Author + information
- Received December 11, 2018
- Revision received February 26, 2019
- Accepted March 7, 2019
- Published online November 4, 2019.
- Gavin A. Lewis, MBChBa,b,
- Susanna Dodd, PhDc,
- Josephine H. Naish, PhDa,
- Joseph B. Selvanayagam, DPhild,e,
- Marc R. Dweck, PhDf and
- Christopher A. Miller, PhDa,b,g,∗ ()
- aDivision of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom
- bManchester University NHS Foundation Trust, Wythenshawe, Manchester, United Kingdom
- cDepartment of Biostatistics, University of Liverpool, Liverpool, United Kingdom
- dFlinders University of South Australia, Adelaide, Australia
- eSouth Australian Health and Medical Research Institute, Adelaide, Australia
- fCentre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, United Kingdom
- gWellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biology, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom
- ↵∗Address for correspondence:
Dr. Christopher A. Miller, Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom.
• The myocardial interstitium is a potential therapeutic target and a potential risk stratifier that can guide interventions.
• Clinical trials focusing on the myocardial interstitium are required to establish causality and improve patient outcomes.
• CMR provides quantitative assessment of the myocardial interstitium and many other features of cardiovascular structure and function and thus can be used to stratify recruitment and to evaluate efficacy and mechanism.
The myocardial interstitium has emerged as a potential therapeutic target and as a biological entity to improve risk stratification and better guide existing interventions. Clinical trials focusing on the myocardial interstitium are required to establish causality and improve patient outcomes. This review will discuss issues around clinical trials targeting the myocardial interstitium, including antifibrotic therapies, efficacy outcome measurements, mechanistic outcome measurements and mediation analysis, sample size, trial duration, considerations for multicenter trials, stratifying trial recruitment according to the interstitium, and approaches to enrich recruitment, using examples of ongoing clinical trials.
Dr. Miller is funded by a Clinician Scientist Award (CS-2015-15-003) from the National Institute for Health Research. Dr. Dweck is supported by the BHF (FS/14/78/31020) and is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015 (15/JTA). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received December 11, 2018.
- Revision received February 26, 2019.
- Accepted March 7, 2019.
- 2019 American College of Cardiology Foundation
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