A Mechanistic Investigation Into How Long-Term Resynchronization Therapy Confers Ongoing Cardiac Functional Benefits and Improved Exercise Capacity

Abstract

The exact mechanisms underpinning the longer term benefits of cardiac resynchronization therapy (CRT) were not fully understood. It was still unclear whether there was any ongoing functional benefit conferred by the partial resynchronization of ventricular contraction. To resolve this, a randomized controlled double-blind crossover trial was conducted to investigate the impact of temporary cessation of CRT on cardiac function both at rest and during peak exercise. Fifteen patients with severe heart failure and a CRT device implanted at least 3 months previously were randomly assigned to have the CRT mode switched to either off or on during exercise tests with central hemodynamic measurements (including noninvasive cardiac output measured using rebreathing methods), then crossed over on separate days to the opposite CRT mode. There were no significant changes in hemodynamic variables at rest with either mode of CRT. When CRT was acutely turned off, there was 19% lower peak exercise cardiac power (2.10 +/- 0.46 vs 2.59 +/- 0.75 W; p <0.005), 6% lower mean arterial pressure (92 +/- 12 vs 98 +/- 13 mm Hg; p <0.05), and 11.5% lower peak cardiac output (10.4 +/- 1.9 vs 11.8 +/- 2.5 L/min; p <0.05). Exercise capacity was also diminished with lower peak oxygen uptake (15.7 +/- 4.3 vs 17.2 +/- 4.9 ml/kg/min; p <0.01) and shorter exercise duration (542 +/- 204 vs 587 +/- 212 seconds; p <0.05). These changes were seen without differences in peak respiratory exchange ratio and peak systemic vascular resistance. In conclusion, these observations provided evidence that after CRT, left ventricular resynchronization continued to confer cardiac functional benefits manifest during peak exercise, but imperceptible at rest.