Baroreflex activation therapy (BAT) improved quality of life and exercise capacity in patients with heart failure and reduced ejection fraction, with a more pronounced impact in patients who had not undergone cardiac resynchronization therapy (CRT). Data from a randomized, phase 2 trial of BAT were presented by Michael Zile, MD, Medical University of South Carolina, Charleston, South Carolina, USA.

BAT acts through a central integrated mechanism to both decrease sympathetic tone and increase parasympathetic tone, rebalancing the autonomic imbalance present in patients with heart failure, explained Dr Zile. The procedure involves surgically implanting a 2 mm lead at the coronary sinus and connecting it to a pulse generator, which is placed in the subcutaneous space. Initial studies demonstrated a positive effect of carotid baroreceptor stimulation on ventricular remodeling, vasodilation, and renal function [Abraham WT et al. JACC Heart Fail. 2015]. Whether the positive response to BAT is uniform across all patients, particularly those who receive guideline-directed medical therapy, is not known.

In the prospective multinational trial, 140 patients with NYHA functional class III heart failure were randomized 1:1 to optimal medical and device therapy alone (control group) or BAT plus optimal medical and device therapy. To be eligible, patients had to have a left ventricular ejection fraction ≤ 35% and a 6-minute hall walk distance of 150 to 400 m. They had to be on stable medical therapy for at least 4 weeks prior to baseline assessment and, if indicated, device therapy for at least 6 months. Of the 140 patients, 45 had undergone CRT.

The primary safety end point was system- or procedure-related major adverse neurological or cardiovascular events at 6 months; the event-free rates were 100% in the CRT group and 96% in the no-CRT group, attesting to the safety of BAT.

In patients without CRT, the Minnesota Living with Heart Failure Quality of Life score improved by 21.6 points from baseline to 6 months in the BAT group, compared with a 3.5-point decrement in the control group (P < .001). In patients with CRT, there was no significant difference in this score between the BAT group and controls (P = .23). The difference in response to BAT between the CRT and no-CRT groups was statistically significant (P-interaction = .04).

In patients without CRT, 6-minute walk distance improved by 85.5 m in the BAT group vs a 3.6-m improvement in the controls (P = .003). No such difference between the BAT groups and controls emerged in the CRT patients (P = .38). Again, the difference in response to BAT on this end point between the CRT and no-CRT groups was significant (P-interaction = .01).

Left ventricular ejection fraction, an exploratory end point, improved significantly from baseline to 6 months in the no-CRT patients who received BAT vs controls (P < .03), with no such difference in the CRT group (P = .71). The difference in response to BAT between the CRT and no-CRT groups was statistically significant (P-interaction = .02).

The observations need to be confirmed in an adequately powered, prospective, randomized clinical outcomes trial, which is scheduled to begin in September 2015, said Dr Zile.