Association between Cardiovascular-Kidney-Metabolic syndrome and clinical outcomes in Patients with Atrial Fibrillation: Insights from COOL-AF registry

BACKGROUND: The Cardiovascular-Kidney-Metabolic (CKM) syndrome has been recently defined to highlight the interconnections between these organ systems on the natural history of disease and clinical outcomes. OBJECTIVE: To demonstrate associations between CKM interconnection and clinical outcomes in patients with atrial fibrillation (AF). METHOD: Using the prospective nationwide COOL-AF registry, patients were classified into each CKM stage aligned with consensus definition. The primary endpoint was composite of all-cause mortality, stroke and systemic embolism, major bleeding, and heart failure. The association of clinical outcomes with compliance to holistic or integrated care management based on the Atrial fibrillation Better Care (ABC) pathway was explored. RESULTS: In 3235 patients with AF (mean age 67.9, SD 11.2; 42.2% female), the proportions with CKM stage 0, 1, 2, 3, and 4 were 4.4%, 5.1%, 30.9%, 12.1% and 47.5%, respectively. Progression of CKM stages was associated with stepwise increase in the incidence rate of the primary outcome (when compared to incidence rate of patients with CKM grade 0-1, adjusted hazard ratios (aHRs) were 1.60, 2.24, 2.88 for CKM stage 2, 3, and 4, respectively). The greatest risk was for heart failure, with CKM stage 4 aHR 7.54 (95%CI 2.79-20.40) compared to CKM stage 0-1. Clinical outcomes in patients with advanced CKM stages were improved with ABC pathway compliance (HR 0.60, 95%CI 0.49-0.73). CONCLUSION: In patients with AF, higher stages of CKM syndrome were associated with greater risks of AF-related clinical outcomes, especially heart failure. Integrated care especially in patients with advanced CKM syndrome improved clinical outcomes.