Heart Failure in African American Individuals, Version 2.0

Abstract

An antecedent body of work established nearly 20 years ago benchmarked the nuanced distinctions of heart failure affecting African American people. Summative statements established a nearly 2-fold higher incidence, earlier onset, greater severity at the time of diagnosis, a more likely nonischemic etiology, a putative pathophysiology attributed to hypertensive heart disease, greater morbidity, and in younger ages (45-64 years) higher mortality. 1,2 The coincident burden of adverse social determinants of health further delineates the disproportionate burden of heart failure in African American individuals. Given that race is a social construct, this peculiar predilection for a nonischemic heart failure phenotype requires further investigation.Though race fails as a surrogate for genetics, 3 race may infer, albeit weakly, genomic ancestry. For those higher-frequency disease-modifying genetic variants associated with African ancestry, it becomes reasonable to revisit genomics in search of additional insight on nonischemic etiologies of heart failure. Transthyretin (TTR) cardiac amyloidosis is known to occur in in the presence of ATTRv-CA (variant) or ATTRwt-CA (wild-type). The most common TTR variant defining the genetic basis of cardiac amyloidosis, Val122Ile, now identified as V142I, originated in western Africa. This causative genetic variant occurs in 3% to 4% of persons in the US who self-identify as African American or Black. 4 Historically, cardiac amyloidosis was considered rare, with a purported incidence of less than 5/10 000 in the general population, qualifying it as an orphan disease. 5 More recent evidence that benefits from noninvasive strategies to facilitate the diagnosis challenges the rarity of cardiac amyloidosis. Based on positive technetium 99m pyrophosphate scans in patients with high pretest likelihood due to the presence of candidate clinical findings in the general population, the prevalence of cardiac amyloidosis may be as high as 10% to 15% in those younger than 70 years and up to 30% in older adults with heart failure. 6,7 Clearly, cardiac amyloidosis is no longer an orphan disease; missed diagnostic opportunities are likely nontrivial, particularly in African American patients with heart failure.In this issue of JAMA, the analysis by Selvaraj et al 8 now allows more precise calibration of this important potential cause of heart failure in African American or Black individuals. Using an impressive aggregation of 4 cohort studies characterized with racial and genomic data, and enriching a sample of participants who self-identify as African American or Black with a size sufficient for natural history studies, the authors present the strong likelihood of carrier status for V142I, heterozygous or homozygous, as a substantial risk factor associated with heart failure, heart failure hospitalizations, and years of life lost. The