Key result
In patients with familial left ventricular noncompaction, the presence of each additional pathogenic variant was associated with increased odds of having a more severe LVNC subtype (OR 2.77).
Why the study?
Left ventricular noncompaction cardiomyopathy can cause heart failure, arrhythmias, thromboembolism, and sudden cardiac death, but its genetic landscape in Russian patients needed clarification.
Does genetic screening using next generation sequencing identify pathogenic variants and predict disease severity in Russian patients with familial left ventricular noncompaction?
Observational (n=214)
Yes
Does genetic screening using next generation sequencing identify pathogenic variants and predict disease severity in Russian patients with familial left ventricular noncompaction?
Comprehensive genetic screening in familial LVNC provides a high diagnostic yield and reveals that a higher burden of pathogenic variants correlates with more severe phenotypic subtypes.
May support genetic risk stratification in familial LVNC; hypothesis-generating and should not yet change practice.
Background: Left ventricular noncompaction (LVNC) cardiomyopathy is a disorder that can be complicated by heart failure, arrhythmias, thromboembolism, and sudden cardiac death. The aim of this study is to clarify the genetic landscape of LVNC in a large cohort of well-phenotyped Russian patients with LVNC, including 48 families (n=214). Methods: All index patients underwent clinical examination and genetic analysis, as well as family members who agreed to participate in the clinical study and/or in the genetic testing. The genetic testing included next generation sequencing and genetic classification according to ACMG guidelines. Results: A total of 55 alleles of 54 pathogenic and likely pathogenic variants in 24 genes were identified, with the largest number in the MYH7 and TTN genes. A significant proportion of variants -8 of 54 (14.8%) -have not been described earlier in other populations and may be specific to LVNC patients in Russia. In LVNC patients, the presence of each subsequent variant is associated with increased odds of having more severe LVNC subtypes than isolated LVNC with preserved ejection fraction. The corresponding odds ratio is 2.77 (1.37 -7.37; p <0.001) per variant after adjustment for sex, age, and family. Conclusion: Overall, the genetic analysis of LVNC patients, accompanied by cardiomyopathy-related family history analysis, resulted in a high diagnostic yield of 89.6%. These results suggest that genetic screening should be applied to the diagnosis and prognosis of LVNC patients.
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Мешков et al. (2023) conducted an observational in Familial left ventricular noncompaction (LVNC) (n=214). Pathogenic genetic variants vs. Fewer or no pathogenic variants was evaluated on More severe LVNC subtypes compared to isolated LVNC with preserved ejection fraction (OR 2.77, 95% CI 1.37-7.37, p=<0.001). In patients with familial left ventricular noncompaction, the presence of each additional pathogenic variant was associated with increased odds of having a more severe LVNC subtype (OR 2.77).
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