OBJECTIVES: The aim of this study was to determine the long-term effects of cardiac resynchronization therapy (CRT) in the European cohort of patients enrolled in the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial. BACKGROUND: Previous data suggest that CRT slows disease progression and improves the outcomes of asymptomatic or mildly symptomatic patients with left ventricular (LV) dysfunction and a wide QRS complex. METHODS: We randomly assigned 262 recipients of CRT pacemakers or defibrillators, with QRS > or =120 ms and LV ejection fraction < or =40% to active (CRT ON; n = 180) versus control (CRT OFF; n = 82) treatment, for 24 months. Mean baseline LV ejection fraction was 28.0%. All patients were in sinus rhythm and receiving optimal medical therapy. The primary study end point was the proportion worsened by the heart failure (HF) clinical composite response. The main secondary study end point was left ventricular end-systolic volume index (LVESVi). RESULTS: In the CRT ON group, 19% of patients were worsened versus 34% in the CRT OFF group (p = 0.01). The LVESVi decreased by a mean of 27.5 +/- 31.8 ml/m(2) in the CRT ON group versus 2.7 +/- 25.8 ml/m(2) in the CRT OFF group (p < 0.0001). Time to first HF hospital stay or death (hazard ratio: 0.38; p = 0.003) was significantly delayed by CRT. CONCLUSIONS: After 24 months of CRT, and compared with those of control subjects, clinical outcomes and LV function were improved and LV dimensions were decreased in this patient population in New York Heart Association functional classes I or II. These observations suggest that CRT prevents the progression of disease in patients with asymptomatic or mildly symptomatic LV dysfunction. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT00271154).