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CLINICAL RESEARCH: CARDIAC RESYNCHRONIZATION

Randomized Trial of Cardiac Resynchronization in Mildly Symptomatic Heart Failure Patients and in Asymptomatic Patients With Left Ventricular Dysfunction and Previous Heart Failure Symptoms

Cecilia Linde, MD, PhD^_*,_*, William T. Abraham, MD, FACC, Michael R. Gold, MD, PhD, Martin St. John Sutton, MD, Stefano Ghio, MD^¶, Claude Daubert, MD^|| REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) Study Group

^_* Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
Division of Cardiovascular Medicine and the Davis Heart and Lung Research Institute, Ohio State University, Columbus, Ohio
Division of Cardiology, Medical University of South Carolina, Charleston, South Carolina
University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
^¶ Policlinico San Matteo, Pavia, Italy
^|| Département de Cardiologie, CHU, Rennes, France

Manuscript received June 13, 2008; revised manuscript received July 31, 2008, accepted August 14, 2008.

^_* Reprint requests and correspondence: Dr. Cecilia Linde, Department of Cardiology, Karolinska University Hospital, S-17176 Stockholm, Sweden (Email: cecilia.linde{at}ki.se).

Objectives: We sought to determine the effects of cardiac resynchronization therapy (CRT) in New York Heart Association (NYHA) functional class II heart failure (HF) and NYHA functional class I (American College of Cardiology/American Heart Association stage C) patients with previous HF symptoms.

Background: Cardiac resynchronization therapy improves left ventricular (LV) structure and function and clinical outcomes in NYHA functional class III and IV HF with prolonged QRS.

Methods: Six hundred ten patients with NYHA functional class I or II heart failure with a QRS 120 ms and a LV ejection fraction 40% received a CRT device (±defibrillator) and were randomly assigned to active CRT (CRT-ON; n = 419) or control (CRT-OFF; n = 191) for 12 months. The primary end point was the HF clinical composite response, which scores patients as improved, unchanged, or worsened. The prospectively powered secondary end point was LV end-systolic volume index. Hospitalization for worsening HF was evaluated in a prospective secondary analysis of health care use.

Results: The HF clinical composite response end point, which compared only the percent worsened, indicated 16% worsened in CRT-ON compared with 21% in CRT-OFF (p = 0.10). Patients assigned to CRT-ON experienced a greater improvement in LV end-systolic volume index (–18.4 ± 29.5 ml/m² vs. –1.3 ± 23.4 ml/m², p < 0.0001) and other measures of LV remodeling. Time-to-first HF hospitalization was significantly delayed in CRT-ON (hazard ratio: 0.47, p = 0.03).

Conclusions: The REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) trial demonstrates that CRT, in combination with optimal medical therapy (±defibrillator), reduces the risk for heart failure hospitalization and improves ventricular structure and function in NYHA functional class II and NYHA functional class I (American College of Cardiology/American Heart Association stage C) patients with previous HF symptoms. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT00271154 [ClinicalTrials.gov] ).

Key Words: cardiac resynchronization therapy • heart failure • randomized controlled trial • biventricular pacing • reverse remodeling

Abbreviations and Acronyms   AEAC = Adverse Event Advisory/Endpoint Committee   CRT = cardiac resynchronization therapy   HF = heart failure   ICD = implantable cardioverter-defibrillator   LV = left ventricular   LVESVI = left ventricular end-systolic volume index   NYHA = New York Heart Association

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