Cardiac remodelling in the era of the recommended four pillars heart failure medical therapy

Abstract

Cardiac remodelling is a key determinant of worse cardiovascular outcome in patients with heart failure (HF) and reduced ejection fraction (HFrEF). It affects both the left ventricle (LV) structure and function as well as the left atrium (LA) and the right ventricle (RV). Guideline recommended medical therapy for HF, including angiotensin-converting enzyme inhibitors/angiotensin receptors II blockers/angiotensin receptor blocker-neprilysin inhibitors (ACE-I/ARB/ARNI), beta-blockers, mineralocorticoid receptor antagonists (MRA) and sodium-glucose transport protein 2 inhibitors (SGLT2i), have shown to improve morbidity and mortality in patients with HFrEF. By targeting multiple pathophysiological pathways, foundational HF therapies are supposed to drive their beneficial clinical effects by a direct myocardial effect. Simultaneous initiation of guideline directed medical therapy (GDMT) through a synergistic effect promotes a 'reverse remodelling', leading to a full or partial recovered structure and function by enhancing systemic neurohumoral regulation and energy metabolism, reducing cardiomyocyte apoptosis, lowering oxidative stress and inflammation and adverse extracellular matrix deposition. The aim of this review is to describe how these classes of drugs can drive reverse remodelling in the LV, LA and RV and improve prognosis in patients with HFrEF.

Keywords: Cardiac remodelling; Heart failure; Medical therapy.

Figure 1

Cardiac remodelling pathophysiology. Heart failure is due to different causes such as cardiomyopathy, coronary artery disease, pressure/volume overload disorders, inflammatory/infective processes and infiltrative disorders. Pathological processes involving cardiomyocytes, the extracellular matrix, the endothelial function and inflammation are responsible for mechanism of cardiac remodelling. GDF‐15, growth differentiation factor‐15; ICAM, intercellular adhesion molecule 1; IL, interleukin; NO, nitric oxide; PICP, carboxy‐terminal propeptide of procollagen type I; RAA, renin‐angiotensin‐aldosterone axis; ROS, reactive oxygen species; TNF‐α, tumour necrosis factor‐α; VCAM, vascular cell adhesion molecule 1.

Figure 2

Four pillars heart failure medical therapy and cardiac reverse remodelling. ACE‐I/ARB/ARNI, beta‐blockers, MRA and SGLT2i promote cardiac reverse remodelling. The reverse remodelling is explained by different pharmacological effects including antioxidant properties, anti‐inflammatory effect, reduction of myocardial fibrosis and sympathetic activation, increase of mitochondrial and endothelial function. These processes eventually lead to reduction of myocardial volumes, mass and filling pressure, increase of LVEF and GLS, improvement of LA and RV structure and function. ACEI/ARB/ARNI, angiotensin‐converting enzyme inhibitors/angiotensin receptors II blockers/angiotensin receptor blocker‐neprilysin inhibitors; cGMP, cyclic guanosine monophosphate; GLS, global longitudinal strain; LA, left atrial; LV, left ventricle; LVEF, left ventricle ejection fraction; MRA, mineralocorticoid receptor antagonists; PA, pulmonary artery; RV, right ventricle; SGLT2i, sodium‐glucose transport protein 2 inhibitors.