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One-Year Follow-Up of Feasibility and Safety of the First U.S., Randomized, Controlled Study Using 3-Dimensional Guided Catheter-Based Delivery of Autologous Skeletal Myoblasts for Ischemic Cardiomyopathy (CAuSMIC Study)

Nabil Dib, MD, MSc, FACC^_*,_*, Jonathan Dinsmore, PhD, Zaki Lababidi, MD, FACC, Bee White, LPN, Susan Moravec, PhD, Ann Campbell, RN, Amy Rosenbaum, BS, Katayoun Seyedmadani, BSE, Wael A. Jaber, MD, Craig S. Rizenhour, RVT, Edward Diethrich, MD

^_* University of California, San Diego, San Diego, California
Mytogen, Charlestown, Massachusetts
Arizona Heart Institute, Phoenix, Arizona
Cleveland Clinic, Cleveland, Ohio

^_* Reprint requests and correspondence: Dr. Nabil Dib, Director, Clinical Cardiovascular Cell Therapy, Associate Professor of Medicine, University of California, San Diego, Mail code 0986, 9350 Campus Point Drive, Suite 1D, La Jolla, California 92037-1300 (Email: ndib{at}cardiostem.com).

Objectives: The aim of this study was to test safety and feasibility of myoblast transplantation with the Biosense-NOGA (Diamond Bar, California) 3-dimensional-guided endomyocardial delivery system.

Background: Previous Phase-1 trials showed feasibility of epicardial injection of myoblasts. However, catheter-based delivery has several advantages: it can be applied on high-risk patients, the procedure can be repeated, and it is associated with less morbidity and mortality.

Methods: Twenty-three subjects, with previous myocardial infarction and heart failure, New York Heart Association (NYHA) functional class II to IV, were enrolled, 11 control and 12 treatment subjects. To assess safety, physical exam, electrocardiogram, continuous rhythm monitoring, quality of life assessments, and heart function were evaluated at baseline and follow-up until 1 year.

Results: There was favorable safety: no difference between groups in arrhythmias, and no deaths. Treated subjects showed sustained improvements in NYHA and Minnesota Living with Heart Failure Questionnaire (MLHFQ) compared with control subjects (NYHA, –1.0 point in treatment vs. +0.3 point in control group, p < 0.0004; MLHFQ, –14 point in treatment vs. +1 point in the control group, p = 0.004). Blinded core laboratory echocardiography evaluations showed sustained reductions in the treatment versus control in end diastolic diameter (–0.03 cm vs. +0.05 cm, p = 0.07) and end systolic diameter (–0.05 cm vs. +0.1 cm, p = 0.07). Finally, NOGA voltage mapping demonstrated improved voltage measurements (+1.0 mV, p = 0.008).

Conclusions: This trial of myoblast transplantation via catheter into heart failure patients demonstrated safety and feasibility. Treated patients showed improvement in NYHA, MLHFQ, ventricular viability, and evidence of reverse ventricular remodeling. These data demonstrate positive safety outcomes and warrant initiation of larger phase 2, double-blind, placebo-controlled clinical trials.

Key Words: catheter • heart failure • muscle cell • myocardial infarction • transplant

Abbreviations and Acronyms   AMT = autologous myoblast transplantation   CRT = cardiac resynchronization therapy   FDA = Food and Drug Administration   ICD = Implantable cardioverter-defibrillator   ILR = implantable loop recorder   MI = myocardial infarction   MLHFQ = Minnesota Living with Heart Failure Questionnaire   MMT = maximal medical therapy   NYHA = New York Heart Association   SAE = serious adverse event   SPECT = single-photon emission computed tomography   3D = three-dimensional