In a 2018 paper, the phase 3 ATTR-ACT investigators demonstrated treatment with tafamidis led to reductions in all-cause mortality and cardiovascular-related hospitalizations, and directionally positive echocardiographic findings in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), compared with placebo.1 Although these data are undoubtedly positive, the relationships between these clinical benefits and observed differences in cardiac remodeling between treatment-naïve and tafamidis-treated patients had not yet been well-defined. A study using a prospective heart failure registry at the Medical University of Vienna aimed to determine the impact of tafamidis treatment on cardiac amyloid deposition and relevant biomarkers in patients with ATTR-CM.
Patients diagnosed with ATTR-CM between May 2015 and June 2020 were screened for eligibility. Patients were excluded if they had the presence of a TTR mutation or were unable to undergo baseline cardiac magnetic resonance (CMR) imaging and follow-up with late gadolinium enhancement (LGE) and T1 mapping.
Of the 125 patients with ATTR-CM screened for eligibility, 69 patients with wild-type ATTR-CM were considered eligible for the study, which included 3 cohorts: treatment-naïve control cohort (n = 19), tafamidis 20-mg cohorta (n = 15), and tafamidis 61-mg cohort (n = 35). CMR was performed at baseline and at a median follow-up of 9, 11, and 12 months for the tafamidis 61-mg group, tafamidis 20-mg group, and control group, respectively.
Significant beneficial effects were seen for the tafamidis 61-mg patients in left ventricular mass index (LVMI; P = .036), extracellular volume (ECV; P = .030), LGE pattern (P = .015), and left ventricular ejection fraction (LVEF; P = .035) compared with treatment-naïve patients who experienced increases in LVMI and ECV, LGE-pattern progression, and LVEF decline. The tafamidis 61-mg cohort also saw significant benefits in New York Heart Association functional class (P = .004), 6-minute walk distance (6MWD; P = .005), and serum N-terminal pro B-type natriuretic peptide levels (NT-proBNP; P = .002) compared with the control group. In contrast, CMR findings in the tafamidis 20-mg cohort and the control cohort did not significantly differ. However, clinical comparison of these 2 cohorts favored the tafamidis 20-mg cohort in serum NT-proBNP levels (P = .003) and 6MWD (P = .023). When comparing CMR parameters with cardiac biomarkers longitudinally, a significant positive correlation between ECV and serum NT-proBNP levels was discovered for the entire study population (P = .034).
These results provide evidence that treatment of patients with ATTR-CM with tafamidis 61 mg daily delays cardiac changes compared with treatment-naïve patients. Despite these positive findings, further research should be conducted with longer study durations to gain a better sense of the long-term impact of tafamidis on cardiac structure and function changes.a The dosing for the tafamidis 20-mg cohort was based on the approval in transthyretin-mediated amyloid polyneuropathy.
Source
Rettl R, Mann C, Duca F, et al. Tafamidis treatment delays structural and functional changes of the left ventricle in patients with transthyretin amyloid cardiomyopathy. Eur Heart J Cardiovasc Imaging. 2022;23(6):767-780.
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