USA) was employed to facilitate the extraction. Results Patient Characteristics The baseline characteristics of the cohort are shown in Table 1. The mean age was 59.6 years (range 43–72), all were
male, and 4 of 6 patients had an ischemic cardiomyopathy. All but 1 of the patients had a continuous flow Heartmate II (HMII) device (Thoratec, Inc., Pleasanton, CA, USA) placed as destination therapy. The remaining patient had an extracorporeal pulsatile flow LVAD (Thoratec, Inc.) placed as a bridge to transplant. Infections and Antibiotic Management As shown in Table 2, bloodstream infections represented 5 of the 6 LVADIs leading to CIED removal, and 1 of these patients also had a concurrent driveline infection. The remaining patient had a CIED pocket infection leading to CIED removal. Of the 5 patients with bloodstream infections, 3 had lead echodensities observed on echocardiography. The causative organisms of the bloodstream infections included gram-positive cocci and nosocomial gram-negative bacilli. The time interval from LVAD implantation to CIED removal ranged from 4 days to 31 months. All patients surviving to discharge after CIED removal (n = 4) completed their guideline recommended antibiotic therapy.16 Two patients were placed on chronic antibiotic suppressive therapy due to either a history of or current LVAD driveline infection. In the patients not maintained on chronic antibiotic suppressive therapy, surveillance blood cultures were obtained for a short period after discharge. In 1 case, cultures were followed monthly for 2 months after the CIED removal. In the case of the CIED pocket infection, a single surveillance culture was obtained 1 month after discharge. There were 4 patients who had a history of a prior LVADI managed without CIED removal (if implanted at the time): driveline infection (n = 1), bloodstream infection (n = 1), bloodstream infection and driveline infection (n = 1), and bloodstream infection and LVAD pocket infection (n = 1). The microbiology of these previous LVADIs for each patient was usually not the same as that of the LVADIs leading to CIED removal (n = 3). These infections occurred at a median of 12.5 months prior to CIED removal. CIED Hardware and Procedural Management Table 3 describes the implanted CIED hardware, procedural management, and complications. All of the patients had a defibrillator and 4 of the 6 patients had a CRT-D device. The mean dwell time of the 16 removed leads was 62 ± 42 months (range 1–179). All patients were prepared for a possible lead extraction; 4 patients required laser lead extraction, whereas 2 patients only required traction. After CIED removal (traction) and reintroduction of anticoagulation for the LVAD, 1 patient developed a pocket hematoma that required surgical evacuation. Another procedure (laser sheath) was complicated by retained lead fragments at both the superior vena cava and distal ICD coils. Outcomes Patient outcomes are shown in Table 4. Despite CIED removal, 1 of 3 patients (n = 2) had early recurrence (within 5 months) of bloodstream infection. Each of these patients (patients 1 and 2) died from progressive sepsis. Patient 2 was eventually managed with an LVAD exchange; however, the patient died 1 month after this procedure. This patient had been maintained on chronic oral antibiotic suppressive therapy until the time of his recurrent infection.
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TABLE 1 Patient Characteristics Patient Age at CIED removal Gender Etiology of CM Diabetes mellitus Creatinine clearance (mL/min/1.73 m2 ) BMI (kg/m2 ) LVAD type LVAD indication
1
2
3
4
5
6
77 Male Ischemic Yes 65 25.0 HM2 DT
55 Male Nonischemic No 45 29.2 HM2 DT
47 Male Ischemic Yes 36 40.1 HM2 DT
72 Male Ischemic Yes 33 26.0 HM2 DT
43 Male Nonischemic No 19 34.7 Extracorporeal pulsatile PVAD BTT
64 Male Ischemic No 56 33.6 HM2 DT
CM = cardiomyopathy; BMI = body mass index; LVAD = left ventricular assist device; HM2 = Heartmate 2; PVAD = peripheral ventricular assist device; DT = destination therapy; BTT = bridge to transplant. TABLE 2 Infection Characteristics Patient LVADI leading to CIED removal Microorganism Echocardiogram pre CIED removal Time from LVAD implant to CIED removal Previous LVADIs before CIED removal
1
2
3
4
5
6
BSI
Driveline infection and BSI P. aerguinosa
BSI
BSI
BSI
CIED pocket infection
VRE faecium
ESBL K. pneumonia
MSSA No lead echodensity 4 days
Recurrent LVADI after CIED removal
Amp sensitive No growth Enterococcus Echodensity on RV Echodensity on RA No lead echodensity Echodensity on RA No lead echodensity lead lead lead 23 months 12 months 4 months 4 days 31 months
None
Driveline infection and BSI
Driveline infection
BSI
None
BSI
BSI
BSI
None
None
BSI and pocket infection from prior LVAD Driveline infection and BSI
LVADI = left ventricular assist device associated infection; CIED = cardiac implantable electronic device; BSI = bloodstream infection; MSSA = methicillin sensitive Staphylococcus aureus; VRE = vancomycin resistant Enterococcus; ESBL = extended spectrum beta lactamase; RA = right atrium; RV = right ventricle. TABLE 3 CIED Characteristics and Procedural Details Patient
1
Type of CIED Dual-chamber ICD removed Last generator 13 implant to CIED removal (months) Lead implant to CIED RA and RV 49, removal (months) CS 2 Removal technique Traction Procedural complications
Pocket hematoma requiring surgical evacuation
2
3
4
5
6
CRT-D
CRT-D
Single-chamber ICD
CRT-D
CRT-D
23
40
1
7
1
RV 72, RA and CS 24 Laser sheath
RA and RV 78, CS 76 Laser sheath
RV 1
None
Retained SVC and distal coil
Traction None
RV 179, RA 92, LV 46 Laser sheath and surgical removal of epicardial LV lead None
RA and RV 75, CS 70 Laser sheath None
ICD = intracardiac defibrillator; CRT-D = cardiac resynchronization therapy defibrillator; CS = coronary sinus; LV = left ventricle; SVC = superior vena cava.
In addition, 2 other patients (patients 3 and 6) had recurrent LVADIs at 1 and 2 years post CIED removal and each died soon thereafter from sepsis. Patient 3 had recurrence of infection 1 year after CIED removal despite chronic suppressive therapy for driveline infection. Patient 6 had their CIED originally removed for a CIED pocket infection. Of the 2 remaining patients, patient 5 did not have recurrence of bloodstream infection after CIED removal but died 8 days after the procedure from continued multiorgan failure. Patient 4, also with a bloodstream infection leading to removal of the CIED, remained free of infection and was alive
after 3 years of follow-up. In total, 5 of the 6 patients died of infection, either during the initial presentation or after repeat presentation for infection. Figure 1 provides a timeline of the clinical course of each patient in the cohort, including CIED implantation, all infections, approximate periods of treatment with antibiotics, CIED removal, and subsequent outcomes. Discussion In a small cohort of patients who underwent CIED removal because of an LVADI, we observed that most patients
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TABLE 4 Clinical Outcomes Patient
1
Clinical outcomes
Early recurrence of BSI
Mortality
Died 1 month after CIED removal from sepsis
2
3
4
Recurrence of BSI Single-chamber ICD after 5 months and reimplanted and LVAD exchanged recurrence of BSI after 1 year Died 1 month after Died 4 months after LVAD exchange recurrent BSI from from sepsis sepsis
had a recurrent infection despite isolated CIED removal. Our findings also show that the prognosis of patients after isolated CIED removal remained poor. The poor outcomes observed highlight the difficulties in the management and treatment of LVADIs, especially in the presence of a concomitant CIED. These findings raise the question as to whether or not concomitant CIED and LVAD removal (i.e., complete hardware removal) should be the treatment of choice for such infections. The most important finding in this descriptive cohort study is that recurrent LVADI was common. Recurrent infections were due to both persistent microorganisms as well as new pathogens. There was significant variance with respect to the time course of recurrent infection, occurring both early (within 5 months) and later. Among the 4 patients in our cohort that had recurrence of an LVADI after CIED removal, 3 of these patients had a history of a previously treated LVADI managed without CIED removal. Two of these 3 patients had a prior driveline infection of the same LVAD that was in place at the time of CIED removal, possibly suggesting colonization of the LVAD even before the onset of the LVADI leading to CIED removal. Moreover, patients with an LVADI recurrence may have had a susceptibility to developing recurrent infections with additional comorbidities and/or risk factors for infection (e.g., diabetes and renal insufficiency).5 For example, among those with diabetes, 2 of 3 of these patients had LVADI recurrence. This predisposition to developing repeat infection may also have accounted for the variance in the microorganisms found with each patient on different presentations. Chronic antibiotic suppressive therapy, as suggested by an alternative analysis, may have delayed LVADI recurrence in the 2 patients treated in this fashion.22 However, treatment with suppressive antibiotics in these 2 patients, initially begun for prior driveline infections, did not prevent multiple recurrent infections from occurring. Thus, despite both CIED removal and chronic antibiotic suppressive therapy, an LVADI recurred in these patients. Ideally, intracardiac infection is treated with complete hardware removal. Based upon the available data, it is unknown if exchange of the LVAD combined with CIED removal results in complete resolution of LVADI and improved long-term survival. Recent observations on patients with an HMII device provide some reassurance on the safety of such a procedure.23 In a cohort of over 1,000 patients with an HMII implanted over a 5-year period, 79 replacements were performed. The most common indications were for percutaneous driveline damage, device thrombosis, and infection. Seven patients (9%) had the device replaced for infection. Although these observational data demonstrated a relatively low
No recurrent infection Alive after 3-year of follow-up
5
6
No recurrence of BSI
Recurrence of driveline and BSI after 2 years
Died 8 days after CIED removal from multiorgan failure
Died 1 month after recurrent infection from sepsis
operative mortality (6.5% within 30 days) with HMII pump exchange, the procedure does require a redo median sternotomy for an infection in order to remove the outflow cannula graft and the LVAD pump. In the 1 patient in whom the LVAD was replaced for infection in our cohort (patient 6 had his LVAD repeatedly exchanged for pump failures), the procedure was ultimately unsuccessful in clearing the LVADI, and the patient died soon thereafter. In addition, a period free from implanted hardware is potentially required in order to sterilize the bloodstream and an infected thoracic space. Such an interval without the hemodynamic support provided by mechanical circulation is often not feasible. Even temporary devices may not provide the necessary support for the required length of time for resolution of the infection. At our center we assess for evidence of myocardial recovery (even partial) in every LVAD-associated complication in order to identify those patients that may tolerate LVAD removal rather than exchange. Myocardial recovery rates, however, remain low in the global experience with durable LVAD support and the likelihood that a patient with an LVADI has sustainable myocardial recovery is small.24 There are risks associated with CIED removal, including lead extraction. The risks remain high when performed for a CIED infection, as observed in patients without an LVAD.25 Two-thirds of the lead extraction procedures required the use of a laser sheath and all were performed in a hybrid operating room with surgical back up. Complications of lead extraction can include myocardial and avulsion injury or septic pulmonary emboli from lead vegetation; major complications and in-hospital mortality have been noted to be less than 2% and 1%, respectively, at centers with experience.26,27 Risk factors for lead extraction complications include the number of leads, lead dwell time, female gender, and removal of ICD leads (especially dual coil leads).28 All of our patients had an ICD lead, and the mean implanted age of the total 16 removed leads was 62 months. In our cohort, 1 patient had partial retained hardware, likely negating the potential benefits of lead removal. Another patient developed a large pocket hematoma requiring surgical evacuation after reintroduction of anticoagulation for prevention of LVAD thrombosis. As LVAD patients are almost always on chronic warfarin therapy for anticoagulation (the exception being for bleeding complications), our practice before proceeding to device extraction is to discontinue warfarin and bridge with an unfractionated heparin infusion.29 Heparin is stopped approximately 6 hours preprocedure (e.g., at midnight) and then restarted approximately 24 hours after the procedure without a bolus. Finally, the role of ICD therapy after LVAD implantation remains in evolution.30 Ventricular arrhythmias (VAs) are
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Figure 1. Patient timelines. *Black horizontal bars represent the approximate time periods antibiotics were administered. For a high quality, full color version of this figure, please see Journal of Cardiovascular Electrophysiology’s website: www.wileyonlinelibrary.com/journal/jce
common after LVAD implantation, despite improvements in cardiac output from the LVAD, and may result from the underlying substrate, right ventricular failure, or position of the inflow cannula abutting the myocardium. Patients may be able to tolerate VAs for prolonged period of time with an LVAD in place. Two recent relatively large analyses report
that though VAs are common after continuous flow LVAD implantation, ICD therapy may not provide a mortality benefit for these patients.31,32 However, alternate analyses have found that VAs post-LVAD are associated with a higher mortality and ICDs are associated with improved survival.33-35 Thus, the decision to electively replace an ICD generator or
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to implant a de novo ICD remains an unresolved question in LVAD patients. Limitations This cohort is small and is from a single institution. This is also a retrospective analysis with all of the inherent limitations. Additionally, we were unable to compare the outcomes to an LVADI cohort without CIED removal. It is important to note, though, that the intent of this analysis was to describe the natural history and outcomes associated with LVADI in the presence of CIED in situ. Finally, all but 1 of the patients in our cohort had a history of bloodstream infection. Therefore, these results may not be generalizable to patients with a localized CIED pocket infection.22 Future Directions Given the increasing number of LVADs in clinical practice and the poor outcomes evident with CIED/LVAD infections, more studies are needed to help inform best practices in the management of LVAD patients. First, clinical studies need to address whether concomitant LVAD removal should always be performed with lead extraction when a bloodstream infection is present. Second (and perhaps more importantly), more data are needed to address whether or not continued ICD therapy/implantation improves survival in patients with LVADs. Conclusions The number of LVAD implantations continues to increase; however, these devices are often complicated by infections. The management of these patients is more challenging when a CIED is present, and, despite CIED removal, LVADIs often reoccur. Recurrence is particularly frequent in cases of a bloodstream infection. Mortality remains high and the primary cause of death in these patients is subsequent or recurrent infection. The risks and benefits of CIED removal and/or LVAD exchange and optimal management strategy in LVADIs with a concomitant CIED require careful consideration and further study. References 1. Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, Kocovic DZ, Packer M, Clavell AL, Hayes DL, Ellestad M, Trupp RJ, Underwood J, Pickering F, Truex C, McAtee P, Messenger J: Cardiac resynchronization in chronic heart failure. N Engl J Med 2002;346:1845-1853. 2. Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML: Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877-883. 3. Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM: Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140-2150. 4. Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, Domanski M, Troutman C, Anderson J, Johnson G, McNulty SE, ClappChanning N, Davidson-Ray LD, Fraulo ES, Fishbein DP, Luceri RM, Ip JH: Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225-237. 5. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L: The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005;352:15391549.
6. Linde C, Abraham WT, Gold MR, St John Sutton M, Ghio S, Daubert C: Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol 2008;52:1834-1843. 7. Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP, Estes NA 3rd, Foster E, Greenberg H, Higgins SL, Pfeffer MA, Solomon SD, Wilber D, Zareba W: Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med 2009;361:13291338. 8. Tang AS, Wells GA, Talajic M, Arnold MO, Sheldon R, Connolly S, Hohnloser SH, Nichol G, Birnie DH, Sapp JL, Yee R, Healey JS, Rouleau JL: Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med 2010;363:2385-2395. 9. Kirklin JK, Naftel DC, Kormos RL, Stevenson LW, Pagani FD, Miller MA, Baldwin JT, Young JB: Fifth INTERMACS annual report: Risk factor analysis from more than 6,000 mechanical circulatory support patients. J Heart Lung Transplant 2013;32:141-156. 10. Miller LW, Pagani FD, Russell SD, John R, Boyle AJ, Aaronson KD, Conte JV, Naka Y, Mancini D, Delgado RM, MacGillivray TE, Farrar DJ, Frazier OH: Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med 2007;357:885-896. 11. Rose EA, Gelijns AC, Moskowitz AJ, Heitjan DF, Stevenson LW, Dembitsky W, Long JW, Ascheim DD, Tierney AR, Levitan RG, Watson JT, Meier P, Ronan NS, Shapiro PA, Lazar RM, Miller LW, Gupta L, Frazier OH, Desvigne-Nickens P, Oz MC, Poirier VL: Longterm use of a left ventricular assist device for end-stage heart failure. N Engl J Med 2001;345:1435-1443. 12. Slaughter MS, Rogers JG, Milano CA, Russell SD, Conte JV, Feldman D, Sun B, Tatooles AJ, Delgado RM, Long JW, Wozniak TC, Ghumman W, Farrar DJ, Frazier OH: Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med 2009;361:2241-2251. 13. Topkara VK, Kondareddy S, Malik F, Wang IW, Mann DL, Ewald GA, Moazami N: Infectious complications in patients with left ventricular assist device: Etiology and outcomes in the continuous-flow era. Ann Thorac Surg 2010;90:1270-1277. 14. Schaffer JM, Allen JG, Weiss ES, Arnaoutakis GJ, Patel ND, Russell SD, Shah AS, Conte JV: Infectious complications after pulsatile-flow and continuous-flow left ventricular assist device implantation. J Heart Lung Transplant 2011;30:164-174. 15. Nienaber JJC, Kusne S, Riaz T, Walker RC, Baddour LM, Wright AJ, Park SJ, Vikram HR, Keating MR, Arabia FA, Lahr BD, Sohail MR: Clinical manifestations and management of left ventricular assist device-associated infections. Clin Infect Dis 2013;57:1438-1448. 16. Baddour LM, Epstein AE, Erickson CC, Knight BP, Levison ME, Lockhart PB, Masoudi FA, Okum EJ, Wilson WR, Beerman LB, Bolger AF, Estes NAM, Gewitz M, Newburger JW, Schron EB, Taubert KA: Update on cardiovascular implantable electronic device infections and their management: A scientific statement from the American Heart Association. Circulation 2010;121:458-477. 17. Hannan MM, Husain S, Mattner F, Danziger-Isakov L, Drew RJ, Corey GR, Schueler S, Holman WL, Lawler LP, Gordon SM, Mahon NG, Herre JM, Gould K, Montoya JG, Padera RF, Kormos RL, Conte JV, Mooney ML: Working formulation for the standardization of definitions of infections in patients using ventricular assist devices. J Heart Lung Transplant 2011;30:375-384. 18. Love CJ: Update on indications, techniques, and complications of cardiac implantable device lead extraction. Curr Treat Options Cardiovasc Med 2012;14:565-570. 19. Mulpuru SK, Pretorius VG, Birgersdotter-Green UM: Device infections: Management and indications for lead extraction. Circulation 2013;128:1031-1038. 20. Wilkoff BL, Love CJ, Byrd CL, Bongiorni MG, Carrillo RG, Crossley GH 3rd, Epstein LM, Friedman RA, Kennergren CE, Mitkowski P, Schaerf RH, Wazni OM: Transvenous lead extraction: Heart Rhythm Society expert consensus on facilities, training, indications, and patient management: This document was endorsed by the American Heart Association (AHA). Heart Rhythm 2009;6:1085-1104. 21. Gaca JG, Lima B, Milano CA, Lin SS, Davis RD, Lowe JE, Smith PK: Laser-assisted extraction of pacemaker and defibrillator leads: The role of the cardiac surgeon. Ann Thorac Surg 2009;87:1446-1450; discussion 1450-1451. 22. Riaz T, Nienaber JJ, Baddour LM, Walker RC, Park SJ, Sohail MR: Cardiovascular implantable electronic device infections in left ventricular assist device recipients. Pacing Clin Electrophysiol 2014;37:225-230.
Krishnamoorthy et al. 23. Moazami N, Milano CA, John R, Sun B, Adamson RM, Pagani FD, Smedira N, Slaughter MS, Farrar DJ, Frazier OH: Pump replacement for left ventricular assist device failure can be done safely and is associated with low mortality. Ann Thorac Surg 2013;95:500-505. 24. Drakos SG, Kfoury AG, Stehlik J, Selzman CH, Reid BB, Terrovitis JV, Nanas JN, Li DY: Bridge to recovery: Understanding the disconnect between clinical and biological outcomes. Circulation 2012;126:230241. 25. Le HY, Sohail MR, Friedman PA, Uslan DZ, Cha SS, Hayes DL, Wilson WR, Steckelber JM, Baddour LM: Impact of timing of device removal on mortality in patients with cardiovascular implantable electronic device infections. Heart Rhythm 2011;8:1678-1685. 26. Byrd CL, Wilkoff BL, Love CJ, Sellers TD, Reiser C: Clinical study of the laser sheath for lead extraction: The total experience in the United States. Pacing Clin Electrophysiol 2002;25:804-808. 27. Wilkoff BL, Byrd CL, Love CJ, Hayes DL, Sellers TD, Schaerf R, Parsonnet V, Epstein LM, Sorrentino RA, Reiser C: Pacemaker lead extraction with the laser sheath: Results of the pacing lead extraction with the excimer sheath (PLEXES) trial. J Am Coll Cardiol 1999;33:16711676. 28. Agarwal SK, Kamireddy S, Nemec J, Voigt A, Saba S: Predictors of complications of endovascular chronic lead extractions from pacemakers and defibrillators: A single-operator experience. J Cardiovasc Electrophysiol 2009;2:171-175. 29. Suarez J, Patel CB, Felker GM, Becker R, Hernandez AF, Rogers JG: Mechanisms of bleeding and approach to patients with axial-flow left ventricular assist devices. Circ Heart Fail 2011;4:779-784.
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