Left Ventricular Reverse Remodeling in Cardiac Resynchronization Therapy and Long-Term Outcomes.

OBJECTIVES: The aim of this study was to evaluate the association between improvement in left ventricular end-systolic volume (LVESV) with cardiac resynchronization therapy (CRT) and mortality and whether this relationship was modified by the presence of a left bundle branch block (LBBB) electrocardiographic pattern. BACKGROUND: Left ventricular reverse remodeling in patients receiving CRT has been shown to predict outcomes. However, the extent to which reverse remodeling contributes to long-term survival is not well understood. METHODS: Changes in LVESV were assessed in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) patients receiving CRT with a defibrillator (CRT-D) and echocardiograms available at 1 year (n = 752), stratified by LBBB, relative to long-term all-cause mortality, compared with those with implantable cardioverter-defibrillators (ICDs) only (n = 684). RESULTS: In patients with LBBB, a reduction in LVESV of >35% (median) translated into significantly lower risk for long-term mortality (hazard ratio [HR]: 0.34; p < 0.001), heart failure (HF) events (HR: 0.21; p < 0.001), and HF or death (HR: 0.27; p < 0.001) compared with patients with ICDs only. Patients with reductions in LVESV ≤35% had a significantly lower risk for HF, and HF or death, and a nonsignificantly lower rate of death compared with those with ICDs only (HR: 0.74; p = 0.13). Risk reduction in HF events was uniform across all LVESV quartiles. In patients without LBBB, there was no survival benefit (HR: 0.68; p = 0.271) despite an LVESV reduction greater than the median (>27.6%). CRT-D patients without LBBB with the least reverse remodeling (quartile 1) had a more than 3-fold increased risk for death compared with those with ICDs only (HR: 3.11; p < 0.001). CONCLUSIONS: In patients with LBBB, CRT-D-induced reduction in LVESV at 1 year is associated with long-term survival benefit. Despite left ventricular reverse remodeling with CRT-D, there is no survival benefit and potential harm in patients without LBBB.

Long-term outcomes of cardiac resynchronization therapy by left ventricular ejection fraction.

AIMS: Despite our prior report suggesting heart failure (HF) risk reduction from cardiac resynchronization therapy with defibrillator (CRT-D) in mild HF patients with higher left ventricular ejection fraction (LVEF > 30%), data on mortality benefit in this cohort are lacking. We aimed to assess long-term mortality benefit from CRT-D in mild HF patients by LVEF > 30%. METHODS AND RESULTS: Among 1274 patients with mild HF and left bundle branch block enrolled in MADIT-CRT, we analysed long-term effects of CRT-D vs. implantable cardioverter defibrillator (ICD) therapy only, and reverse remodelling to CRT-D (left ventricular end-systolic volume percent change ≥ median at 1 year), on all-cause mortality and HF for the LVEF ≤ 30% and LVEF > 30 subgroups using Kaplan-Meier and Cox analyses. During long-term follow-up, CRT-D vs. ICD was associated with reduction in all-cause mortality in both patients with LVEF > 30% and LVEF ≤ 30% [hazard ratio (HR) 0.47, 95% confidence interval (CI) 0.25-0.85, P = 0.036 vs. HR 0.69, 95% CI 0.49-0.98, P = 0.013, interaction P = 0.261]. The efficacy of CRT-D vs. ICD only to reduce HF was similar in those with LVEF above and below 30% (HR 0.36, 95% CI 0.35-0.61, P < 0.001 vs. HR 0.46, 95% CI 0.35-0.61, P < 0.001; interaction P = 0.342). Patients with CRT-D-induced reverse remodelling had significant mortality reduction when compared to ICD, with either LVEF > 30% or LVEF ≤ 30% (HR 0.17 and 0.39), but no mortality benefit was seen in patients with less reverse remodelling. HF events, however, were reduced in both CRT-D-induced high and low reverse remodelling vs. ICD only, in both LVEF subgroups. CONCLUSIONS: In MADIT-CRT, left bundle branch block patients with higher LVEF (> 30%) derive long-term mortality benefit from CRT-D when exhibiting significant reverse remodelling. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID NCT00180271, NCT01294449, and NCT02060110.

Extended use of the wearable cardioverter-defibrillator in patients at risk for sudden cardiac death.

Aims: Data on outcomes in patients using the wearable cardioverter-defibrillator (WCD) > 90 days are limited. We aimed to analyse the clinical course of patients with WCD use ≤90 days vs. WCD use >90 days. Methods and results: We assessed arrhythmia events during WCD use, and ejection fraction (EF) improvement/implantable cardioverter-defibrillator (ICD) implantation at the end of WCD use in patients with WCD use ≤90 days vs. WCD use >90 days enrolled in the WEARIT-II registry, further assessed by disease aetiology (ischaemic vs. non-ischaemic vs. congenital/inherited heart disease). There were 981 (49%) patients with WCD use >90 days, and 1019 patients with WCD use ≤90 days (median 120 vs. 55 days). There was a lower incidence of sustained ventricular tachycardia/ventricular fibrillation (VT/VF) events (11 vs. 50 events per 100 patient-years, P < 0.001), WCD treated VT/VF events (1 vs. 8 events per 100 patient-years, P < 0.001), and non-sustained VT events (21 vs. 51 events per 100 patient-years, P = 0.008) with WCD use >90 vs. WCD use ≤90 days. Non-ischaemic cardiomyopathy patients presented with similar rates of sustained VT/VF events during WCD use >90 vs. ≤90 days (13.4 vs. 13.7 events per 100 patient-years, P = 0.314), while most of these events terminated spontaneously. One-third of the patients with extended WCD use further improved their EF and they were not implanted with an ICD, with similar rates among ischaemic and non-ischaemic patients. Conclusions: In WEARIT-II, patients with extended WCD use >90 days remain at risk for ventricular arrhythmia events. One-third of the patients with WCD use >90 days further improved their EF, avoiding the need to consider ICD implantation.

Experience with the wearable cardioverter-defibrillator in older patients: Results from the Prospective Registry of Patients Using the Wearable Cardioverter-Defibrillator.

BACKGROUND: Use of the wearable cardioverter-defibrillator (WCD) in older patients has not been described previously. OBJECTIVE: The purpose of this study was to assess WCD wear time, risk of arrhythmic events during WCD use, and implantable cardioverter-defibrillator (ICD) implantation rates after the end of WCD use in patients with age ≥65 years vs <65 years. METHODS: We stratified 1732 patients with ischemic and nonischemic cardiomyopathy from the Prospective Registry of Patients Using the Wearable Defibrillator Registry into 2 subgroups by age: those with age ≥65 years and those with age <65 years. Wear time, arrhythmic events, and end-of-use decisions, specifically ICD implantation or improvement in ejection fraction, were evaluated for each age group. RESULTS: There were 722 patients with age ≥65 years (41.7%) and 1010 patients with age <65 years (58.3%). Daily WCD wear time was longer in the older population (median 22.8 h/d (IQR 21.5 - 23.2) vs 22.3 h/d (IQR 19.5 - 23.0); P < .001). Patients with age ≥65 years experienced higher event rates, per 100 patient-years, for any sustained ventricular tachycardia/ventricular fibrillation (31.95 vs 9.82; P = .027) and ventricular tachycardia/ventricular fibrillation treated with WCD shock (6.92 vs 2.37; P = .034), particularly with ischemic cardiomyopathy. Younger patients experienced a trend toward a higher event rate for atrial arrhythmias with nonischemic cardiomyopathy (150.07 vs 74.86; P = .055). At the end of WCD use, ICD implantation was more frequent in older patients (41.8% vs 36.5%; P = .034). CONCLUSION: Older patients had good compliance with the WCD, presented with more frequent ventricular arrhythmias, and were more likely to receive an ICD at the end of WCD use. The WCD may play a role in risk stratification of the older population.

Impact of non-cardiovascular disease burden on thirty-day hospital readmission in heart failure patients.

BACKGROUND: Little is known about the impact of non-cardiovascular disease (CVD) burden on 30- -day readmission in heart failure (HF) patients. The aim of the study was to assess the role of non-CVD burden on 30-day readmission in HF patients. \ METHODS: We analyzed the effect of non-CVD burden by frequency of ICD-9 code categories on readmis-sions of patients discharged with a primary diagnosis of HF. We first modeled the probability of readmis-sion within 30 days as a function of demographic and clinical covariates in a randomly selected training dataset of the total cohort. Variable selection was carried out using a bootstrap LASSO procedure with 1000 bootstrap samples, the final model was tested on a validation dataset. Adjusted odds ratios and confidence intervals were reported in the validation dataset. RESULTS: There were a total of 6228 HF hospitalizations, 1523 (24%) with readmission within 30 days of discharge. The strongest predictor for 30-day readmissions was any hospital admission in the prior year (p < 0.001). Cardiovascular risk factors did not enter the final model. However, digestive system diseases increased the risk for readmission by 17% for each diagnosis (p = 0.046), while respiratory diseases and genitourinary diseases showed a trend toward a higher risk of readmission (p = 0.07 and p = 0.09, respectively). Non-CVDs out-competed cardiovascular covariates previously reported to predict readmission. CONCLUSIONS: In patients with HF hospitalization, prior admissions predicted 30-day readmission. Diseases of the digestive system also increase 30-day readmission rates. Assessment of non-CVD burden in HF patients could serve as an important risk marker for 30-day readmissions.

Heart failure severity, inappropriate ICD therapy, and novel ICD programming: a MADIT-RIT substudy.

BACKGROUND: The effects of heart failure (HF) severity on risk of inappropriate implantable cardioverter-defibrillator (ICD) therapy have not been thoroughly investigated. We aimed to study the association between HF severity and inappropriate ICD therapy in MADIT-RIT. METHODS: MADIT-RIT randomized 1,500 patients to three ICD programming arms: conventional (Arm A), high-rate cut-off (Arm B: ≥200 beats/min), and delayed therapy (Arm C: 60-second delay for ≥170 beats/min). We evaluated the association between New York Heart Association (NYHA) class III (n = 256) versus class I-II (n = 251) and inappropriate ICD therapy in Arm A patients with ICD-only and cardiac resynchronization therapy with defibrillator (CRT-D). We additionally assessed benefit of novel ICD programming in Arms B and C versus Arm A by NYHA classification. RESULTS: In Arm A, the risk of inappropriate therapy was significantly higher in those with NYHA III versus NYHA I-II for both ICD (hazard ratio [HR] = 2.55, confidence interval [CI]: 1.51-4.30, P < 0.001) and CRT-D patients (HR = 3.73, CI: 1.14-12.23, P = 0.030). This was consistent for inappropriate ATP and inappropriate ICD therapy < 200 beats/min, but not for inappropriate shocks. Novel ICD programming significantly reduced inappropriate therapy in patients with both NYHA III (Arm B vs Arm A: HR = 0.08, P < 0.001; Arm C vs Arm A: HR = 0.17, P < 0.001) and NYHA I-II (Arm B vs Arm A: HR = 0.25, P < 0.001; Arm C vs Arm A: HR = 0.28, P < 0.001). CONCLUSION: Patients with more severe HF are at increased risk for inappropriate ICD therapy, particularly ATP due to arrhythmias < 200 beats/min. Novel programming with high-rate cut-off or delayed detection reduces inappropriate ICD therapies in both mild and moderate HF.