Heart Failure Network - Nitrate's Effect on Activity Tolerance in Heart Failure with Preserved Ejection Fraction (HFN NEAT-BioLINCC)

<b style="text-decoration-line: underline;">Data Access NOTE:</b> Please refer to the "Authorized Access" section below for information about how access to the data from this accession differs from many other dbGaP accessions.

<u>Related Studies</u><br>Echo images are available with HFN-NEAT Imaging.

<u>Objectives</u><br>To determine the effect of isosorbide mononitrate on daily activity in patients with heart failure and preserved ejection fraction.

<u>Background </u><br>Nitrates are commonly prescribed for symptom relief in patients with heart failure. Early studies in patients with heart failure with a reduced ejection fraction concluded that long-acting nitrates improve activity tolerance; however, approximately half of heart failure patients have preserved ejection fraction. The effects of nitrates in patients with heart failure and a preserved ejection fraction have not been extensively studied and the overall effect of nitrates on activity tolerance in such patients is uncertain.

<u>Participants</u><br>There were a total of 110 participants enrolled with 51 participants assigned to receive isosorbide mono-nitrate first and placebo second, and 59 participants assigned to receive placebo first and isosorbide mononitrate second.

<u>Design </u><br>Enrolled participants underwent baseline assessments, including echocardiography, quality-of-life scores, 6-minute walk test distance, and NT-proBNP levels. participants were also supplied with two kinetic activity monitors containing high-sensitivity triaxis accelerometers, to be worn 24 hours per day. The accelerometer measurements were expressed as arbitrary accelerometer units and stored every 15 minutes equaling 96 data points per day. The 15-minute cumulative accelerometer units were totaled over a 24-hour period to provide daily accelerometer units.

Participants were assigned to one of two treatment groups: 6 weeks of placebo first with crossover to 6 weeks of isosorbide mononitrate, or 6 weeks of isosorbide mononitrate first with crossover to 6 weeks of placebo. The study drugs were prepared as 30-mg tablets of isosorbide mononitrate and matching placebo.

During each 6-week period, participants were instructed to take no study drug for the first 2 weeks followed by one tablet (30 mg daily) for 1 week, two tablets (60 mg once daily) for 1 week, and four tablets (120 mg once daily) until the next study visit, for a treatment duration of at least 2 weeks and up to 4 weeks. After each 6-week period, participants returned to the study center to repeat end-point assessments.

The primary outcome for the study was the comparison of average daily accelerometer units during the period in which participants were receiving the 120-mg dose of isosorbide mononitrate compared to the period in which participants received the placebo.

Other secondary end points included the 6-minute walk distance and the post-walk Borg dyspnea score, scores on the Kansas City Cardiomyopathy Questionnaire and the Minnesota Living with Heart Failure Questionnaire, and NT-proBNP levels. In addition, participants completed a questionnaire indicating in which period (first, second, no preference) they felt better.

<u>Conclusions </u><br>Participants were active for fewer hours of the day during the 120-mg phase of receipt of isosorbide mononitrate as compared with placebo. Furthermore, during all study-drug regimens combined (30 mg to 120 mg), participants were less active during receipt of isosorbide mononitrate as compared with placebo. There was no significant effect of isosorbide mononitrate on secondary outcomes.

<u>数据获取须知</u>：请参阅下文「授权获取」章节，了解本收录数据集的获取流程与多数其他dbGaP收录数据集的差异。

<u>相关研究</u>
回声图像可与HFN-NEAT Imaging一同获取。

<u>研究目标</u>
本研究旨在探讨单硝酸异山梨酯（isosorbide mononitrate）对射血分数保留型心力衰竭（heart failure with preserved ejection fraction）患者日常活动能力的影响。

<u>研究背景</u>
硝酸酯类药物常被用于缓解心力衰竭患者的临床症状。既往针对射血分数降低型心力衰竭（heart failure with reduced ejection fraction）患者的早期研究表明，长效硝酸酯类药物可提升其活动耐量；然而，约半数心力衰竭患者为射血分数保留型。目前针对射血分数保留型心力衰竭患者使用硝酸酯类药物的研究尚不够充分，此类患者使用硝酸酯类药物后的整体活动耐量变化仍不明确。

<u>研究对象</u>
本研究共纳入110名受试者，其中51名受试者先接受单硝酸异山梨酯治疗，后续序贯安慰剂治疗；剩余59名受试者先接受安慰剂治疗，后续序贯单硝酸异山梨酯治疗。

<u>研究设计</u>
纳入受试者后需完成基线评估，包括超声心动图（echocardiography）、生活质量评分、6分钟步行试验（6-minute walk test）距离以及NT-proBNP（N-terminal pro B-type natriuretic peptide）水平检测。研究人员还为受试者配备了两台搭载高灵敏度三轴加速度计（high-sensitivity triaxis accelerometers）的动态活动监测仪，要求受试者每日24小时佩戴。加速度计的测量值以任意加速度单位表示，每15分钟存储一次数据，单日可生成96个数据点。研究人员将24小时内的15分钟累计加速度单位求和，得到每日加速度总单位。

受试者被随机分为两个治疗组：一组先接受6周安慰剂治疗，随后交叉接受6周单硝酸异山梨酯治疗；另一组先接受6周单硝酸异山梨酯治疗，随后交叉接受6周安慰剂治疗。研究药物为30mg规格的单硝酸异山梨酯片与匹配安慰剂片。

在每个6周治疗周期内，受试者需在前2周停用研究药物，随后1周每日服用1片（30mg，每日1次），再1周每日服用2片（60mg，每日1次），最后服用4片（120mg，每日1次）直至下一次研究随访，单药治疗时长为2周至4周不等。每完成1个6周治疗周期后，受试者需返回研究中心重复终点评估。

本研究的主要终点为对比受试者接受120mg剂量单硝酸异山梨酯治疗期间与安慰剂治疗期间的平均每日加速度总单位。

其他次要终点包括6分钟步行试验距离、步行后Borg呼吸困难评分（Borg dyspnea score）、堪萨斯城心肌病问卷（Kansas City Cardiomyopathy Questionnaire）评分、明尼苏达心力衰竭生活质量问卷（Minnesota Living with Heart Failure Questionnaire）评分以及NT-proBNP水平。此外，受试者需填写问卷，表明自身在两个治疗周期（第一周期、第二周期）或无偏好中更偏好哪一阶段。

<u>研究结论</u>
与安慰剂治疗阶段相比，受试者在接受120mg剂量单硝酸异山梨酯治疗阶段的每日活动时长更短。此外，综合所有研究药物给药方案（30mg至120mg），受试者在接受单硝酸异山梨酯治疗期间的活动量均低于安慰剂治疗阶段。单硝酸异山梨酯对次要终点无显著影响。