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IV stem cell treatment safe, effective in patients with nonischemic HF
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A single administration of IV allogeneic mesenchymal stem cells was safe and improved certain outcomes in patients with nonischemic HF with reduced ejection fraction, according to the results of a phase 2a study presented at the European Society of Cardiology Congress.
Previous studies of stem cell therapy for patients with HF “were largely suggestive of potential benefits,” but the therapies were injected into the patient’s coronary arteries or myocardium, so the researchers wanted to investigate whether an IV therapy might also work, presenter Javed Butler, MD, MPH, MBA, FACC, FAHA, FESC, said in an interview with Cardiology Today.
“If repeated injections are needed, then the intramyocardium or the intracoronary route becomes more of a challenge,” said Butler, chief of cardiology and professor of medicine, Stony Brook University, and co-director, Stony Brook University Heart Institute, New York. “So the reason to do this study was to see whether IV therapy is safe, to confirm it does not have any untoward side effects on a systemic level, and whether there is any suggestion that it can improve patients’ outcomes.”
Javed Butler
Butler and colleagues randomly assigned 23 patients (mean age, 47 years; 59% men) to IV allogeneic mesenchymal stem cells (CardioCell LLC) or placebo injection; at 90 days, all patients were crossed over to the other therapy. All patients had nonischemic cardiomyopathy with EF of 40% or less, NYHA class II or III and stability for at least 3 months on evidence-based medical therapy. One patient did not undergo infusion, so the analysis consisted of 22 patients.
The 90-day safety endpoints were procedural complications, laboratory metrics, pulmonary function, arrhythmia and clinical events (all-cause mortality and hospitalization.) The 90-day efficacy endpoints were left ventricular EF and volumes, Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, 6-minute walk distance, NYHA functional class and inflammatory and immune markers.
Butler, a member of the Cardiology Today Editorial Board, said there were no deaths or serious adverse events in either group, there was one cell-related adverse event related to the infusion in the stem cell group, there was one hospitalization in the placebo group, and overall adverse events were similar in both groups (placebo, 34; stem cell, 35).
There were no safety signals related to organ function, kidney function, pulmonary function, liver function and arrhythmias, he told Cardiology Today.
Between-group difference in overall 6-minute walk distance favored the stem cell group (difference, 36.47 m; 95% CI, 5.98-66.97), as did the between-group percent change from baseline difference in change in 6-minute walk distance (P = .03), Butler said.
KCCQ clinical summary score favored the stem cell group (difference, 5.22; 95% CI, 0.7-9.74), and there was a trend toward better KCCQ functional status score in the stem cell group (difference, 5.65; 95% CI, –0.11 to 11.41), according to Butler.
There was no significant change in measures of LV function or LV volume, and no difference between the groups in 90-day improvement in NYHA functional class (P = .33), Butler said.
“We found some suggestion of improvement in cardiac volumes [from] the data for the first 3 months,” he told Cardiology Today. “However, when we combined the entirety of data, that signal was not there anymore.”
However, the stem cell group showed a greater decrease in natural killer cells, a measure that was associated with improvement in LV function (R2 = 0.31; P = .01), he said.
“This was an early experience with 22 patients, but the findings provide enough signals that we need to move it to a more definitive and larger trial,” Butler told Cardiology Today. “There is a good chance that this therapy in an appropriately powered phase 3 trial may prove a clinical improvement.” – by Erik Swain
Reference:
Butler J, et al. Hot Line: Heart failure and innovative approaches. Presented at: European Society of Cardiology Congress; Aug. 27-31, 2016; Rome.
Disclosure: The study was funded by CardioCell LLC. Butler reports consulting for CardioCell.
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Randall C. Starling, MD, MPH, FACC, FESC
This was a small safety study of IV administration of mesenchymal cells versus placebo with crossover. There were no safety issues identified. The stem cell therapy had no impact on LV function, but those who received it showed improvement in 6-minute walk distance. Because of the size, the data must be considered exploratory.
While the findings have the potential to impact clinical practice, we need to understand if there is a dose response and whether an adequate number of cells have been injected.
I would not begin trials of this therapy in ischemic cardiomyopathy and until more convincing outcomes data are provided in nonischemic cardiomyopathy. I would advise generation of dose-response data, as no safety issues have been identified.
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