ArticleJACC. CardioOncology2026
Systemic Manifestations and Mortality Risk in Transthyretin V142I Variant Carriers: A Million Veteran Program Analysis.
Article in JACC. CardioOncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- p.(V142I)-Associated Variant Transthyretin Amyloid Cardiomyopathy Complicating Complex Congenital Heart Disease: A Lethal Combination.JACC. Case reports · 2026Article
- Overcoming barriers to early diagnosis and treatment of p.Val142Ile amyloid transthyretin (ATTR) cardiomyopathy.Heart failure reviews · 2026Review
- Calling All Carriers: Closing the Gap in V142I Recognition.JACC. CardioOncology · 2026Article
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19 authors.
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Abstract
backgroundThe most common pathogenic transthyretin variant underlying variant transthyretin amyloidosis in the United States is c.424G>A, p.Val142Ile (V142I). In affected individuals, disease manifests predominantly as heart failure (HF) and cardiomyopathy (CM), with atrial fibrillation (AF) or atrial flutter (AFL), carpal tunnel syndrome (CTS), spinal stenosis (SS), and neuropathy also common.
objectivesThe aim of this study was to investigate the association of TTR V142I carrier status with these established outcomes.
methodsA retrospective cohort study was conducted among individuals of African ancestry enrolled in the MVP (Million Veteran Program). Participants with at least 1 V142I allele were matched to control subjects on the basis of race, sex, and birth year. Outcomes included HF or CM, AF or AFL, CTS, SS, neuropathy, all-cause mortality, cardiovascular mortality, and HF-related hospitalization. Cumulative incidence and multivariable Cox proportional hazards regression models were used to compare V142I carriers with control subjects.
resultsThe final study cohort included 2,658 V142I carriers and 13,459 matched control subjects. After multivariable adjustment, V142I carriers had significantly higher risks for HF or CM (HR: 1.20; 95% CI: 1.10-1.31), AF or AFL (HR: 1.26; 95% CI: 1.13-1.40), CTS (HR: 1.43; 95% CI: 1.30-1.57), SS (HR: 1.17; 95% CI: 1.07-1.28), and neuropathy (HR: 1.24; 95% CI: 1.13-1.36) compared with control subjects. A higher risk for HF or CM was observed among V142I carriers than matched control subjects with the following amyloidosis-related red-flag symptoms: AF or AFL (HR: 1.26; 95% CI: 1.03-1.52), CTS (HR: 1.40; 95% CI: 1.20-1.64), SS (HR: 1.26; 95% CI: 1.06-1.49), and neuropathy (HR: 1.28; 95% CI: 1.11-1.48). V142I carriers also had a significantly higher risk for all-cause mortality (HR: 1.12; 95% CI: 1.01-1.25), cardiovascular mortality (HR: 1.37; 95% CI: 1.14-1.65), and HF-related hospitalization (HR: 1.25; 95% CI: 1.07-1.45).
conclusionsThese findings highlight the systemic manifestations of variant transthyretin amyloidosis associated with the TTR V142I variant and underscore the need for increased awareness and earlier diagnostic efforts in high-risk populations.
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