The role of comorbidities on periprocedural complications and outcomes in patients with defibrillators and cardiac resynchronization therapy: insights from the German device registry.

Atrial fibrillation (AF) is a cardiac arrhythmia frequently documented in patients requiring implantable cardioverter defibrillators (ICDs) and/or cardiac resynchronization therapy with defibrillator (CRT-D). Patients with diagnosed AF at the point of ICD or CRT-D implantation may have an impaired follow-up outcome. The German DEVICE I-II registry is a nationwide prospective multicentre database of patients implanted with ICD and CRT-D with clinical follow-up data. We analysed a 1-year follow up of implanted patients with AF and with sinus rhythm (SR). A total of 4,929 ICD/CRT patients are included in the present analysis: 946 (19.2%) were in AF and 3,983 (80.8%) were SR at time of device implantation. AF patients had a significantly more comorbid profile including older age {72 [interquartile range (IQR), 66-77] vs. 66 (IQR, 56-73) years; P<0.001}, and higher rate of patients with left ventricular ejection fraction <30% (68.2% vs. 61.0%; P<0.001), peripheral artery disease (4.5% vs. 2.7%; P=0.002), diabetes (33.6% vs. 25.5%; P<0.001), hypertension (58.4% vs. 51.1%; P<0.001) and renal failure (22.6% vs. 15.3%; P<0.001). The intra-hospital complication rate was 4.3% in the AF and 3.6% in the SR group (P=0.38). In 1-year follow-up AF patients experienced a significantly higher rate of defibrillator shocks (25% vs. 15.3%; P<0.001). One-year estimated mortality was 10.8% in the AF and 5.9% in the SR group (P<0.001), while estimated 1-year major adverse cardiac and cerebrovascular events (MACCE) rate was 11.2% vs. 7.0% (P<0.001). The effects of AF on electrical shocks and mortality persisted after adjusting for age, sex, advanced New York Heart Association (NYHA) class, severely impaired left ventricular ejection fraction (LVEF), coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM), chronic renal failure (CRF), QRS duration, and type of indication for electronic device implantation. Our clinical data on an extended cohort of contemporary patients confirm the significant impact of AF, and its associated comorbidities, upon mortality and major adverse events after implantation of ICD/CRT.

Complications and Mortality Following CRT-D Versus ICD Implants in Older Medicare Beneficiaries With Heart Failure

Cardiac Resynchronization Defibrillator Therapy for Nonspecific Intraventricular Conduction Delay Versus Right Bundle Branch Block

Data on the time-dependent benefit of cardiac resynchronization therapy with defibrillator (CRT-D) compared with a dual-chamber implantable cardioverter-defibrillator (ICD) to reduce death or ventricular tachycardia (VT) or ventricular fibrillation (VF) are limited. We aimed to evaluate the time-related risk of death or sustained VT or VF in patients receiving CRT-D vs. ICD in the MADIT-RIT trial. Kaplan-Meier survival analyses and multivariate Cox regression models were utilized to compare the incidence and the risk of death or sustained VT/VF in the CRT-D and ICD subgroups by the elapsed time after device implantation (6 months). Of the ICD (n = 742) and CRT-D (n = 757) patients enrolled, the risk of death was lower in CRT-D vs. in ICD early after device implantation [hazard ratio (HR) = 0.42, 95% confidence interval (CI): 0.17-1.03, P = 0.058] and beyond 6 months of follow-up (HR = 0.39, 95% CI: 0.21-0.73, P = 0.004), with the 6-month interaction P = 0.899. The overall risk of sustained VT/VF was reduced in CRT-D vs. ICD patients (HR = 0.73, 95% CI: 0.52-1.03, P = 0.07). However, the risk was similar in the first 6 months (HR = 1.00, 95% CI: 0.62-1.62, P = 0.988), and a lower risk emerged 6 months after CRT-D implantation (HR = 0.58, 95% CI: 0.38-0.88, P = 0.011), with the 6-month interaction P = 0.059. The reduced mortality risk of CRT-D compared with an ICD alone began early after device implantation and was sustained during long-term follow-up; the reduced risk for ventricular tachyarrhythmias did not emerge until 6 months after device implantation. http://clinicaltrials.gov/ct2/show/NCT00947310.

Mid-term feasibility and safety of downgrade procedure from defibrillator to pacemaker with cardiac resynchronization therapy

The mode of death in implantable cardioverter-defibrillator and cardiac resynchronization therapy with defibrillator patients: Results from routine clinical practice

Background Limited data exist on the effects of cardiac resynchronization therapy with defibrillator (CRT-D) on clinical outcomes in patients with advanced left ventricular dysfunction. Purpose This study aimed to evaluate the clinical benefits of CRT-D compared with an implantable cardioverter defibrillator (ICD) in patients with very low left ventricular ejection fraction (LVEF ≤20%) and a wide QRS complex. Methods This study included 820 patients with LVEF ≤20% and QRS duration ≥130 ms, enrolled in five major trials (MADIT-II, MADIT-CRT, MADIT-RIT, MADIT-RISK, RAID). The primary outcome was a composite of heart failure (HF) or death. Secondary outcomes included death, first HF event, recurrent HF, ventricular tachycardia or fibrillation (VT/VF), and appropriate ICD shocks. Outcomes were stratified by the presence of left bundle branch block (LBBB). Results Among 508 CRT-D patients (70% LBBB) and 364 ICD patients (72% LBBB), CRT-D vs. ICD was associated with a significant reduction in the 3-year cumulative event rate of HF or death in LBBB patients (20% vs. 40%, p&amp;lt;0.001 [Figure Panel A]) but not in non-LBBB patients (37% vs. 42%, p=0.499 [Figure Panel B]). Multivariate analysis showed that CRT-D significantly reduced HF or death in LBBB patients (HR=0.46, p&amp;lt;0.001) but showed no benefit in non-LBBB patients (HR=1.16, p=0.566; p-value for interaction =0.001). Similarly, in LBBB patients, CRT-D was associated with reductions in death (HR=0.60, p=0.069), first HF event (HR=0.42, p&amp;lt;0.001), recurrent HF (HR=0.39, p&amp;lt;0.001), VT/VF (HR=0.64, p=0.011), and appropriate ICD shocks (HR=0.35, p&amp;lt;0.001). In contrast, CRT-D did not significantly reduce any of these outcomes in non-LBBB patients (p&amp;gt;0.1 for all comparisons; p for interaction device-by-LBBB &amp;lt;0.05 for all). Conclusions CRT-D provides significant clinical benefits in patients with advanced left ventricular dysfunction and LBBB. These findings should be considered when evaluating the need for advanced HF intervention therapies in this population.

In MADIT-CRT, patients with non-LBBB (right bundle branch block or nonspecific ventricular conduction delay) and a prolonged PR-interval derived significant clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D) compared to an implantable cardioverter defibrillator (ICD)-only. We aimed to study the long-term outcome of non-LBBB patients by baseline PR-interval with CRT-D versus ICD-only. Non-LBBB patients (n=534) were dichotomized based on baseline PR-interval: normal PR (PR<230ms), and markedly prolonged PR (PR≥230ms). The primary end point was heart failure (HF) or death. Secondary end points were HF only and all-cause death. In patients with a prolonged PR-interval, CRT-D treatment related to a 67% significant reduction in the risk of HF/death (HR=0.33, 95% CI 0.16-0.69, p=0.003), 69% decrease in HF (HR=0.31, 95% CI 0.14-0.68, p=0.003), and 76% reduction in the risk of death (HR=0.24, 95% CI 0.07-0.80, p=0.020) compared to ICD-only (median follow-up 5.8years). In normal PR-interval patients, CRT-D therapy was associated with a trend towards increased risk of HF/death (HR=1.49, 95% CI 0.98-2.25, p=0.061), and significantly increased mortality (HR=2.27, 95% CI 1.16-4.44, p=0.014). Significant statistical interaction with the PR-interval was demonstrated for all end points. Results were consistent for QRS 130-150ms and QRS>150ms. In MADIT-CRT, non-LBBB patients with a prolonged PR-interval derive sustained long-term clinical benefit with reductions in heart failure or death from CRT-D implantation, compared to an ICD-only. Our findings support implantation of CRT-D in non-LBBB patients with prolonged PR-interval irrespective of baseline QRS duration.

Multiple Comorbidities and Response to Cardiac Resynchronization Therapy: MADIT-CRT Long-Term Follow-Up

Background Over a quarter of all cardiac resynchronization therapy (CRT) implants are upgrades from previous devices, mainly from implantable cardioverter-defibrillator (ICD). In comparison to CRT with defibrillator (CRT-D) de novo implantation, upgrade from ICD to CRT-D carries higher risk of complications. Limited number of studies evaluated predictors of death in patients undergoing upgrade from ICD to CRT-D. Aim To determine mortality predictors and outcome in patients undergoing upgrade from ICD to CRT-D in comparison to subjects with CRT-D de novo implantation. Methods Study population consisted of 595 consecutive patients with CRT-D implanted between 2002 and 2015 in tertiary care university hospital, in a densely inhabited, urban region of Poland (480 subjects [84.3%] with CRT-D de novo implantation; 115 patients [15.7%] upgraded from ICD to CRT-D). Results The median follow-up was 1692 days (range: 457–3067). All-cause mortality in patients upgraded from ICD was significantly higher than in subjects with CRT-D implanted de novo (43.5% vs. 35.5%, P=0.045). On multivariable regression analysis, left ventricular end-systolic diameter (HR 1.07, 95% CI 1.02–1.11, P=0.002), creatinine level at baseline (HR 1.01, 95% CI 1.00–1.02, P=0.01), NYHA IV class at baseline (HR 2.36, 95% CI 1.00–5.53, P=0.049) and cardiac device-related infective endocarditis (CDRIE) during follow up (HR 2.42, 95% CI 1.02–5.75, P=0.046) were identified as independent predictors of higher mortality in patients with CRT-D upgraded from ICD. Conclusions Mortality rate in patients upgraded from ICD is higher in comparison to CRT-D de novo implanted subjects, and reaches almost 45% within 4.5 years. Left ventricular dimensions, creatinine level, high NYHA class at baseline and infective endocarditis during follow up are independent mortality predictors in patients with CRT-D upgraded from ICD.

Guidelines of heart failure therapy include cardiac resynchronization as standard of care in patients with severely depressed left ventricular function and wide QRS complex. It has been shown that patients benefit regarding mortality and morbidity. However, early mortality precludes longterm benefits from the device. The aim of the study was to identify predictors for early occurrence of both death and first-ever implantable cardioverter-defibrillator (ICD) therapy using a large combined database of patients with cardiac resynchronization therapy with defibrillator (CRT-D). From two registries (tertiary care centers) 904 patients were identified, no single patient was excluded. Early death was defined as death occurring within the 3 years after implantation whereas early ICD therapy as such occurring within the first year. 33 baseline parameters were compared using uni- and multivariate analysis with the Cox model and binary logistic regression. The population was predominantly male (77%), with mean age of 63 ± 11 years and primary prevention indication in 80%. Mean follow-up was 55 ± 38 months. 256 (28%) patients had ICD therapies whereof the first-ever event occurred early in 52%. 270 (30%) patients died after 41 ± ± 31 months, mostly from advancing heart failure (41%), 141 (52%) patients of them early. Independent predictors for early ICD therapy were secondary prevention and renal failure. Independent predictors for early mortality were a history of percutaneous coronary intervention and of peripheral vascular disease. Predictors for early mortality after CRT-D implantation were a history of percutaneous coronary intervention and peripheral vascular disease, present in only a minority of patients, thus limiting their use in clinical practice.

Background: Implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy with defibrillator (CRT-D) are established efficient therapies, but negative effects of their shocks have been reported. Purpose: We assessed if ICD shock or anti-tachycardia pacing (ATP) is associated with poor prognosis, and which factor predicts shocks in ICD and CRT-D patients. Subjects and Methods: A total of 161 consecutive patients who received ICD (n=132) or CRT-D (n=29) (age 57.2±14.3 years, 78% male, 76% non-ischemic cardiomyopathy (NICM)) were retrospectively analyzed. Results: During the follow-up period of 27.0±20.2 months, cardiac events occurred in 14 patients (1 sudden death, 2 death or 11 hospitalization for heart failure). Patients who experienced at least 1 ICD shock had significantly higher incidence of cardiac events and hazard risk was 1.92 (p<0.05). Such an effect on the prognosis was not observed for ATP. Multivariate analysis indicates that class I anti-arrhythmic agents and non-use of amiodarone were independent predictor of appropriate shock and that of inappropriate shock, respectively. Conclusion: ICD shock, but not ATP, was associated with increase in cardiac events in a group which mainly consists of NICM. Untoward effect of class I anti-arrhythmic agents and benefit of amiodarone on ICD shock incidence need to be considered.

Current guidelines lack clear recommendations between the implantation of cardiac resynchronization therapy (CRT) with defibrillator (CRT-D) and CRT with pacemaker (CRT-P). We hypothesized that modified model for end-stage liver disease score including albumin (MELD-Albumin score), could be used to select patients who may not benefit from CRT-D. We consecutively included patients with CRT-P or CRT-D implantation between 2010 and 2022. The primary endpoint was the composite of all-cause mortality or worsening heart failure. We performed multivariable-adjusted Cox proportional hazard regression. We assessed the interaction between the MELD-Albumin score and the effect of adding a defibrillator with CRT.A total of 752 patients were included in this study, with 291 implanted CRT-P. During a median follow-up of 880 days, 205 patients reached the primary endpoint. MELD-Albumin score was significantly associated with the primary endpoint in the CRT-D group [HR 1.16 (1.09-1.24); P < 0.001] but not in the CRT-P group [HR 1.03 (0.95-1.12); P = 0.49]. There was a significant interaction between the MELD-Albumin score and the effect of CRTD (P = 0.013). The optimal cut-off value of the MELD-Albumin score was 12. For patients with MELD-Albumin ≥ 12, CRT-D was associated with a higher occurrence of the primary endpoint [HR 1.99 (1.10-3.58); P = 0.02], whereas not in patients with MELD-Albumin < 12 [HR 1.19 (0.83-1.70); P = 0.35). Our findings suggest that CRT-D is associated with an excess risk of composite clinical endpoints in HF patients with higher MELD-Albumin score.

VT begets VT—and other bad stuff—in patients treated with CRT-D

POSTER PRESENTATIONS