Importance Tafamidis has been shown to improve survival in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) compared with placebo. However, its effect on cardiac function has not been fully characterized. Objective To examine the effect of tafamidis on cardiac function in patients with ATTR-CM. Design, Setting, and Participants This was an exploratory, post hoc analysis of the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), a multicenter, international, double-blind, placebo-controlled phase 3 randomized clinical trial conducted from December 2013 to February 2018. The ATTR-ACT included 48 sites in 13 counties and enrolled patients aged 18 to 90 years with ATTR-CM. Data were analyzed from July 2018 to September 2023. Intervention Patients were randomized to tafamidis meglumine, 80 mg or 20 mg, or placebo for 30 months. Main Outcomes and Measures Patients were categorized based on left ventricular (LV) ejection fraction at enrollment as having heart failure with preserved ejection fraction (≥50%), mildly reduced ejection fraction (41% to 49%), or reduced ejection fraction (≤40%). Changes from baseline to month 30 in LV ejection fraction, LV stroke volume, LV global longitudinal strain, and the ratio of early mitral inflow velocity to septal and lateral early diastolic mitral annular velocity (E/e') were compared in patients receiving tafamidis, 80 mg, vs placebo. Results A total of 441 patients were randomized in ATTR-ACT, and 436 patients had available echocardiographic data. Of 436 included patients, 393 (90.1%) were male, and the mean (SD) age was 74 (7) years. A total of 220 (50.5%), 119 (27.3%), and 97 (22.2%) had heart failure with preserved, mildly reduced, and reduced LV ejection fraction, respectively. Over 30 months, there was less pronounced worsening in 4 of the echocardiographic measures in patients receiving tafamidis, 80 mg (n = 176), vs placebo (n = 177) (least squares mean difference: LV stroke volume, 7.02 mL; 95% CI, 2.55-11.49; P = .002; LV global longitudinal strain, -1.02%; 95% CI, -1.73 to -0.31; P = .005; septal E/e', -3.11; 95% CI, -5.50 to -0.72; P = .01; lateral E/e', -2.35; 95% CI, -4.01 to -0.69; P = .006). Conclusions and Relevance Compared with placebo, tafamidis, 80 mg, attenuated the decline of LV systolic and diastolic function over 30 months in patients with ATTR-CM. Approximately half of patients had mildly reduced or reduced LV ejection fraction at enrollment, suggesting that ATTR-CM should be considered as a possible diagnosis in patients with heart failure regardless of underlying LV ejection fraction. Trial Registration ClinicalTrials.gov Identifier: NCT01994889.

中文翻译：

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Tafamidis 对运甲状腺素蛋白淀粉样心肌病患者心功能的影响：ATTR-ACT 随机临床试验的事后分析。

重要性 与安慰剂相比，Tafamidis 已被证明可以提高转甲状腺素蛋白淀粉样心肌病 (ATTR-CM) 患者的生存率。然而，其对心脏功能的影响尚未完全确定。目的探讨他法米迪对 ATTR-CM 患者心功能的影响。设计、设置和参与者 这是对 Tafamidis 在转甲状腺素蛋白心肌病临床试验 (ATTR-ACT) 中的探索性事后分析，该试验是一项多中心、国际、双盲、安慰剂对照 3 期随机临床试验，于 2013 年 12 月至 2013 年 12 月进行。 2018 年 2 月。ATTR-ACT 包括 13 个县的 48 个地点，并纳入了 18 至 90 岁的 ATTR-CM 患者。数据分析时间为 2018 年 7 月至 2023 年 9 月。 干预 患者被随机分配至 tafamidis 葡甲胺 80 毫克或 20 毫克，或安慰剂 30 个月。主要结果和措施 入组时根据左心室 (LV) 射血分数将患者分为射血分数保留的心力衰竭（≥50%）、射血分数轻度降低（41% 至 49%）或射血分数降低（≤ 40%）。比较接受tafamidis治疗的患者从基线到第30个月的左心室射血分数、左心搏出量、左心室整体纵向应变以及早期二尖瓣流入速度与间隔和侧向舒张早期二尖瓣环速度的比率（E/e'）的变化， 80 毫克，对比安慰剂。结果共有 441 名患者被随机分配到 ATTR-ACT 中，其中 436 名患者有可用的超声心动图数据。在 436 名患者中，393 名 (90.1%) 为男性，平均 (SD) 年龄为 74 (7) 岁。共有 220 例 (50.5%)、119 例 (27.3%) 和 97 例 (22.2%) 患者分别患有左心室射血分数保留、轻度降低和降低的心力衰竭。30 个月内，与安慰剂组 (n = 177) 相比，接受他法米迪 (80 mg) 治疗的患者 (n = 176) 的 4 项超声心动图测量结果恶化程度不太明显（最小二乘平均差：左心室每搏输出量，7.02 mL；95%） CI，2.55-11.49；P = .002；左室整体纵向应变，-1.02%；95% CI，-1.73 至 -0.31；P = .005；间隔 E/e'，-3.11；95% CI，-5.50至 -0.72；P = .01；横向 E/e'，-2.35；95% CI，-4.01 至 -0.69；P = .006）。结论和相关性 与安慰剂相比，tafamidis 80 mg 可减轻 ATTR-CM 患者 30 个月内左室收缩和舒张功能的下降。大约一半的患者在入组时左心室射血分数轻度降低或降低，这表明无论潜在的左心室射血分数如何，ATTR-CM都应被视为心力衰竭患者的可能诊断。试验注册 ClinicalTrials.gov 标识符：NCT01994889。