Author + information
- Received May 1, 2013
- Revision received July 21, 2013
- Accepted August 19, 2013
- Published online January 21, 2014.
- Konstantinos Malliaras, MD∗,
- Raj R. Makkar, MD∗,
- Rachel R. Smith, PhD∗,
- Ke Cheng, PhD∗,
- Edwin Wu, MD†,
- Robert O. Bonow, MD†,
- Linda Marbán, PhD∗,
- Adam Mendizabal, MS‡,
- Eugenio Cingolani, MD∗,
- Peter V. Johnston, MD§,
- Gary Gerstenblith, MD§,
- Karl H. Schuleri, MD§,
- Albert C. Lardo, PhD§,‖ and
- Eduardo Marbán, MD, PhD∗∗ ()
- ∗Cedars-Sinai Heart Institute, Los Angeles, California
- †Division of Cardiology, Department of Medicine, Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, Illinois
- ‡EMMES Corporation, Rockville, Maryland
- §Division of Cardiology, Department of Medicine, The Johns Hopkins University, Baltimore, Maryland
- ‖Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland
- ↵∗Reprint requests and correspondence:
Dr. Eduardo Marbán, Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, California 90048.
Objectives This study sought to report full 1-year results, detailed magnetic resonance imaging analysis, and determinants of efficacy in the prospective, randomized, controlled CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction) trial.
Background Cardiosphere-derived cells (CDCs) exerted regenerative effects at 6 months in the CADUCEUS trial. Complete results at the final 1-year endpoint are unknown.
Methods Autologous CDCs (12.5 to 25 × 106) grown from endomyocardial biopsy specimens were infused via the intracoronary route in 17 patients with left ventricular dysfunction 1.5 to 3 months after myocardial infarction (MI) (plus 1 infused off-protocol 14 months post-MI). Eight patients were followed as routine-care control patients.
Results In 13.4 months of follow-up, safety endpoints were equivalent between groups. At 1 year, magnetic resonance imaging revealed that CDC-treated patients had smaller scar size compared with control patients. Scar mass decreased and viable mass increased in CDC-treated patients but not in control patients. The single patient infused 14 months post-MI responded similarly. CDC therapy led to improved regional function of infarcted segments compared with control patients. Scar shrinkage correlated with an increase in viability and with improvement in regional function. Scar reduction correlated with baseline scar size but not with a history of temporally remote MI or time from MI to infusion. The changes in left ventricular ejection fraction in CDC-treated subjects were consistent with the natural relationship between scar size and ejection fraction post-MI.
Conclusions Intracoronary administration of autologous CDCs did not raise significant safety concerns. Preliminary indications of bioactivity include decreased scar size, increased viable myocardium, and improved regional function of infarcted myocardium at 1 year post-treatment. These results, which are consistent with therapeutic regeneration, merit further investigation in future trials. (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction [CADUCEUS]; NCT00893360)
Funded by U.S. National Heart, Lung, and Blood Institute (U54-HL081028) and Cedars-Sinai Board of Governors Heart Stem Cell Center. Drs. Eduardo Marbán and Linda Marbán are founders and equity holders in Capricor. Dr. Eduardo Marbán is a scientific advisor for Capricor. Drs. Smith and Linda Marbán are employed by Capricor as well as employed part time by the Cedars-Sinai Medical Center. Dr. Malliaras receives consulting fees from Capricor. No one associated with Capricor participated in the recruitment and consent of subjects, in the performance of investigational procedures or in the assessment of adverse events. Capricor provided no funding for this study, nor did the company have approval rights over publications or presentations. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received May 1, 2013.
- Revision received July 21, 2013.
- Accepted August 19, 2013.
- American College of Cardiology Foundation