Daniel J. Cantillon

Percutaneous Implantation of an Entirely Intracardiac Leadless Pacemaker

BACKGROUND Cardiac pacemakers are limited by device-related complications, notably infection and problems related to pacemaker leads. We studied a miniaturized, fully self-contained leadless pacemaker that is nonsurgically implanted in the right ventricle with the use of a catheter. METHODS In this multicenter study, we implanted an active-fixation leadless cardiac pacemaker in patients who required permanent single-chamber ventricular pacing. The primary efficacy end point was both an acceptable pacing threshold (≤2.0 V at 0.4 msec) and an acceptable sensing amplitude (R wave ≥5.0 mV, or a value equal to or greater than the value at implantation) through 6 months. The primary safety end point was freedom from device-related serious adverse events through 6 months. In this ongoing study, the prespecified analysis of the primary end points was performed on data from the first 300 patients who completed 6 months of follow-up (primary cohort). The rates of the efficacy end point and safety end point were compared with performance goals (based on historical data) of 85% and 86%, respectively. Additional outcomes were assessed in all 526 patients who were enrolled as of June 2015 (the total cohort). RESULTS The leadless pacemaker was successfully implanted in 504 of the 526 patients in the total cohort (95.8%). The intention-to-treat primary efficacy end point was met in 270 of the 300 patients in the primary cohort (90.0%; 95% confidence interval [CI], 86.0 to 93.2, P=0.007), and the primary safety end point was met in 280 of the 300 patients (93.3%; 95% CI, 89.9 to 95.9; P<0.001). At 6 months, device-related serious adverse events were observed in 6.7% of the patients; events included device dislodgement with percutaneous retrieval (in 1.7%), cardiac perforation (in 1.3%), and pacing-threshold elevation requiring percutaneous retrieval and device replacement (in 1.3%). CONCLUSIONS The leadless cardiac pacemaker met prespecified pacing and sensing requirements in the large majority of patients. Device-related serious adverse events occurred in approximately 1 in 15 patients. (Funded by St. Jude Medical; LEADLESS II ClinicalTrials.gov number, NCT02030418.).

Cardiac implantable electronic device infections: Presentation, management, and patient outcomes

BACKGROUND Indications for cardiac implantable electronic devices (CIEDs) are increasing. Although CIED infections occur infrequently, the impact of this outcome is expected to be substantial. OBJECTIVE The purpose of this study was to the evaluate the outcome of patients undergoing removal of infected CIEDs. METHODS A retrospective study was conducted of all patients with proven or suspected infected CIEDs who were referred to the Cleveland Clinic for system removal from January 2002 through March 2007. RESULTS A total of 412 patients (age 68 +/- 15 years) were included in the study. The majority of patients (241 [59%]) presented with localized infection involving the device pocket. The remaining 171 patients (41%) presented with endovascular infection but no evidence of inflammation of the device pocket. Of the total 414 pathogens isolated, 366 (88%) were aerobic gram-positive organisms, of which 90% were Staphylococcus species, and almost half of these were methicillin resistant. In-hospital mortality was 4.6% (19 patients). Only 2 deaths were extraction related. One-year mortality was 17%. Among the total cohort, 8 (1.9%) patients had relapsing infection within the first year. Among patients who had device replacement during the same hospitalization, 6 (2.6%) had relapsing infections within 1 year of reimplantation; 5 of these patients had systemic symptoms and were bacteremic upon initial presentation. CONCLUSION CIED infections are most often caused by Staphylococcus species, half of which are methicillin resistant. Percutaneous lead and device removal along with antibiotic therapy are effective as primary interventions. The overall relapse rate is 1.9%, and the relapse rate among patients who had reimplantation during the same hospitalization is 2.6%.

Clinical predictors of adverse patient outcomes in an experience of more than 5000 chronic endovascular pacemaker and defibrillator lead extractions

BACKGROUND It is difficult to predict adverse patient outcomes associated with transvenous lead extraction (TLE) procedures. OBJECTIVE The purpose of this study was to examine the safety and efficacy of chronic endovascular pacemaker and implantable cardioverter-defibrillator (ICD) lead extraction and risk factors associated with adverse patient outcomes. METHODS Consecutive patients undergoing TLE at the Cleveland Clinic between August 1996 and August 2011 were included in the analysis. Univariate and multivariable logistic regression analyses were performed to evaluate for associations with outcomes. Continuous data are given as median (25th, 75th percentile). Categorical data are given as number (percentage). RESULTS In total, 5521 leads (4137 [74.9%] pacemaker, 1384 [25.1%] ICD) were extracted during 2999 TLE procedures (patient age 67.2 [55.2, 76.2] years, 30.2% female). Lead implant duration was 4.7 (2.4, 8.3) years, and 2.0 (1.0, 2.0) leads were extracted per procedure. Powered sheaths were used in 74.9% of procedures. Overall, there was 95.1% complete procedural success, 98.9% clinical success, and 1.1% failure, with 3.6% minor complications and 1.8% major complications. All-cause mortality within 30 days of TLE was 2.2%. Multivariable predictors of major complications included cerebrovascular disease, ejection fraction ≤15%, lower platelet count, international normalized ratio ≥1.2, mechanical sheaths, and powered sheaths. Multivariable predictors of all-cause mortality within 30 days of TLE included body mass index <25 kg/m(2), end-stage renal disease, higher New York Heart Association functional class, lower hemoglobin, higher international normalized ratio, lead extraction for infection, and extraction of a dual-coil ICD lead. CONCLUSION TLE in this single-center experience was highly successful. Risk factors associated with adverse patient outcomes were identified.

Improved survival among ventricular assist device recipients with a concomitant implantable cardioverter-defibrillator.

BACKGROUND Ventricular tachyarrhythmia events (VTE) are common among refractory heart failure patients requiring ventricular assist device (VAD) support. It is unknown whether implantable cardioverter-defibrillator (ICD) detection and therapy can extend survival in the VAD population. OBJECTIVE The purpose of this study was to evaluate the survival experience of refractory heart failure patients requiring VAD support with and without a concomitant ICD. METHODS Multivariable analysis of the Cleveland Clinic registry of consecutive patients with and without an ICD who underwent VAD placement between 1991 and 2008 using traditional and propensity-matched methods. The primary endpoint was all-cause mortality. RESULTS Among 478 VAD recipients (age 53.5 +/- 12.0 years, 80% male), 90 patients (18.8%) had an ICD at the time of VAD placement. VTE occurred in 26 patients (28.9%) at a mean of 32.4 +/- 47.1 days, with appropriate treatment in 24 patients (75% initial shock, 25% successful antitachycardia pacing). A concomitant ICD during VAD support was associated with a significant reduction in mortality (hazard ratio [HR] 0.55 [confidence interval 0.32-0.94]; P = .028) after adjustment for age, gender, left ventricular ejection fraction, VAD type, year placed, diagnosis and duration, complications, dialysis-dependent renal failure, and extended survival (median survival 295 vs. 226 days; P = .024). A propensity-matched analysis of 134 patients with and without ICD also demonstrated that a concomitant ICD was associated with lower all-cause mortality (odds ratio 0.42 [confidence interval 0.19-0.95]; P = .04). CONCLUSION A concomitant ICD among VAD recipients is associated with extended survival.

Electrophysiologic characteristics and catheter ablation of ventricular tachyarrhythmias among patients with heart failure on ventricular assist device support

BACKGROUND Ventricular tachyarrhythmias (VT) are common among ventricular assist device (VAD) recipients, yet electrophysiologic (EP) characteristics and catheter ablation outcomes remain uncharacterized. OBJECTIVE To evaluate the EP characteristics and catheter ablation outcomes for VTs among heart failure patients on VAD support. METHODS The Cleveland Clinic registry of consecutive patients undergoing VAD placement in 1991-2010 with medically refractory, symptomatic VT referred for EP study and catheter ablation. RESULTS Among 611 recipients of VAD (mean age 53.3 ± 12.4 years, 80% men), 21 patients (3.4%) were referred for 32 EP procedures, including 11 patients (52%) presenting with implantable cardioverter-defibrillator therapy (13 shocks, 26 antitachycardia pacing). Data from 44 inducible tachycardias (mean cycle length 339 ± 59 ms) demonstrated monomorphic VT (n = 40, 91%; superior axis 52%, right bundle branch block morphology 41%) and polymorphic ventricular tachycardia (PMVT)/ventricular fibrillation (n = 4, 8%). Electroanatomic mapping of 28 tachycardias in 20 patients demonstrated reentrant VT related to intrinsic scar (n = 21 of 28, 75%) more commonly than the apical inflow cannulation site (n = 4 of 28, 14%), focal/microreentry VT (n = 2 of 28, 7%), or bundle branch reentry (n = 1 of 28, 3.5%). Catheter ablation succeeded in 18 of 21 patients (86%). VT recurred in 7 of 21 patients (33%) at a mean of 133 ± 98 days, and 6 patients (29%) required repeat procedures, with subsequent recurrence in 4 of 21 patients (19%). CONCLUSIONS Catheter ablation of VT is effective among recipients of VAD. Intrinsic myocardial scar, rather than the apical device cannulation site, appears to be the dominant substrate.

Transvenous extraction of implantable cardioverter-defibrillator leads under advisory—A comparison of Riata, Sprint Fidelis, and non-recalled implantable cardioverter-defibrillator leads

BACKGROUND Comparative safety and efficacy associated with transvenous lead extraction (TLE) of recalled and non-recalled implantable cardioverter-defibrillator (ICD) leads has not been well characterized. OBJECTIVES To compare the indications, techniques, and procedural outcomes of recalled vs non-recalled ICD lead extraction procedures. METHODS TLE procedures performed at our institution from June 2002 to June 2012 in which Riata, Sprint Fidelis, or non-recalled ICD leads were extracted were included in the analysis. RESULTS ICD lead extraction procedures were performed in 1079 patients, including 430 patients with recalled leads (121 Riata, 308 Sprint Fidelis, and 1 Riata and Sprint Fidelis) and 649 patients with non-recalled ICD leads. A total of 2056 chronic endovascular leads were extracted, of which 1215 (59.1%) were ICD leads. Overall, there was 96.8% complete procedural success, 99.1% clinical success, and 0.9% failure, with 3.9% minor complications and 1.5% major complications. Procedural outcomes for Riata and Sprint Fidelis TLE procedures were no different. Lead implant duration was significantly less in recalled than in non-recalled ICD lead TLE procedures. Complete procedural success was higher in recalled (424 of 430 [98.6%]) than in non-recalled (621 of 649 [95.7%]; P = .007) ICD lead TLE procedures. Minor complications were lower in recalled (10 of 430 [2.3%]) than in non-recalled (32 of 649 [5.0%]; P = .030) ICD lead TLE procedures. Rates of clinical success, failure, and major complications were no different in the recalled and non-recalled ICD lead TLE procedures. CONCLUSION In our experience, recalled ICD leads were extracted with safety and efficacy comparable to that of non-recalled ICD leads.

Long-term outcomes and clinical predictors for pacemaker-requiring bradyarrhythmias after cardiac transplantation: Analysis of the UNOS/OPTN cardiac transplant database

BACKGROUND Pacemaker-requiring bradyarrhythmias after cardiac transplantation are common, and rarely can lead to sudden cardiac death. Prior outcomes studies have been limited to single-center data. OBJECTIVE This study sought to define the long-term outcomes and clinical predictors for pacemaker-requiring bradyarrhythmias in the cardiac transplant population. METHODS This study used multivariable analysis of the United Network for Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN) database of sequential U.S. cardiac transplant recipients from 1997 to 2007 stratified by postoperative bradyarrhythmias requiring a pacemaker. The primary end point was all-cause mortality. RESULTS Among 35,987 cardiac transplant recipients (age 46.1 ± 18.3 years, 76% male, 22% bicaval technique) with a follow-up of 6.3 ± 4.7 years, pacemaker-requiring bradyarrhythmias occurred in 3,940 patients (10.9%). Pacemaker recipients demonstrated improved survival (median 8.0 years vs. 5.2 years, P < .001), decreased 5-year mortality (13.8% vs. 17.7%, P < .001), and overall crude mortality (42.9% vs. 45.9%, P < .001). Multivariable propensity-score-adjusted analysis demonstrated improved survival among pacemaker recipients (adjusted hazard ratio 0.84, 95% confidence interval [CI] 0.80 to 0.88, P < .001) after adjustment for donor/recipient age, UNOS listing status, donor heart ischemic time, surgical technique, graft rejection, and other common comorbidities. The bicaval surgical technique was strongly protective against a postoperative pacemaker requirement (odds ratio [OR] 0.33, 95% CI 0.29 to 0.36, P < .001) in multivariable analysis. Among the other variables studied, only increasing donor age (OR 1.04, 95% CI 1.00 to 1.09, P < .001) and recipient age (OR 1.09, 95% CI 1.0 to 1.12, P < .001) were associated with a permanent pacemaker requirement. CONCLUSION Cardiac transplant recipients with pacemaker-requiring bradyarrhythmias have an excellent long-term prognosis. Increased mortality in the nonpacemaker group merits further investigation. Biatrial surgical technique and increasing donor/recipient age are associated with postoperative pacemaker requirement.

Incidence and predictors of right ventricular pacing-induced cardiomyopathy in patients with complete atrioventricular block and preserved left ventricular systolic function

BACKGROUND Right ventricular (RV) pacing may worsen left ventricular cardiomyopathy in patients with reduced left ventricular ejection fraction (LVEF) and advanced atrioventricular block. OBJECTIVE The objectives of this study were to calculate incidence and identify predictors of RV pacing-induced cardiomyopathy (PICM) in complete heart block (CHB) with preserved LVEF and to describe outcomes of subsequent cardiac resynchronization therapy (CRT) upgrade. METHODS An analysis of consecutive patients receiving permanent pacemaker (PPM) from 2000 to 2014 for CHB with LVEF >50% was performed. PICM was defined as CRT upgrade or post-PPM LVEF ≤40%. PICM association was determined via multivariable regression analysis. CRT response was defined by LVEF increase ≥10% or left ventricular end-systolic volume decrease ≥15%. RESULTS Of the 823 study patients, 101 (12.3%) developed PICM over the mean follow-up of 4.3 ± 3.9 years, with post-PPM LVEF being 33.7% ± 7.4% in patients with PICM vs 57.6% ± 6.1% in patients without PICM (P < .001). In multivariable analysis, lower pre-PPM LVEF (hazard ratio [HR] 1.047 per 1% LVEF decrease; 95% confidence interval [CI] 1.002-1.087; P = .042) and RV pacing % both as a continuous (HR 1.011 per 1% RV pacing; 95% CI 1.002-1.02; P = .021) and as a categorical (<20% or ≥20% RV pacing) (HR 6.76; 95% CI 2.08-22.0; P = .002) variable were independently associated with PICM. Only 29 patients with PICM (28.7%) received CRT upgrade despite an 84% responder rate (LVEF increase 18.5% ± 8.1% and left ventricular end-systolic volume decrease 45.1% ± 15.0% in responders). CRT upgrade was associated with greater post-PPM LVEF decrease, lower post-PPM LVEF, and post-PPM LVEF ≤35% (P = .006, P = .004, and P = .004, respectively). CONCLUSION PICM is not uncommon in patients receiving PPM for CHB with preserved LVEF and is strongly associated with RV pacing burden >20%. CRT response rate is high in PICM, but is perhaps underutilized.

QRS narrowing is associated with reverse remodeling in patients with chronic right ventricular pacing upgraded to cardiac resynchronization therapy

BACKGROUND Patients with chronic right ventricular pacing (RVP) upgraded to cardiac resynchronization therapy (CRT) have been excluded from the majority of clinical trials of CRT. Little is known about the predictors of response in this population. We hypothesized that reversal of RVP-induced electrical dyssynchrony (indexed by QRS duration) by CRT would predict a favorable response. OBJECTIVE The purpose of this study was to identify baseline characteristics associated with response in patients upgraded to CRT from chronic RVP. METHODS Consecutive patients presenting for CRT at the Cleveland Clinic between September 30, 2003, and July 8, 2008, with chronic RVP and serial echocardiograms were included in this analysis. RVP was defined as>85% pacing on a pre-CRT device check, previous AV nodal ablation, or complete pacer dependency per chart notes. Response was defined as a reduction in left ventricular end-systolic volume ≥ 15% from baseline. Clinical, ECG, and echocardiographic data were extracted to determine covariates associated with response. RESULTS One hundred twelve patients met inclusion criteria, of whom 72 (64.3%) met criteria for response over median follow-up of 9.9 months (interquartile range [6.5-14.7]). No significant differences were noted in terms of male gender (68.1% vs 75.0%; P = .52), ischemic cardiomyopathy (55.6% vs 55.0%; P = 1), pre-CRT QRS duration (189.1 ± 20.7 ms vs 185.5 ± 26.8 ms; P = .47), duration of RVP before CRT upgrade (5.8 ± 3.9 years vs 6.2 ± 4.0 years; P = .57), or baseline left ventricular end-systolic volume (160.0 ± 60.7 mL vs 172.8 ± 67.2 mL; P = .32) between responders and nonresponders, respectively. Percent reduction in QRS duration between the right ventricular-paced and first biventricular-paced waveforms was significantly greater in responders compared with nonresponders (14.4% ± 13.2% vs 7.2%± 14.0%; P = .01). In multivariate analysis, percent reduction in QRS narrowing was the lone factor associated with response (odds ratio 0.02 [0.001-0.42]; P = .01). CONCLUSION Reversal of electrical dyssynchrony predicts response to CRT in chronically RV-paced patients upgraded to CRT. Traditional factors associated with a favorable response to CRT in de novo implants (female gender, nonischemic cardiomyopathy, and wider baseline QRS duration) are not significantly associated with response in upgraded patients. Duration of RVP before CRT upgrade is not an important determinant of response.

Long-term Outcomes and Clinical Predictors for Pacing After Cardiac Transplantation

BACKGROUND Prior studies have yielded inconsistent results on bradyarrhythmias requiring a permanent pacemaker (PPM) after cardiac transplant. This study evaluated the predictors for PPM requirement, long-term outcomes, and influence of implant timing and device programming on prognosis after cardiac transplant. METHODS This study prospectively evaluated 1,307 recipients from 1985 to 2007 at Cleveland Clinic by structured follow-up and compared the outcomes of patients with and without bradyarrhythmias requiring PPM after transplantation. The primary end point was all-cause mortality or retransplant. RESULTS Recipients, aged 50 +/- 15 years (donors, 33 +/- 14 years), were monitored 82 +/- 59 months, with PPM indicated in 106 (8.1%), including 61 (57.5%) early and 44 (42.5%) late. Biatrial technique strongly predicted PPM requirement (OR [odds ratio], 2.61; 95% confidence interval [CI], 1.63-4.20; p < 0.001), and survival/retransplant outcomes were comparable between those with early, late, and no PPM requirement: 5-year primary event-free rate was 80.4% (early) vs 72.6% (late; p = 0.480) and 80.4% (early) vs 73.2% (none, p = 0.550) and 72.6% (late) vs 73.2% (none; p = 0.960). Excess atrial fibrillation was noted among PPM recipients (PPM, 12.3% vs no PPM, 6.3%; p = 0.02) with high initial DDD programming in 92.5% (98 of 106). Sinus rhythm with intact atrioventricular conduction at 6 months was present in 69 (85%), yet 67 (67%) remained DDD programmed, with mean 26.0% +/- 38.0% right ventricular pacing. CONCLUSIONS No excess mortality is associated with a PPM after cardiac transplantation, and biatrial technique strongly predicts PPM requirement. Increased atrial fibrillation among PPM recipients may be related to right ventricular stimulation with dual-chamber pacing.