075: Cardiac safety and tolerability, and effects on cardiac function of tafamidis in patients with non-V30M TTR-FAP

Background Transthyretin familial amyloid polyneuropathy (TTR-FAP) is an autosomal dominant disease characterized by extracellular amyloid deposition in the nerves and heart. Orthotopic liver transplant (OLT) is recommended to remove the source of mutated TTR and stop amyloid deposition. However, progressive cardiomyopathy due to continuing amyloidosis has been described following OLT in patients with non-V30M mutations. Tafamidis prevents dissociation of TTR into monomers and formation of amyloid. Objectives To evaluate cardiac safety and tolerability of tafamidis in patients with non-V30M TTR-FAP. Methods Patients (N=21) with TTR-FAP due to non-V30M TTR mutations and no OLT history were studied in a phase 2 open-label trial. Cardiac assessments included ECG, 24-hour Holter monitoring, echocardiogram, and cardiac biomarkers (troponin I and NT-pro-BNP) at baseline and 6 and 12 months. Results Of the 21 patients enrolled, mean (SD) age, LVEF, troponin I, and NT-pro-BNP at baseline were 63.1 (9.86) years, 60.3 (9.96)%, 0.023(0.04) ng/mL, and 1248.9 (1529.4) pg/mL, respectively. Nine patients had a history of cardiac events. Six of these 9 experienced peripheral edema or dyspnea related to heart failure while on treatment, and 3 patients were hospitalized for other cardiovascular events (AV block, coronary stenosis, TIA). Eighteen patients completed the study, with no significant changes in troponin I, LVEF, or cardiac remodeling. NT-pro-BNP, while elevated at baseline, remained stable with no clinically relevant changes. The pattern of Holter monitoring abnormalities was similar at baseline and while on treatment (eg, atrial tachycardia, 52.4% [11/21] vs 44.4% [4/9]). The percentage of patients with normal heart rate variability (HRV) increased from 21% (4/19) at baseline to 42% (8/19) at month 12. Discussion This study showed no deleterious effects of tafamidis on cardiac function among a cohort of treated TTR-FAP patients. The number of patients with normal HRV improved. Conclusion Tafamidis was safe and well tolerated in patients with non-V30M TTR-FAP.