Clinical Research
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)

https://doi.org/10.1016/j.jcin.2008.11.003Get rights and content
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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

Cited by (0)

This study was sponsored by and funded by Mytogen, Inc., Charlestown, Massachusetts. Injection and mapping catheters were donated by Cordis/Biodelivery Systems, Inc., Diamond Bar, California.