Introduction : Hereditary transthyretin cardiac amyloidosis (hATTR CA) is a systemic disease associated with a rapidly progressive cardiomyopathy as well as extra-cardiac manifestations including polyneuropathy, spinal stenosis, and carpal tunnel syndrome. The Valine 122 Isoleucine (V122I) mutation is the most prevalent hereditary variant in the United States, affecting 3.4% of Black Americans. Orthotopic heart transplant (OHT) has been performed on V122I patients with end-stage cardiomyopathy; however, this therapy does not address extra-cardiac manifestations. New transthyretin (TTR) targeted therapies (Tafamidis, Patisiran) are now FDA approved in hATTR CA and hATTR polyneuropathy respectively, but their role in post-transplant management is unclear. Methods : We conducted a retrospective chart review of patients enrolled in Emory University's Cardiac Amyloidosis Clinic who underwent OHT between January 2014 and April 2021. Extra-cardiac manifestations were recorded at hATTR CA diagnosis and followed post-OHT. Results : Ten patients with V122I hATTR CA underwent OHT. All patients were Black males, with an average age of 63 ± 4 years. Mean ejection fraction was 21 ± 8% and mean left ventricular mass index was 200 ± 85 g/m2 at time of transplant. Survival to date is 80% with a median follow-up time of 4.1 years (3.6 - 6.4). Pre-OHT, seven (70%) patients had extra-cardiac manifestations. All seven had carpal tunnel syndrome (CTS) - five with unilateral and two with bilateral involvement. Three patients (30%) had additional extra-cardiac manifestations; including polyneuropathy, spinal stenosis, and/or gastroparesis. Post-OHT, one patient with bilateral CTS developed severe gastroparesis necessitating gastric tube placement and peroral endoscopic myotomy, as well as worsening polyneuropathy with autonomic dysfunction. Another patient with unilateral CTS and polyneuropathy pre-OHT developed spinal stenosis necessitating laminectomy as well as worsening polyneuropathy. Patisiran was initiated in both of these patients after worsening neuropathy was documented. Finally, a third patient progressed from unilateral to bilateral CTS necessitating bilateral release. Conclusions : OHT outcomes in patients with V122I hATTR CA are overall favorable in terms of cardiac function and survival. However, progression and/or development of extra-cardiac manifestations can significantly affect quality of life post-OHT. Annual neurologic and orthopedic evaluations should be incorporated into routine post-transplant care. Despite the advent of safe and effective TTR targeted therapies, these medications do not currently carry an indication for prophylactic use post-OHT. More data is needed to develop clinical best practices, including guidelines for use of targeted TTR therapies, in V122I patients undergoing OHT. : Hereditary transthyretin cardiac amyloidosis (hATTR CA) is a systemic disease associated with a rapidly progressive cardiomyopathy as well as extra-cardiac manifestations including polyneuropathy, spinal stenosis, and carpal tunnel syndrome. The Valine 122 Isoleucine (V122I) mutation is the most prevalent hereditary variant in the United States, affecting 3.4% of Black Americans. Orthotopic heart transplant (OHT) has been performed on V122I patients with end-stage cardiomyopathy; however, this therapy does not address extra-cardiac manifestations. New transthyretin (TTR) targeted therapies (Tafamidis, Patisiran) are now FDA approved in hATTR CA and hATTR polyneuropathy respectively, but their role in post-transplant management is unclear. : We conducted a retrospective chart review of patients enrolled in Emory University's Cardiac Amyloidosis Clinic who underwent OHT between January 2014 and April 2021. Extra-cardiac manifestations were recorded at hATTR CA diagnosis and followed post-OHT. : Ten patients with V122I hATTR CA underwent OHT. All patients were Black males, with an average age of 63 ± 4 years. Mean ejection fraction was 21 ± 8% and mean left ventricular mass index was 200 ± 85 g/m2 at time of transplant. Survival to date is 80% with a median follow-up time of 4.1 years (3.6 - 6.4). Pre-OHT, seven (70%) patients had extra-cardiac manifestations. All seven had carpal tunnel syndrome (CTS) - five with unilateral and two with bilateral involvement. Three patients (30%) had additional extra-cardiac manifestations; including polyneuropathy, spinal stenosis, and/or gastroparesis. Post-OHT, one patient with bilateral CTS developed severe gastroparesis necessitating gastric tube placement and peroral endoscopic myotomy, as well as worsening polyneuropathy with autonomic dysfunction. Another patient with unilateral CTS and polyneuropathy pre-OHT developed spinal stenosis necessitating laminectomy as well as worsening polyneuropathy. Patisiran was initiated in both of these patients after worsening neuropathy was documented. Finally, a third patient progressed from unilateral to bilateral CTS necessitating bilateral release. : OHT outcomes in patients with V122I hATTR CA are overall favorable in terms of cardiac function and survival. However, progression and/or development of extra-cardiac manifestations can significantly affect quality of life post-OHT. Annual neurologic and orthopedic evaluations should be incorporated into routine post-transplant care. Despite the advent of safe and effective TTR targeted therapies, these medications do not currently carry an indication for prophylactic use post-OHT. More data is needed to develop clinical best practices, including guidelines for use of targeted TTR therapies, in V122I patients undergoing OHT.