Cardiac resynchronization therapy in patients with right bundle branch block: Analysis of pooled data from the MIRACLE and Contak CD trials

Background

Clinical trials of cardiac resynchronization therapy (CRT) have not included many patients with right bundle branch block (RBBB).

Objectives

We pooled data from two randomized controlled trials of CRT (Multicenter InSync Randomized Clinical Evaluation [MIRACLE] and Contak CD) in order to assess outcomes of patients with RBBB.

Methods

A total of 61 patients with RBBB were identified, 34 of whom were randomized to the CRT group and 27 to the control group. The data from these patients were entered into a new database and analyzed.

Results

Baseline demographics were not different between the two groups (mean age 65.5 ± 11.3 years vs 69.5 ± 9.6 years; male gender 91% vs 85%; patients with coronary disease 76.5% vs 88%; QRS duration 167 ms vs 164 ms; all P = NS). Outcome variables (New York Heart Association [NYHA] class, 6-minute hall walk distance, peak oxygen consumption (VO₂), Minnesota Living with Heart Failure quality-of-life scores, left ventricular ejection fraction, and norepinephrine levels) were analyzed at randomization, 3 months, and 6 months.

Conclusions

(1) With the exception of NYHA class, patients with RBBB as the qualifying wide QRS did not derive significant benefit from CRT in any of the other parameters studied at 3 or 6 months. (2) RBBB patients who received active CRT showed significant improvements in NYHA class by 6 months and trends toward improvement in 6-minute walk distance, quality-of-life scores, and norepinephrine levels. However, control patients also showed significant improvement in NYHA class by 6 months but showed no improvement in objective measurements (VO₂, 6-minute walk distance, left ventricular ejection fraction, and norepinephrine levels), consistent with a placebo effect. Analysis of a larger cohort of patients with RBBB undergoing CRT may demonstrate significant benefit, but the current analysis does not support the use of CRT in patients with RBBB.

Introduction

Cardiac resynchronization therapy (CRT) restores the dyssynchronous ventricular activation imposed by the electrical conduction delays in patients with congestive heart failure. Several studies have demonstrated clinical improvement in patients with moderate-to-severe heart failure and intraventricular conduction delays (QRS duration >120.1, 2, 3, 4 However, the majority of patients in these studies demonstrate left bundle branch block (LBBB) morphology, with a minority showing nonspecific conduction delays or right bundle branch block (RBBB). Except for patients with congenital heart disease, isolated right ventricular failure and RBBB⁵ and for isolated case reports,⁶ patients with RBBB and congestive heart failure have not been adequately evaluated because of underrepresentation in the referenced studies. We performed an analysis of pooled data from two randomized controlled trials of CRT—Multicenter InSync Randomized Clinical Evaluation (MIRACLE)² and Contak CD⁴—in order to assess the outcomes of patients with RBBB.

The MIRACLE trial² enrolled 453 patients with moderate or severe (New York Heart Association [NYHA] class III or IV) chronic heart failure. All patients had left ventricular ejection fraction (LVEF) ≤35%, left ventricular end-diastolic dimension ≥55 mm, QRS interval ≥130 ms, and a 6-minute walking distance ≤450 m. All patients received optimal medical therapy for heart failure. Patients who had successful implantation were randomized to an atrial synchronized biventricular pacing group or to a no pacing control group. Patients were evaluated at 1, 3, and 6 months, during which heart medications were held constant. The study had three primary endpoints: NYHA class, quality of life as defined by the Minnesota Living with Heart Failure score, and distance (in meters) walked in 6 minutes. Secondary endpoints included peak oxygen consumption (VO₂) and LVEF, among others.

The Contak CD study was a prospective randomized, controlled, multicenter, double-blind study that enrolled a total of 581 patients.⁴ Entry criteria for participation included patients with NYHA class II to IV, LVEF ≤35%, QRS duration ≥120 ms, and conventional indications for implantable cardioverter-defibrillator placement. Patients in this trial also were randomized to the CRT group or the no CRT group. Study analysis included a phase I study with a cross-over design followed for 3 months and the modified phase II study of a parallel design followed for 6 months. The primary endpoints were progression of heart failure, defined as a composite of all-cause mortality, hospitalization for worsening heart failure, and ventricular tachyarrhythmia requiring device therapy. Secondary endpoints included VO₂, 6-minute walk, quality of life, and NYHA class.