International prevalence of transthyretin amyloid cardiomyopathy in high-risk patients with heart failure and preserved or mildly reduced ejection fraction.

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure (HF).

Methods: This epidemiology study assessed the international prevalence of ATTR-CM among patients aged ≥60 years with a history of HF, left ventricular ejection fraction (LVEF) >40%, an end-diastolic interventricular septum thickness (IVST) ≥12 mm, but without diagnosed amyloidosis, history of LVEF ≤40%, cardiomyopathy of known cause, severe valvular, or coronary heart disease. ATTR-CM was determined using cardiac scintigraphy alongside exclusionary testing for light chain amyloidosis. The study was terminated early due to slow recruitment, without safety concerns.

Results: Overall, 56/315 (18%; 95% CI: 13.7-22.5) patients with evaluable scintigraphy had ATTR-CM, with a numerically higher prevalence in: Europe (24%) vs. other regions (9% Asia; 5% North America); at specialist vs non-specialist centres (26% vs. 11%); in males vs. females (24% vs. 10%); and in older vs. younger patients (e.g. >40% among those ≥85 years). Other risk markers (p<.05) included a history of carpal tunnel syndrome, higher N-terminal pro B-type natriuretic peptide concentration, and higher end-diastolic IVST.

Conclusions: ATTR-CM was diagnosed in 18% (95% CI: 13.7-22.5) of evaluable patients with HF, LVEF >40%, and risk markers for ATTR-CM, but no previous diagnosis of amyloidosis. Recruitment bias may have contributed to regional variability. NCT04424914.