Effects of Patisiran, an RNA Interference Therapeutic, on Regional Left Ventricular Myocardial Deformation in Hereditary Transthyretin Amyloidosis: The APOLLO Study

Abstract

Cardiac amyloidosis patients demonstrate reduced myocardial strain with relative sparing of the cardiac apex. in APOLLO patisiran reduced NT-proBNP and left ventricular (LV) wall thickness and improved global longitudinal strain (GLS) relative to PBO in patients with hereditary transthyretin mediated (hATTR) amyloidosis. An exploratory analysis from APOLLO, a randomized double-blind, PBO-controlled Ph3 trial in h ATTR amyloidosis with polyneuropathy, assessed effects of patisiran on LV regional strain. Patients were randomized 2:1 to receive 0.3 mg/kg patisiran or PBO via IV infusion once every 3 weeks for 18 months. The prespecified cardiac subpopulation ( n = 126) comprised patients with baseline LV wall thickness ≥ 13 mm and no history of hypertension or aortic valve disease. Patient underwent two-dimensional and speckle tracking echocardiography. At baseline, average strain was lowest in the basal segments with apical sparing. Patisiran reduced GLS (LSM difference ± SE; −1.36 ± 0.56%, P = 0.014) compared with PBO at 18 months, with the greatest reduction in LV strain was observed in the basal region, (overall LSM difference −2.08 ± 0.75%, P = 0.006), and no significant differences in the mid and apical regions among groups ( Figure 1 ). Patisiran improved LV GLS driven primarily by improvements in the basal region, suggesting that basal regional longitudinal strain may be a more sensitive marker to evaluate treatments for the cardiomyopathy in hATTR amyloidosis ( Figure 1 : Least-squares mean change in LV longitudinal strain from baseline at 18 months).