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178 Circulating Micrornas for Predicting and Monitoring Response to Mechanical Circulatory Support from a left Ventricular Assist Device
  1. Andrew Morley-Smith1,
  2. Adam Mills2,
  3. Steven Jacobs3,
  4. Bart Meyns3,
  5. Filip Rega3,
  6. Andre Simon1,
  7. John Pepper1,
  8. Alexander Lyon1,
  9. Thomas Thum4
  1. 1Imperial College London and Royal Brompton/Harefield
  2. 2Imperial College London
  3. 3University Hospitals Leuven
  4. 4Hannover Medical School and Imperial College London

Abstract

Purpose There are few non-invasive techniques to predict and monitor patients’ responses to left ventricular assist device (LVAD) therapy. MicroRNAs (miRs) are small noncoding RNAs with intricate roles in cardiovascular disease. They remain stable in the circulation, are readily quantified, and may be useful as new biomarkers. This study sought to identify candidate miR biomarkers for further investigation and to investigate whether these circulating miRs were of myocardial origin.

Methods and Results We studied 55 serial plasma and myocardial samples from 19 patients who underwent HeartMate II LVAD implantation, and used a screening microarray to analyse the change in expression of 1,113 miRs from pre-implant and 6 months follow-up. Twelve miRs showed significant variation and underwent validation, with miR-1202 and miR-483–3p selected for further study. The key findings in the test cohort (n = 8) were: (1) miR-483–3p showed upregulation after 6 months of LVAD therapy in circulating plasma (median fold change 2.32 (1.30–2.44); p = 0.021) and in ventricular myocardium (median fold change 1.799 (0.717–4.719; p = 0.169). This mirrored the reduction in NT-proBNP levels at 6 months (fold change 0.30 (0.08–0.43); p = 0.004; see Figure). (2) Using change in NT-proBNP at 3 months as a marker of clinical response to LVAD therapy, baseline expression of plasma miR-1202 identified good versus poor LVAD responders (absolute expression 1.296 (1.293–1.306) vs. 1.311 (1.310–1.318) A.U.; p = 0.004). (3) Both miR-483–3p and miR-1202 are also enriched in ventricular myocardium suggesting the heart as the possible source of these plasma miRs.

Abstract 178 Figure 1

Box plots showing changes miR-483-3p expression and NT-proBNP levels after 6 months LVAD therapy. There is upregulation of plasma (A) and myocardial (B) miR-483-3p expression, with fold change 2.32 (1.30-2.44;p = 0.021) and 1.799 (0.717-4.719; p = 0.169) respectively. NT-proBNP shows a corresponding significant reduction. Outlier results are shown with -.*Significant to p

Conclusions This is the first report of circulating miR biomarkers in LVAD patients. We demonstrate the feasibility of this approach, and report the potential for miR-483–3p and miR-1202 respectively to monitor and predict response to LVAD therapy. We suggest that changes in miR-483–3p expression could provide a more specific assessment of ventricular function that complements the changes in systemic neuroendocrine milieu recorded by serial measurement of natriuretic peptides, and suggest that miR-1202 could be valuable for judging the likelihood of good response to LVAD support. However, these conclusions are weakened by small sample size and retrospective analysis. We propose further work to study these hypotheses further and elucidate roles for miR-483–3p and miR-1202 in clinical practice and in underlying biological processes.

  • microRNA
  • left ventricular assist device
  • biomarker

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