Key Information
Abstract
Background/Objectives: Cardiac amyloidosis (CA) is a rare and severe multisystem disorder, associated with an average survival of approximately five years. Recently, Tafamidis has emerged as a promising treatment for transthyretin-related CA. This retrospective study aimed to assess disease progression through echocardiographic findings in patients with transthyretin-related CA, with a specific focus on evaluating the impact of Tafamidis in a cohort managed at our Cardiomyopathy Clinic. Methods: A total of 39 patients were included, of whom 28 received Tafamidis treatment, while 11 did not. Clinical, electrocardiographic, echocardiographic, biological, and other imaging data were collected at diagnosis. Comprehensive echocardiographic data were collected every six months over a two-year period (2021–2023). Results: At 1-year follow-up, the Tafamidis-treated cohort demonstrated stable global systolic and diastolic function. Left ventricular (LV) global longitudinal strain (GLS) and global work index (GWI) showed minimal change (GLS −12.9% (−15.6; −10.7) vs. −13.0% (−14.0; −10.7), p = 0.054; GWI 1113 mmHg/% (963; 1301) vs. 1208 mmHg/% (850; 1420), p = 0.054), and there was no significant increase in indexed LV mass (135.0 g/m2 (118.0; 167.0) vs. 148.0 (128.0; 173.0), p = 0.25). Similarly, valvular heart disease severity remained unchanged. Longitudinal analysis using generalized linear mixed models further confirmed the stability of echocardiographic parameters over the 2-year follow-up period. Systolic function metrics, including LV ejection fraction (slope: −0.0098 ± 0.011, p = 0.38) and GLS (slope: 0.0036 ± 0.0041, p = 0.39) showed no significant decline. Diastolic function assessed through E/A ratio (slope: −0.0007 ± 0.0013, p = 0.59) and E/e’ (slope: −0.0042 ± 0.0073, p = 0.57) also remained stable. Indexed LV mass exhibited no significant progression (slope: 0.050 ± 0.061, p = 0.41). These findings were consistent across the various subgroups. Conclusions: Tafamidis appears to effectively stabilize transthyretin-related CA, limiting disease progression over the follow-up period.
Keywords: cardiac amyloidosis, Tafamidis, echocardiography
1. Introduction
In recent years, interest in cardiac amyloidosis (CA) among healthcare professionals has grown significantly. Therapeutic advances and the emergence of targeted treatments for transthyretin-related cardiac amyloidosis (ATTR-CA) have markedly improved patient outcome [1external link, opens in a new tab,2external link, opens in a new tab,3external link, opens in a new tab,4external link, opens in a new tab,5external link, opens in a new tab]. Since 2020, Tafamidis has been approved for the treatment of both wild-type and hereditary ATTR-CA [6external link, opens in a new tab]. This oral stabilizer of the transthyretin tetrameric protein prevents its dissociation into monomers or oligomers, which are key contributors to amyloid deposition. The phase III multicenter ATTR-ACT trial demonstrated the efficacy of Tafamidis in managing cardiac involvement and reported a 30% reduction in overall mortality after 30 months compared to placebo, with survival curves diverging as early as the 18th month of treatment [7external link, opens in a new tab]. Additionally, a significant reduction in the risk of cardiovascular hospitalization was observed, along with improvements in quality of life and functional decline as early as six months. The efficacy of Tafamidis appears to remain consistent even over an extended follow-up period [8external link, opens in a new tab]. However, Tafamidis appears slightly less effective in patients with advanced heart failure and dyspnea on minimal exertion (New York Heart Association—NYHA class III). Managing these patients remains challenging, particularly in determining reliable parameters to evaluate treatment response and monitor disease progression. Echocardiography continues to be the cornerstone of monitoring, with several markers proposed for detecting adverse progression function [9external link, opens in a new tab]. This study aimed to evaluate the impact of Tafamidis on echocardiographic parameters in transthyretin-related CA, focusing on its role in stabilizing cardiac structure and function and identifying reliable markers for treatment monitoring.
2. Research Protocol and Methods
This was a retrospective, single-center study conducted over two years, from January 2021 to December 2023 at the Centre Hospitalier Universitaire (CHU) of Liège, Belgium. We analyzed baseline demographic, clinical, biological, and instrumental data from patients diagnosed with ATTR-CA. The progression of echocardiographic and biological parameters was then evaluated, comparing patients treated with Tafamidis to those untreated, to assess its effectiveness. Subgroup analyses were conducted based on indexed left ventricular (LV) mass, age, LV ejection fraction (EF), and NYHA functional class. Our data were compared with published studies, including the ATTR-ACT trial and research on Tafamidis’ impact on echocardiographic parameters such as global longitudinal strain (GLS) and myocardial work [7external link, opens in a new tab,10external link, opens in a new tab,11external link, opens in a new tab]. For data collection, we used the OmniPro medical software version 2.26.6 (Zorgi SA, Bruxelles, Belgium) and the Reseau de Santé Wallon digital medical record (Fédération Régionale des Associations de Télématique Médicale de Wallonie, Liège, Belgium). The study adhered to the principles outlined in the Declaration of Helsinki and received approval from the Ethics Committee of Liege University Hospital (protocol code: 2023/3039).