Abstract 13667: Earlier Onset in Homozygous Val122Ile Hereditary Transthyretin Cardiac Amyloidosis Allows for Advanced Therapies

Introduction: Transthyretin cardiac amyloidosis (TTR-CM) is a progressive disease characterized by the misfolding and deposition of amyloid fibrils extracellularly in the myocardium. The most common mutation in the U.S. is Val122Ile, which is estimated to occur in 3.4% of all African Americans. While this mutation is believed to have a more malignant phenotype, the differences in homozygous vs. heterozygous carriers of this autosomal dominant disease are not known. Methods: We conducted a retrospective chart review of patients enrolled in Emory University's Cardiac Amyloidosis Clinic between January 2014 and April 2021. Patients who carried one or more alleles for the Val122Ile mutation were included in this study. Means testing was performed and all data reported as mean ± standard deviation or count (percentage). Kaplan-Meier analysis was performed with Breslow test. Results: Among 74 patients who had the Val122Ile mutation, 6 were homozygotes and 68 were heterozygotes. Homozygotes were significantly younger than heterozygotes at diagnosis (61±6.5 vs. 74±7.1 years, p < 0.01) and were more likely to present with stage 4 heart failure (p = 0.02). Compared to patients with heterozygous mutation, patients with homozygous mutation were more likely to receive heart transplantation (p = 0.04). Kaplan-Meier analysis revealed lower rate of survival for homozygotes when compared to heterozygotes (p = 0.04). Extracardiac manifestations of amyloidosis including carpal tunnel syndrome, lumbar stenosis, polyneuropathy, and autonomic dysfunction did not differ significantly between the two groups. Conclusion: Val122Ile homozygotes were diagnosed at a younger age than Val122Ile heterozygotes, presented more frequently with advanced stage heart failure, and had worse survival time. There was no difference in extracardiac manifestations of amyloidosis between the two groups.