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Dilated cardiomyopathy: a new insight into the rare but common cause of heart failure

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Abstract

Heart failure is a global health burden responsible for high morbidity and mortality with a prevalence of greater than 60 million individuals worldwide. One of the major causes of heart failure is dilated cardiomyopathy (DCM), characterized by associated systolic dysfunction. During the last few decades, there have been remarkable advances in our understanding about the genetics of dilated cardiomyopathy. The genetic causes were initially thought to be associated with mutations in genes encoding proteins that are localized to cytoskeleton and sarcomere only; however, with the advancement in mechanistic understanding, the roles of ion channels, Z-disc, mitochondria, nuclear proteins, cardiac transcription factors (e.g., NKX-2.5, TBX20, GATA4), and the factors involved in calcium homeostasis have also been identified and found to be implicated in both familial and sporadic DCM cases. During past few years, next-generation sequencing (NGS) has been established as a diagnostic tool for genetic analysis and it has added significantly to the existing candidate gene list for DCM. The animal models have also provided novel insights to develop a better treatment strategy based on phenotype–genotype correlation, epigenetic and phenomic profiling. Most of the DCM biomarkers that are used in routine genetic and clinical testing are structural proteins, but during the last few years, the role of mi-RNA has also emerged as a biomarker due to their accessibility through noninvasive methods. Our increasing genetic knowledge can improve the clinical management of DCM by bringing clinicians and geneticists on one platform, thereby influencing the individualized clinical decision making and leading to precision medicine.

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  1. Cytogenetics Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Uttar Pradesh, Varanasi-5, India

    Prerna Giri, Amrita Mukhopadhyay, Mohini Gupta & Bhagyalaxmi Mohapatra

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Prerna Giri performed the literature survey and prepared the original draft including all figures and table. Dr. Bhagyalaxmi Mohapatra sketched the outline for the article, critically supervised and revised the manuscript at every single step. Amrita Mukhopadhyay prepared and formatted the reference list and collected literature related to next-generation sequencing. Mohini Gupta did formatting of the in-text citations and collected literature on mitochondrial proteins. All authors read and approved the final manuscript.

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Giri, P., Mukhopadhyay, A., Gupta, M. et al. Dilated cardiomyopathy: a new insight into the rare but common cause of heart failure. Heart Fail Rev 27, 431–454 (2022). https://doi.org/10.1007/s10741-021-10125-6

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