ESCaPE CMD – Autologous CD34 Cell Transfer for the Management of Microvascular Angina

Trial Reference
ESCaPE-CMD, AHA 2019 Scientific Sessions
Expert Comment

JC Kaski, DSc, MD, FESC, FRCP, FACC, FAHA, FRSM – London, UK

Background

Myocardial ischaemia can be triggered by different mechanisms, including obstructive coronary artery disease, coronary artery spasm and coronary microvascular dysfunction. Both men and women can develop all these three forms of angina pectoris. Women not only can suffer from ischaemic heart disease, but symptoms may present differently than those in men. Moreover, women may be more susceptible to developing certain types of ischaemic heart disease such as INOCA (myocardial ischaemia without obstructive coronary artery disease (CAD), takotsubo syndrome, some forms of myocardial infarction without obstructive CAD (MINOCA) and some forms of coronary microvascular dysfunction (CMD). CMD can result from functional and/or structural mechanisms taking place in the microcirculation. Capillary rarefaction features prominently among the latter and particularly associated with hypertension, and left ventricular hypertrophy caused by different conditions. Both diagnosis and treatment of the different types of ischaemic heart disease associated with CMD are challenging at present. CMD often presents itself with typical symptoms similar to those that occur in patients with atherosclerotic narrowings affecting the large coronary arteries. Treatment of the condition is also challenging at present as specific pharmacological agents used are mainly those suitable for the management of obstructive CAD.

ESCaPE-CMD trial

The results of a recent small (n=20 patients) proof of concept trial, ESCaPE-CMD, looking at the effects CLBS16, a CD34 cell that is associated with pre-programmed microvessel repair after different types of vascular cell injury were presented at the recent AHA 2019 SCIENTIFIC SESSIONS. The authors, from Cedars-Sinai (Los Angeles), Mayo Clinic (Rochester, Minnessotta) and The Christ Hospital (Cincinnati), aimed to ascertain whether taking advantage of the body’s own ability to restore damaged structures after ischemic injuries could be used to treat CMD. They speculated that the patient’s own CD34+ cells administered locally can restore microcirculation function by promoting the growth of new capillaries. The trial was designed to evaluate the effect of CLBS16 on CMD symptoms i.e. angina frequency, Canadian Cardiovascular Society (CCS) angina classification and adverse events as well as assessing changes of coronary flow reserve (CFR) at six months of follow up after treatment administration.

The investigators observed that CMD patients who received CD34+ cell therapy showed an increase in the functional capacity of the coronary microvessels, as assessed by measurements of coronary flow reserve, which was also associated with symptomatic improvement in these individuals. Thus – for the first time in the clinical arena- cell-based tissue repair and regeneration has been demonstrated in patients with CMD. The trial showed statistically significant (p=0.0087) increases in CFR after one intracoronary administration of CD34+ cells as well as significant reductions in angina frequency and improvements in CCS class. Importantly, no cell-related adverse events were reported.

This very small proof of concept study is of importance and research in this field should continue as many patients with structural abnormalities of the coronary microvessels may benefit from this treatment modality in the future.

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