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Journal Article
Review
Insights into the Inherited Basis of Valvular Heart Disease.
Current Cardiology Reports 2024 April 7
PURPOSE OF REVIEW: Increases in the availability of genetic data and advances in the tools and methods for their analyses have enabled well-powered genetic association studies that have significantly enhanced our understanding of the genetic factors underlying both rare and common valve diseases. Valvular heart diseases, such as congenital valve malformations and degenerative valve lesions, increase the risk of heart failure, arrhythmias, and sudden death. In this review, we provide an updated overview of our current understanding of the genetic mechanisms underlying valvular heart diseases. With a focus on discoveries from the past 5 years, we describe recent insights into genetic risk and underlying biological pathways. RECENT FINDINGS: Recently acquired knowledge around valvular heart disease genetics has provided important insights into novel mechanisms related to disease pathogenesis. Newly identified risk loci associated valvular heart disease mainly regulate the composition of the extracellular matrix, accelerate the endothelial-to-mesenchymal transition, contribute to cilia formation processes, and play roles in lipid metabolism. Large-scale genomic analyses have identified numerous risk loci, genes, and biological pathways associated with degenerative valve disease and congenital valve malformations. Shared risk genes suggest common mechanistic pathways for various valve pathologies. More recent studies have combined cardiac magnetic resonance imaging and machine learning to offer a novel approach for exploring genotype-phenotype relationships regarding valve disease. Progress in the field holds promise for targeted prevention, particularly through the application of polygenic risk scores, and innovative therapies based on the biological mechanisms for predominant forms of valvular heart diseases.
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