Prognostic significance of the left atrioventricular coupling index (LACI) in transthyretin cardiomyopathy (ATTR-CM): advancing risk stratification with a novel echocardiographic metric

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive infiltrative disease characterized by left ventricular hypertrophy and atrial remodeling, ultimately leading to restrictive heart failure. Despite the availability of disease-modifying therapies, risk stratification remains inadequate, emphasizing the need for refined prognostic markers. The Left Atrioventricular Coupling Index (LACI)—an echocardiographic parameter quantifying left atrial (LA) to left ventricular (LV) interaction—has demonstrated prognostic relevance in patients with heart failure. However, its role in ATTR-CM remains unexplored. Purpose This study aims to evaluate the prognostic significance of LACI in patients with ATTR-CM, specifically its association with all-cause mortality and heart failure (HF) hospitalization. Methods A retrospective analysis was conducted on 335 patients diagnosed with either wild-type (ATTRwt) or hereditary (ATTRv) transthyretin amyloidosis, all of whom underwent comprehensive clinical and echocardiographic evaluation. The left atrioventricular coupling index (LACI) was derived from conventional echocardiography, calculated as the ratio of left atrial minimal volume (measured at the end of LV diastole) to left ventricular end-diastolic volume (LVEDV). The primary endpoint was all-cause mortality and/or HF hospitalization. Results The median age of patients was 83 years, with 85% male predominance. Among the cohort, 95% had wild-type ATTR-CM, while 5% had hereditary ATTR-CM. Patients were predominantly classified as NYHA class II (62%) and III (24%). According to NAC score, 52% were in NAC stage I, 30% in NAC stage II and 18% in NAC stage III. Over a median follow-up period of 22 months (IQR: 8–40 months), 39% (132 patients) experienced the composite endpoint of all-cause mortality and/or HF hospitalization. Multivariate analysis identified elevated LACI as an independent predictor of adverse outcomes in patients younger than 83 years (HR= 2.59 [95% CI: 1.36–4.95], p=0.0039), irrespective of tafamidis therapy. ROC curve established an optimal LACI cutoff value of 0.67. Kaplan-Meier survival analysis stratified patients under 83 years based on this cutoff, defining the high-risk cohort as LACI ≥ 0.67 (Fig.1). This group exhibited a significantly higher cumulative incidence of all-cause mortality and/or HF hospitalization (log-rank p = 0.034) Conclusion LACI is as a simple, non-invasive marker that identifies younger ATTR-CM patients at higher risk for adverse outcomes. Its integration into routine echocardiographic assessment holds potential to enhance risk stratification, optimize follow-up strategies, and inform therapeutic decisions.Figure 1