Long-term vagal stimulation for heart failure: Eighteen month results from the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) trial.
Int J Cardiol. 2017 Jun 10;:
Authors: De Ferrari GM, Stolen C, Tuinenburg AE, Wright DJ, Brugada J, Butter C, Klein H, Neuzil P, Botman C, Castel MA, D'Onofrio A, de Borst GJ, Solomon S, Stein KM, Schubert B, Stalsberg K, Wold N, Ruble S, Zannad F
BACKGROUND: The NECTAR-HF study evaluated safety and feasibility of vagal nerve stimulation (VNS) for the treatment of heart failure patients. The first six-month randomized phase of the study did not show improvement in left ventricular remodelling in response to VNS. This study reports the 18-month results and provides novel findings aiming to understand the lack of efficacy of VNS, including a new technique assessing the effects of VNS.
METHODS: Ninety-six patients were randomized 2:1 to active or inactive VNS for 6months, thereafter VNS was activated for all patients. The primary safety endpoint was 18-month all-cause mortality.
RESULTS: Ninety-one patients continued in the long-term evaluation with active VNS. The on-therapy survival estimate at 18months was 95% with a 95% one-sided lower confidence limit of 91%, (better than the predefined criterion). Left ventricular systolic volume decreased in the crossover group (VNS OFF→ON; 144±37 to 139±40, p<0.05) after VNS activation; LVESD (5.02±0.77 to 4.96±0.82, p>0.05) and LVEF (33.2±4.9 to 33.3±6.5, p>0.05) did not change. A new technique to detect subtle heart rate changes during Holter recordings, i.e. "heat maps", revealed that VNS evoked heart rate response in only 13/106 studies (12%) at 6 and 12months with active VNS.
CONCLUSIONS: Although a favourable long-term safety profile was found, improvements in the efficacy endpoints were not seen with VNS. A new technique for detecting acute heart rate responses to VNS suggests that the recruitment of nerve fibres responsible for heart rate changes were substantially lower in NECTAR-HF than in pre-clinical models.
PMID: 28663046 [PubMed - as supplied by publisher]