射血分数保留的心力衰竭中冠状动脉微血管功能障碍的患病率及其相关因素：PROMIS-HFpEF。
Prevalence and correlates of coronary microvascular dysfunction in heart failure with preserved ejection fraction: PROMIS-HFpEF.
机构信息
Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
National Heart Centre Singapore, Duke-National University of Singapore, Singapore.
出版信息
Eur Heart J. 2018 Oct 1;39(37):3439-3450. doi: 10.1093/eurheartj/ehy531.
AIMS
To date, clinical evidence of microvascular dysfunction in patients with heart failure (HF) with preserved ejection fraction (HFpEF) has been limited. We aimed to investigate the prevalence of coronary microvascular dysfunction (CMD) and its association with systemic endothelial dysfunction, HF severity, and myocardial dysfunction in a well defined, multi-centre HFpEF population.
METHODS AND RESULTS
This prospective multinational multi-centre observational study enrolled patients fulfilling strict criteria for HFpEF according to current guidelines. Those with known unrevascularized macrovascular coronary artery disease (CAD) were excluded. Coronary flow reserve (CFR) was measured with adenosine stress transthoracic Doppler echocardiography. Systemic endothelial function [reactive hyperaemia index (RHI)] was measured by peripheral arterial tonometry. Among 202 patients with HFpEF, 151 [75% (95% confidence interval 69-81%)] had CMD (defined as CFR <2.5). Patients with CMD had a higher prevalence of current or prior smoking (70% vs. 43%; P = 0.0006) and atrial fibrillation (58% vs. 25%; P = 0.004) compared with those without CMD. Worse CFR was associated with higher urinary albumin-to-creatinine ratio (UACR) and NTproBNP, and lower RHI, tricuspid annular plane systolic excursion, and right ventricular (RV) free wall strain after adjustment for age, sex, body mass index, atrial fibrillation, diabetes, revascularized CAD, smoking, left ventricular mass, and study site (P < 0.05 for all associations).
CONCLUSIONS
PROMIS-HFpEF is the first prospective multi-centre, multinational study to demonstrate a high prevalence of CMD in HFpEF in the absence of unrevascularized macrovascular CAD, and to show its association with systemic endothelial dysfunction (RHI, UACR) as well as markers of HF severity (NTproBNP and RV dysfunction). Microvascular dysfunction may be a promising therapeutic target in HFpEF.
目的
迄今为止，射血分数保留的心力衰竭（HFpEF）患者微血管功能障碍的临床证据有限。我们旨在研究明确诊断的多中心 HFpEF 人群中冠状动脉微血管功能障碍（CMD）的患病率及其与全身内皮功能障碍、HF 严重程度和心肌功能障碍的关系。
方法和结果
这项前瞻性多国多中心观察性研究纳入了符合当前指南严格标准的 HFpEF 患者。那些已知有未经血运重建的大血管冠状动脉疾病（CAD）的患者被排除在外。采用腺苷负荷经胸多普勒超声心动图测量冠状动脉血流储备（CFR）。通过外周动脉张力测定系统内皮功能[反应性充血指数（RHI）]。在 202 例 HFpEF 患者中，151 例（75%（95%置信区间 69-81%））存在 CMD（定义为 CFR <2.5）。与无 CMD 的患者相比，CMD 患者当前或既往吸烟（70%比 43%；P=0.0006）和心房颤动（58%比 25%；P=0.004）的患病率更高。经过年龄、性别、体重指数、心房颤动、糖尿病、血运重建 CAD、吸烟、左心室质量和研究地点的调整后，CFR 更差与更高的尿白蛋白/肌酐比值（UACR）和 NTproBNP、更低的 RHI、三尖瓣环平面收缩期位移和右心室（RV）游离壁应变相关（所有关联 P<0.05）。
结论
PROMIS-HFpEF 是第一项前瞻性多中心、多国研究，表明在没有未经血运重建的大血管 CAD 的情况下，HFpEF 中存在 CMD 的高患病率，并表明其与全身内皮功能障碍（RHI、UACR）以及 HF 严重程度标志物（NTproBNP 和 RV 功能障碍）相关。微血管功能障碍可能是 HFpEF 的一个有前途的治疗靶点。
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