Atrial cardiomyopathy as the central substrate linking arterial hypertension to incident atrial fibrillation

Background Atrial fibrillation (AF) frequently complicates arterial hypertension (AH), yet the mechanistic transition from pressure overload to arrhythmia remains incompletely understood. Chronic diastolic burden and vascular stiffening may induce inflammatory–fibrotic atrial remodeling, giving rise to a structural and mechanical substrate of atrial cardiomyopathy (ACM) that precedes clinically overt AF. Aim To determine whether ACM represents the mechanistic substrate underlying incident AF in patients with AH and to assess the role of left atrial (LA) mechanical dysfunction in arrhythmic transition. Methods This multicenter cohort included 307 patients with AH and no prior AF. Baseline assessment comprised inflammatory–fibrotic biomarkers: high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), transforming growth factor beta 1 (TGF-β1) and comprehensive transthoracic echocardiography including peak atrial longitudinal strain (PALS), indexed minimal and maximal LA volumes (LAVImin, LAVImax), average E/e′ and left ventricular global longitudinal strain (LV GLS). Arterial stiffness was quantified using the cardio-ankle vascular index (CAVI). Patients were followed for 3 years for incident AF. Independent predictors were identified using age- and sex-adjusted multivariable logistic regression (two-sided p<0.05). Results Incident AF occurred in 99/307 patients (32%). Compared with those remaining in sinus rhythm, patients who developed AF had lower PALS (20.3±3.4% vs 28.6±4.9%, p<0.001), higher E/e′ (16.2±3.4 vs 11.8±2.9, p<0.001) and larger LAVImin (14.2±5.0 vs 10.4±4.2 ml/m², p<0.001). LAVImax was within normal limits and did not differ between groups (28.4±5.6 vs 27.1±6.1 ml/m², p=0.31), suggesting that LA mechanical dysfunction precedes overt dilatation. Inflammatory–fibrotic markers were higher in the AF group: hsCRP (7.9±1.4 vs 4.2±1.3 mg/L, p<0.002), IL-6 (6.4±0.8 vs 3.6±1.2 pg/ml, p=0.03) and TGF-β1 (1240±75 vs 900±43 pg/ml, p=0.02). CAVI was increased (9.5±0.21 vs 8.3±0.76, p=0.01), whereas LV GLS showed a non-significant trend (−18.1±1.9% vs −20.2±1.8%, p=0.07). A PALS <25% identified a high-risk arrhythmogenic phenotype. In multivariable analysis adjusted for age and sex, impaired PALS (OR 3.78, p<0.001) was the strongest independent determinant of incident AF, followed by TGF-β1 (OR 3.54, p=0.02), CAVI (OR 3.25, p=0.01), hsCRP (OR 1.83, p<0.002) and E/e′ (OR 1.76, p<0.001). Addition of LA mechanical parameters significantly improved model discrimination beyond clinical and hemodynamic variables. Conclusions Incident AF in AH is driven by a pre-existing arrhythmogenic substrate of ACM characterized by LA mechanical dysfunction, inflammatory–fibrotic activation and vascular stiffening. PALS emerges as a central integrator of this process and a pivotal imaging biomarker for early identification of patients at risk of arrhythmic transition.