TARGETED THERAPIES IN HEART FAILURE: A NARRATIVE REVIEW OF MOLECULAR MECHANISMS AND EMERGING THERAPEUTIC STRATEGIES

Abstract

Heart failure is a cardiovascular syndrome associated with high morbidity and mortality, characterized by a complex and heterogeneous pathophysiology involving neurohormonal activation, ventricular remodeling, systemic inflammation, immunometabolic alterations, and intracardiac cellular dysfunction, all of which contribute to disease progression, recurrent hospitalizations, and elevated cardiovascular mortality. In light of the expansion of translational knowledge in cardiology and the development of targeted therapies directed at specific molecular pathways, the present study aimed to conduct a narrative literature review addressing the pathophysiological bases of heart failure and contemporary advances related to emerging targeted therapies, emphasizing their mechanisms of action, clinical applicability, therapeutic limitations, and future perspectives within the context of precision cardiovascular medicine. This narrative review, descriptive, analytical, and interpretative in nature, was conducted using the PubMed/MEDLINE, SciELO, VHL, Scopus, and Google Scholar databases, including original articles, systematic reviews, meta-analyses, clinical guidelines, scientific consensuses, and clinical trials published between 2020 and 2025, in addition to seminal studies of high scientific relevance. The findings demonstrated that heart failure should be understood as a molecularly complex syndrome resulting from the simultaneous interaction among neurohormonal, inflammatory, metabolic, and structural mechanisms, highlighting the role of systemic inflammation, myocardial fibrosis, immunometabolism, and mitochondrial dysfunction in disease progression. Furthermore, advances in the understanding of these pathophysiological pathways have enabled significant therapeutic expansion, particularly through the consolidation of sodium-glucose cotransporter-2 inhibitors, sacubitril/valsartan, and novel metabolic and contractile modulators. Nevertheless, important challenges remain regarding the marked phenotypic heterogeneity of the syndrome, especially in heart failure with preserved ejection fraction, as well as variability in therapeutic response and limitations related to the broad clinical implementation of precision cardiovascular medicine. It is concluded that the integration of pathophysiological knowledge, translational innovation, and molecular stratification may significantly contribute to the development of more individualized, biologically oriented, and potentially more effective therapeutic strategies in the contemporary management of heart failure.