LEFT VENTRICULAR REMODELING IN HEART FAILURE (PART I): CURRENT UNDERSTANDING OF PATHOMECHANISMS AND RELATED MYOCARDIAL DYSFUNCTION

Abstract

Aim: to provide a literature review of the current data on various pathomechanisms of left ventricular (LV) remodeling in heart failure (HF) patients and their role in the development and progression of myocardial dysfunction. This paper is a first part of the review, devoted to the current state of pathophysiology of LV remodeling in HF. Material and methods. The thematic scientific papers, published during the last decade, constituted the study material. The research methodology involved bibliosemantic method and structural and logical analysis. Results and discussion. LV remodeling is the result of complex changes at the molecular, cellular and tissue levels, affecting the myocardial mass, geometry and performance, and ultimately leading to HF development and progression. LV systolic dysfunction occurs through the numerous mechanisms, including the defects in sarcomere function, abnormal excitation-contraction coupling and calcium homeostasis, ion channel dysfunction, mitochondrial and metabolic abnormalities, depressed cardiomyocytes survival signaling, redox pathobiology, inflammation and inadequate vasculogenesis. The term «LV diastolic dysfunction» covers the alterations in diastolic distensibility, filling or relaxation of the LV, regardless of whether LV (global) systolic function is normal or abnormal, and regardless of whether the patient has clinical manifestations of HF. The up-to-date pathophysiological paradigm of the development and progression of HF with LV diastolic dysfunction and preserved LV (global) systolic function considers systemic inflammation as a key pathomechanism of structural and functional changes of the myocardium, promoted by various cardiovascular and extracardiac conditions. In its turn, the systemic inflammation promotes endothelial dysfunction, contributing to multiple end-organ damage. Conclusion. The deepening one`s knowledge of various pathomechanisms of LV remodeling and related myocardial dysfunction in HF patients is an important prerequisite for identifying new perspectives on further fundamental research аnd more rational designing of future clinical trials.

Keywords

• left ventricle
• remodeling
• heart failure
• pathophysiology
• pathomechanism
• myocardium
• dysfunction