Prognostic value of disproportionate left atrial myopathy in patients with heart failure

Abstract Background Left atrial (LA) function is a key determinant of clinical outcomes in heart failure (HF). LA reservoir strain (LArS) has been shown to independently predict adverse events irrespective of left ventricular (LV) ejection fraction. Nevertheless, because LArS is partly influenced by mitral annular descent, its interpretation requires consideration of LV longitudinal function. Indeed, a substantial proportion of patients with HF exhibit a disproportionately reduced LArS relative to LV global longitudinal strain (LVGLS). This phenotype, recently termed disproportionate LA myopathy, may reflect intrinsic atrial dysfunction beyond ventricular impairment. However, its prognostic significance has never been fully understood. Purpose To investigate the prognostic value of disproportionate LA myopathy in patients with HF. Methods We prospectively analyzed 1,041 patients with chronic HF enrolled in a multicentre registry across 29 sites between January 2020 and March 2025 after excluding those with unmeasurable LArS or LVGLS and those with significant left sided valvular disease. Patients were classified into three groups according to studentized residuals derived from the LArS to LVGLS regression model: predominant LA myopathy defined as residual < −1, balanced LA/LV myopathy defined as residual within ±1, and preserved LA function defined as residual > +1. The primary outcome was a composite of cardiac death and hospitalization for worsening HF. Results Of the 1,041 patients, 486 (46.7%) had predominant LA myopathy, 136 (13.1%) had balanced LA/LV myopathy, and 419 (40.3%) had preserved LA function (Figure 1). Patients with predominant LA myopathy were older, more frequently had atrial fibrillation, had higher NT-proBNP levels and lower estimated glomerular filtration rate (eGFR), and showed larger LA volume index with more reduced LArS (all P<0.001). During a median follow-up of 881 days (IQR 545 to 1429), the primary outcome occurred in 135 patients. Event rates were significantly higher in patients with predominant LA myopathy compared with the other groups (Figure 2). In multivariable Cox regression analyses, disproportionate LA myopathy remained independently associated with the primary outcome after adjustment for age, sex, systolic blood pressure, NYHA class, diabetes, serum sodium, eGFR, and log NT-proBNP (HR 1.74; 95%CI 1.08 to 2.82), with no interaction by sex (P = 0.10) or HFrEF vs. non-HFrEF (P = 0.24). This association also remained after adjustment for log NT-proBNP and the MAGGIC risk score (HR 1.74; 95%CI 1.15 to 2.62). Conclusions Disproportionate LA myopathy is independently associated with adverse clinical outcomes in patients with HF. This phenotype likely reflects intrinsic atrial dysfunction and identifies patients at increased vulnerability to pulmonary congestion. Evaluation of LA function in relation to LV longitudinal performance may provide incremental value for risk stratification in HF.