Long-term vagal stimulation for heart failure: Eighteen month results from the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) trial.

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.

Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial.

AIM: The neural cardiac therapy for heart failure (NECTAR-HF) was a randomized sham-controlled trial designed to evaluate whether a single dose of vagal nerve stimulation (VNS) would attenuate cardiac remodelling, improve cardiac function and increase exercise capacity in symptomatic heart failure patients with severe left ventricular (LV) systolic dysfunction despite guideline recommended medical therapy. METHODS: Patients were randomized in a 2 : 1 ratio to receive therapy (VNS ON) or control (VNS OFF) for a 6-month period. The primary endpoint was the change in LV end systolic diameter (LVESD) at 6 months for control vs. therapy, with secondary endpoints of other echocardiography measurements, exercise capacity, quality-of-life assessments, 24-h Holter, and circulating biomarkers. RESULTS: Of the 96 implanted patients, 87 had paired datasets for the primary endpoint. Change in LVESD from baseline to 6 months was -0.04 ± 0.25 cm in the therapy group compared with -0.08 ± 0.32 cm in the control group (P = 0.60). Additional echocardiographic parameters of LV end diastolic dimension, LV end systolic volume, left ventricular end diastolic volume, LV ejection fraction, peak V02, and N-terminal pro-hormone brain natriuretic peptide failed to show superiority compared to the control group. However, there were statistically significant improvements in quality of life for the Minnesota Living with Heart Failure Questionnaire (P = 0.049), New York Heart Association class (P = 0.032), and the SF-36 Physical Component (P = 0.016) in the therapy group. CONCLUSION: Vagal nerve stimulation as delivered in the NECTAR-HF trial failed to demonstrate a significant effect on primary and secondary endpoint measures of cardiac remodelling and functional capacity in symptomatic heart failure patients, but quality-of-life measures showed significant improvement.

Does stenosis severity of native vessels influence bypass graft patency? A prospective fractional flow reserve-guided study.

BACKGROUND: After coronary bypass surgery, occlusion or narrowing of bypass grafts may occur over time. The present study prospectively evaluated the angiographic patency of bypass grafts after 1 year in relation to the preoperative angiographic and functionally severity of the coronary lesion assessed by fractional flow reserve measurement to test the hypothesis that grafting of less critical stenosis may be a risk factor for early dysfunction of the graft. METHODS: The study comprised 164 patients eligible for coronary artery bypass surgery who were not suitable for percutaneous intervention and with at least one intermediate lesion. Fractional flow reserve was measured in all lesions to be grafted to establish if a lesion was functionally significant. The surgeon was blinded to the results of these measurements. One year after surgery, coronary angiography was performed to establish bypass graft patency. RESULTS: At coronary angiography after 1 year, 8.9% of the bypass grafts on functionally significant lesions were occluded, and 21.4% of the bypass grafts on functionally nonsignificant lesions were occluded. There was no difference in angina class or repeat interventions between patients with or without occluded bypass grafts. CONCLUSIONS: The patency of bypass grafts on functionally significant lesions is significantly higher than the patency of bypass grafts on nonsignificant lesions; however, this finding has no clinical relevance because patients with patent or occluded bypass grafts on nonsignificant lesions did not experience an excess of angina or repeat interventions.

Value of magnetic resonance imaging, angiography, and fractional flow reserve to evaluate the left main coronary artery after direct surgical angioplasty.

BACKGROUND: Direct surgical angioplasty of the left main coronary artery is aimed to restore a more physiologic blood flow through the left main coronary artery compared with conventional bypass surgery and allows subsequent percutaneous coronary interventions of more distal coronary lesions. Some data on anatomic evaluation with coronary angiography and magnetic resonance imaging (MRI) are known, and we conducted a study to report the physiologic evaluation. METHODS: Coronary angiography, MRI, and fractional flow reserve measurements were performed in 18 patients 8 years after direct surgical angioplasty of the left main coronary artery. RESULTS: At coronary angiography and MRI, a dilated funnel-shaped left main coronary artery was seen in all 18 patients, but both methods failed to demonstrate a flow-limiting lesion in the distal left main coronary artery in 1 patient. The functional severity was shown by fractional flow reserve measurement, and subsequently, this patient underwent repeated bypass grafting surgery. CONCLUSIONS: After long-term follow-up, 17 of 18 patients had an excellent result of direct surgical angioplasty of the left main coronary artery. MRI is a safe and noninvasive way to visualize the left main coronary artery after direct surgical angioplasty, but quantitative assessment of a lesion is not reliable. Fractional flow reserve measurements are mandatory to evaluate the hemodynamic properties of the left main coronary artery after direct surgical angioplasty.

Long-term outcome after surgical left main coronary angioplasty.

BACKGROUND: Direct surgical angioplasty of the left main coronary artery is aimed to restore a more physiologic flow of the left coronary artery compared with conventional coronary artery bypass graft surgery and allows subsequent percutaneous coronary interventions of more distal coronary lesions if necessary. Relatively little data are known about long-term outcome in these patients. METHODS: In 1996 and 1997, in 31 patients in our hospital, surgical angioplasty of the left main coronary artery was attempted. The left main coronary artery was approached in the anterior way. Follow-up was performed during 8 years and concluded by invasive anatomic and functional evaluation of the left main coronary artery. RESULTS: In 4 of these patients, the procedure was converted to conventional coronary artery bypass graft surgery owing to calcification of the left main coronary artery. Of the remaining 27 patients, 3 patients died in the perioperative period and 4 other patients died during follow-up. In 18 of the 20 survivors, coronary angiography was performed after 8 years, and the left main coronary artery was also evaluated by intravascular ultrasound and coronary pressure-based fractional flow reserve measurement. At angiography and intravascular ultrasound, a dilated funnel-shaped left main coronary artery was seen in all of these patients. In 1 patient, a hemodynamically significant left main coronary artery stenosis was present (fractional flow reserve < 0.75), and in this patient coronary artery bypass graft surgery was performed. CONCLUSIONS: Although the total mortality of 23% was somewhat disappointing, the majority of the survivors had an excellent anatomic and physiologic result after direct surgical angioplasty of the left main coronary artery. Therefore, this technique deserves a place in the surgical armamentarium.