Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction: A Multiorgan Roadmap.
Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction: A Multiorgan Roadmap.
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DOI：
10.1161/circulationaha.116.021884
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发表时间：
2016-07-05
期刊：
影响因子：
37.8
通讯作者：
Paulus WJ
中科院分区：
文献类型：
--
作者：
Shah SJ;Kitzman DW;Borlaug BA;van Heerebeek L;Zile MR;Kass DA;Paulus WJ
射血分数（EF）保留的心力衰竭（HF）（HFpEF）占HF病例的50%，其患病率相对于EF降低的HF（HFrEF）持续上升。与HFrEF相反，在HFpEF中测试神经体液抑制的大型试验未能达到积极的结果。这种失败最近归因于HFpEF中不同的全身和心肌信号传导以及HFpEF表型的多样性。在这篇综述中，HFpEF治疗策略提出了解决HFpEF特异性信号和表型多样性。在HFpEF中，心外合并症如代谢风险、动脉高血压和肾功能不全通过全身炎症和冠状动脉微血管内皮功能障碍驱动左心室（LV）重塑和功能障碍。后者通过导致间质纤维化的巨噬细胞浸润和通过改变的对心肌细胞的旁分泌信号传导影响LV舒张功能障碍，心肌细胞由于低一氧化氮（NO）和环磷酸鸟苷（cGMP）而变得肥大和僵硬。全身性炎症还影响其他器官，如肺、骨骼肌和肾，分别导致肺动脉高压、肌无力和钠潴留。这些信号级联的各个步骤可以通过特定的干预措施来实现：热量限制导致的代谢风险，他汀类药物导致的全身炎症，磷酸二酯酶（PDE）5抑制剂导致的肺动脉高压，运动训练导致的肌无力，利尿剂和监测装置导致的钠潴留，无机硝酸盐-亚硝酸盐导致的心肌NO生物利用度，通过脑啡肽酶或PDE 9抑制剂测定心肌cGMP含量，通过螺内酯测定心肌纤维化。由于HFpEF的表型多样性，提出了个性化的治疗策略，其被配置在矩阵中，横坐标为HFpEF呈现，纵坐标为HFpEF倾向。
Heart failure (HF) with preserved ejection fraction (EF) (HFpEF) accounts for 50% of HF cases and its prevalence relative to HF with reduced EF (HFrEF) continues to rise. In contrast to HFrEF, large trials testing neurohumoral inhibition in HFpEF failed to reach a positive outcome. This failure was recently attributed to distinct systemic and myocardial signaling in HFpEF and to diversity of HFpEF phenotypes. In this review, a HFpEF treatment strategy is proposed which addresses HFpEF-specific signaling and phenotypic diversity. In HFpEF, extracardiac comorbidities such as metabolic risk, arterial hypertension and renal insufficiency drive left ventricular (LV) remodeling and dysfunction through systemic inflammation and coronary microvascular endothelial dysfunction. The latter affects LV diastolic dysfunction through macrophage infiltration resulting in interstitial fibrosis and through altered paracrine signaling to cardiomyocytes, which become hypertrophied and stiff because of low nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). Systemic inflammation also affects other organs such as lungs, skeletal muscle and kidneys leading respectively to pulmonary hypertension, muscle weakness and sodium retention. Individual steps of these signaling cascades can be targeted by specific interventions: metabolic risk by caloric restriction, systemic inflammation by statins, pulmonary hypertension by phosphodiesterase (PDE) 5 inhibitors, muscle weakness by exercise training, sodium retention by diuretics and monitoring devices, myocardial NO bioavailability by inorganic nitrate-nitrite, myocardial cGMP content by neprilysin or PDE 9 inhibition and myocardial fibrosis by spironolactone. Because of phenotypic diversity in HFpEF, personalized therapeutic strategies are proposed, which are configured in a matrix with HFpEF presentations in the abscissa and HFpEF predispositions in the ordinate.