Bioactive compounds and metabolic pathways in heart failure: Mechanisms, biomarkers, and targeted therapies

Heart failure has increasingly been recognized as a complex, metabolism-driven syndrome that extends far beyond traditional models of hemodynamic dysfunction. At its core, the pathophysiology of heart failure encompasses profound shifts in cardiac energy substrate utilization, mitochondrial impairment, insulin resistance, and dysregulated amino acid and lipid metabolism. These factors converge with altered inflammatory–metabolic signaling, resulting in maladaptive cardiac remodeling and pump dysfunction. Simultaneously, a diverse array of bioactive compounds—including endogenous metabolites, lipid mediators, gut microbiome–derived molecules, hormones, polyphenols and nutraceutical derivatives—interact with these metabolic pathways, influencing not only myocardial function but also vascular health and multi-organ cross-talk. The precise roles, clinical significance, and translational opportunities associated with these bioactive molecules are still being unveiled, particularly given the heterogeneity of heart failure phenotypes (HFrEF, HFpEF, HFmrEF) and prevalent comorbidities such as obesity, diabetes, kidney disease, and cachexia.This Research Topic aims to integrate basic, translational, and clinical insights into the roles of bioactive compounds across major metabolic pathways in heart failure. The main objective is to clarify the mechanistic basis for how metabolic remodeling and specific molecular mediators contribute to disease onset, progression, and response to therapy. By harnessing the latest advances in metabolomics, lipidomics, multi-omics, and precision medicine, the initiative aspires to accelerate the identification of clinically actionable biomarkers and metabolic signatures that could enable individualized diagnostics, risk stratification, and therapeutic targeting. Special emphasis is placed on studies that elucidate novel metabolic or signaling networks, bridge molecular findings to clinical phenotypes, or propose new metabolic interventions based on emerging concepts in cardiometabolic health.To gather further insights into the interplay between metabolism and heart failure, we welcome articles addressing, but not limited to, the following themes:o Mechanisms of metabolic remodeling in heart failure, including energy substrate choice, mitochondrial energetics, and redox signalingo The impact of bioactive metabolites and lipid mediators (e.g., acylcarnitines, ceramides, ketones, eicosanoids, branched-chain amino acids) on cardiac structure and functiono The gut–heart axis: roles of microbiome-derived metabolites, intestinal permeability, and immune–metabolic crosstalk in heart failureo Endocrine/paracrine regulators (adipokines, myokines, hepatokines, cardiokines) and their contributions to cardiac metabolism, cachexia, and obesity-associated heart failureo Discovery and clinical integration of metabolic biomarkers for patient phenotyping, prognostication, and therapeutic monitoringo Therapeutic strategies: metabolic modulators, dietary or lifestyle interventions, nutraceuticals, drug repurposing, and precision approaches tailored by heart failure phenotype and comorbiditieso Association of polyphenols (phenolic acids, flavonoids, lignans) with heart failure (HFrEF, HFpEF, HFmrEF)The Research Topic encourages submission of all article types. By emphasizing the intersection of metabolism, molecular signaling, and clinical intervention, this initiative aims to foster breakthroughs in the prevention and treatment of heart failure and its metabolic underpinnings. Topic editors: Rita De Cássia Avellaneda Guimarães, Priscila Aiko Hiane, Karine De Cássia Freitas Source: https://www.frontiersin.org/research-topics/77788/bioactive-compounds-and-metabolic-pathways-in-heart-failure-mechanisms-biomarkers-and-targeted-therapies