A Hemodynamic Echocardiographic Approach to Disease Severity and Prognosis in Transthyretin Amyloid Cardiomyopathy

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) causes heart failure and poor outcomes. Prognostic stratification is fundamental, yet validated staging systems rely exclusively on biomarkers, neglecting structural and functional cardiac parameters. Objectives: This study evaluates a noninvasive hemodynamic echocardiographic approach to stratify patients with ATTR-CM. Methods: Patients were categorized into 3 groups based on stroke volume index (SVi) and systolic pulmonary artery pressure (sPAP), markers of forward flow and elevated filling pressures. We compared receiver operating characteristic curves for various potentially predictive hemodynamic parameters to identify these as the most robust candidates for risk stratification. Optimal cutoffs (30 mL/m2 for SVi and 40 mm Hg for sPAP) were determined using the Liu index, supported by both univariable and multivariable survival analyses. The primary endpoint was the composite of all-cause mortality and heart failure hospitalization. Prognostic utility was evaluated using multivariable Cox regression, adjusted for age, sex, and disease-modifying therapy. Results: The cohort included 293 patients with ATTR-CM: group 1 (normal SVi/sPAP, n = 115 [39%]), group 2 (low SVi or high sPAP, n = 129), and group 3 (low SVi/high sPAP, n = 49). The primary outcome occurred in 108 (37%) patients. The multivariable analysis confirmed the staging system as an independent predictor of the composite outcome (group 2 HR: 1.70, 95% CI: 1.05-2.71; group 3 HR: 2.50, 95% CI: 1.44-4.30; P < 0.001). Conclusions: The noninvasive hemodynamic approach provides an alternative and promising method to stratify the risk of clinical outcome in patients with ATTR-CM, potentially improving management strategies.