Left atrial volume and the benefit of cardiac resynchronization therapy in the MADIT-CRT trial.

BACKGROUND Left atrial volume (LAV) is an important marker of heart failure (HF) severity. We hypothesized that LAV independently correlates with clinical outcomes in patients who receive cardiac resynchronization therapy with a defibrillator (CRT-D) and can be used for improved risk assessment in this population. METHODS AND RESULTS The benefit of CRT-D versus defibrillator-only therapy in reducing the risk of HF or death was assessed by LAV (dichotomized at the upper quartile>52 mL/m2) among 1785 patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) study. Landmark analysis was used to evaluate the relationship between LAV response to CRT-D and subsequent clinical outcomes. Multivariable analysis showed that patients with a higher baseline LAV experienced 69% (P<0.001) and 59% (P=0.02) increased hazard for HF or death and for all-cause mortality, respectively, independently of baseline left ventricular volume. CRT-D was associated with a significant reduction in LAV compared with defibrillator-only therapy (-28% versus -10%, respectively; P<0.001). Landmark analysis showed that after CRT-D implantation each 1% reduction in LAV was independently associated with a corresponding 4% reduction in the hazard of subsequent HF or death (P<0.001). The assessment of LAV change after CRT implantation improved prediction of clinical response to the device compared with assessment of the corresponding changes in left ventricular volume. CONCLUSIONS LAV is an independent correlate of clinical outcomes in mildly symptomatic HF patients treated with CRT-D. CRT exerts pronounced reverse remodeling effects on the left atrium that independently correlate with improved clinical outcomes after device implantation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.