Early cardiac resynchronization therapy and reverse remodeling in patients with mild heart failure: is it time?

Cardiac resynchronization therapy (CRT) has been shown to consistently improve cardiac performance and exercise capacity, leading to reversal of cardiac remodeling and improvement in survival in patients with advanced heart failure and a significant ventricular conduction delay. The strategy of CRT for the treatment of advanced heart failure was secured in 2005 by the landmark Cardiac Resynchronization in Heart Failure (CARE-HF) study.1 Recently, 2 studies have extended these observed benefits of CRT to patients with less advanced (New York Heart Association [NYHA] class I/II) signs and symptoms who still fulfilled standard indications for resynchronization therapy. The recently published Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) study demonstrated 34% relative risk reduction in death or heart failure events with CRT and defibrillator (CRT-D) compared with implantable cardioverterdefibrillator alone in 1820 subjects with left ventricular (LV) ejection fraction 30% and QRS duration 130 ms, which was largely driven by reduction in heart failure events and associated with reverse remodeling. 2 Although the primary end point of a heart failure clinical composite response was not met in the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) trial, observed improvement in the prospectively powered secondary end point of LV end-systolic volume index in the presence of CRT suggests that early implementation of CRTD in 610 patients with mild heart failure (NYHA class I/II, LV ejection fraction 40% and LV end-diastolic dimension 55 mm by echocardiography, QRS duration 120 ms) may be considered a beneficial strategy. 3 The article by St John Sutton and colleagues4 extends the concept of reverse remodeling of CRT by carefully examining the time course of reverse remodeling and identifying the subgroups that may have a particularly favorable response. The investigators now provide a more expansive analysis of the remodeling data, which is internally consistent and highly favorable. The authors go on to conclude that progressive LV remodeling can be prevented or even reversed by CRT in patients with mild heart failure with the use of resynchronization criteria to the same extent as in those with advanced heart failure, particularly in those with nonischemic etiology. Article see p 1858