Cardiac amyloidosis (CA) is present in approximately 10% of patients with heart failure worldwide, with wild-type transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) accounting for the majority of cases, according to a recent study preprint on Research Square.
CA is an infiltrative cardiomyopathy caused by extracellular deposition of misfolded amyloid proteins in the heart and is a more common contributor to heart failure than previously thought, especially with advances in noninvasive diagnostics like technetium-labeled bone scintigraphy.
The 2 main subtypes are light-chain amyloidosis (AL-CA), produced by plasma cell disorders, and ATTR-CM, which includes wild-type and variant forms. Historically underdiagnosed due to reliance on biopsy, CA is now better detected, revealing higher prevalence in older adults with heart failure with preserved ejection fraction or unexplained hypertrophy.
Read more about ATTR-CM epidemiology
Disease-modifying therapies are now available (eg, transthyretin stabilizers and silencers for ATTR-CM, chemotherapy/immunotherapy for AL-CA) and are most effective when started early, underscoring the urgency of improved global screening.
“CA is present in [1 in 10] patients with [heart failure] worldwide, with [wild-type ATTR-CM] being the predominant subtype. Uneven geographic distribution may suggest underdiagnosis, particularly in underrepresented regions and in females,” the authors wrote.
The study’s authors aimed to provide the first comprehensive global estimate of the prevalence of CA in patients with heart failure through a systematic review and meta-analysis to highlight gaps in detection and guide more equitable screening strategies worldwide. They examined geographic variations, subtype distribution, sex differences, and study design effects.
The researchers searched PubMed, EMBASE, Web of Science, and Cochrane from inception through 2025, identified 28 eligible studies (including 7393 patients with heart failure, among whom 627 were diagnosed with CA), and performed random-effects meta-analysis to estimate the pooled prevalence.
They found an overall CA prevalence of around 10%, with wild-type ATTR-CM comprising 76% of cases and prevalence highest in Asia and lowest in North America, though regional differences were not statistically significant.
The authors noted substantial heterogeneity and publication bias in the study. Females represented only around 24% of CA cases.
Study improvements could include more multinational prospective studies from underrepresented regions, standardized diagnostic criteria and screening protocols across centers, larger sample sizes to reduce heterogeneity, and routine reporting of sex-stratified and temporal data to better track evolving prevalence.
“These findings support broader, standardized screening and the need for multinational studies to better define the global burden of CA,” the authors concluded.
Clinicians: Are your patients looking for news and insights on ATTR-CM? Refer them to ATTR-CM Companion.