Pathophysiology of Cardiac Remodeling in Heart Failure: Mechanisms and Therapeutic Targets
Pathophysiology of Cardiac Remodeling in Heart Failure: Mechanisms and Therapeutic Targets.
Cardiac remodeling is a term that refers to the structural and functional changes that occur in the heart as a result of various stimuli, such as myocardial infarction, hypertension, or valvular disease. Cardiac remodeling can be adaptive or maladaptive, depending on the type, duration, and intensity of the stimulus, as well as the genetic and environmental factors that influence the response of the myocardium. Adaptive remodeling aims to preserve or improve cardiac function and maintain hemodynamic stability, while maladaptive remodeling leads to progressive deterioration of cardiac function and increased risk of heart failure (HF) and death.
The pathophysiology of cardiac remodeling involves complex interactions among mechanical stress, neurohumoral activation, inflammation, oxidative stress, apoptosis, autophagy, fibrosis, hypertrophy, and angiogenesis. These processes affect the cardiomyocytes, the extracellular matrix (ECM), and the coronary vasculature, resulting in changes in the size, shape, mass, and composition of the cardiac chambers. The most common type of cardiac remodeling is left ventricular (LV) remodeling, which is characterized by LV dilation, spherical deformation, wall thinning, increased LV mass, and reduced LV ejection fraction (LVEF). LV remodeling is associated with increased LV wall stress, impaired diastolic and systolic function, arrhythmias, and adverse clinical outcomes.
Several therapeutic strategies have been developed to prevent or reverse cardiac remodeling and improve the prognosis of patients with HF. These include pharmacological interventions, such as angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), neprilysin inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and anti-inflammatory agents; device-based therapies, such as cardiac resynchronization therapy (CRT), implantable cardioverter-defibrillators (ICDs), left ventricular Help devices (LVADs), and transcatheter aortic valve replacement (TAVR); and surgical procedures, such as coronary artery bypass grafting (CABG), mitral valve repair or replacement, and ventricular reconstruction. These therapies target different aspects of the pathophysiological mechanisms of cardiac remodeling and aim to restore or improve cardiac structure and function.
In this paper, we will review the current knowledge on the pathophysiology of cardiac remodeling in HF, focusing on the molecular and cellular mechanisms involved in the process. We will also discuss the therapeutic targets and interventions that have been shown to modulate cardiac remodeling and their clinical implications.
References:
– Colucci WS. Pathophysiology of heart failure with reduced ejection fraction: Hemodynamic alterations and remodeling. UpToDate. 2022. Available from: https://www.uptodate.com/contents/pathophysiology-of-heart-failure-with-reduced-ejection-fraction-hemodynamic-alterations-and-remodeling
– Chai R., Xue W., Shi S., et al. Cardiac Remodeling in Heart Failure: Role of Pyroptosis and Its Therapeutic Implications. Front Cardiovasc Med. 2022;9:870924. doi: 10.3389/fcvm.2022.870924
– Fuster V., Kelly B.B., Vedanthan R., eds. Promoting Cardiovascular Health in the Developing World: A Critical Challenge to Achieve Global Health. Washington (DC): National Academies Press (US); 2010.
