A Comprehensive Outlook on Dilated Cardiomyopathy (DCM): State-Of-The-Art Developments with Special Emphasis on OMICS-Based Approaches

Abstract

Dilated cardiomyopathy (DCM) remains an enigmatic cardiovascular disease (CVD) condition characterized by contractile dysfunction of the myocardium due to dilation of the ventricles. DCM is one of the major forms of CVD contributing to heart failure. Dilation of the left or both ventricles with systolic dysfunction, not explained by known causes, is a hallmark of DCM. Progression of DCM leads to heart failure. Genetic and various other factors greatly contribute to the development of DCM, but the etiology has still remained elusive in a large number of cases. A significant number of studies have been carried out to identify the genetic causes of DCM. These candidate-gene studies revealed that mutations in the genes of the fibrous, cytoskeletal, and sarcomeric proteins of cardiomyocytes result in the development of DCM. However, a significant proportion of DCM patients are idiopathic in nature. In this review, we holistically described the symptoms, causes (in adults and newborns), genetic basis, and mechanistic progression of DCM. Further, we also summarized the state-of-the-art diagnosis, available biomarkers, treatments, and ongoing clinical trials of potential drug regimens. DCM-mediated heart failure is on the rise worldwide including in India. The discovery of biomarkers with a better prognostic value is the need of the hour for better management of DCM-mediated heart failure patients. With the advent of next-generation omics-based technologies, it is now possible to probe systems-level alterations in DCM patients pertaining to the identification of novel proteomic and lipidomic biomarkers. Here, we also highlight the onset of a systems-level study in Indian DCM patients by applying state-of-the-art mass-spectrometry-based “clinical proteomics” and “clinical lipidomics”.

Hafif Akut Miyokarditli Genç Hastalarda İnteratriyal Blok ve Ventriküler Repolarizasyon Parametreleri

“…[20][21][22] An important component of acute myocarditis is apoptosis seen in cardiomyocytes, which is considered to be the main pathology leading to DCM or HF. 23 In an experimental autoimmune myocarditis study, it is observed that the cholesterol efflux mechanisms of cardiomyocytes are impaired. The inflammatory process is observed to be regressed and cardiac functions improved, following draining of cholesterol out of the cardiomyocytes by a cholesterol depleting agent, called methyl -β-cyclodextrin.…”

Cardiomyopathies in Children: Genetics, Pathomechanisms and Therapeutic Strategies

“…Others are found in LMN, DES, VCL (Vinculin), TTR (transthyretin), BAG3 (associated with apoptosis), MT-TS2 (encoding a mitochondrial small RNA), or transcription factor encoding PRDM16 [74][75][76][77][78]. In adult and pediatric DCM, the same genes seem to be affected, though unfortunately, most genetic testings have been performed in adults [79]. Besides the genetic causes, inflammation may lead to DCM, the main non-genetic cause in children.…”

A comprehensive review of acute cardio-renal syndrome: need for novel biomarkers

“…BNP (B-type natriuretic peptide) is predominantly synthesized by LV cardiomyocytes as a protective mechanism against pressure or volume overload ( Cao et al, 2019 ; Okamoto et al, 2019 ). BNP mimics ventricular stress by decreasing the kidney tubule vascular resistance and increasing GFR ( Okamoto et al, 2019 ; Sarohi et al, 2022a ). However, hyperactivation of RAAS and SNS inhibit the BNP activity and worsens the condition ( Okamoto et al, 2019 ).…”