Across 18 studies encompassing 3,646 patients with transthyretin amyloid cardiomyopathy (ATTR-CM), disease-modifying therapies — including transthyretin stabilizers like tafamidis and RNA-silencing agents like patisiran and vutrisiran — significantly attenuated deterioration in global longitudinal strain (mean difference −0.69%; 95% CI −1.10 to −0.29) and preserved left ventricular ejection fraction (MD +1.62%; 95% CI 0.73–2.51). Diastolic function markers (E/e′ ratio) and stroke volume were also preserved. Critically, no significant treatment effect emerged for interventricular septal thickness, LV mass, or end-diastolic volume — the hallmarks of amyloid infiltration.
This finding reframes what patients and clinicians can realistically expect from current ATTR-CM pharmacotherapy. Prior landmark trials like ATTR-ACT demonstrated mortality and hospitalization benefits from tafamidis, but structural endpoints received less systematic attention. This meta-analysis clarifies the mechanism of benefit: these drugs appear to freeze progression rather than induce structural regression, analogous to cytostatic rather than cytotoxic cancer therapy. For the estimated 300,000–500,000 Americans with undiagnosed ATTR-CM, this underscores the urgency of early detection — initiating therapy before irreversible amyloid deposition accrues likely maximizes structural preservation. The pooled design pools RCTs with observational data, introducing heterogeneity risk, and follow-up durations vary across included studies. This is a preprint not yet peer-reviewed, so findings warrant cautious interpretation pending independent validation. Still, the mechanistic clarity here is clinically valuable and broadly confirmatory of existing biological understanding.
