Interruption of short-term cardiac resynchronization therapy (CRT) has been shown to acutely worsen left ventricular (LV) function, mitral regurgitation, and LV dyssynchrony. The present study aims to assess whether LV reverse remodeling influences interruption of CRT, and, more practically, whether long-term continuous pacing is necessary in patients with reverse LV remodeling. A total of 135 recipients of CRT were selected after showing LV reverse remodeling defined as a decrease in LV end-systolic volume > or =15% after 6 months of CRT ("responders"). Echocardiography was performed at baseline and after 6 months with intermittent CRT on and off. LV dyssynchrony was determined using tissue Doppler imaging. During interruption of CRT, an acute deterioration in LV function, mitral regurgitation, and LV desynchronization were noted in responder patients. Of note, worsening of these echocardiographic measurements was observed, but they did not return to baseline values. For comparison, 100 nonresponder patients (without LV reverse remodeling) showed no significant echocardiographic changes during interruption. In conclusion, despite the presence of LV reverse remodeling, interruption of CRT resulted in worsening of LV function and desynchronization. Therefore, continuous long-term pacing is warranted to maintain the beneficial effects.