The Cardiovascular–Kidney–Metabolic (CKM) Syndrome and Heart Failure: From Multi-Organ Pathophysiology to Precision Therapeutics

The formalization of Cardiovascular–Kidney–Metabolic (CKM) Syndrome by the American Heart Association in 2023 redefined how clinicians and researchers conceptualize the intersection of heart failure (HF), chronic kidney disease (CKD), obesity, and metabolic dysfunction. Yet the most consequential development in the field is not the classification itself — it is the emergence of an entirely new therapeutic logic. The convergence of SGLT2 inhibitors, GLP-1 receptor agonists, and non-steroidal mineralocorticoid receptor antagonists (ns-MRAs) offers, for the first time, agents capable of acting simultaneously across the cardiovascular, renal, and metabolic axes. Translating this combinatorial opportunity into precision care pathways — across heterogeneous patient phenotypes, diverse healthcare settings, and historically underserved populations — is the defining clinical and scientific challenge of the next decade.This Research Topic brings together original research, systematic reviews, clinical perspectives, and policy analyses addressing CKM syndrome through the lens of heart failure. Contributions are organized around four thematic pillars:I. Pathophysiology & Phenotyping Mechanisms of cardiorenal and cardiometabolic crosstalk; adipokine signalling; systemic inflammation; HFpEF versus HFrEF phenotypes within the CKM framework; sex, age, and ethnicity as modulators of disease trajectory.II. Precision Therapeutics Clinical trial evidence and real-world data on SGLT2 inhibitors, GLP-1 receptor agonists, and ns-MRAs as monotherapy and in combination; drug sequencing and tolerability across CKM stages; pharmacological mechanisms beyond neurohormonal blockade; emerging and investigational agents.III. Staging, Risk Stratification & Biomarkers Clinical validation of the AHA CKM staging framework; novel cardiac, renal, and metabolic biomarkers; AI-assisted phenotyping and risk prediction; digital health tools for integrated cardiorenal-metabolic decision support.IV. Advanced Therapies, Implementation & Equity Device-based strategies and transplant considerations in the metabolic era; integrated multi-specialty care models; health systems implementation; disparities in CKM burden and access to novel therapies across populations and regions; policy and guideline implications.We welcome contributions from cardiologists, nephrologists, endocrinologists, diabetologists, transplant specialists, health systems researchers, and data scientists. This collection is intentionally cross-disciplinary: the shared pathophysiology of CKM syndrome demands a shared scientific conversation.The field is at peak translational momentum — clinical trials are reporting, phenotyping cohorts are maturing, and international guidelines are converging. This Research Topic is designed to capture that moment, and to accelerate the path from multi-organ pathophysiology to precision, equitable care. Topic editors: Ravi Dhingra, Akshat Banga Source: https://www.frontiersin.org/research-topics/81657/the-cardiovascular-kidney-metabolic-ckm-syndrome-and-heart-failure-from-multi-organ-pathophysiology-to-precision-therapeutics