Effects of Cardiac Resynchronization Therapy on Cardiac Remodeling and Contractile Function: Results From Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE)

BACKGROUND: Cardiac resynchronization therapy results in improved ejection fraction in patients with heart failure. We sought to determine whether these effects were mediated by changes in contractility, afterload, or volumes. METHODS AND RESULTS: In 610 patients with New York Heart Association class I/II heart failure from the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) study, we performed detailed quantitative echocardiography assessment prior to and following cardiac resynchronization therapy. We derived measures of contractility (the slope [end-systolic elastance] and the volume intercept of the end-systolic pressure–volume relationship, stroke work, and preload recruitable stroke work), measures of arterial load and ventricular–arterial coupling, and measures of chamber size (volume intercept, end-systolic and end-diastolic volumes). At 6 and 12 months, cardiac resynchronization therapy was associated with a reduction in the volume intercept and end-systolic and end-diastolic volumes (P<0.01). There were no consistent effects on end-systolic elastance, stroke work, preload recruitable stroke work, or ventricular–arterial coupling. In the active cardiac resynchronization therapy population, baseline measures of arterial load were associated with the clinical composite score (odds ratio 1.30, 95% CI 1.04 to 1.63, P=0.02). The volume intercept was associated with mortality (hazard ratio 1.90, 95% CI 1.01 to 3.59, P=0.047) and more modestly with the combined end point of mortality or heart failure hospitalization (hazard ratio 1.48, 95% CI 0.8 to 2.25, P=0.06). In contrast, end-systolic elastance, stroke work, preload recruitable stroke work, and ventricular–arterial coupling were not associated with any outcomes. CONCLUSION: In patients with NYHA Class I/II heart failure, cardiac resynchronization therapy exerts favorable changes in left ventricular end-systolic and end-diastolic volumes and the volume intercept. The volume intercept may be useful to gain insight into prognosis in heart failure. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00271154.