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 0.3mg/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 ≥ 13mm 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).