Clinical phenotypes and echocardiographic profiles in young patients with atrial fibrillation: insights from european and asian cohorts

Background

Atrial fibrillation (AF) in younger adults is a highly heterogeneous condition, encompassing a broad clinical spectrum and associated with markedly different cardiovascular outcomes.

Purpose

We aimed to identify distinct clinical–echocardiographic phenotypes of AF in patients aged <65 years and to evaluate their associations with adverse outcomes across large European and Asian cohorts.

Methods

We analysed patients aged <65 years enrolled in the European (EORP-AF) and Asian (APHRS-AF) registries. Latent Class Analysis (LCA) integrating demographic, cardiovascular, and echocardiographic variables was performed to identify clinical phenotypes. The primary outcome was a composite of all-cause death, major adverse cardiovascular events (MACE), acute coronary syndrome (ACS), and thromboembolic events (TEE). Associations between phenotype membership and outcomes were assessed using Cox proportional-hazards models, with the low-risk class serving as the reference group.

Results

Among 2,547 patients, LCA identified three distinct phenotypes: Class 1 – Cardiometabolic–Early Remodelling (40%) included middle-aged, overweight patients (median age 60 years, BMI 27 kg/m²) with a high prevalence of hypertension (77%), dyslipidaemia (44%), and diabetes (19%), but largely preserved systolic function (LVEF 60%) and normal chamber dimensions. Class 2 – Low-Risk Normal Structure (28%) comprised the youngest participants (median age 52 years, 79% male) with minimal comorbidities (hypertension 5%, diabetes <1%), normal LV and LA size, and the lowest CHA₂DS₂-VASc and HAS-BLED scores; this phenotype was more common among Asian patients (53%). Class 3 – High-Risk Cardiomyopathic (32%) included predominantly European patients (80%) with advanced structural remodelling, enlarged LV and LA (LVEDD 56 mm; LA 48 mm), reduced systolic function (LVEF 45%), and frequent heart failure (70%) or coronary artery disease (33%), representing an overtly remodelled and high-risk phenotype.

Compared with the Low-Risk Normal Structure, High-Risk Cardiomyopathic showed markedly higher risk for the composite outcome (HR 4.49, 95% CI 2.37–8.52), MACE (HR 3.76, 95% CI 1.90–7.44), all-cause death (HR 14.23, 95% CI 3.43–59.12), and ACS (HR 2.56, 95% CI 1.03–6.39). Cardiometabolic–Early Remodelling exhibited intermediate risk across all endpoints.

Conclusions

Three reproducible AF phenotypes emerged, spanning from idiopathic to cardiometabolic and cardiomyopathic forms associated with worsening outcomes. These findings emphasize the clinical heterogeneity of AF and the value of phenotype-driven risk stratification.Baseline characteristics across LCAKaplan–Meier curves for the composite outcome