BACKGROUND The PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction) trial tested the efficacy of sacubitril-valsartan in patients with heart failure with preserved ejection fraction (HFpEF). Existing data on cardiac structure and function in patients with HFpEF suggest significant heterogeneity. OBJECTIVES The aim of this study was to characterize cardiac structure and function, quantify their associations with clinical outcomes, and contextualize these findings with other HFpEF studies. METHODS Echocardiography was performed in 1,097 of 4,822 PARAGON-HF patients within 6 months of enrollment. Associations with incident first heart failure hospitalization or cardiovascular death were assessed using Cox proportional hazards models adjusted for age, sex, region of enrollment, randomized treatment, N-terminal pro-brain natriuretic peptide, and clinical risk factors. RESULTS Average age was 74 ± 8 years, 53% of patients were women, median N-terminal pro-brain natriuretic peptide level was 918 pg/ml (interquartile range: 485 to 1,578 pg/ml), 94% had hypertension, and 35% had atrial fibrillation. The mean left ventricular (LV) ejection fraction was 58.6 ± 9.8%, prevalence of LV hypertrophy was 21%, prevalence of left atrial enlargement was 83%, prevalence of elevated E/e' ratio was 53%, and prevalence of pulmonary hypertension was 31%. Heart failure hospitalization or cardiovascular death occurred in 288 patients at 2.8-year median follow-up. In fully adjusted models, higher LV mass index (hazard ratio [HR]: 1.05 per 10 g/m2; 95% confidence interval [CI]: 1.00 to 1.10; p = 0.03), E/e' ratio (HR: 1.04 per unit; 95% CI: 1.02 to 1.06; p < 0.001), pulmonary artery systolic pressure (HR: 1.51 per 10 mm Hg; 95% CI: 1.29 to 1.76; p < 0.001), and right ventricular end-diastolic area (HR: 1.04 per cm2; 95% CI: 1.01 to 1.07; p = 0.003) were each associated with this composite, while LV ejection fraction and left atrial size were not (p > 0.05 for all). Appreciable differences were observed in cardiac structure compared with other HFpEF clinical trials, despite similar E/e' ratio, pulmonary artery systolic pressure, and event rates. CONCLUSIONS Diastolic dysfunction, left atrial enlargement, and pulmonary hypertension were common in PARAGON-HF. LV hypertrophy, elevated left- and right-sided pressures, and right ventricular enlargement were independently predictive of incident heart failure hospitalization or cardiovascular death. Echocardiographic differences among HFpEF trials despite similar clinical event rates highlight the heterogeneity of this syndrome. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).

中文翻译：

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心力衰竭保留左心室射血分数患者的超声心动图特征

背景 PARAGON-HF（射血分数保留的 HF 的 ARNI 与 ARB 全球结果的前瞻性比较）试验测试了沙库巴曲缬沙坦对射血分数保留的心力衰竭 (HFpEF) 患者的疗效。HFpEF 患者心脏结构和功能的现有数据表明存在显着的异质性。目的 本研究的目的是表征心脏结构和功能，量化它们与临床结果的关联，并将这些发现与其他 HFpEF 研究结合起来。方法 在入组 6 个月内，对 4,822 名 PARAGON-HF 患者中的 1,097 名进行了超声心动图检查。使用 Cox 比例风险模型评估与首次心力衰竭住院或心血管死亡的关联，并根据年龄、性别、入组地区、随机治疗、N 端脑钠肽前体和临床危险因素。结果 平均年龄为 74 ± 8 岁，53% 的患者为女性，中位 N 端脑钠肽前体水平为 918 pg/ml（四分位距：485 至 1,578 pg/ml），94% 患有高血压，35 % 有房颤。平均左心室 (LV) 射血分数为 58.6 ± 9.8%，LV 肥厚的患病率为 21%，左心房扩大的患病率为 83%，E/e' 比率升高的患病率为 53%，肺动脉高压的患病率为31%。中位随访 2.8 年，288 名患者发生心力衰竭住院或心血管死亡。在完全调整的模型中，更高的 LV 质量指数（风险比 [HR]：1.05 每 10 g/m2；95% 置信区间 [CI]：1.00 至 1.10；p = 0.03）、E/e' 比（HR：1.04 每单元; 95% CI：1.02 到 1.06；p < 0.001）、肺动脉收缩压（HR：1.51/10 mm Hg；95% CI：1.29 至 1.76；p < 0.001）和右心室舒张末期面积（HR：1.04/cm2；95% CI：1.01至 1.07；p = 0.003）均与该复合材料相关，而 LV 射血分数和左心房大小则无关（p > 0.05）。尽管 E/e' 比、肺动脉收缩压和事件发生率相似，但与其他 HFpEF 临床试验相比，在心脏结构方面观察到了明显的差异。结论 舒张功能障碍、左心房扩大和肺动脉高压在 PARAGON-HF 中很常见。LV 肥厚、左侧和右侧压力升高以及右心室扩大是发生心力衰竭住院或心血管死亡的独立预测因素。尽管临床事件发生率相似，但 HFpEF 试验之间的超声心动图差异突出了该综合征的异质性。（与缬沙坦相比，LCZ696 对射血分数保留的心力衰竭患者的发病率和死亡率的疗效和安全性 [PARAGON-HF]；NCT01920711）。