Differential effects of Tafamidis on cardiac remodelling in transthyretin amyloid cardiomyopathy: evidence from contemporary imaging data
T Quader, K Patel, A Jirjis, J Sindone, S Khanna, A Bhat, H Chen, G Gan, N Nerlekar, S Eshoo, N Bart, L Thomas, A SindoneAbstract
Background
Tafamidis is the only approved disease-modifying therapy for Transthyretin amyloid cardiomyopathy in Australia. Although its clinical efficacy is established, its effects on cardiac remodelling assessed by contemporary multimodality imaging remain incompletely defined.
Purpose
To evaluate the impact of tafamidis on serial cardiac remodelling parameters measured by transthoracic echocardiography (TTE), cardiac magnetic resonance (CMR), and bone-tracer scintigraphy in patients with ATTR-CM.
Methods
MEDLINE, Embase, and Cochrane databases were systematically searched from 2000–2025. Observational studies comparing 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 pooled estimates. Outcomes were expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs) using random-effects modelling. A two-sided p<0.05 was considered statistically significant.
Results
Of 951 studies screened, 13 met our inclusion criteria for a total of 1,014 patients (figure 1). Over a mean follow-up of 16 months (table 1), 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). No consistent effects were seen for left ventricular parameters including LVEF, LV-GLS, LV mass index, wall thickness, diastolic indices, pulmonary pressures, tissue characterization markers (native T1, ECV), or heart-to-contralateral lung (H/CL) ratio, despite trends toward benefit in some measures.
Conclusions
Tafamidis demonstrates selective remodelling effects in ATTR-CM, with the greatest benefits observed in left atrial function and right ventricular systolic performance rather than conventional left ventricular structural or functional parameters. Imaging markers such as LASr, LAVi, and RVEF may represent sensitive surrogate endpoints of therapeutic response in future clinical trials and provide mechanistic insights beyond traditional LV metrics.