Prevalence and outcomes of cardiac amyloidosis in all-comer referrals for bone scintigraphy

Abstract

AIMS: The prevalence of cardiac amyloidosis (CA) in the general population and associated prognostic implications remain poorly understood. We aimed to identify CA prevalence and outcomes in bone scintigraphy referrals. METHODS AND RESULTS: Consecutive all-comers undergoing 99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic-acid (DPD) bone scintigraphy between 2010 and 2020 were included. Perugini grade-1 was defined as low-grade uptake and grade-2/3 as confirmed CA. All-cause mortality, cardiovascular death and heart failure hospitalization (HHF) served as endpoints. In total, 17,387 scans from 11,527 subjects (61±16 y/o, 63.0% female, 73.6% cancer) were analyzed. Prevalence of DPD positivity was 3.3% (n = 376/11,527; grade-1: 1.8%, grade-2/3: 1.5%), and was higher among cardiac vs. non-cardiac referrals (18.2% vs. 1.7%). In individuals with >1 scan, progression from grade-1 to grade-2/3 was observed. Among patients with biopsy-proven CA, the portion of light-chain (AL)-CA was significantly higher in grade-1 vs. grade-2/3 (73.3% vs. 15.4%). After a median of 6 years, clinical event rates were: 29.4% mortality, 2.6% cardiovascular death, and 1.5% HHF, all independently predicted by positive DPD. Overall, adverse outcomes were driven by confirmed CA (vs. grade-0, mortality: adjusted hazard ratio [AHR] 1.46 [95% confidence interval 1.12-1.90]; cardiovascular death: AHR 2.34 [1.49-3.68]; HHF: AHR 2.25 [1.51-3.37]). One-year mortality was substantially higher in cancer vs. non-cancer patients. Among non-cancer patients, also grade-1 had worse outcomes than grade-0 (HHF/death: AHR 1.45 [1.01-2.09]), presumably due to longer observation/higher prognostic impact of early infiltration. CONCLUSION: Positive DPD was identified in a substantial number of consecutive DPD referrals and associated with adverse outcomes.