Impact of Left Ventricular vs Biventricular Pacing on Reverse Remodelling: Insights From the Evaluation of Resynchronization Therapy for Heart Failure (EARTH) Trial

Abstract

Background: Studies comparing biventricular (BiV) cardiac resynchronization therapy (CRT) and left ventricular (LV) pacing alone have yielded conflicting results. We recently reported the results of the Greater Evaluation of Resynchronization Therapy for Heart Failure (GREATER-EARTH) trial demonstrating similar clinical benefits of BiV and LV-CRT on exercise tolerance. We report the prespecified secondary outcomes of the GREATER-EARTH trial, comparing the impact of BiV vs LV-CRT on structural and biochemical cardiac remodelling.

Methods: Patients with a LV ejection fraction (LVEF) ≤ 35% and a QRS duration ≥ 120 ms were randomized to BiV-CRT or LV-CRT for a 6-month period, followed by crossover. The primary end point was a change in LV end-systolic volume (LVESV). Secondary end points included changes in LVEF, right ventricular (RV) dimensions and function, mitral regurgitation (MR), indices of diastolic function, systolic pulmonary artery pressure (sPAP), and disease-specific biomarkers.

Results: One hundred twenty patients (60.9 ± 8.8 years; 75.0% men; LVEF, 24.4% ± 6.3%) were enrolled. A similar reduction in LVESV was observed, from a baseline of 162.4 ± 57.2 mL to 130.4 ± 63.4 mL with BiV pacing and 130.3 ± 59.9 mL with LV pacing (P = 0.679, BiV pacing vs LV pacing). Improvements in LVEF, RV remodelling, and N-terminal pro b-type natriuretic peptide were similar between groups. BiV pacing yielded superior outcomes with respect to LV diastolic function, indexed left atrial volume, degree of MR, and sPAP (all P < 0.05), together with decreased N-terminal propeptide of type III collagen with LV-CRT.

Conclusions: In this randomized double-blind crossover trial, BiV and LV pacing resulted in similar improvements in the primary LV remodelling end point (LVESV). Analyses of secondary end points revealed advantages of BiV pacing over LV pacing on several other features of cardiac remodelling, providing mechanistic insights to support the main finding of the GREATER-EARTH trial.