Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction.
Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction.
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DOI：
10.1161/circulationaha.114.009625
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发表时间：
2015-02-10
期刊：
影响因子：
37.8
通讯作者：
Redfield MM
中科院分区：
文献类型：
--
作者：
Mohammed SF;Hussain S;Mirzoyev SA;Edwards WD;Maleszewski JJ;Redfield MM
保存射血分数（HFpEF）的心力衰竭（HF）心肌结构变化的表征一直受到人类心脏组织有限可用性的阻碍。心脏肥大、冠状动脉疾病（CAD）、冠状动脉微血管稀疏和心肌纤维化可能导致HFpEF的病理生理。我们确定了HFpEF患者（n=124）和与年龄相适应的对照患者（非心源性死亡，无HF诊断；n=104），他们进行了尸检。心脏重量和冠心病严重程度从尸检报告中获得。采用全视野数码显微镜和自动分析算法对左室全层切片进行微血管密度（MVD）、心肌纤维化及其相互关系的定量分析。HFpEF患者的心脏较重（中位数为538 g；年龄/性别/体型占预期心脏重量的169%，比335 g；对照组为112%），更严重的CAD (HFpEF患者中65%有≥1条血管直径狭窄，比对照组为13%)，更严重的左室纤维化（中位数面积纤维化，9.6比7.1）和更低的MVD（中位数961比1316血管/ mm2），比对照组（p <0.0001）。心肌纤维化随着MVD （r = - 0.28, p=0.004）和HFpEF （r = - 0.26, p=0.004）的降低而增加。调整MVD降低了纤维化的组间差异。合并冠心病的HFpEF患者的心脏重量、纤维化和MVD相似。在本研究中，HFpEF患者的心肌肥厚、心外膜CAD、冠状动脉微血管稀疏和心肌纤维化均高于对照组。这些发现都可能导致HFpEF特征的左室舒张功能障碍和心脏储备功能损害。
Characterization of myocardial structural changes in heart failure (HF) with preserved ejection fraction (HFpEF) has been hindered by limited availability of human cardiac tissue. Cardiac hypertrophy, coronary artery disease (CAD), coronary microvascular rarefaction and myocardial fibrosis may contribute to HFpEF pathophysiology. We identified HFpEF patients (n=124) and age-appropriate control patients (non-cardiac death, no HF diagnosis; n=104) who underwent autopsy. Heart weight and CAD severity were obtained from the autopsy reports. Using whole field digital microscopy and automated analysis algorithms in full thickness left ventricular (LV) sections, microvascular density (MVD), myocardial fibrosis and their relationship were quantified. Subjects with HFpEF had heavier hearts (median 538 g; 169% of age/sex/body size expected heart weight vs. 335 g; 112% in controls), more severe CAD (65% with ≥ one vessel with >50% diameter stenosis in HFpEF vs 13% in controls), more LV fibrosis (median % area fibrosis, 9.6 vs. 7.1) and lower MVD (median 961 vs. 1316 vessels per mm2) than control (p <0.0001 for all). Myocardial fibrosis increased with decreasing MVD in controls (r = − 0.28, p=0.004) and HFpEF (r = − 0.26, p=0.004). Adjusting for MVD attenuated the group differences in fibrosis. Heart weight, fibrosis and MVD were similar in HFpEF patients with vs without CAD. In this study, patients with HFpEF had more cardiac hypertrophy, epicardial CAD, coronary microvascular rarefaction and myocardial fibrosis than controls. Each of these findings may contribute to the LV diastolic dysfunction and cardiac reserve function impairment characteristic of HFpEF.