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abstractpubmed· abstract· item 42325163

BACKGROUND: Cardiac amyloidosis (CA) is an under-recognized cause of heart failure. Its prevalence in screening studies, and the extent to which selective confirmatory testing affects prevalence estimates, remain uncertain across clinical settings. METHODS: We systematically searched PubMed/MEDLINE and EMBASE up to 10 August 2025. Two reviewers independently screened studies and extracted data. We grouped studies by clinical setting and combined prevalence estimates using random-effects meta-analysis. For each study, we calculated CA prevalence in (1) the whole enrolled cohort and (2) the subgroup who underwent confirmatory testing. RESULTS: Eighty-three studies were included. Pooled CA prevalence (whole cohort; tested subgroup) was highest in left ventricular hypertrophy/hypertrophic cardiomyopathy [LVH/HCM] (15.1%; 35.4%), followed by heart failure (HF)-mainly HF with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF)-(12.6%; 13.6%) and aortic stenosis (AS) (9.6%; 11.6%). Orthopaedic cohorts were lower overall (4.1%) but higher in tested subgroups (12.4%); 'no specific red flags' showed 1.8% vs. 7.8%; non-cardiac bone scintigraphy was 0.49% in both denominators. Across settings, transthyretin CA predominated over light-chain CA. Several studies approached systematic screening in the general elderly; however, they were few and still applied referral criteria to second-level examinations. CONCLUSION: This meta-analysis shows that CA is relatively frequent in HFpEF/HFmrEF, severe AS, and LVH/HCM. To obtain reliable population estimates, future studies should test either all eligible participants or a predefined random sample, rather than only those with suspected disease. In clinical practice, screening strategies should clearly define which higher-risk individuals are referred for second-level tests, balancing diagnostic yield with feasibility.