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Intracoronary Cardiosphere-Derived Cells for Heart Regeneration After Myocardial Infarction (CADUCEUS): A Prospective, Randomised Phase 1 Trial
Study Questions:
What is the effect of intracoronary injection of autologous cardiosphere-derived cells (CDCs) on outcomes and left ventricular (LV) function following acute myocardial infarction (MI)?
Methods:
In the prospective, randomized CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction) trial, patients were randomized 2-4 weeks after MI in a 2:1 ratio to receive CDCs or standard care. For the CDC group, autologous cells grown from endomyocardial biopsy specimens were infused into the infarct-related artery 1.5-3 months after MI. Patients were followed for 6 months for cardiac events and myocardial function.
Results:
Twenty-five patients were included in the protocol. Mean baseline LV ejection fraction (EF) was 39 ±12% with scar occupying 24 ± 10% of LV mass. By 6 months, no patients had died, developed cardiac tumors, or major adverse cardiac events in either group. Four patients (24%) in the CDC group had serious adverse events compared with one control (13%; p = 1.00). Compared with controls at 6 months, magnetic resonance imaging analysis of patients treated with CDCs showed reductions in scar mass (p = 0.001), increases in viable heart mass (p = 0.01) and regional contractility (p = 0.02), and regional systolic wall thickening (p = 0.015). However, changes in end-diastolic volume, end-systolic volume, and LVEF did not differ between groups by 6 months.
Conclusions:
The authors concluded that intracoronary infusion of autologous CDCs after MI is safe, warranting phase 2 study. The unprecedented increases noted in viable myocardium, which are consistent with therapeutic regeneration, merit further assessment of clinical outcomes.
Perspective:
Cell-based therapy trials of myocardial regeneration have been largely disappointing to date. Even in trials with positive results, the mechanism(s) by which infused cells confer benefit remains obscure. However, the recent SCIPIO trial demonstrated that intracoronary infusion of autologous c-Kit+ cardiac stem cells (CSCs) was effective in improving LV systolic function and reducing infarct size in patients with heart failure after MI. The current trial supports the idea that CSCs/CDCs might be effective in regenerating viable myocardium following MI. Whether or not these interventions will translate into meaningful clinical benefit will require further study. Assessing safety will require study of many more patients.
Keywords: Myocardial Infarction, Ventricular Dysfunction, Ventricular Function, Left, Stem Cells, Biopsy, Chenodeoxycholic Acid, Magnetic Resonance Imaging, Systole, Heart Diseases, Cicatrix, Regeneration, Heart Failure, Polyesters, United States, Heart Neoplasms
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