Reduction in CMR Derived Extracellular Volume With Patisiran Indicates Cardiac Amyloid Regression

OBJECTIVES The purpose of this study was to determine the effect of patisiran on the cardiac amyloid toad as measured by cardiac magnetic resonance and extracellular volume (ECV) mapping in cases of transthyretin cardiomyopathy (ATTR-CM). BACKGROUND Administration of patisiran, a TTR-specific small interfering RNA (siRNA), has been shown to benefit neuropathy in patients with hereditary ATTR amyloidosis, but its effect on ATTR-CM remains uncertain. METHODS Patisiran was administered to 16 patients with hereditary ATTR-CM who underwent assessment protocols at the UK National Amyloidosis Centre. Twelve of those patients concomitantly received diflunisal as a TTR-stabilizing drug. Patients underwent serial monitoring using cardiac magnetic resonance, echocardiography, cardiac biomarkers, bone scintigraphy, and 6-min walk tests (6MWTs). Findings of amyloid types and extracellular volumes were compared with those of 16 patients who were retrospectively matched based on cardiac magnetic resonance results. RESULTS Patisiran was well tolerated. Median serum TTR knockdown among treated patients was 86% (interquartile range [IQR]: 82% to 90%). A total of 82% of cases showed >80% knockdown. Patisiran therapy was typically associated with a reduction in ECV (adjusted mean difference between groups: 6.2% [95% confidence interval [CI]: -9.5% to 3.0%]; p 0.001) accompanied by a fall in N-terminal pro-B-type natriuretic peptide concentrations (adjusted mean difference between groups: 1,342 ng/l [95% CI: -2,364 to 322]; p = 0.012); an increase in 6MWT distances (adjusted mean differences between groups: 169 m [95% CI: 57 to 2,80]; p = 0.004) after 12 months of therapy; and a median reduction in cardiac uptake by bone scintigraphy of 19.6% (IQR: 9.8% to 27.1%). CONCLUSIONS Reductions in ECV by cardiac magnetic resonance provided evidence for ATTR cardiac amytoid regression in a proportion of patients receiving patisiran. (C) 2021 by the American College of Cardiology Foundation.

Automated summary

The study found that treatment with Patisiran led to reductions in extracellular volume, decreases in N-terminal pro-B-type natriuretic peptide concentrations, increases in 6-minute walk test distances, and evidence of regression in cardiac amyloid in some patients.