Application of next generation sequencing in cardiology: current and future precision medicine implications

Abstract

Inherited cardiovascular diseases are highly heterogeneous conditions with multiple genetic loci involved. The application of advanced molecular tools, such as Next Generation Sequencing, has facilitated the genetic analysis of these disorders. Accurate analysis and variant identification are required to maximize the quality of the sequencing data. Therefore, the application of NGS for clinical purposes should be limited to laboratories with a high level of technological expertise and resources. In addition, appropriate gene selection and variant interpretation can result in the highest possible diagnostic yield. Implementation of genetics in cardiology is imperative for the accurate diagnosis, prognosis and management of several inherited disorders and could eventually lead to the realization of precision medicine in this field. However, genetic testing should also be accompanied by an appropriate genetic counseling procedure that clarifies the significance of the genetic analysis results for the proband and his family. In this regard, a multidisciplinary collaboration among physicians, geneticists, and bioinformaticians is imperative. In the present review, we address the current state of knowledge regarding genetic analysis strategies employed in the field of cardiogenetics. Variant interpretation and reporting guidelines are explored. Additionally, gene selection procedures are accessed, with a particular emphasis on information concerning gene-disease associations collected from international alliances such as the Gene Curation Coalition (GenCC). In this context, a novel approach to gene categorization is proposed. Moreover, a sub-analysis is conducted on the 1,502,769 variation records with submitted interpretations in the Clinical Variation (ClinVar) database, focusing on cardiology-related genes. Finally, the most recent information on genetic analysis's clinical utility is reviewed.

Exploring Health Care Disparities in Genetic Testing and Research for Hereditary Cardiomyopathy: Current State and Future Perspectives

“… 50 In RCM, TTE findings of diastolic dysfunction with atrial enlargement could be observed, but cardiac magnetic resonance could be of greater diagnostic value with high specificity to differentiate from other mimics, such as constrictive pericarditis. 51 52 …”

“…Patients with these variants are often associated with debilitating outcomes, requiring implantable cardiac defibrillators to prevent sudden cardiac death. 52 Yet, almost 55% of pathogenic variants in DCM are idiopathic and may overlap with variants causing ACM, highlighting the need to implement better classification in a genotypic setting. 55 …”

MEK inhibitors: a promising targeted therapy for cardiovascular disease

“…This approach offers the potential for more effective and personalized treatments and improved patient outcomes ( 11 ). The primary advantage of targeted therapies is their precision in addressing the root causes of the diseases ( 16 ). Instead of relying solely on broad-spectrum medications, these therapies can pinpoint specific molecular pathways, proteins, and cellular processes involved in disease pathogenesis ( 17 ).…”