Abstract
Introduction: The prevalence of cardiac amyloidosis (CA) in the general population as well as prognostic implications remain poorly understood. Hypothesis: We aimed to identify CA prevalence and outcomes in bone scintigraphy referrals. Methods: Between 2010 and 2020, consecutive all-comers undergoing 99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy were included retrospectively. CA was defined as positive cardiac tracer uptake (Perugini grade-1: subclinical CA; grade-2/3: clinical CA). All-cause mortality, cardiovascular (CV) death and hospitalization for heart failure (HHF) served as endpoints. Results: 17387 scans from 11527 subjects (61±16 y/o, 63.0% female, 73.6% cancer) were analyzed. Prevalence of CA was 3.3% (n=376/11527; grade-1: 1.8%, grade-2/3: 1.5%), and was higher among cardiac vs. non-cardiac referrals (18.2% vs. 1.7%). In 4 individuals with >1 scan, progression from subclinical to clinical CA was observed. Cardiac biopsy revealed underlying transthyretin CA in 3 grade-1 patients. After a median of 6 years, clinical event rates were: 29.4% mortality, 2.6% CV death, and 1.5% HHF, all independently predicted by CA. Overall, adverse outcomes were driven by clinical CA (clinical vs. no CA, mortality: adjusted hazard ratio [AHR] 1.46 [95% confidence interval 1.12-1.90]; CV death: AHR 2.34 [1.49-3.68]; HHF: AHR 2.25 [1.51-3.37]). In non-cancer patients, subclinical CA had equally increased mortality to clinical CA (log-rank, p >0.05), presumably due to longer observation/life expectancy. Conclusions: CA was identified in a substantial number of consecutive DPD referrals and associated with adverse outcomes. Subclinical (grade-1) progressed to clinical (grade-2/3) CA at follow-up and both had similarly increased mortality among non-cancer patients. Thus, in grade-1, clarification of the underlying pathology using myocardial biopsy is indicated to enable timely targeted therapy.
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