Differential Effects of Tafamidis on Cardiac Remodelling in Transthyretin Amyloid Cardiomyopathy: Evidence From Contemporary Imaging Data

IF 4.1 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation Pub Date : 2026-08-12 DOI:10.1111/eci.70246

Tameem Quader, Krisha Patel, James Sindone, Shaun Khanna, Aditya Bhat, Henry Chen, Gary Gan, Nitesh Nerlekar, Suzanne Eshoo, Nicole Bart, Liza Thomas, Andrew Sindone

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引用次数: 0

Abstract

Background

Tafamidis is the only approved disease-modifying therapy for transthyretin amyloid cardiomyopathy (ATTR-CM) in Australia. Although its clinical efficacy is established, its effects on cardiac remodelling assessed by contemporary multimodality imaging remain incompletely defined.

Methods

MEDLINE, Embase and Cochrane databases were systematically searched from 2000 to 2025. Observational studies evaluating tafamidis-treated versus untreated/control patients that reported serial TTE, CMR or bone-tracer scintigraphy measurements were eligible. Change-from-baseline values were used to derive measures. Outcomes were pooled as standardised mean differences (SMDs) with 95% confidence intervals using random-effects modelling. A two-sided p < 0.05 was considered statistically significant.

Results

Over a mean follow-up of 16 months, tafamidis was associated with significant improvements in left atrial reservoir strain (LASr) (SMD +0.58, 95% CI +0.27 to +0.89; p < 0.001; I² = 0) on TTE and right ventricular ejection fraction (RVEF) (SMD +0.51, 95% CI +0.16 to +0.86; p = 0.004; I² = 0) on CMR. A reduction in left atrial volume index (LAVi) was observed (SMD –0.24, 95% CI –0.46 to −0.02; p = 0.034; I² = 0) on TTE. No consistent effects were seen for LV parameters including LVEF, LV-GLS, LV mass index, wall thickness, diastolic indices, pulmonary pressures, tissue characterisation markers (native T1, ECV), or H/CL ratio, despite trends toward benefit in some.

Conclusions

Tafamidis demonstrates selective remodelling effects in ATTR-CM, with the most benefits noted in left atrial function and RV systolic performance, rather than LV structural or functional parameters. Imaging parameters such as LASr, LAVi, and RVEF may serve as sensitive endpoints of therapeutic response in future clinical trials, offering mechanistic insights beyond conventional LV metrics.

Study Registration

PROSPERO CRD420251145891.

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他法非地对转甲状腺素淀粉样心肌病心脏重构的不同影响：来自当代影像学资料的证据。

背景：他法非底是澳大利亚唯一批准的治疗甲状腺素淀粉样心肌病（atr - cm）的疾病改善疗法。虽然它的临床疗效是确定的，但它对心脏重塑的影响，通过当代多模态成像评估仍然不完全确定。方法：系统检索2000 ~ 2025年的MEDLINE、Embase和Cochrane数据库。评价他非他汀治疗与未治疗/对照患者的观察性研究符合条件，这些患者报告了一系列TTE、CMR或骨示踪闪烁成像测量。使用基线变化值来推导度量。采用随机效应模型将结果汇总为95%置信区间的标准化平均差异（SMDs）。双侧p结果：在平均16个月的随访中，他法非地与左房储层张力（LASr）（SMD +0.58, 95% CI +0.27至+0.89;p 2 = 0）的TTE和右心室射血分数（RVEF）（SMD +0.51, 95% CI +0.16至+0.86;p = 0.004; I2 = 0）的CMR显著改善相关。观察到TTE组左房容积指数（LAVi）降低（SMD -0.24, 95% CI -0.46 ~ -0.02; p = 0.034; I2 = 0）。左室参数包括LVEF、LV- gls、左室质量指数、壁厚、舒张指数、肺动脉压、组织特征标志物（原生T1、ECV）或H/CL比，尽管在某些方面有获益的趋势，但未见一致的影响。结论：他法非地在atr - cm中表现出选择性重构作用，对左房功能和右室收缩性能最有利，而不是左室结构或功能参数。在未来的临床试验中，诸如LASr、LAVi和RVEF等成像参数可以作为治疗反应的敏感终点，提供超越传统左室指标的机制见解。研究注册：PROSPERO CRD420251145891。

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来源期刊

European Journal of Clinical Investigation 医学-医学：内科

CiteScore

9.50

自引率

3.60%

发文量

192

审稿时长

1 months

期刊介绍： EJCI considers any original contribution from the most sophisticated basic molecular sciences to applied clinical and translational research and evidence-based medicine across a broad range of subspecialties. The EJCI publishes reports of high-quality research that pertain to the genetic, molecular, cellular, or physiological basis of human biology and disease, as well as research that addresses prevalence, diagnosis, course, treatment, and prevention of disease. We are primarily interested in studies directly pertinent to humans, but submission of robust in vitro and animal work is also encouraged. Interdisciplinary work and research using innovative methods and combinations of laboratory, clinical, and epidemiological methodologies and techniques is of great interest to the journal. Several categories of manuscripts (for detailed description see below) are considered: editorials, original articles (also including randomized clinical trials, systematic reviews and meta-analyses), reviews (narrative reviews), opinion articles (including debates, perspectives and commentaries); and letters to the Editor.