Impact of cardiovascular-kidney-metabolic conditions on clinical outcomes in patients with atrial fibrillation: results from a prospective cohort
M Vitolo, M Mantovani, J F Imberti, D A Mei, N Bonini, E Tartaglia, B Cherubini, P Trapanese, M Paolini, F Tritto, E Battigaglia, G BorianiAbstract
Background
Cardiovascular-kidney-metabolic (CKM) conditions are frequently encountered in the clinical practice. While the individual effects of each comorbidity on outcomes in AF patients have been previously reported, their combined impact - particularly in the form of CKM multimorbidity - remains poorly understood. Additionally, while AF is well known to be associated with atrial remodeling, and CKM conditions are also thought to impair left atrial (LA) structure and function, the effect of CKM multimorbidity on myocardial atrial remodeling in AF patients has yet to be fully explored
Purpose
The aim of this study was to investigate the prevalence and impact of CKM conditions on LA remodeling and the risk of adverse cardiovascular events in patients with AF.
Methods
Patients with AF enrolled in a single-center prospective study were stratified based on the presence of CKM comorbidities. We aimed to assess the impact of CKM status on long-term adverse outcomes and left atrial (LA) remodeling. The primary outcome was a composite of all-cause death, acute coronary syndrome (ACS), ischemic stroke and transient ischemic attack (TIA), and hospitalization for heart failure (hHF).
Results
A total of 1236 patients (median age 75 [66-82]; 37.5% females) were included. Among them, 43.4% had no CKM conditions, 34.6% of patients had 1 CKM condition, 16.7% had 2 CKM conditions, and 5.3% of patients had 3 CKM conditions (Figure 1A). The proportion of patients with LA dilation progressively increased in parallel with higher CKM burden (from 24.2% up until 40% and 40.5% in patients with 2 or 3 CKM conditions). After a median follow-up of 524 [217-1297] days, 283 (27.5%) events of the primary outcome were reported (Figure 1B). Compared to patients with 0 CKM conditions, there was a progressively and indepent higher risk of adverse events for patients with 1 (aHR, 95% CI: 1.56, 1.14-2.12), 2 (1.98, 1.40-2.79), and 3 (2.55, 1.61-4.02) CKM conditions (Figure 1B). No significant interaction was observed with sex, obesity, hypertension, HF, COPD, and AF type (Figure 2A). Age showed a progressive, linear association with adverse events (p < 0.001; p for non-linearity = 0.139). LAVi (Figure 2D) was significantly associated with the risk of the primary endpoint (p<0.001), with a non-linear relationship (p for non-linearity =0.003), but no significant interaction was observed with CKM status (p int=0.499).
Conclusion
CKM multimorbidity was highly prevalent in AF patients and closely linked to progressive LA remodeling and adverse clinical outcomes. The increasing CKM burden was associated with a stepwise rise in the risk of adverse events, independent of conventional risk factors, underscoring the pivotal role of CKM dysfunction as a systemic substrate underlying AF progression and highlighting the need for integrated, multidisciplinary care.Figure 1Figure 2