Midlife Screening with Echocardiography of Individuals Who Carry the V122I TTR Gene May Help Predict Risk of Symptomatic Heart Failure

The V122I variant of the transthyretin (TTR) gene is common in individuals of African ancestry and is linked with increased risk of heart failure (HF) in older patients.

Prevention of HF may be most effective earlier in life, but it is unclear whether screening with echocardiography can identify subclinical cardiac abnormalities during middle age, enabling patients to be stratified by risk. Researchers examined the association between the V122I TTR variant and cardiac structure and function during middle age in those patients without prevalent HF.

Black participants (N = 875) in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort were included in this serial cross-sectional study. This study was conducted at 4 urban sites across the United States and completed between 1985 and 1986. Follow-up examinations were conducted 25 to 30 years later.

Black adults from the CARDIA cohort who underwent TTR genotyping were included in the study, and data analysis was completed from January 2020 to October 2020. At years 25 and 30 of follow-up, longitudinal systolic strain, left ventricular (LV) structure, and LV circumference were measured. Adjustments for age, genetic ancestry, sex, echocardiography quality, and field center were included in the analyses.

The mean age of study participants was 49.4 years at year 25 of the study. Sixty-two percent of the participants were women (N = 543). The study included 31 participants who were heterozygous for the V122I TTR variant and 1 who was homozygous.

At year 25 of follow-up, of the adults who had an echocardiogram, 46% had hypertension, 15% had diabetes, and 19% were current smokers. This did not differ significantly between the cohorts (ie, those who did not carry V122I TTR). At year 25, there was no difference in LV circumferential strain, longitudinal strain, or LV structure between those who did carry the V122I TTR variant and those who did not.

Compared with those who did not carry the variant, at year 30, those who carried V122I TTR had significantly lower absolute LV circumferential strain. At that time, carriers of V122I TTR also had significantly higher LV mass index values (97.5 [34.1] g/m2) than those who did not (83.7 [22.6] g/m2).

The researchers concluded that V122I TTR variant carrier status is associated with specific subclinical cardiac abnormalities in middle age, including worse LV systolic function and higher LV mass, and these have been associated with increased risk of incident HF. They suggest that midlife screening of individuals who carry V122I TTR with echocardiography may help predict risk of symptomatic HF, thereby informing prevention strategies.

Source: Sinha A, Zheng Y, Nannini D, et al. Association of the V122I transthyretin amyloidosis genetic variant with cardiac structure and function in middle-aged black adults: Coronary Artery Risk Development in Young Adults (CARDIA) study [published online ahead of print, 2020 Dec 23]. JAMA Cardiol. 2020;e206623.

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