The following is a summary of “Genotype-First Approach to Cardiomyopathy Outcomes,” published in the April 2024 issue of Cardiology by Asatryan et al.

The presence of cardiomyopathy-associated predicted deleterious variants is associated with an increased risk for all-cause mortality, clinical diagnosis of cardiomyopathy, and composite cardiomyopathy-related outcomes.

Researchers conducted a retrospective study monitoring mortality risk and composite cardiomyopathy-related outcomes correlated with predicted deleterious variants in cardiomyopathy-associated genes. 

They analyzed gene variants linked to cardiomyopathy using ClinGen Expert Panel curations that were annotated using REVEL (≥0.65) and ANNOVAR (predicted loss-of-function), considering gene-disease mechanisms. Genotype-positive (CMP-G+) and genotype-negative groups were compared for all-cause mortality and secondary outcomes like developing cardiomyopathy or a combination of heart-related issues. Cox regression corrected for sex and used age as a timescale. 

The results showed 200,619 participants (age 56.46 ± 8.1 years), 2.64% (5,292) had ≥1 predicted deleterious variants. Individuals with CMP-G+ had higher all-cause mortality risk (HR 1.13, 95%CI, 1.01-1.25, P=0.027), increased cardiomyopathy diagnosis risk (HR 5.75, 95% CI, 4.58-7.23; P<0.0001), and elevated composite outcome risk (HR 1.29, 95% CI, 1.20-1.39, P<0.0001). Higher risks were consistent across cardiomyopathy subgroups.

Investigators concluded that predicted deleterious variants in cardiomyopathy-associated genes increase mortality and cardiomyopathy-related risks.

Source: acc.org/Latest-in-Cardiology/Journal-Scans/2024/04/17/16/10/predicted-deleterious-variants