LA cardiomyopathy in ATTR-CM: the incremental prognostic value of LA strain

Introduction Cardiac amyloidosis due to transthyretin deposition (ATTR-CM) may lead to progressive diastolic dysfunction, increased left ventricular (LV) filling pressures, and atrial mechanical impairment. Left atrial (LA) strain emerged as a sensitive marker of atrial function, often detecting dysfunction earlier than traditional volumetric parameters. However, the prognostic value of LA strain impairment for predicting adverse outcomes in ATTR-CM has not been fully elucidated. Aim To assess the prognostic value of LA strain in a cohort of patients with ATTR-CM. Methods We conducted a single-centre retrospective study of consecutive patients with symptomatic HF due to ATTR-CM followed from 2019-2025. Diagnosis was established according to the recommended algorithm. Echocardiographic data was collected from the first transthoracic echocardiogram (TTE) performed at our institution. LA strain analysis was performed according to the up-to-date EACVI/ASE recommendations. The primary endpoint was a composite of all-cause death or cardiovascular hospitalization at 3 years. Survival was assessed using Cox regression models. The best cut-off for LA strain-derived parameters was determined by ROC curve analysis. Results A total of 286 ATTR-CM patients were identified, of whom 177 had an available baseline TTE and were included – median age 83 [78-87] years; 82% male; 72% on TTR stabilizers; 45% in AF; median LAVI 52 [43–63] mL/m2; median LA reservoir strain 6.5 [4.5–11] % and LA contractile strain 1 [0–4]%; median follow-up of 1.9 [1.0–3.0] years. The primary endpoint occurred in 64 patients (36%), of whom 48 died. In univariate analysis, LA reservoir, contractile and conduit strain, NYHA, left ventricular ejection fraction (LVEF), NT-proBNP, serum sodium, creatinine, and tafamidis therapy were significantly associated with the primary endpoint. LA volume was not associated with the primary outcome. In a multivariate model adjusted for NYHA, atrial fibrillation, LVEF, NT-proBNP, sodium, creatinine, and tafamidis, both LA reservoir strain (HR 0.92 per 1% increase; 95% CI 0.86–0.98; p=0.007) and LA contractile strain (HR 0.89 per 1% increase; 95% CI 0.82–0.97; p=0.007) remained independent predictors of death or cardiovascular hospitalization. A LA reservoir strain <10% (n=118; 66%) and a LA contractile strain <4% (n=123; 69%) independently predicted the primary endpoint (HR 2.34; 95% CI 1.17–4.67; p=0.016 and HR 2.17; 95% CI 1.09–4.35; p=0.029, respectively). Conclusion In a cohort of patients with ATTR-CM, LA reservoir and contractile strain added significant prognostic value beyond well-established clinical, biochemical, and echocardiographic markers. A LA reservoir strain <10% and LA contractile strain < 4% more than doubled the risk of death or cardiovascular hospitalization, thus highlighting its value as meaningful independent markers for risk stratification.