Multimodal Assessment of Disease Progression Risk Among Transthyretin Amyloid Cardiomyopathy Patients Under Disease-Modifying Therapy

J. Piwowarski (Berlin)¹, J. Gröschel (Berlin)¹, E. Romero Dorta (Berlin)², H. Pernice (Berlin)³, J. Zernikow (Berlin)⁴, N. Wieder (Berlin)³, E. Asaad (Berlin)³, P. Wetzel (Berlin)³, B. Heidecker (Berlin)⁴, S. Werhahn (Berlin)⁵, G. Barzen (Berlin)¹, G. Hindricks (Berlin)², K. Hahn (Berlin)⁶, S. Spethmann (Berlin)^7
1Amyloidosis Center Charité Berlin (ACCB), Deutsches Herzzentrum der Charité, Charité - Universitätsmedizin Berlin Klinik für Kardiologie, Angiologie und Intensivmedizin Berlin, Deutschland; ²Charité - Universitätsmedizin Berlin CC11: Med. Klinik m. S. Kardiologie und Angiologie Berlin, Deutschland; ³Charité - Universitätsmedizin Berlin Berlin, Deutschland; ⁴Charité - Universitätsmedizin Berlin CC 11: Med. Klinik für Kardiologie Berlin, Deutschland; ⁵Deutsches Herzzentrum der Charité Kardiologie Berlin, Deutschland; ⁶Klinik für Neurologie Amyloidosis Center Charite Berlin Berlin, Deutschland; ⁷Charité - Universitätsmedizin Berlin Klinik für Kardiologie, Angiologie und Intensivmedizin Berlin, Deutschland

Background

Validated approach for the detection of disease progression (DiP)  in transthyretin amyloid cardiomyopathy (ATTR-CM) exists, yet predicting DiP under disease-modifying therapy remains an unmet clinical need.

Objectives

To identify parameters with discriminative ability for predicting DiP and to develop a risk stratification model for DiP in ATTR-CM patients receiving disease-modifying therapy.

Methods

In this prospective registry study, we included all ATTR-CM patients who received disease-modifying therapy and completed one-year follow-up at the Amyloidosis Center Charité Berlin. DiP was defined according to validated criteria involving sufficient NT-proBNP rise or any loop diuretic dose increase at one-year follow-up (Ioannou, A, Cappelli, F, Emdin, M. et al. Stratifying Disease Progression in Patients With Cardiac ATTR Amyloidosis. JACC. 2024 Apr, 83 (14) 1276–1291.). Except for DiP and follow-up-related parameters, all data were obtained exclusively from examinations performed as part of the initial diagnostic assessment. Left atrial strain measurements were performed in line with current guidelines, using 2D speckle tracking echocardiography, measured according to the zero strain reference at end-diastole.

Results

Among 171 included patients, 62 (36%) met criteria for DiP.  General characteristics at baseline visit were largely comparable between groups; however, progressors exhibited greater dyspnea burden and nearly 2.5-fold higher prevalence of nonspecific intraventricular conduction delay (NICD) on ECG. Median high-sensitivity troponin T levels were 70% higher among progressors (34 vs. 58 ng/L, p < 0.001). Moderate tricuspid regurgitation was the only conventional echocardiographic parameter significantly associated with DiP, occurring approximately twice as frequently among progressors. Left atrial function analysis identified peak left atrial longitudinal strain (PALS) < 7.90% as the most discriminative among all evaluated parameters (Youden’s index 38.8%). A multivariable risk model integrating NICD, high-sensitivity troponin T, and PALS achieved an AUC of 0.75 (95%CI: 0.68-0.83) for predicting DiP.

Conclusion

Multimodal evaluation provides prognostic information regarding DiP risk in ATTR-CM patients undergoing disease-modifying therapy. Findings of this study may support clinical decision-making and improve identification of high-risk patients, who may benefit from intensified monitoring.