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. 2022 Nov 8:43:101134.
doi: 10.1016/j.ijcha.2022.101134. eCollection 2022 Dec.

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

Iwan Harries  1 , Giovanni Biglino  1   2   3 , Kerrie Ford  1 , Martin Nelson  1 , Gui Rego  1 , Prashant Srivastava  2 , Matthew Williams  1 , Bostjan Berlot  1 , Estefania De Garate  1 , Anna Baritussio  1 , Kate Liang  1 , Mai Baquedano  3 , Nikesh Chavda  4 , Christopher Lawton  1 , Andrew Shearn  1 , Sophie Otton  5 , Lisa Lowry  6 , Angus K Nightingale  1 , Juan Carlos Plana  7 , David Marks  4 , Costanza Emmanueli  2   3 , Chiara Bucciarelli-Ducci  8   9
Affiliations

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

Iwan Harries et al. Int J Cardiol Heart Vasc. .

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.

Keywords: CMR, cardiovascular magnetic resonance; Cancer therapeutics-related cardiac dysfunction; Cardio-oncology; Cardiovascular magnetic resonance; ECV, extracellular volume; LAVi, left atrial volume indexed; LGE, late gadolinium enhancement; LV, left ventricle; LVEF, left ventricular ejection fraction; MAPSE, mitral annular plane systolic excursion; MiRNAs, MicroRNAs; iLVEDV, left ventricular end-diastolic volume indexed; iLVESV, indexed left ventricular end-systolic volume indexed.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Study enrolment and follow-up.
Fig. 2
Fig. 2
Panel A: Baseline CMR MAPSE according to tertile of LVEF recovery; Panel B temporal absolute % change in LVEF by tertile.
Fig. 3
Fig. 3
Dysregulation of miRNAs at baseline according to tertile of LVEF recovery. X axis represents the count per million of each miRNA in the sequencing, reflecting relative expression levels in plasma. Y axis represents the difference in expression between tertile 1 (poor recovery) and tertile 3 (good recovery). miRNA 181a-5p and miRNA 221-3p were upregulated at baseline in patients with poor recovery of lV ∼ EF, relative to those with good LVEF recovery. CPM = count per million, DE = dysregulated expression.
See this image and copyright information in PMC

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