Clinical Phenogroups in Heart Failure With Preserved Ejection Fraction Detailed Phenotypes, Prognosis, and Response to Spironolactone
Clinical Phenogroups in Heart Failure With Preserved Ejection Fraction Detailed Phenotypes, Prognosis, and Response to Spironolactone
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DOI：
10.1016/j.jchf.2019.09.009
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发表时间：
2020-03-01
影响因子：
13
通讯作者：
Chirinos, Julio A.
中科院分区：
文献类型：
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作者：
Cohen, Jordana B.;Schrauben, Sarah J.;Chirinos, Julio A.
本研究旨在评估临床表型组在综合生物标志物特征、心脏和动脉结构/功能以及对螺内酯治疗的反应方面是否存在差异。（表型组）与保留射血分数（HFpEF）的心力衰竭患者。（用醛固酮拮抗剂试验治疗保留心脏功能的心力衰竭）参与者，我们进行了潜在分类分析，以根据标准临床特征鉴定HFpEF表型组，并评估了从冷冻血浆中测量的多种生物标志物的差异;预后;结果HFpEF有3种表型。表型组1（n = 1，214）表现出较年轻的年龄，较高的吸烟率，保留功能等级，以及最少的左心室（LV）肥大和动脉僵硬的证据。表型组2（n = 1，329）年龄较大，具有正常营养向心性LV重构、房颤、左心房增大、大动脉硬化以及先天免疫和血管钙化的生物标志物。表型组3（n = 899）表现出更多的功能障碍，肥胖，糖尿病，慢性肾脏疾病，向心性左心室肥大，高肾素，肿瘤坏死因子-α介导的炎症，肝纤维化和组织重塑的生物标志物。与表型组1相比，表型组3表现出心血管死亡、心力衰竭住院或心脏骤停流产等主要终点的最高风险（风险比[HR]：3.44; 95%置信区间[CI]：2.79 - 4.24）;表型组2和表型组3表现出相似的全因死亡率（表型2 HR：2.36; 95% CI：1.89至2.95;表型3 HR：2.26，95% CI：1.77至2.87）。螺内酯随机化治疗与表型组3中主要终点风险的更显著降低相关（HR：0.75; 95% CI：0.59 - 0.95;相互作用p = 0.016）。结果相似后，排除参与者从EasternEuropea.CONCLUSIONS，我们确定了重要的差异，循环生物标志物，心脏/动脉的特点，预后，并在临床HFpEF表型之间的螺内酯。这些发现表明，HFpEF的临床可识别表型组之间存在不同的潜在机制，可能受益于不同的靶向干预措施。(C)2020年由美国心脏病学会基金会。
OBJECTIVES This study sought to assess if clinical phenogroups differ in comprehensive biomarker profiles, cardiac and arterial structure/function, and responses to spironolactone therapy.BACKGROUND Previous studies identified distinct subgroups (phenogroups) of patients with heart failure with preserved ejection fraction (HFpEF).METHODS Among TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial) participants, we performed latent-class analysis to identify HFpEF phenogroups based on standard clinical features and assessed differences in multiple biomarkers measured from frozen plasma; cardiac and arterial structure/function measured with echocardiography and arterial tonometry; prognosis; and response to spironolactone.RESULTS Three HFpEF phenogroups were identified. Phenogroup 1 (n = 1,214) exhibited younger age, higher prevalence of smoking, preserved functional class, and the least evidence of left ventricular (LV) hypertrophy and arterial stiffness. Phenogroup 2 (n = 1,329) was older, with normotrophic concentric LV remodeling, atrial fibrillation, left atrial enlargement, large-artery stiffening, and biomarkers of innate immunity and vascular calcification. Phenogroup 3 (n = 899) demonstrated more functional impairment, obesity, diabetes, chronic kidney disease, concentric LV hypertrophy, high renin, and biomarkers of tumor necrosis factor-alpha-mediated inflammation, liver fibrosis, and tissue remodeling. Compared with phenogroup 1, phenogroup 3 exhibited the highest risk of the primary endpoint of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest (hazard ratio [HR]: 3.44; 95% confidence interval [CI]: 2.79 to 4.24); phenogroups 2 and 3 demonstrated similar all-cause mortality (phenotype 2 HR: 2.36; 95% CI: 1.89 to 2.95; phenotype 3 HR: 2.26, 95% CI: 1.77 to 2.87). Spironolactone randomized therapy was associated with a more pronounced reduction in the risk of the primary endpoint in phenogroup 3 (HR: 0.75; 95% CI: 0.59 to 0.95; p for interaction = 0.016). Results were similar after excluding participants from Eastern Europe.CONCLUSIONS We identified important differences in circulating biomarkers, cardiac/arterial characteristics, prognosis, and response to spironolactone across clinical HFpEF phenogroups. These findings suggest distinct underlying mechanisms across clinically identifiable phenogroups of HFpEF that may benefit from different targeted interventions. (C) 2020 by the American College of Cardiology Foundation.