Abstract 15751: Inorganic Nitrate Improves Exercise Tolerance and Symptoms in Heart Failure With Preserved Ejection Fraction - A Dose Finding Study
Background: Heart Failure with Preserved Ejection Fraction (HFpEF) leads to significant impairments in exercise and quality of life (QOL). Inorganic nitrate has been shown to improve exercise in HFpEF. We sought to (1) determine the dose-response effect of potassium nitrate (KNO3) on exercise; (2) determine the population-specific safety of KNO3.
Methods and Results: We randomized 12 subjects with HFpEF to either KNO3 or potassium chloride (KCl) capsules in a 3:1 ratio. Subjects received 6 mmol twice-daily (Week-1) followed by 6 mmol thrice-daily (Week-2). Supine cycle ergometry and gas-exchange measurements were performed at baseline, after Week-1, and after Week-2. QOL was assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ). An activity monitor was used to track outpatient activity. Data was analyzed using mixed models. Study medications were well-tolerated. KNO3 led to asymptomatic modest reductions in systolic blood pressure (P=0.037). No clinically-significant elevation in methemoglobin occurred. Exercise duration significantly increased with KNO3 (Baseline: median 9.75 [IQR 6.63,10.12); Week-1 median 9.81 [7.99,12.53]; Week-2 median 11.10 [7.52,12.87] minutes, P=0.002). KCCQ scores improved with KNO3: Total Symptom score (Baseline median 57.3 [39.6,76.0]; Week-1 median 64.6 [55.2,87.5]; Week-2 median 66.7 [58.3,81.3]; P=0.016) and Functional Status score (Baseline median 60.9 [IQR 46.9,72.4]; Week-1 median 63.5 [IQR 58.3,78.1]; Week-2 median 68.2 [IQR 64.6,78.1]; P=0.01). None of these changes occurred with KCl. KNO3 did not alter outpatient activity.
Conclusions: KNO3 is well-tolerated in HFpEF, improves exercise, and QOL. This study reinforces the efficacy of KNO3 and establishes a dose (18 mmol/day) to be tested in a larger trial.
Author Disclosures: P. Zamani: None. V. Tran: None. H. Soto-Calderon: None. M. Beraun: None. J.A. Brandimarto: None. L. Trieu: None. S. Varakantam: None. P. Doulias: None. R.R. Townsend: Consultant/Advisory Board; Modest; for Medtronic, Fukuda Denshi, Relypsa.. J. Chittams: None. K.B. Margulies: None. T.P. Cappola: Consultant/Advisory Board; Modest; Novartis. D.C. Poole: None. H. Ischiropoulos: None. J.A. Chirinos: Research Grant; Significant; NIH, American College of Radiology Network, Fukuda Denshi, Bristol Myers Squibb, Microsoft and CVRx Inc. Other Research Support; Modest; Fukuda Denshi, Withings, Atcor Medical. Consultant/Advisory Board; Modest; Fukuda Denshi, Microsoft Research, Merck and Vital Labs. Consultant/Advisory Board; Significant; Bristol Myers Squibb, OPKO Healthcare.
- © 2016 by American Heart Association, Inc.