CURRENT CHALLENGES IN HEART FAILURE: MECHANISMS AND THERAPEUTIC OPPORTUNITIES

Abstract

Heart failure (HF) occurs when the heart is unable to provide the necessary cardiac output for tissue demands, or when it is unable to do so without elevated ventricular filling pressure. In the initial phase of HF, a noxa causes damage to the heart, which then undergoes a process of remodeling. Myocardial damage or injury and decreased myocardial distensibility (leading to what is known as HF with preserved ejection fraction or HFpEF) are two fundamental mech anisms of HF. In this regard, the concept of reverse remodeling in HF and the role of the Rho kinase cell signaling and pro-remodeling pathway are reviewed here. There are many emerging mechanisms of HF, and significant clinical advances have been made in recent years. HFpEF associated with obesity, where epicardial fat plays a pathogenic role, is very prevalent, and in the last few years, significant therapeutic advances have been observed with clear improvement in symptoms and reductions in hospital admissions for HF using glucagon-like peptide-1 (GLP 1) receptor agonists. On the other hand, amyloid cardiomyopathy (AC) typically manifests as HFpEF due to diastolic dysfunction secondary to amyloid infiltration, which occurs via two primary mechanisms: by light chains and by transthyretin. For both forms of AC, novel ther apeutic agents are currently available that have been demonstrated to enhance quality of life and reduce mortality.