Abstract
Abstract Objectives Cardiac amyloidosis (CA) is increasingly identified as a cause of heart failure due to diagnostic advances and enhanced disease awareness. Screening ascertainments have unveiled a significant proportion of (coexisting) CA for various cardiac conditions, but the true prevalence of CA in the general population as well as prognostic implications remain unknown. Methods Consecutive all-comer referrals for 99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy between January 2010 and August 2020 were included retrospectively. CA was defined as positive cardiac tracer uptake (Perugini grade 0: negative; grades 1 to 3: increasingly positive). Owing to the study design, CA subtype (transthyretin vs. light chain) was not assessed. Indications for DPD, laboratory, and clinical data were retrieved from medical records. Mortality was captured from the Austrian death registry. Combined hospitalization for heart failure (HHF) and all-cause death was defined as study endpoint. Outcome analysis was performed using Kaplan Meier estimates and multivariate Cox regression. Results 17202 scans from 11549 subjects (61.2±16.1 y/o, 62.9% female, 73.7% cancer patients) were analyzed. Follow-up scans for patients with >1 test yielded identical Perugini grades in all cases. Prevalence of CA for the overall population was 5.5% (n=638/11549; grade 1: 4.0%, grade 2/3: 1.5%), increased with age (<60 y/o: 2.5%, 60–70 y/o: 5.4%, 70–80 y/o: 7.6%, >80 y/o: 14.2%, p<0.001, Figure), and was higher in men vs. women (7.4% vs. 4.4%, p<0.001). Also, CA was more prevalent in cardiac (19.1%, n=207/1081) vs. non-cardiac referrals (4.1%, n=431/10468; p<0.001). Across all age groups of non-cardiac referrals, CA patients more often had atrial fibrillation and cardiomyopathy, and displayed worse renal function (p for all<0.05). Following DPD, 3490 patients (30.2%) had reached the study endpoint (84 HHF, 3313 death, 93 both) after 5.9±3.3 years. By Kaplan Meier estimates, the presence of CA among all-comers predicted adverse outcomes (log-rank, p<0.001, Figure). After adjustment for age and cancer, CA remained significantly associated with outcomes by multivariate Cox regression (hazard ratio [HR]: 1.30, 95% confidence interval [CI] 1.14–1.48, p<0.001). This effect was consistent across subgroups of cardiac (HR: 1.41, 95% CI 1.06–1.89, p=0.018) and non-cardiac referrals (HR: 1.20, 95% CI 1.03–1.39, p=0.018). Outcomes were similar in grade 1 vs. 2/3 CA patients (p>0.05). Conclusion Cardiac tracer uptake is present in 1 in 20 patients referred for bone scintigraphy, and independently predicts prognosis – even in this population with significantly reduced life expectancy due to the high rate of malignancy. With novel CA-specific drugs available – especially for transthyretin CA – diagnosis of CA is even more crucial to improve patient outcomes. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Pfizer Cardiac Tracer Uptake in DPD Referrals
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