Systemic Manifestations and Mortality Risk in Transthyretin V142I Variant Carriers: A Million Veteran Program Analysis

doi:10.1016/j.jaccao.2025.12.006

Systemic Manifestations and Mortality Risk in Transthyretin V142I Variant Carriers: A Million Veteran Program Analysis

JACC CardioOncolPublication date not resolvedRetrospective cohort study

Cite

Authors' conclusion

These findings highlight the systemic manifestations of variant transthyretin amyloidosis associated with the TTR V142I variant

Study context

Population: Individuals of African ancestry enrolled in the Million Veteran Programmatched cohort
Participants: 2,658 vs 13,459

Exposure: TTR V142I carriers vs matched controls
V142I carriersn = 2,658
Controln = 13,459reference
Outcome: Heart failure (HF) or cardiomyopathy (CM), atrial fibrillation (AF) or atrial flutter (AFL), carpal tunnel syndrome (CTS), spinal stenosis (SS), neuropathy

Methodological detailsmatched

Matched

Main finding

As reported in the abstract

Established manifestations (multivariable-adjusted)

V142I carriers vs ControlHazard ratio (95% CI)

HF or CM

1.20(1.10–1.31)

AF or AFL

1.26(1.13–1.40)

CTS

1.43(1.30–1.57)

SS

1.17(1.07–1.28)

Neuropathy

1.24(1.13–1.36)

Observational data: associations, not effects.

Further findings

Outcome	← Lower risk with V142I carriers ←→ Higher risk with V142I carriers →	HR (95% CI)
HF or CM among those with red-flag symptoms (subgroup) — V142I carriers vs Control · with AF or AFL	0.512	1.26 (1.03–1.52)
HF or CM among those with red-flag symptoms (subgroup) — V142I carriers vs Control · with CTS	0.512	1.40 (1.20–1.64)
HF or CM among those with red-flag symptoms (subgroup) — V142I carriers vs Control · with SS	0.512	1.26 (1.06–1.49)
HF or CM among those with red-flag symptoms (subgroup) — V142I carriers vs Control · with neuropathy	0.512	1.28 (1.11–1.48)
All-cause mortality, CV mortality, HF-related hospitalization — V142I carriers vs Control · all-cause mortality	0.512	1.12 (1.01–1.25)
All-cause mortality, CV mortality, HF-related hospitalization — V142I carriers vs Control · CV mortality	0.512	1.37 (1.14–1.65)
All-cause mortality, CV mortality, HF-related hospitalization — V142I carriers vs Control · HF-related hospitalization	0.512	1.25 (1.07–1.45)
	0.512Hazard ratio (log scale)

Original publication

Systemic Manifestations and Mortality Risk in Transthyretin V142I Variant Carriers: A Million Veteran Program Analysis. JACC CardioOncol. doi:10.1016/j.jaccao.2025.12.006

Read the original article ↗PubMed

Summarised from the published abstract; every number is checked against it