Echocardiography-derived stroke volume holds an independent and additive prognostic value in patients with transthyretin cardiac amyloidosis

Abstract Background Transthyretin cardiac amyloidosis (ATTR-CA) is increasingly recognized as a significant cause of heart failure. Current risk stratification primarily relies on the National Amyloidosis Centre (NAC) staging system, which comprises renal function and NT-proBNP levels. However, the role of cardiac hemodynamics—particularly non-invasive echocardiographic assessment—remains understudied. Given the limitations of right heart catheterization in routine practice, echocardiography offers a practical alternative for evaluating hemodynamics in ATTR-CA. Aims This study aimed to assess the prognostic significance of echocardiography-derived hemodynamic parameters in patients with ATTR-CA, focusing on left ventricular filling pressure (ePCWP) and forward stroke volume index (SVi). Methods We prospectively evaluated consecutive ATTR-CA patients who underwent comprehensive echocardiography. Left ventricular filling pressures were estimated using a validated algorithm (derived from pulmonary capillary wedge pressure, ePCWP; normal 15 mmHg). Forward stroke volume index (SVi, normal ≥35 mL/m²) was calculated from LV outflow tract velocity-time integral and cross-sectional area. Patients were followed for the composite endpoint of all-cause mortality and first heart failure-related hospitalization. Results Among 197 patients (96% wild-type, 86% male, mean age 79±6 years, LVEF 50±10%), 48%, 33%, and 19% were classified as NAC stages I, II, and III, respectively. Elevated ePCWP (≥15 mmHg) was present in 60% of patients, while reduced SVi (35 mL/m²) was observed in 14%. Patients with elevated ePCWP had more advanced symptoms (NYHA III/IV: 37% vs. 10%), higher NT-proBNP (3756 vs. 1522 ng/L), and worse LV function (LVEF 47% vs. 55%, all p0.05). Similarly, reduced SVi was associated with worse clinical profiles, including higher heart rates, more severe mitral regurgitation, and lower TAPSE (all p0.05). Over a median follow-up of 2.3 years, 47% of patients reached the primary endpoint (70 deaths, 53 HF hospitalizations). Event rates increased progressively: 27% (normal ePCWP/SVi), 49% (elevated ePCWP only), and 80% (both elevated ePCWP and reduced SVi; log-rank p0.001). At multivariable regression analysis, adjusted for age, NAC stage, atrial fibrillation, moderate-to-severe MR, LVEF, and TAPSE, SVi 35 mL/m² (hazard ratio 1.9 95% CI 1.1–3.3, p=0.02) was an independent predictor of the primary endpoint, improving risk prediction Conclusion In patients with ATTR-CA, elevated ePCWP and reduced SVi are linked to worse outcomes. Elevated ePCWP reflects amyloid-induced restrictive physiology, while reduced SVi may result from various coexisting factors, such as biventricular systolic dysfunction and significant MR. The independent and additive prognostic value of echocardiography-derived SVi could enhance risk stratification and potentially guide therapeutic decisions in patients with ATTR-CA. Multivariable model