• Scott M Damrauer, Kumardeep Chaudhary, Judy H Cho, Lusha W Liang, Edgar Argulian, Lili Chan, Amanda Dobbyn, Marie A Guerraty, Renae Judy, Jenna Kay, Rachel L Kember, Michael G Levin, Aparna Saha, Tielman Van Vleck, Shefali S Verma, JoEllen Weaver, Noura S Abul-Husn, Aris Baras, Julio A Chirinos, Brian Drachman, Eimear E Kenny, LoosRuth J FRJFThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York.Mindic, Jagat Narula, John Overton, Jeffrey Reid, Marylyn Ritchie, Giorgio Sirugo, Girish Nadkarni, Daniel J Rader, and Ron Do.
• Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
• JAMA. 2019 Dec 10; 322 (22): 219122022191-2202.

ImportanceHereditary transthyretin (TTR) amyloid cardiomyopathy (hATTR-CM) due to the TTR V122I variant is an autosomal-dominant disorder that causes heart failure in elderly individuals of African ancestry. The clinical associations of carrying the variant, its effect in other African ancestry populations including Hispanic/Latino individuals, and the rates of achieving a clinical diagnosis in carriers are unknown.ObjectiveTo assess the association between the TTR V122I variant and heart failure and identify rates of hATTR-CM diagnosis among carriers with heart failure.Design, Setting, And ParticipantsCross-sectional analysis of carriers and noncarriers of TTR V122I of African ancestry aged 50 years or older enrolled in the Penn Medicine Biobank between 2008 and 2017 using electronic health record data from 1996 to 2017. Case-control study in participants of African and Hispanic/Latino ancestry with and without heart failure in the Mount Sinai BioMe Biobank enrolled between 2007 and 2015 using electronic health record data from 2007 to 2018.ExposuresTTR V122I carrier status.Main Outcomes And MeasuresThe primary outcome was prevalent heart failure. The rate of diagnosis with hATTR-CM among TTR V122I carriers with heart failure was measured.ResultsThe cross-sectional cohort included 3724 individuals of African ancestry with a median age of 64 years (interquartile range, 57-71); 1755 (47%) were male, 2896 (78%) had a diagnosis of hypertension, and 753 (20%) had a history of myocardial infarction or coronary revascularization. There were 116 TTR V122I carriers (3.1%); 1121 participants (30%) had heart failure. The case-control study consisted of 2307 individuals of African ancestry and 3663 Hispanic/Latino individuals; the median age was 73 years (interquartile range, 68-80), 2271 (38%) were male, 4709 (79%) had a diagnosis of hypertension, and 1008 (17%) had a history of myocardial infarction or coronary revascularization. There were 1376 cases of heart failure. TTR V122I was associated with higher rates of heart failure (cross-sectional cohort: n = 51/116 TTR V122I carriers [44%], n = 1070/3608 noncarriers [30%], adjusted odds ratio, 1.7 [95% CI, 1.2-2.4], P = .006; case-control study: n = 36/1376 heart failure cases [2.6%], n = 82/4594 controls [1.8%], adjusted odds ratio, 1.8 [95% CI, 1.2-2.7], P = .008). Ten of 92 TTR V122I carriers with heart failure (11%) were diagnosed as having hATTR-CM; the median time from onset of symptoms to clinical diagnosis was 3 years.Conclusions And RelevanceAmong individuals of African or Hispanic/Latino ancestry enrolled in 2 academic medical center-based biobanks, the TTR V122I genetic variant was significantly associated with heart failure.

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