• Cardiology
• Heart Failure
• Cardiology Clinical Trials

• Cardiology
• Heart Failure
• Cardiology Clinical Trials

Vagal nerve stimulation (VNS) did not reduce the primary end point of cardiac remodeling at 6 months in patients who had heart failure (HF) with reduced ejection fraction in the first sham-controlled, double-blind clinical trial to evaluate this approach. The Neutral Cardiac Therapy for Heart Failure study [NECTAR-HF; Zannad F et al. Eur Heart J. 2014], led by Faiez Zannad, MD, PhD, Inserm, University of Lorraine, Lorraine, France, sought to determine whether an implanted VNS system would reset the altered autonomic nervous system balance found in HF. The 6-month data were presented, and follow-up will continue to 18 months.

NECTAR-HF researchers randomized patients who were receiving optimal medical therapy to a VNS system that stimulated the right vagal nerve with therapy turned on (therapy group; n = 63) or off (control group; n = 32). Criteria included the following: New York Heart Association (NYHA) class II to III HF, a left ventricular (LV) ejection fraction ≤ 35%, and LV end diastolic diameter ≥ 5.5 cm. The mean age of the patients was 59 years, most were men (therapy group, 89%; control group, 81%), and most had NYHA class III HF (51 and 22 patients, respectively). The number of patients who had an implantable cardioverter defibrillator, cardiac resynchronization therapy with defibrillation, or no device was 51, 5, and 7 in the therapy group and 22, 4, and 6 in the control group, respectively.

The 6-month safety results showed a similar number of events in each group. The infection rate was low at 7.4% (7 infections), the device was removed from 3 patients, and antibiotic treatment was used in 4 patients. The modified intention-to-treat analysis included 59 patients in the therapy group and 28 patients in the control group with paired data sets. After 6 months, therapy was turned on for all patients.

The primary end point of LV end systolic diameter was similar at baseline and at 6 months in the therapy group (4.9 cm for both) and control group (5.2 and 5.1 cm, respectively). The secondary end points evaluating cardiac remodeling were also similar at 6 months in both groups. The secondary end points of peak oxygen consumption and N-terminal pro—brain natriuretic peptide were similar in both groups at baseline and 6 months. More patients had an improvement in their NYHA class in the therapy group versus the control group (62.1% vs 44.8%), while more patients in the control group versus the therapy group had worsening HF (10.3% vs 0.2%). The secondary end point measure of quality of life showed a significant improvement with therapy versus control for 2 functional questionnaires but not for the short form-36 mental health survey.

Regarding the improvement in symptoms and quality of life despite the lack of improvement in cardiac remodeling, Prof Zannad acknowledged that insufficient blinding may have contributed to the positive findings for the more subjective data. Although the primary echocardiography end point was blinded, many patients felt the stimulation (slight vibration in neck) and correctly guessed their assigned group.

This feasibility, proof-of-concept study did not demonstrate an improvement in its primary end point of cardiac remodeling with VNS. There were no safety concerns at 6 months. The trial design did support the use of sham control for further study of VNS and highlighted the need for sufficient blinding.

• © 2014 MD Conference Express®