Combination therapy in a patient with ttrv amyloidosis

Abstract 73 year old male. He has a brother with an unspecified heart disease, three children, all in good health. Former smoker, arterial hypertension, bilateral carpal tunnel syndrome for several years. Therapy used: zofenopril 7.5 mg 1 cp/day. In August 2019 hospitalization for acute heart failure. Echocardiogram showed severe concentric left ventricular hypertrophy with a granular sparkling myocardial appearance, moderately reduced EF, moderate mitral regurgitation, restrictive transmitral pattern, and pulmonary hypertension (PAPS 60 mmHg). ICV with increased dimensions and not collapsible. Moderate circum–cardiac pericardial effusion. During this hospitalization, therapy with an ACE inhibitor, beta blocker and MRI was started with clear clinical benefit. He also started anticoagulant therapy for evidence of atrial fibrillation. At discharge, NYHA class II. Myocardial scintigraphy with bone tracer was positive for the presence of grade 2 myocardial uptake according to the Perugini score. Blood chemistry tests were performed to exclude the AL form and finally the genetic test showed the presence of a mutation on the transthyretin Val122Ile gene (mutation associated with a variant of amyloidosis with a predominantly cardiological phenotype). Then, heart failure therapy was optimized and disease modifying therapy was started with Tafamidis 61 mg/day. Over time there was a reduction in left ventricular function, so sacubitril/valsartan was started; this drug was not tolerated due to hypotensive episodes. The NYHA class has however always remained stable (class II). During the follow–up in September 2022 he had a new hospitalization for heart failure during which the therapy was optimized with the insertion of the SGLT–2 inhibitor, which was well tolerated. During this hospitalization, symptoms related to the neurological involvement of the pathology emerged: severe weight loss and paresthesias in the four limbs for which it was decided to associate therapy with patisiran IV. To date, the approved therapy for amyloid cardiomyopathy is tafamidis but, in consideration of the neurological symptoms and the results obtained from patisiran in patients with the variant form, it was decided to associate the two therapies, taking care to also optimize therapy for heart failure.