Background:Patients with heart failure (HF) and preserved left ventricular ejection fraction comprise a heterogeneous group including some with mildly reduced EF. We hypothesized that mode of death differs by EF in ambulatory patients with HF and preserved left ventricular ejection fraction.Methods:PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor With Angiotensin-Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction) compared clinical outcomes in 4796 patients with chronic HF and EF ≥45% randomly assigned to sacubitril/valsartan or valsartan. We examined the mode of death in relation to baseline EF in logistic regression models and the effect of randomized treatment on cause-specific death in Cox regression models. Nonlinear relationships with continuous EF were modelled using quadratic and cubic terms.Results:Of 691 deaths during the trial, 416 (60%) were ascribed to cardiovascular, 220 (32%) to noncardiovascular, and 55 (8%) to unknown causes. Of cardiovascular deaths, 154 (37%) were due to sudden death, 118 (28%) were due to HF, 35 (8%) to stroke, 27 (6%) to myocardial infarction, and 82 (20%) to other cardiovascular causes. Rates of all-cause, cardiovascular, and sudden death were higher in those with lower left ventricular ejection fraction (all P<0.001), while rates of non-cardiovascular death were greater in patients with higher EF. Sacubitril/valsartan did not reduce overall death, cardiovascular death, or sudden death compared with valsartan, irrespective of baseline EF (all P for interaction >0.30).Conclusions:Among patients with HF and preserved left ventricular ejection fraction enrolled in PARAGON-HF, the proportion of cardiovascular and sudden death were higher in those with lower left ventricular EF, and the proportion of noncardiovascular death rose with EF. Regardless of EF, sacubitril/valsartan did not reduce death from any cause compared with valsartan.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.

中文翻译：

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心力衰竭和射血分数保留患者的死亡模式：来自 PARAGON-HF 试验的见解

背景：心力衰竭 (HF) 和保留左心室射血分数的患者构成异质组，包括一些 EF 轻度降低的患者。我们假设在具有保留的左心室射血分数的非卧床 HF 患者中，死亡模式因 EF 不同而不同。方法：PARAGON-HF 试验（血管紧张素受体-脑啡肽酶抑制剂与血管紧张素受体阻滞剂在保留射血分数的心力衰竭中的前瞻性比较) 比较了随机分配到沙库巴曲/缬沙坦或缬沙坦组的 4796 名慢性 HF 和 EF ≥45% 的患者的临床结果。我们在逻辑回归模型中检查了与基线 EF 相关的死亡模式，以及在 Cox 回归模型中随机治疗对特定原因死亡的影响。使用二次和三次项对与连续 EF 的非线性关系进行建模。结果：在试验期间的 691 例死亡中，416 例（60%）归因于心血管，220 例（32%）归因于非心血管，55 例（8%）归因于未知原因。在心血管死亡中，154 人（37%）死于猝死，118 人（28%）死于心力衰竭，35 人（8%）死于中风，27 人（6%）死于心肌梗塞，82 人（20%）死于其他心血管原因。左心室射血分数较低的患者全因死亡率、心血管死亡率和猝死率较高（所有 82 (20%) 与其他心血管原因有关。左心室射血分数较低的患者全因死亡率、心血管死亡率和猝死率较高（所有 82 (20%) 与其他心血管原因有关。左心室射血分数较低的患者全因死亡率、心血管死亡率和猝死率较高（所有P <0.001)，而 EF 较高的患者的非心血管死亡率较高。与缬沙坦相比，沙库巴曲/缬沙坦并未降低总体死亡、心血管死亡或猝死，与基线 EF 无关（交互作用的所有P > 0.30）。左心室射血分数较低的患者心血管死亡和猝死的比例较高，非心血管死亡的比例随射血分数升高而升高。不考虑 EF，与缬沙坦相比，沙库巴曲/缬沙坦并未减少任何原因的死亡。注册：网址：https://www.clinicaltrials.gov；唯一标识符：NCT01920711。