Postinfarct Left Ventricular Remodelling: A Prevailing Cause of Heart Failure

Abstract

Heart failure is a chronic disease with high morbidity and mortality, which represents a growing challenge in medicine. A major risk factor for heart failure with reduced ejection fraction is a history of myocardial infarction. The expansion of a large infarct scar and subsequent regional ventricular dilatation can cause postinfarct remodelling, leading to significant enlargement of the left ventricular chamber. It has a negative prognostic value, because it precedes the clinical manifestations of heart failure. The characteristics of the infarcted myocardium predicting postinfarct remodelling can be studied with cardiac magnetic resonance and experimental imaging modalities such as diffusion tensor imaging can identify the changes in the architecture of myocardial fibers. This review discusses all the aspects related to postinfarct left ventricular remodelling: definition, pathogenesis, diagnosis, consequences, and available therapies, together with experimental interventions that show promising results against postinfarct remodelling and heart failure.

Molecular Imaging to Monitor Left Ventricular Remodeling in Heart Failure

“…Intense fibrosis leads to scar formation [7••, 8-11], which further changes the shape and function of the left ventricle (LV) and can be manifested as dilation and thinning of the myocardium, hypertrophy of the remote areas surrounding MI, and overall decline of the heart function ( Fig. 1) [3,[12][13][14]. All of these features can be accessed by kinematic imaging over the heart cycle [3].…”

Safety and Tolerability of the Chymase Inhibitor Fulacimstat in Patients With Left Ventricular Dysfunction After Myocardial Infarction—Results of the CHIARA MIA 1 Trial

“…Improved standard of care (SoC) and increased use of revascularization procedures have reduced the 6‐month mortality rates of patients after acute ST‐segment‐elevation myocardial infarction (STEMI) during the past 2 decades . However, STEMI survivors are at risk of developing heart failure (HF) — a disease exhibiting 50% mortality rates within 5 years of diagnosis . Adverse cardiac remodeling is one of the major risk factors for the development of post‐myocardial infarction (MI) HF, and patients suffering from post‐MI HF exhibit higher mortality and rehospitalization rates .…”

“…Adverse cardiac remodeling can be defined as a 20% increase in end‐diastolic volume over 1 year compared with baseline values and is characterized by cardiomyocyte hypertrophy, interstitial fibrosis, loss of chamber geometry, and left ventricular dysfunction (LVD) . Despite advanced interventional and pharmacological treatment options, up to one‐third of patients develop adverse cardiac remodeling after MI . Chymase is a chymotrypsin‐like serine protease that is secreted from activated mast cells and other cells such as cardiomyocytes after tissue injury .…”

“…1 However, STEMI survivors are at risk of developing heart failure (HF) -a disease exhibiting 50% mortality rates within 5 years of diagnosis. 2 Adverse cardiac remodeling is one of the major risk factors for the development of post-myocardial infarction (MI) HF, and patients suffering from post-MI HF exhibit higher mortality and rehospitalization rates. 3 Adverse cardiac remodeling can be defined as a 20% increase in end-diastolic volume over 1 year compared with baseline values 4 and is characterized by cardiomyocyte hypertrophy, interstitial fibrosis, loss of chamber geometry, and left ventricular dysfunction (LVD).…”

“…5 Despite advanced interventional and pharmacological treatment options, up to one-third of patients develop adverse cardiac remodeling after MI. 2,[6][7][8][9] Chymase is a chymotrypsin-like serine protease that is secreted from activated mast cells and other cells such as cardiomyocytes after tissue injury. 10,11 Chymase is active only after secretion and generates or activates locally profibrotic factors such as angiotensin (Ang) II, transforming growth factor (TGF) β, and matrix metalloproteinases that are involved in adverse cardiac remodeling post-MI.…”