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

Abstract

Background: Data regarding cardiac resynchronization therapy (CRT) in patients with multiple comorbidities are limited.

Objectives: This study evaluated the association of multiple comorbidities with the benefits of CRT over implantable cardioverter-defibrillator (ICD) alone.

Methods: We examined 1,214 MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy) study patients with left bundle branch block (LBBB) and 0, 1, 2, or ≥3 comorbidities, including renal dysfunction, hypertension (HTN), diabetes, coronary artery disease, history of atrial arrhythmias, history of ventricular arrhythmias, current smoking, and cerebrovascular accident. In an adjusted analysis, we analyzed risk of heart failure (HF) events or death by comorbidity group in all patients and in patients with CRT with defibrillator (CRT-D) versus ICD. Then we examined percent change in left ventricular (LV) end-diastolic volume, LV end-systolic volume, LV ejection fraction, left atrial volume, and LV dyssynchrony at 1-year in CRT-D patients by comorbidity group.

Results: There was an inverse relationship between comorbidity burden and improvements in LV end-systolic volume, LV end-diastolic volume, left ventricular ejection fraction, left atrial volume, and LV dyssynchrony. In an adjusted model, there was an increasing risk of death or nonfatal HF events with increasing comorbidity burden regardless of treatment group (p < 0.001). During a mean follow-up of 4.65 years, there was no interaction with respect to comorbidity burden and the benefit of CRT-D versus ICD only for death or nonfatal HF events (interaction p = 0.943). In the groups with greatest comorbidity burden (2 and ≥3), the absolute risk reduction associated with CRT-D over ICD alone appeared greater than that seen for groups with less comorbidity burden (0 and 1).

Conclusions: During long-term follow-up of MADIT-CRT study patients with LBBB randomized to CRT-D, there were differences in HF or death risk and in the degree of reverse remodeling among comorbidity groups. However, the burden of comorbidity does not appear to compromise the clinical benefits of CRT-D compared with ICD alone.

Keywords: cardiac resynchronization therapy; heart failure; mortality.

Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

Kaplan-Meier Curves for Mortality or Nonfatal HF Events by Treatment Group Stratified by Number of Comorbidities (0, 1, 2, ≥3) (A) Overall, (B) cardiac resynchronization therapy with defibrillator (CRT-D), and (C) implantable cardioverter-defibrillator (ICD) only. In the overall MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy) study population, the greatest comorbidity burden was associated with the greatest risk of death or heart failure (HF). This relationship was true when the population was divided by treatment assignment (CRT-D vs. ICD). In both cases, patients with ≥3 comorbidities had the highest risk, and those with 0 comorbidities had the lowest risk. In the ICD group, comorbidity burden had a clearer association with this risk whereas in the CRT-D group, there did not appear to be an important difference between the groups with 1 and 2 comorbidities. Cm = comorbidity.

Figure 2.

Forest Plot of Unadjusted Hazard of Mortality or Nonfatal HF Events by Treatment Group (CRT-D vs. ICD) According to Comorbidities The hazard ratio (HR) for death or HF is plotted for each comorbidity independently. In nearly all cases, CRT-D is statistically favored. In those cases in which the 95% CI crosses unity, there is a clear trend favoring CRT-D. There is no interaction of any single comorbidity with the treatment assignment (ICD vs. CRT-D) with respect to the outcome of HF or death (interaction p > 0.50 for all). AA = atrial arrhythmia; CI = confidence interval; GFR = glomerular filtration rate; Pts = patients; VA = ventricular arrhythmia; other abbreviations as in Figure 1.

Central Illustration.

Treatment Effect of CRT-D Versus ICD in Comorbidity Groups (A) Zero comorbidities, (B) 1 comorbidity, (C) 2 comorbidities, (D) ≥3 comorbidities. These 4 Kaplan-Meier curves divide the population by comorbidity group and compare probability of heart failure or death during 7 years of follow-up between treatment groups: implantable cardioverter-defibrillator (ICD) versus cardiac resynchronization therapy with defibrillator (CRT-D). In all cases, patients assigned to CRT-D had on average decreased probability of heart failure (HF) or death. This difference was statistically significant for the 1, 2, and ≥3 comorbidity groups. The greatest absolute risk reduction was observed in the groups with 2 or ≥3 comorbidities.