Early Recurrence of Myocardial Transthyretin Amyloid Deposition Three Years Post Heart Transplantation for Hereditary V40I Amyloidosis

Transthyretin (ATTR) amyloidosis is an increasingly recognized cause of heart failure. For ATTR patients who undergo isolated heart transplantation, recurrent amyloid deposition in the graft myocardium is uncommon. Introduction A 58 year old man presented with heart failure and severe concentric left ventricular hypertrophy consistent with infiltrative cardiomyopathy on cardiac MRI. He was diagnosed with hereditary ATTR amyloidosis (V40I variant) on endomyocardial biopsy and subsequent genotyping. Case Description The patient also had a history of coronary artery disease, hypertension, hyperlipidemia and spinal stenosis. He was enrolled in a tafamidis clinical trial, but developed stage D heart failure, and within two years required (isolated) cardiac transplantation, after which he was excluded from the tafamidis trial. Nine months post transplant, he required decompressive lumbar foraminotomies for spinal stenosis, and two years post transplant he developed worsening peripheral neuropathy. Routine echocardiograms, endomyocardial biopsies and coronary angiography did not suggest any recurrent infiltrative cardiomyopathy or allograft vasculopathy until 3 years post transplant, where the endomyocardial biopsy demonstrated subendocardial amyloid deposition. The patient was initiated on patisiran for the indication of amyloid neuropathy, with early follow up of clinical response pending. Discussion Recurrence of transthyretin cardiac amyloid deposition after heart transplantation is uncommon. Some patients undergo heart-liver transplantation which would obviate the source of ATTR production, but even in patients with isolated heart transplantation, development of cardiac amyloidosis within three years is uncommon. A previous case series of patients with the V40I variant (the “Wagshurst study”) reported that no patients who underwent isolated heart transplantation showed evidence of amyloid recurrence in the donor graft up to 8 years of followup. Conclusion In the era of increasing diagnosis and new treatments for ATTR amyloidosis, we report an early recurrence of cardiac amyloidosis, which raises questions for further study including surveillance and the potential role of new ATTR therapies in post heart transplant patients with hereditary amyloidosis.