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Prevalence of Transthyretin Amyloid Cardiomyopathy in Heart Failure With Preserved Ejection Fraction
JAMA Cardiology  (IF14.676),  Pub Date : 2021-11-01, DOI: 10.1001/jamacardio.2021.3070
Omar F. AbouEzzeddine, Daniel R. Davies, Christopher G. Scott, Ahmed U. Fayyaz, J. Wells Askew, Paul M. McKie, Peter A. Noseworthy, Geoffrey B. Johnson, Shannon M. Dunlay, Barry A. Borlaug, Panithaya Chareonthaitawee, Veronique L. Roger, Angela Dispenzieri, Martha Grogan, Margaret M. Redfield

Importance Heart failure (HF) with preserved ejection fraction (HFpEF) is common, is frequently associated with ventricular wall thickening, and has no effective therapy. Transthyretin amyloid cardiomyopathy (ATTR-CM) can cause the HFpEF clinical phenotype, has highly effective therapy, and is believed to be underrecognized.

Objective To examine the prevalence of ATTR-CM without and with systematic screening in patients with HFpEF and ventricular wall thickening.

Design, Setting, and Participants This population-based cohort study assessed ATTR-CM prevalence in 1235 consecutive patients in southeastern Minnesota with HFpEF both without (prospectively identified cohort study) and with (consenting subset of cohort study, n = 286) systematic screening.Key entry criteria included validated HF diagnosis, age of 60 years or older, ejection fraction of 40% or greater, and ventricular wall thickness of 12 mm or greater. In this community cohort of 1235 patients, 884 had no known ATTR-CM, contraindication to technetium Tc 99m pyrophosphate scanning, or other barriers to participation in the screening study. Of these 884 patients, 295 consented and 286 underwent scanning between October 5, 2017, and March 9, 2020 (community screening cohort).

Exposures Medical record review or technetium Tc 99m pyrophosphate scintigraphy and reflex testing for ATTR-CM diagnosis.

Main Outcomes and Measures The ATTR-CM prevalence by strategy (clinical diagnosis or systematic screening), age, and sex.

Results A total of 1235 patients participated in the study, including a community cohort (median age, 80 years; interquartile range, 72-87 years; 630 [51%] male) and a community screening cohort (n = 286; median age, 78 years; interquartile range, 71-84 years; 149 [52%] male). In the 1235 patients in the community cohort without screening group, 16 patients (1.3%; 95% CI, 0.7%-2.1%) had clinically recognized ATTR-CM. The prevalence was 2.5% (95% CI, 1.4%-4.0%) in men and 0% (95% CI, 0.0%-0.6%) in women. In the 286 patients in the community screening cohort, 18 patients (6.3%; 95% CI, 3.8%-9.8%) had ATTR-CM. Prevalence increased with age from 0% in patients 60 to 69 years of age to 21% in patients 90 years and older (P < .001). Adjusting for age, ATTR-CM prevalence differed by sex, with 15 of 149 men (10.1%; 95% CI, 5.7%-16.1%) and 3 of 137 women (2.2%; 95% CI, 0.4%-6.3%) having ATTR-CM (P = .002).

Conclusions and Relevance In this cohort study based in a community-based setting, ATTR-CM was present in a substantial number of cases of HFpEF with ventricular wall thickening, particularly in older men. These results suggest that systematic evaluation can increase the diagnosis of ATTR-CM, thereby providing therapeutically relevant phenotyping of HFpEF.