Use of Patisiran Following Heart Transplant in a Patient with Hereditary Transthyretin Cardiac Amyloidosis and Polyneuropathy

Abstract

Introduction For patients with end-stage hereditary transthyretin (TTR) cardiac amyloidosis, heart or heart-liver transplant can be considered. Due to advances in treatment, liver transplant may no longer be necessary, even if concomitant polyneuropathy is present as there are novel therapies that may halt, and in some cases reverse the burden of disease. We present a case of mixed phenotype TTR amyloidosis (cardiac involvement and polyneuropathy) successfully treated with orthotopic heart transplant (OHT) and patisiran therapy. Case Report A 73-year-old previously healthy African American male was referred for evaluation due to new-onset dyspnea. Electrocardiogram revealed atrial flutter with a controlled ventricular response. Echocardiogram was notable for severe biventricular hypertrophy, severe biatrial enlargement, severely depressed ejection fraction, and a pericardial effusion. An endomyocardial biopsy confirmed amyloid deposits. Mass spectrometry and genetic testing confirmed the presence of a pathogenic mutation in the TTR gene. During that same time period, the patient reported neuropathy. Nerve conduction studies revealed decrement in conduction consistent with an amyloid polyneuropathy. Despite initiation of tafamidis, the patient s clinical picture deteriorated, and he eventually required initiation of inotropes as a bridge to OHT. He successfully underwent OHT and was discharged home soon after. His immediate and long-term post-operative course was uneventful up until 10 months post-transplant, when the patient began to report worsening symptoms of neuropathy. Neurologic evaluation confirmed the clinical presence of an amyloid polyneuropathy, previously supported by nerve conduction studies. The patient was initiated on patisiran, an anti-transthyretin RNA interference agent, approximately one-year following transplant. At 18 months, the patient reports stability of his polyneuropathy symptoms and has not had any complications from patisiran infusions. Summary In patients undergoing OHT for hereditary TTR cardiac amyloidosis with concomitant polyneuropathy, post-transplant treatment with patisiran can be considered to halt progression of polyneuropathy. Effects on other organs including the transplanted heart may also be favorable, although this area is absent supporting data.