Long-term trajectories of left atrial remodeling and their prognostic impact in hypertrophic cardiomyopathy

Background Hypertrophic cardiomyopathy (HCM) is traditionally defined by left ventricular hypertrophy, but growing evidence highlights the pivotal role of left atrial (LA) remodelling in disease progression. Static LA measurements have been established as risk markers, failing, however, to capture the dynamic changes that occur over time. Purpose This study aimed to characterize long-term trajectories of LA size in HCM patients and to evaluate their prognostic value in predicting adverse cardiovascular outcomes, specifically atrial fibrillation (AF), sudden cardiac death, and heart failure death. Methods 210 HCM patients (36% women, age 45±17 years) followed up over 35 years represented the study population. We applied group-based trajectory modelling to identify distinct LA remodelling longitudinal patterns. The occurrence of Atrial Fibrillation (AF), of sudden cardiac death (SCD) or a composite of heart transplantation or death for heart failure, represented independent endpoints. Cox regression analyses assessed the association between these trajectories and clinical outcomes, comparing their predictive power against traditional baseline LA measurements. Results Three distinct LA remodelling trajectories adjusted for age and sex were identified (Figure 1, upper panel). The baseline characteristics of patients, stratified by trajectory clusters, are presented in Table 1. Patients in the moderate (cluster B) and severe (Cluster C) remodelling groups had significantly higher probability of developing AF (log-rank p < 0.001) compared to the stable group (Figure 1, lower left panel). The severe remodelling trajectory was also associated with an increased probability of SCD (log-rank p = 0.031) and heart failure death (log-rank p = 0.028) (Figure 1, lower central and right panel). Trajectory-based group assignments also outperformed baseline LA size groups in predicting AF risk (respectively Cluster C aHR 9.30 vs 5.03 and Cluster B aHR 2.79 vs 2.55), and were able to significantly predict SCD (Cluster C aHR 3.61), highlighting the superior prognostic value of the longitudinal pattern. Conclusion LA remodelling trajectories provide a dynamic and robust assessment of risk in HCM patients, offering greater prognostic insight than baseline LA measurements alone. Incorporating longitudinal LA data into clinical practice may enhance risk stratification and guide more personalized management strategies.Figure 1 Table 1