Incorporating right ventricular function into the Eeuropean modified Mayo staging system for improved prognosis in light chain amyloidosis

Abstract Background Light chain amyloidosis (AL) is a severe and progressive protein misfolding systemic disease. Cardiac involvement is the main determinant of prognosis, typically assessed by cardiac biomarkers such as serum troponins and NT-proBNP. Purpose Recent evidence suggests that right ventricular (RV) longitudinal function provides additional prognostic value in cardiac amyloidosis. We aimed to incorporate routinely used RV echocardiographic parameters in a new staging system in order to identify those at highest risk. Methods We retrospectively analyzed patients evaluated at two tertiary centers between 2018 and 2023. Diagnosis of AL amyloidosis was defined as presence monoclonal gammopathy and confirmed by extracardiac biopsy. Cardiac involvement was defined according to the current international recommendations. RV function was assessed using tricuspid annular plane systolic excursion (TAPSE), tricuspid S wave velocity. Survival probabilities were assessed using the Kaplan-Meier method. Association between baseline variables and mortality was evaluated by Cox proportional hazards regression. Results A total of 92 patients (62% male) were diagnosed, with a median age at diagnosis of 59 years 53–66. Median NT-proBNP was 7479 ng/L 2861–14834, and median troponin I was 0.079 ng/mL 0.03–0.26. During a median follow-up period of 30.3 months 3.4-36.0, there were 45 (48.9%) deaths. Patients were stratified using the European modified Mayo staging: 25 were Stage II, 26 Stage IIIA, and 41 Stage IIIB. Median TAPSE was 16 mm 13–20, while median RV S velocity was 10 cm/s 8–13. On multivariate analysis, TAPSE was an independent predictor of overall survival (HR 1.14 95% CI 1.04–1.16, p=0.006), even after accounting for Mayo stage (II vs. IIIA: HR 2.49 1.07–8.09, p=0.035; II vs. IIIB: HR 3.91 1.47–10.39, p0.001) and left ventricular ejection fraction (LVEF) HR 1.01 0.97-1.02, p=0.630. There was a significant correlation between TAPSE and RV S (R=0.751), the HR for RV S was inferior to that of TAPSE (HR 1.13 95% CI 1.03 – 1.22, p=0.014) Using Contal and O’Quigley’s method, a TAPSE cut-off of 14 mm provided a sensitivity of 78.7% and specificity of 62.2% for survival prediction. We then incorporated TAPSE 14 mm alongside NT-proBNP 8500 ng/L and troponin I 0.1 ng/mL into the European modified Mayo classification, defining a new high-risk group (Stage IIIC). This subgroup had a 12-month survival probability of 22.7% (10.5–49.1). Compared to Stage II, the HR for death in Stage IIIA was 4.42 (1.23–15.87, p=0.022), Stage IIIB was 7.27 (2.02–26.11, p=0.002), and Stage IIIC was 19.29 (95% CI 5.67–65.65, p0.001). Conclusion We propose a novel staging system that augments the European modified Mayo model by including TAPSE, a routine echocardiographic measure of RV function. This approach improves identification of high-risk patients with AL who may benefit from closer monitoring and more aggressive therapies.Figure 1. Figure 2.