Potassium Nitrate in Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial.

Prior pilot studies have shown improvements in exercise tolerance with single-dose and short-term inorganic nitrate administration.

先前的小型试点研究显示，单剂量和短期无机硝酸盐给药可以改善运动耐受性。

Background

To assess the impact of chronic inorganic nitrate administration on exercise tolerance in a larger trial of participants with HFpEF.

评估慢性无机硝酸盐给药对心功能保留型心力衰竭（HFpEF）患者运动耐受性的影响，通过更大规模的试验进行研究。

DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized double-blinded crossover trial was conducted at the University of Pennsylvania, the Philadelphia Veterans Affairs Medical Center, and Northwestern University between October 2016 and July 2022.

设计、地点和参与者：这项多中心随机双盲交叉试验于2016年10月至2022年7月在宾夕法尼亚大学、费城退伍军人事务医学中心和西北大学进行。

Participants included patients with symptomatic (New York Heart Association class II/III) HFpEF who had objective signs of elevated left ventricular filling pressures.

参与者包括有症状（纽约心脏协会II/III级）的HFpEF患者，这些患者有左心室充盈压力升高客观体征。

Image quantification, physiological data modeling and biochemical measurements, unblinding, and statistical analyses were completed in 2024.

图像量化、生理数据建模和生化测量、揭盲以及统计分析已于2024年完成。

intervention

Potassium nitrate (KNO3) (6 mmol 3 times daily) vs equimolar doses of potassium chloride (KCl) for 6 weeks, each with a 1-week washout in between.

硝酸钾（KNO3）（每天三次，每次6毫摩尔）与等摩尔剂量的氯化钾（KCl）进行为期6周的比较，每次比较之间有1周的洗脱期。

main_outcomes_and_measures

The coprimary end points included peak oxygen uptake and total work performed during a maximal effort incremental cardiopulmonary exercise test.

主要终点包括在最大努力递增心肺运动测试期间的峰值氧摄取量和完成的总工作量。

Secondary end points included the exercise systemic vasodilatory reserve (ie, reduction in systemic vascular resistance with exercise) and quality of life assessed using the Kansas City Cardiomyopathy Questionnaire.

次要终点包括运动系统性血管舒张储备（即运动时系统血管阻力的降低）和使用堪萨斯城心肌病问卷评估的生活质量。

Results

Eighty-four participants were enrolled.

共有84名参与者被纳入研究。

Median age was 68 years and 58 participants were women (69.0%).

中位年龄为68岁，58名参与者为女性（占69.0%）

Most participants had NYHA class II disease (69%) with a mean 6-minute walk distance of 335.5 (SD, 97.3) m.

大多数参与者患有NYHA II级疾病（占69%），平均6分钟步行距离为335.5（标准差，97.3）米

Seventy-seven participants received the KNO3 intervention and 74 received the KCl intervention.

77名参与者接受了KNO3干预，74名接受了KCl干预。

KNO3 increased trough levels of serum nitric oxide metabolites after 6 weeks (KNO3, 418.4 [SD, 26.9] uM vs KCl, 40.1 [SD, 28.3] uM; P < .001).

6周后，KNO3提高了血清一氧化氮代谢产物的谷值水平（KNO3，418.4 [标准差，26.9] uM 对比 KCl，40.1 [标准差，28.3] uM；P < .001）。

KNO3 did not improve peak oxygen uptake (KNO3, 10.23 [SD, 0.43] mL/min/kg vs KCl, 10.17 [SD, 0.43] mL/min/kg; P = .73) or total work performed (KNO3, 25.9 [SD, 3.65] kilojoules vs KCl, 23.63 [SD, 3.63] kilojoules; P = .29).

KNO3并未改善峰值氧摄取量（KNO3，10.23 [标准差，0.43] mL/min/kg 与 KCl，10.17 [标准差，0.43] mL/min/kg；P = .73）或完成的总工作量（KNO3，25.9 [标准差，3.65] 千焦 vs KCl，23.63 [标准差，3.63] 千焦；P = .29）。

KNO3 nitrate did not improve the vasodilatory reserve or quality of life, though it was well-tolerated.

KNO3硝酸盐并未改善血管舒张储备或生活质量，尽管它被良好地耐受。

conclusions_and_relevance

In this study, potassium nitrate did not improve aerobic capacity, total work, or quality of life in participants with HFpEF.

在这项研究中，硝酸钾并未改善心功能保留射血分数（HFpEF）参与者的有氧能力、总工作量或生活质量。

trial_registration

ClinicalTrials.gov Identifier: NCT02840799.

临床试验注册号：NCT02840799。