Phenotypic clustering of atrial fibrillation patients using latent class analysis and its potential utility for ablation strategy: insights from the DIRECT-Extend and EARNEST-PVI studies

Figures

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  Figure 1. Study flow chart. Flow diagram of cohort assembly. Among 7512 patients initially enrolled across three AF registries (DIRECT, SAKURA-AF, Osaka University), those without echocardiographic data were excluded (including all SAKURA-AF patients due to lack of echo collection), yielding 2741 patients for latent class analysis (LCA). The final analysis set included clinical, laboratory, and echocardiographic variables with <20% missingness after imputation. PVI, pulmonary vein isolation.

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  Figure 2. Discriminative power ranking. Discriminative power of the 16 variables selected by latent class analysis is shown as a bar graph. We computed the discriminative power of each variable as the logarithm of the ratio between the probability that the variable is relevant for clustering and the probability that it is irrelevant for clustering. CRP, C-reactive protein; IVSTd, interventricular septum thickness in diastole; LVEF, LV EF; LVDd, LV diastolic dimension; LVPWTd, LV posterior wall thickness in diastole; LADs, left atrial diameter in systole.

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  Figure 3. Clinical features in three phenotypes. Relative differences in the clinical features among the three phenotypes are illustrated in the radar chart. Phenotype 1 (‘low comorbidity/healthy AF’)—higher LVEF, higher haemoglobin, lower CRP; Phenotype 2 (‘cardiomyopathy & CKD’)—lower LVEF, larger LA size, impaired renal function, higher prevalence of diabetes, and heart failure history; Phenotype 3 (‘inflammatory-enriched AF’)—elevated CRP and increased ventricular wall thickness. Panel shows medians or proportions scaled to cohort distribution; darker colour indicates a higher relative value. Continuous variables are displayed as means of Z-standardized values, and categorical variables are displayed as proportions. For visualization purposes, AF type was grouped into paroxysmal AF and persistent/long-standing persistent AF, and smoking status was grouped into non-smoker and current or past smoker. CRP, C-reactive protein; IVSTd, interventricular septum thickness in diastole; LVDd, LV diastolic dimension; LVPWTd, LV posterior wall thickness in diastole; LVEF, LV EF; LADs, left atrial diameter in systole; CKD, chronic kidney disease; LV, left ventricle; LA, left atrium; HF, heart failure.

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  Figure 4. Clinical outcomes in the DIRECT-extend registry. Survival analysis was conducted with Kaplan–Meier methods for a composite of all-cause death, acute myocardial infarction, any stroke, and major bleeding according to the International Society on Thrombosis and Haemostasis criteria.

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  Figure 5. Ablation strategy outcomes by phenotype in the EARNEST-PVI trial. Freedom from atrial arrhythmia recurrence after ablation, stratified by phenotype and randomized strategy: pulmonary-vein isolation alone (PVI-alone) vs. PVI with extensive ablation (PVI-plus). PVI, pulmonary vein isolation.