Cardiac resynchronization therapy restores muscular metaboreflex control

The muscular metaboreflex, whose activation regulates blood flow during isometric and aerobic exercise, is blunted in patients with heart failure (HF), and cardiac resynchronization therapy (CRT) may restore this regulatory reflex.

To evaluate metaboreflex responses after CRT.

Thirteen HF patients and 12 age-matched healthy control subjects underwent the following evaluations (pre- and post-CRT implantation in the patient group): (a) heart rate, blood pressure, and forearm blood flow measurements; (b) muscle sympathetic nerve activity (MSNA) evaluation; and (c) peak oxygen consumption (VO_2peak ). Examinations were performed at rest, during moderate isometric exercise (IE), and during forearm ischemia (metaboreflex activation). The primary outcome was the increment in MSNA during limb ischemia compared to the rest moment (ΔMSNA rest to metaboreflex activation).

After CRT, rest MSNA decreased in the HF participants: 50.4 ± 9.2 bursts/min pre-CRT vs 34.0 ± 14.4 bursts/min post-CRT, P = .001, accompanied by an improvement in systolic blood pressure and in rate-pressure product. MSNA during limb ischemia decreased: 56.6 ± 11.5 bursts/min pre-CRT vs 43.6 ± 12.7 bursts/min post-CRT, P = .001, and the ΔMSNA rest to metaboreflex activation increased: 0% (interquartile range [IQR)], -7 to 9) vs 13% (IQR, 5-30), P = .03. An augmentation of mean blood pressure during limb ischemia post-CRT was noticed: 94 mmHg (IQR, 81-104) vs 110 mmHg (IQR, 100-117), P = .04. CRT improved VO_2peak , and this improvement was correlated with diminution in ΔMSNA pre- to post-CRT at rest moment (r_s = -0.74, P = .006).

CRT provides metaboreflex sensitization and MSNA enhancement. The restoration of sympathetic responsiveness correlates with the improvement in functional capacity.