Autologous CD34-positive stem cells may improve coronary flow reserve and angina symptoms in patients with microvascular dysfunction, proof-of-concept testing suggests.
Evidence of microvascular dysfunction is present in about 50% to 70% of patients with ischemia and no obstructive coronary artery disease (INOCA), a rapidly growing patient population that is disproportionately female and has an elevated risk for major cardiovascular events.
CD34-positive cells are naturally occurring endothelial progenitors that have been shown to stimulate microvascular angiogenesis in ischemic tissue but have not been tested in microvascular dysfunction, coprincipal investigator Timothy D. Henry, MD, The Christ Hospital in Cincinnati, noted.
The single-arm ESCaPE-CMD trial enrolled 20 patients who had microvascular dysfunction defined by a coronary flow reserve (CFR) of 2.5 or less in the left anterior descending (LAD) artery. They were treated at two US centers with 300 × 106 CD34-positive cells administered by intracoronary infusion through a balloon catheter into the proximal LAD.
Patients (85% female; mean age 54.3 years) had angina at least three times per week at baseline and 80% were taking nitrates, 55% beta blockers, 50% calcium-channel blockers, and 25% ranolazine.
Six months after a single injection of CD34 cells, coronary flow reserve increased from a mean of 2.08 to 2.68, which is a “pretty substantial improvement,” Henry said during a virtual presentation at the Society for Cardiovascular Angiography and Interventions (SCAI) 2020 meeting.
Four patients had no improvement in CFR and three saw no reduction in angina. Overall, there was an average reduction of 2.3 angina episodes per week (P = .0036).
“To correlate this, ranolazine was approved with a reduction of less than two episodes a week; so again, this is a pretty substantial improvement in anginal episodes,” Henry observed.
This also tracked with significant improvements in Canadian Cardiovascular Society classification among 15 of the 20 patients and in all five quality-of-life domains of the Seattle Angina Questionnaire.
With regard to serious adverse events, there was one procedure-related focal dissection with stent placement, but no myocardial infarction or repeat revascularization, cell-related adverse events, or mortality, he said.
During a discussion of the study, Henry said these are proof-of-concept results from injections in the LAD, “but certainly it’s possible that repeat injections or injections into more territories might make a bigger difference.”
SCAI President Cindy Grines, MD, Northside Hospital Cardiovascular Institute in Atlanta, asked how many patients presented with the clinical scenario but were excluded because their CFR in the LAD was not below 2.5 and, if so, whether the investigators went to other vessels to find low CFR.
Henry said CFR was used because it is most familiar to interventional cardiologists and typically reported in previous studies but that roughly a third of these patients will have an abnormal CFR, a third will have an abnormal ostium coronary response, and a third will have both.
“We chose coronary flow reserve but it’s a much broader spectrum that that,” he said. “I hope what this does is stimulates an increase in coronary reactivity testing because I think it’s an unmet need and there’s plenty of patients who have chest pain and who have normal coronaries,” he said. “Too often they’re under-recognized and [it’s] underappreciated the actual influence on quality of life.”
During a press briefing, moderator Kirk Garratt, MD, MSc, medical director of the Center for Heart and Vascular Health, Christiana Care Health System in Newark, Delaware, asked whether there is evidence that the infused cells actually remain in the region and that the treatment could be beneficial without direct coronary infusion.
Henry said the CD34-cell therapy data are “very strong” in refractory angina from three placebo-controlled trials, all of which used intramyocardial delivery and demonstrated improved exercise time, reduced angina, and improved mortality.
“We think that with refractory angina, a lot of the benefit is also at the microvasculature,” he said. “If you look at all the preclinical data, the improvement in microvasculature is impressive.”
Based on the present results, a large, phase 2/3 sham-controlled trial is being planned to begin later this year, Henry said.
“I think this really changes overall care for this patient population because we have been able to identify them, they have significant impairment in their quality of life, and this holds out hope that we might actually have a therapy for them that would be effective in improving their quality of life,” he said.
The trial was sponsored by Caladrius Biosciences and the National Heart, Lung, and Blood Institute. Henry disclosed no relevant industry relationships.
Society for Cardiovascular Angiography and Interventions (SCAI) 2020: Abstract 11492. Presented May 14, 2020.