UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Fontana, M; Martinez-Naharro, A; Chacko, L; Rowczenio, D; Gilbertson, JA; Whelan, CJ; Strehina, S; ... Gillmore, JD; + view all (2021) Reduction in CMR Derived Extracellular Volume With Patisiran Indicates Cardiac Amyloid Regression. JACC: Cardiovascular Imaging , 14 (1) pp. 189-199. 10.1016/j.jcmg.2020.07.043.

[img] Text
Chacko_Reduction in CMR Derived Extracellular Volume With Patisiran Indicates Cardiac Amyloid Regression_AAM.pdf - Accepted version
Access restricted to UCL open access staff until 29 October 2021.

Download (474kB)

Abstract

OBJECTIVES: The purpose of this study was to determine the effect of patisiran on the cardiac amyloid load 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 amyloid regression in a proportion of patients receiving patisiran.

Type: Article
Title: Reduction in CMR Derived Extracellular Volume With Patisiran Indicates Cardiac Amyloid Regression
Location: United States
DOI: 10.1016/j.jcmg.2020.07.043
Publisher version: https://doi.org/10.1016/j.jcmg.2020.07.043
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: ATTR, RNAi, amyloidosis, patisiran
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Eastman Dental Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Clinical Science
URI: https://discovery.ucl.ac.uk/id/eprint/10119685
Downloads since deposit
1Download
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item