ImportanceHeart failure with improved ejection fraction (HFimpEF), defined as prior left ventricular ejection fraction (LVEF) 40% or lower that has increased to greater than 40%, is understudied.ObjectiveTo examine mode of death and the association of dapagliflozin with reductions in cause-specific death in patients with HFimpEF.Design, Setting, and ParticipantsThis was a post hoc analysis from the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) randomized clinical trial, conducted from August 2018 to December 2020. The trial randomly assigned patients with HF with LVEF greater than 40%, New York Heart Association class II to IV symptoms, and elevated natriuretic peptides to treatment with dapagliflozin (10 mg, once daily) or placebo. The presence of HFimpEF was captured through study case report forms. The primary outcome was a composite of worsening HF events (hospitalization or urgent HF visits) or cardiovascular death. Clinical outcomes were adjudicated by a blinded clinical end points committee. Data were analyzed from May 2022 to August 2023.InterventionDapagliflozin vs placebo.Main Outcomes and MeasuresThe mode of death in relation to HFimpEF status was examined, as well as the association of randomized treatment with cause-specific death in Cox regression models.ResultsOf 1151 patients with HFimpEF in DELIVER, 190 (16.5%) died, compared with 833 patients (16.3%) of 5112 with LVEF consistently greater than 40%. The overall distribution of mode of death was similar in those with HFimpEF compared with those with LVEF consistently greater than 40% (noncardiovascular death: 103 of 190 [54%] vs 428 of 833 [51%]; cardiovascular death: 87 of 190 [46%] vs 405 of 833 [49%], respectively). Most deaths in individuals with HFimpEF were noncardiovascular (103 of 180 [54%]). For cardiovascular deaths, sudden deaths were most common (36 of 190 events [19%]), followed by HF-related (29 of 190 events [15%]). Among patients with HFimpEF, treatment with dapagliflozin was associated with lower rates of cardiovascular death relative to placebo, a difference primarily due to lower rates of sudden death (hazard ratio, 0.38; 95% CI, 0.18-0.79; P for interaction = .01).Conclusions and RelevanceThe findings in this study support current guideline recommendations for use of sodium-glucose transport protein 2 inhibitor therapy, and further suggest that the addition of a sodium-glucose transport protein 2 inhibitor therapy to other guideline-directed medical therapies may help reduce cardiovascular mortality in patients with HFimpEF.Trial RegistrationClinicalTrials.gov Identifier: NCT03619213

中文翻译：

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达格列净与射血分数改善的心力衰竭患者的死亡方式

重要性射血分数改善的心力衰竭 (HFimpEF) 定义为既往左心室射血分数 (LVEF) 40% 或更低，但已增加至大于 40%，目前仍在研究中。 目的检查死亡模式以及达格列净与死因减少的关系- HFimpEF 患者的特定死亡。设计、设置和参与者这是对 2018 年 8 月至 2020 年 12 月进行的达格列净改善射血分数保留性心力衰竭患者的生活 (DELIVER) 随机临床试验的事后分析。该试验将 LVEF 大于 40%、纽约心脏协会 II 级至 IV 级症状、钠尿肽升高的心力衰竭患者随机分配至达格列净（10 毫克，每日一次）或安慰剂治疗组。HFimpEF 的存在是通过研究病例报告表捕获的。主要结局是心衰事件恶化（住院或紧急心衰就诊）或心血管死亡的综合结果。临床结果由盲法临床终点委员会判定。分析了 2022 年 5 月至 2023 年 8 月的数据。干预措施达格列净与安慰剂相比。主要结果和措施检查了与 HFimpEF 状态相关的死亡模式，以及 Cox 回归模型中随机治疗与特定原因死亡的关联。结果 1151 名患者DELIVER 中出现 HFimpEF 的患者中有 190 名患者 (16.5%) 死亡，而 5112 名患者中有 833 名患者 (16.3%) 的 LVEF 始终大于 40%。与 LVEF 持续大于 40% 的患者相比，HFimpEF 患者的死亡模式总体分布相似（非心血管死亡：190 人中的 103 人 [54%] vs 833 人中的 428 人 [51%]；心血管死亡：190 人中的 87 人[ 46%] vs 833 中的 405 [49%]）。HFimpEF 患者的大多数死亡是非心血管疾病（180 例中有 103 例 [54%]）。对于心血管死亡，猝死最常见（190 起事件中的 36 起 [19%]），其次是心力衰竭相关死亡（190 起事件中的 29 起 [15%]）。在 HFimpEF 患者中，与安慰剂相比，达格列净治疗与较低的心血管死亡率相关，差异主要是由于猝死率较低（风险比，0.38；95% CI，0.18-0.79；磷相互作用 = .01）。结论和相关性本研究的结果支持当前关于使用钠-葡萄糖转运蛋白 2 抑制剂治疗的指南建议，并进一步建议在其他指南中添加钠-葡萄糖转运蛋白 2 抑制剂治疗 -定向药物治疗可能有助于降低 HFimpEF 患者的心血管死亡率。试验注册ClinicalTrials.gov 标识符：NCT03619213