Multi-modality imaging in the CIRCULATE-AMI pilot study cohort: a framework for an imaging-based randomized controlled trial of Wharton jelly mesenchymal stem cell use to stimulate myocardial repair/regeneration

Myocardial ischaemic loss in acute myocardial infarction (AMI) remains the most significant contributor to chronic heart failure and sudden cardiac death [1]. Despite the progress in pharmacological and invasive management of AMI, the prevalence of ischaemic heart failure will grow substantially in the next decades [2]. Novel therapeutic approaches, including stimulation of cardiac repair and regeneration, are needed [2, 3]. Evidence in animal models [4] and humans [5–7] shows a modifiable balance between the irreversible and reversible myocardial injury in acute ischaemia (depending on factors such as the timing of revascularization and associated therapy), presenting a mechanistic room for novel therapeutic approaches.
In our recent pilot study, transcoronary administration of 30 × 106 standardized, multipotent Wharton jelly mesenchymal stem cells (WJMSC) 5 to 7 days after AMI was safe [5], and it was associated with minimal left ventricular remodelling and improved haemodynamics throughout 3 years of follow-up [8], providing the basis for a larger-scale clinical trial. Here, we present multi-modality imaging in the CIRCULATE-AMI pilot study cohort as a framework for an imaging endpoint-powered, randomized controlled trial of WJMSC use to stimulate myocardial repair/regeneration.
A 57-year-old man with hypertension and hypercholesterolaemia was admitted to the Jagiellonian University Department of Cardiac and Vascular Diseases, John Paul II Hospital in Krakow, Poland due to an acute anterior ST-segment elevation AMI as the first manifestation of coronary artery disease. The patient reported acute chest pain and dyspnoea that lasted 4 h before the first medical contact. Urgent coronary angiography showed an acute occlusion in the proximal segment of the left anterior descending artery (LAD) and a severe stenosis of the marginal branch (Figure 1 I A). Primary percutaneous coronary intervention (PCI) with stent implantation (XienceTM 3.5 mm, Abbott, USA) was performed, followed by a second stage PCI of the marginal branch (XienceTM 2.75 mm, Abbott, USA) 3 days later, resulting in complete coronary revascularization (Figure 1 I B). The peak hs-troponin T level was 4.28 ng/ml (ULN < 0.014 ng/ml), and CK-MB activity peaked at 272 U/L (ULN < 24 U/l), consistent with a major myocardial tissue loss. Maximized guideline-indicated pharmacotherapy was introduced for acute-phase AMI and post-AMI left ventricular (LV) dysfunction prevention.
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