麻豆传媒

A percutaneous dose of CD34-positive cells appeared to ease ischemia and improve symptoms in coronary microvascular dysfunction, the ESCaPE-CMD pilot study showed.

Microvascular function as measured by coronary flow reserve (CFR) improved from a mean 2.08 at baseline to 2.68 at 6 months (P=0.0045), a "very remarkable improvement," Timothy Henry, MD, of The Christ Hospital in Cincinnati,

Angina class also improved in the 6-month, single-arm, 20-patient study. The number of patients in New York Heart Association class IV went from 10 to four; in class III from five to one; in class II from four to six; and in class I from one to eight.

Quality of life as measured on the Seattle Angina Questionnaire scale improved across the board, with significant gains in physical limitation, angina stability, angina frequency, treatment satisfaction, and disease perception.

"This study showed an interesting signal of benefit. I sure hope we can finally fulfill the promise of cell therapy," commented Deepak Bhatt, MD, MPH, of Brigham and Women's Hospital in Boston. "Of course, we will have to wait and see what larger, randomized trials show."

"This is a group of patients for whom there has not been a real successful therapy in the past," commented Hadley Wilson, MD, of the Sanger Heart and Vascular Institute in Charlotte, North Carolina, and an American College of Cardiology spokesperson. "Here's a really novel therapy that might be useful in this patient category of several million patients each year that really don't have good treatments right now and continue to suffer with anginal chest pain."

CD34-positive cells are naturally-occurring endothelial progenitors that have been shown to stimulate microvascular angiogenesis in ischemic tissue, Henry noted.

CD34-positive cell treatments have been tried in phase II studies in refractory disabling angina patients for whom there are no surgical or interventional options as well as in other advanced cardiovascular disease, such as critical limb ischemia and dilated cardiomyopathy.

Henry called findings in those settings consistent with therapeutic effects such as improved left ventricular function and reduced angina, even reduced mortality and amputation.

However, Wilson called the results . "That's why we don't see that as a major therapy available at multiple centers around the country and the world. I wouldn't say that means it's not effective but we have not been able to, at this point, solidly show the best patient categories where it's helpful and to be able to show it is significantly helpful to justify the procedure and expense and the patient risk as well."

No cell-related adverse events were seen among the 20 patients treated with 300 million CD34-positive cells administered by intracoronary infusion through radial artery access at two U.S. centers in the open-label study, although there was one focal dissection. All patients had coronary microvascular dysfunction defined by a CFR at or below the threshold of 2.5.

The procedure involved granulocyte-colony stimulating factor for 5 days, followed by apheresis to collect a patient's own CD34-positive cells from peripheral blood, which are then delivered 48 hours later with a balloon catheter into the proximal left anterior descending coronary artery.

Based on the findings, a randomized, blinded phase II/III clinical trial is being planned to start later in 2020, Henry said.

A sham treatment arm would be nice, although risks to the placebo group from the percutaneous intervention would have to be weighed, Wilson noted.

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