Clin Res Cardiol (2022). https://doi.org/10.1007/s00392-022-02002-5

Assessment of the therapeutic value of tafamidis in patients with wild-type transthyretin amyloidosis (ATTRwt) with cardiomyopathy based on cardiovascular magnetic resonance (CMR) imaging
B. Chamling1, M. Bietenbeck2, D. Korthals3, S. Drakos2, V. Vehof2, P. Stalling2, M. Weil2, C. Meier2, A. Yilmaz2
1Department für Kardiologie und Angiologie, Universitätsklinikum Münster, Muenster; 2Department für Kardiologie und Angiologie, Universitätsklinikum Münster, Münster; 3Klinik für Kardiologie II - Rhythmologie, Universitätsklinikum Münster, Münster;

Aims: Tafamidis was approved in Europe for the treatment of cardiomyopathy (CM) in patients with transthyretin amyloidosis (ATTR) in April 2020. So far, real-world data addressing the therapeutic value of tafamidis for the treatment of ATTR-CM are scarce. The purpose of this study was to carefully analyse the therapeutic benefit of tafamidis in patients with wild-type ATTR (ATTRwt) and CM (ATTRwt-CM) after one year of therapy based on serial multi-parametric cardiovascular magnetic resonance (CMR) imaging.

Methods: The present study comprised N=32 patients with ATTRwt-CM who underwent two serial multi-parametric CMR studies within a follow-up period of 12 ± 3 months. Baseline (BL) clinical parameters, serum biomarkers and CMR findings were compared to follow-up (FU) values in patients with treated with tafamidis 61mg daily (N=16, group A) and those without tafamidis therapy (N=16, group B). CMR studies were performed on a 1.5-T system and comprised (amongst others) cine-imaging for assessment of cardiac anatomy and function including 3D longitudinal strain assessment. In addition, a modified Look-Locker inversion recovery (MOLLI) T1-mapping sequence was performed for measurement of pre- and post-contrast myocardial T1-values with additional calculation of extracellular volume fraction (ECV)-values.

Results: Analyses of CMR data at FU compared to BL revealed some minor, however, significant differences between both groups: While left ventricular ejection fraction (LV-EF) remained unchanged in the tafamidis group A, a slight reduction in LV-EF was observed in the untreated group B (∆p=0.014). Accordingly, left ventricular mass index (LVMi) as well as left ventricular wall thickness (LVWT) remained rather constant in the treated group A, while a subtle increase in LVMi (∆p=0.014) and LVWT (∆p=0.006) was observed in the untreated group B. Regarding myocardial mapping analyses, a subtle increase in native T1- and ECV-values was observed in the untreated group B compared to the treated group A during FU (∆p=0.034 and ∆p=0.040, respectively). Based on 3D segmental longitudinal strain analyses, a worsening in apical / (basal + mid) strain ratio (reflecting worsened apical sparing) was only observed in the untreated group B (∆p=0.035). Serum NT-proBNP levels showed an overall increase in both the groups, however, the untreated group B showed a higher increase compared to the treated group [∆NT-proBNP: +144 pg/ml vs. +1154 pg/ml, ∆p=0.037]. Clinical assessment of NYHA class did not result in significant intra-group differences when BL were compared with FU, but a trend to improvement was observed in the treated group A compared to a worsening trend in group B (∆p=0.007).

Conclusion: Tafamidis does not improve cardiac phenotype in patients with ATTRwt-CM after one year of therapy. However, tafamidis seems to delay cardiac disease progression in patients with ATTRwt-CM, since patients with ATTRwt-CM but without tafamidis treatment showed a measurable cardiac disease progression already within one year of monitoring based on multi-parametric CMR imaging.


https://dgk.org/kongress_programme/jt2022/aV1259.html