Differential Effects of Tafamidis on Cardiac Remodelling in Transthyretin Amyloid Cardiomyopathy: Evidence From...

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.

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.

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.

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.

PROSPERO CRD420251145891.