Fontana Marianna, Maurer Mathew S, Gillmore Julian D, Bender Shaun, Jay Patrick Y, Solomon Scott D
National Amyloidosis Centre, University College London, Division of Medicine, Royal Free Hospital, London, United Kingdom.
Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.
J Am Coll Cardiol. 2025 Feb 25;85(7):744-752. doi: 10.1016/j.jacc.2024.10.097. Epub 2025 Jan 22.
Outpatient worsening heart failure (HF), defined by initiation or intensification of diuretics, is adversely prognostic for patients with either reduced or preserved ejection fraction.
This study sought to investigate the prognostic value of outpatient worsening HF in transthyretin amyloidosis with cardiomyopathy and the effect of patisiran treatment.
Post hoc analyses of the APOLLO-B trial (NCT03997383) evaluated the associations between outpatient worsening HF (defined by oral diuretic initiation or intensification), measures of disease progression, and a composite endpoint of all-cause mortality and cardiovascular (CV) events. We further examined the effect of patisiran on outpatient worsening HF over 24 months (ie, during the double-blind and open-label extension periods).
In APOLLO-B, 144 (40.1%) patients had no event, 157 (43.7%) had outpatient worsening HF, 13 (3.6%) required an urgent HF visit, 118 (32.9%) had a CV hospitalization, and 47 (13.1%) died. Outpatient worsening HF was associated with an increased risk of all-cause mortality and CV events (HR: 2.21; 95% CI: 1.58-3.08), as well as a greater deterioration in 6-minute walk test distance, Kansas City Cardiomyopathy Questionnaire-Overall Summary score, and NYHA functional class and a greater increase in N-terminal prohormone of B-type natriuretic peptide. Addition of outpatient diuretic initiation or intensification to the composite endpoint of all-cause mortality and CV events increased the overall number of patients having an event from 141 to 215 (a 52% increase). Patisiran reduced the risk of outpatient worsening HF (HR: 0.70; 95% CI: 0.51-0.96) over 24 months.
During APOLLO-B, outpatient worsening HF in patients with transthyretin amyloidosis with cardiomyopathy was frequent, prognostic, and reduced by patisiran.
门诊心力衰竭（HF）恶化定义为利尿剂起始或强化使用，对射血分数降低或保留的患者预后不良。
本研究旨在探讨门诊HF恶化在转甲状腺素蛋白淀粉样变心肌病中的预后价值以及帕替沙兰治疗的效果。
对APOLLO-B试验（NCT03997383）进行事后分析，评估门诊HF恶化（定义为口服利尿剂起始或强化）、疾病进展指标与全因死亡率和心血管（CV）事件复合终点之间的关联。我们进一步研究了帕替沙兰在24个月内（即双盲和开放标签延长期）对门诊HF恶化的影响。
在APOLLO-B试验中，144例（40.1%）患者无事件发生，157例（43.7%）出现门诊HF恶化，13例（3.6%）需要紧急HF就诊，118例（32.9%）因CV住院，47例（13.1%）死亡。门诊HF恶化与全因死亡率和CV事件风险增加相关（HR：2.21；95%CI：1.58-3.08），同时6分钟步行试验距离、堪萨斯城心肌病问卷-总体总结评分、纽约心脏协会功能分级恶化更明显，B型利钠肽前体N末端水平升高更显著。将门诊利尿剂起始或强化纳入全因死亡率和CV事件复合终点后，发生事件的患者总数从141例增加到215例（增加52%）。帕替沙兰在24个月内降低了门诊HF恶化风险（HR：0.70；95%CI：0.51-0.96）。
在APOLLO-B试验期间，转甲状腺素蛋白淀粉样变心肌病患者门诊HF恶化情况常见、具有预后价值，且帕替沙兰可降低其发生率。
