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Clinical Phenogroups in Heart Failure With Preserved Ejection Fraction: Detailed Phenotypes, Prognosis, and Response to Spironolactone.
JACC: Heart Failure ( IF 10.3 ) Pub Date : 2020-01-08 , DOI: 10.1016/j.jchf.2019.09.009 Jordana B Cohen 1 , Sarah J Schrauben 1 , Lei Zhao 2 , Michael D Basso 2 , Mary Ellen Cvijic 2 , Zhuyin Li 2 , Melissa Yarde 2 , Zhaoqing Wang 2 , Priyanka T Bhattacharya 3 , Diana A Chirinos 4 , Stuart Prenner 5 , Payman Zamani 5 , Dietmar A Seiffert 2 , Bruce D Car 2 , David A Gordon 2 , Kenneth Margulies 5 , Thomas Cappola 5 , Julio A Chirinos 5
JACC: Heart Failure ( IF 10.3 ) Pub Date : 2020-01-08 , DOI: 10.1016/j.jchf.2019.09.009 Jordana B Cohen 1 , Sarah J Schrauben 1 , Lei Zhao 2 , Michael D Basso 2 , Mary Ellen Cvijic 2 , Zhuyin Li 2 , Melissa Yarde 2 , Zhaoqing Wang 2 , Priyanka T Bhattacharya 3 , Diana A Chirinos 4 , Stuart Prenner 5 , Payman Zamani 5 , Dietmar A Seiffert 2 , Bruce D Car 2 , David A Gordon 2 , Kenneth Margulies 5 , Thomas Cappola 5 , Julio A Chirinos 5
Affiliation
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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 Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) 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.
中文翻译：
射血分数保留的心力衰竭的临床表型：详细的表型、预后和对螺内酯的反应。
目的 本研究旨在评估临床表型在综合生物标志物概况、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。背景先前的研究确定了射血分数保留的心力衰竭（HFpEF）患者的不同亚组（表型组）。方法在醛固酮拮抗剂治疗保留心脏功能心力衰竭试验（TOPCAT）参与者中，我们进行了潜在类别分析，根据标准临床特征识别 HFpEF 表型，并评估了从冷冻血浆中测量的多种生物标志物的差异；通过超声心动图和动脉张力测量测量心脏和动脉结构/功能；预后；以及对螺内酯的反应。结果 鉴定出三个 HFpEF 表型组。表型组 1 (n = 1,214) 表现出更年轻的年龄、更高的吸烟率、保留的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，存在营养正常的同心左心室重构、心房颤动、左心房扩大、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、慢性肾病、同心左心室肥厚、高肾素以及肿瘤坏死因子-α 介导的炎症、肝纤维化和组织重塑的生物标志物。与表组 1 相比，表组 3 的主要终点风险最高，包括心血管死亡、心力衰竭住院或心脏骤停中止（风险比 [HR]：3.44；95% 置信区间 [CI]：2.79 至 4。24);表型 2 和表型 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）。螺内酯随机治疗与表组 3 中主要终点风险的显着降低相关（HR：0.75；95% CI：0.59 至 0.95；交互作用 p = 0.016）。排除来自东欧的参与者后，结果相似。结论 我们发现临床 HFpEF 表型组在循环生物标志物、心脏/动脉特征、预后和螺内酯反应方面存在重要差异。这些发现表明临床可识别的 HFpEF 表型组存在不同的潜在机制，可能受益于不同的针对性干预措施。
更新日期：2020-01-09
中文翻译：
射血分数保留的心力衰竭的临床表型：详细的表型、预后和对螺内酯的反应。
目的 本研究旨在评估临床表型在综合生物标志物概况、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。背景先前的研究确定了射血分数保留的心力衰竭（HFpEF）患者的不同亚组（表型组）。方法在醛固酮拮抗剂治疗保留心脏功能心力衰竭试验（TOPCAT）参与者中，我们进行了潜在类别分析，根据标准临床特征识别 HFpEF 表型，并评估了从冷冻血浆中测量的多种生物标志物的差异；通过超声心动图和动脉张力测量测量心脏和动脉结构/功能；预后；以及对螺内酯的反应。结果 鉴定出三个 HFpEF 表型组。表型组 1 (n = 1,214) 表现出更年轻的年龄、更高的吸烟率、保留的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，存在营养正常的同心左心室重构、心房颤动、左心房扩大、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、慢性肾病、同心左心室肥厚、高肾素以及肿瘤坏死因子-α 介导的炎症、肝纤维化和组织重塑的生物标志物。与表组 1 相比，表组 3 的主要终点风险最高，包括心血管死亡、心力衰竭住院或心脏骤停中止（风险比 [HR]：3.44；95% 置信区间 [CI]：2.79 至 4。24);表型 2 和表型 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）。螺内酯随机治疗与表组 3 中主要终点风险的显着降低相关（HR：0.75；95% CI：0.59 至 0.95；交互作用 p = 0.016）。排除来自东欧的参与者后，结果相似。结论 我们发现临床 HFpEF 表型组在循环生物标志物、心脏/动脉特征、预后和螺内酯反应方面存在重要差异。这些发现表明临床可识别的 HFpEF 表型组存在不同的潜在机制，可能受益于不同的针对性干预措施。
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