The Genetic Pathways Underlying Immunotherapy in Dilated Cardiomyopathy

Abstract

Heart failure (HF) is a global public health threat affecting 26 million individuals worldwide with an estimated prevalence increase of 46% by 2030. One of the main causes of HF and sudden death in children and adult is Dilated Cardiomyopathy (DCM). DCM is characterized by dilation and systolic dysfunction of one or both ventricles. It has an underlying genetic basis or can develop subsequent to various etiologies that cause myocardium inflammation (secondary causes). The morbidity and mortality rates of DCM remains high despite recent advancement to manage the disease. New insights have been dedicated to better understand the pathogenesis of DCM in respect to genetic and inflammatory basis by linking the two entities together. This cognizance in the field of cardiology might have an innovative approach to manage DCM through targeted treatment directed to the causative etiology. The following review summarizes the genetical and inflammatory causes underlying DCM and the pathways of the novel precision-medicine-based immunomodulatory strategies to salvage and prevent the associated heart failure linked to the disease.

New Insights into the Role of Ferroptosis in Cardiovascular Diseases

“…The genetic form accounts for only 20–30% of dilated cardiomyopathy while the bulk of dilated cardiomyopathy is secondary to cardiomyopathies such as ischemic heart disease, diabetic cardiomyopathy, septic cardiomyopathy, etc. [ 178 , 179 ]. The mechanisms which contribute to ferroptosis in the genetic dilated cardiomyopathy are similar to those described in hypertrophic cardiomyopathy [ 180 ].…”

Identification of Immune Markers in Dilated Cardiomyopathies with Heart Failure by Integrated Weighted Gene Coexpression Network Analysis

“…Additionally, a number of autoantibodies against different cardiomyocyte proteins in DCM have been found [ 8 ]. Owing to the disorder of the immune system in DCM, immunotherapy relying on precision medicine came into being, including immunosuppressants and immunoadsorption [ 9 ]. However, an increase in antibodies and a decrease in contractility were observed in DCM 12 months after immunoadsorption therapy and subsequent IgG replacement (IA/IgG) treatment [ 10 ].…”

A novel likely pathogenic variant in the FBXO32 gene associated with dilated cardiomyopathy according to whole‑exome sequencing

“…Dilated cardiomyopathy (DCM) is a common cause of heart failure and is characterized by the dilatation and impaired function of 1 or both ventricles, resulting in an ejection fraction below 50% [1][2][3]. The incidence of DCM is 7 cases per 100,000 people yearly, with the disease affecting 1 in 250 individuals in the general population, worldwide [4,5].…”

“…The incidence of DCM is 7 cases per 100,000 people yearly, with the disease affecting 1 in 250 individuals in the general population, worldwide [ 4 , 5 ]. DCM may be considered the primary indication of heart transplantation [ 2 ] and can be developed by such agents as infections, toxins, drugs, nutritional deficiencies, genetic variants, inborn metabolism problems, endocrine disorders, immune and neuromuscular disorders, and the structure/function disruption of sarcomeres, cytoskeletons, sarcoplasmic reticula, and nuclear envelopes [ 1 , 6 , 7 ]. DCM is genetically heterogeneous, and approximately 30–48% of all cases are genetic forms.…”