Pathophysiology

Mitochondrial Function and Dysfunction in Dilated Cardiomyopathy

“…Dilated cardiomyopathy (DCM) is a leading cause of heart failure worldwide with a higher incidence in underdeveloped countries, however its prevalence varies due to geographic and socioeconomic conditions ( Bozkurt et al, 2016 ). It is a form of heart disease that presents with dilation of the left or both ventricles and leads to systolic dysfunction and subsequent heart failure ( Figure 4 ; Dellefave and McNally, 2010 ; De Paris et al, 2019 ). DCM is also considered idiopathic if no other vascular conditions such as hypertension are detected ( Mestroni et al, 1999 ).…”

“…Between 20–35% of idiopathic DCM cases may be linked to a family history with an inherited gene defect ( Hershberger et al, 2010 ). Primarily mutations in genes that are involved in sarcomere structure and contractility, cytoskeletal arrangement, electrolytes balance and mitochondrial function ( De Paris et al, 2019 ) are linked to DCM. In DCM, the cardiac muscle becomes thin and weakened causing the open area of the chamber to become enlarged.…”

“…As a result, the heart is unable to pump blood efficiently ( NIH, 2020 ). In order to maintain cardiac output, ventricular volumes increase and sarcomere contractility is reduced thereby, producing the thin-walled dilated appearance that characterizes DCM ( De Paris et al, 2019 ). This ventricular remodeling is driven by irregular cardiomyocyte pathophysiology encompassing cardiomyocyte hypertrophy, impaired calcium cycling, apoptosis and fibrosis.…”

“…This ventricular remodeling is driven by irregular cardiomyocyte pathophysiology encompassing cardiomyocyte hypertrophy, impaired calcium cycling, apoptosis and fibrosis. A decrease in cardiac efficiency, as measured by myocardial oxygen consumption, leads to a progressive weakening of energy-starved cardiac myocytes pushing the heart toward heart failure ( De Paris et al, 2019 ; Chen, 2020 ).…”

A Comprehensive Insight and Mechanistic Understanding of the Lipidomic Alterations Associated With DCM

“… 7 Pathophysiological changes perceived in DCM are reduction in stroke volume (ie, the volume of blood pumped out of the left ventricle of the heart during each systolic cardiac contraction) and cardiac output (ie, the volume of blood being pumped by both ventricles of the heart per unit time), impairment of ventricular filling and escalation in end-diastolic pressure (ie, the volume of blood in the left ventricle at the end of ventricular filling). 8 DCM also leads to the remodeling of the left ventricle into a spherical shape along with its dilatation. 9 Various compensatory changes in the vascular system are also visible during DCM, such as elevation in wall stress due to an increase in cardiac preload (amount of sarcomere stretch experienced by cardiac muscle cells that is, cardiomyocytes at the end of the ventricular filling during diastole) and afterload (ie, the pressure that must be worked against by the heart to eject blood during systole).…”