Time course of effects of cardiac resynchronization therapy in chronic heart failure: benefits in patients with preserved exercise capacity.

Objectives: To assess in patients with chronic heart failure the effect of cardiac resynchronization therapy (CRT) over 12 months' follow-up the time course of the changes in functional and neurohormonal indices and to identify responders to CRT.

Methods: Eighty-nine patients (74.1 +/- 1 years, left ventricular ejection fraction [LVEF] < 35%), QRS complex duration >150 ms, in stable New York Heart Association (NYHA) class III or IV on optimal medical treatment were prospectively randomized either in a control (n = 45) or CRT (n = 44) group and underwent clinical evaluation, cardiopulmonary exercise testing (CPET), 2D-Echo, heart rate variability (HRV), carotid baroreflex (BRS), and BNP assessments before and at 6- and 12-month follow-up.

Results: In the CRT group, improvement of cardiac indices and BNP concentration were evident at medium term (over 6 months) follow-up, and these changes persisted on a longer term (12 months) (all P < 0.05). Instead CPET indices and NYHA class improved after 12 months associated with restoration of HRV and BRS (all P < 0.05). We identified 26 responders to CRT according to changes in LVEF and diameters. Responders presented less depressed hemodynamic (LVEF 25 +/- 1.0 vs 22 +/- 0.1%), functional (peak VO(2) 10.2 +/- 0.2 vs 6.9 +/- 0.3 ml/kg/min), and neurohormonal indices (HRV 203.6 +/- 15.7 vs 147.6 +/- 10.ms, BRS 4.9 +/- 0.2 vs 3.6 +/- 0.3 ms/mmHg) (all P < 0.05). In the multivariate analysis, peak VO(2) was the strongest predictor of responders.

Conclusions: Improvement in functional status is associated with restoration of neurohormonal reflex control at medium term. Less depressed functional status (peak VO(2)) was the strongest predictor of responders to CRT.