Surveillance for Transthyretin Amyloidosis Progression after Heart Transplantation in the Era of Novel Disease Modifying Therapies

Purpose Transthyretin amyloidosis (ATTR) predominantly involves the heart (ATTR-cardiac amyloidosis [CA]) and nerves, and may involve other organs or tissues. Disease modifying therapies improve outcomes in those with ATTR-CA or with neurologic involvement, however their utility post heart transplant (HT) or combined heart/liver transplant is uncertain. We evaluated patients who underwent HT for ATTR-CA to determine the incidence of de novo development or progression of neurologic, GI and soft tissue manifestations of ATTR deposition. Methods We performed a review of all patients who underwent HT for ATTR-CA at our center. Baseline demographics and post HT manifestations of TTR deposition were collected. All patients completed the Composite Autonomic Symptom Score (COMPASS-31) and Polyneuropathy Disability Score (PDS). The COMPASS-31 is a questionnaire of autonomic symptoms, with a higher score (0 - 100) indicating more severe autonomic dysfunction. The PDS ranges from 0 (asymptomatic) to 4 (confined to wheelchair/bed). Results Twelve patients were included. Mean age at HT was 67 ± 5 yrs, 83.3% male, and 50% Black. Five patients had wild-type and 7 had variant ATTR-CA (6 V122I, 1 T60A). At a mean of 5.2 ± 3.9 yrs post-transplant, 8 patients had symptoms of progressive or de novo ATTR deposition with 4 having involvement in ≥ 2 systems (Figure 1). None had cardiac involvement on PYP imaging (n=5) or serial endomyocardial biopsy . The mean COMPASS-31 was 19.5 (range 0.9 - 45.8) at a median time from HT of 3.9 ± 3.5 years. Three subjects had a PDS of 1 and 1 each scored 2, 3b, and 4, the latter patient was homozygous for the V122I variant. Conclusion In our single-center study, > 50% of patients had evidence of progressive or de novo TTR deposition post HT. This adds significant morbidity despite a functioning cardiac allograft. These observations underscore an unmet need for TTR modifying therapies that could slow TTR deposition and significantly improve quality of life post HT for ATTR-CA.