Prospective multiparametric CMR characterization and MicroRNA profiling of anthracycline cardiotoxicity: A pilot translational study

Iwan Harries, Giovanni Biglino, Kerrie Ford, Martin Nelson, Gui Rego, Prashant Srivastava, Matthew Williams, Bostjan Berlot, Estefania De Garate, Anna Baritussio, Kate Liang, Mai Baquedano, Nikesh Chavda, Christopher Lawton, Andrew Shearn, Sophie Otton, Lisa Lowry, Angus K Nightingale, Juan Carlos Plana, David MarksCostanza Emmanueli, Chiara Bucciarelli-Ducci*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

6 Citations (Scopus)

Abstract

BACKGROUND: Anthracycline cardiotoxicity is a significant clinical challenge. Biomarkers to improve risk stratification and identify early cardiac injury are required.

OBJECTIVES: The purpose of this pilot study was to prospectively characterize anthracycline cardiotoxicity using cardiovascular magnetic resonance (CMR), echocardiography and MicroRNAs (MiRNAs), and identify baseline predictors of LVEF recovery.

METHODS: Twenty-four patients (age 56 range 18-75 years; 42 % female) with haematological malignancy scheduled to receive anthracycline chemotherapy (median dose 272 mg/m2 doxorubicin equivalent) were recruited and evaluated at three timepoints (baseline, completion of chemotherapy, and 6 months after completion of chemotherapy) with multiparametric 1.5 T CMR, echocardiography and circulating miRNAs sequencing.

RESULTS: Seventeen complete datasets were obtained. CMR left ventricular ejection fraction (LVEF) fell significantly between baseline and completion of chemotherapy (61 ± 3 vs 53 ± 3 %, p < 0.001), before recovering significantly at 6-month follow-up (55 ± 3 %, p = 0.018). Similar results were observed for 3D echocardiography-derived LVEF and CMR-derived longitudinal, circumferential and radial feature-tracking strain. Patients were divided into tertiles according to LVEF recovery (poor recovery, partial recovery, good recovery). CMR-derived mitral annular plane systolic excursion (MAPSE) was significantly different at baseline in patients exhibiting poor LVEF recovery (11.7 ± 1.5 mm) in comparison to partial recovery (13.7 ± 2.7 mm), and good recovery (15.7 ± 3.1 mm; p = 0.028). Furthermore, baseline miRNA-181-5p and miRNA-221-3p expression were significantly higher in this group. T2 mapping increased significantly on completion of chemotherapy compared to baseline (54.0 ± 4.6 to 57.8 ± 4.9 ms, p = 0.001), but was not predictive of LVEF recovery. No changes to LV mass, extracellular volume fraction, T1 mapping or late gadolinium enhancement were observed.

CONCLUSIONS: Baseline CMR-derived MAPSE, circulating miRNA-181-5p, and miRNA-221-3p were associated with poor recovery of LVEF 6 months after completion of anthracycline chemotherapy, suggesting their potential predictive role in this context. T2 mapping increased significantly on completion of chemotherapy but was not predictive of LVEF recovery.

Original languageEnglish
Article number101134
Pages (from-to)101134
JournalInternational Journal of Cardiology: Heart and Vasculature
Volume43
Early online date8 Nov 2022
DOIs
Publication statusPublished - 1 Dec 2022

Bibliographical note

Funding Information:
This study was supported by the following grants: NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol (to CBD). British Heart Foundation: Program grant and personal Chair awards (RG/15/5/31446, CH/15/1/31199) (to CE). Above and Beyond Hospital Charity (No. 1170973). CE is the vice-Chair of the Cardiac RNA cost action CA17129 - Catalysing transcriptomics research in cardiovascular disease.

Publisher Copyright:
© 2022

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