Original article
Cardiovascular
Myocardial Assistance by Grafting a New Bioartificial Upgraded Myocardium (MAGNUM Trial): Clinical Feasibility Study

https://doi.org/10.1016/j.athoracsur.2007.10.052Get rights and content

Background

Cell transplantation for the regeneration of ischemic myocardium is limited by poor graft viability and low cell retention. In ischemic cardiomyopathy, the extracellular matrix is deeply altered; therefore, it could be important to associate a procedure aiming at regenerating myocardial cells and restoring the extracellular matrix function. We evaluated the feasibility and safety of intrainfarct cell therapy associated with a cell-seeded collagen scaffold grafted onto infarcted ventricles.

Methods

In 20 consecutive patients presenting with left ventricular postischemic myocardial scars and indication for coronary artery bypass graft surgery, bone marrow cells were implanted during surgery. In the last 10 patients, we added a collagen matrix seeded with bone marrow cells, placed onto the scar.

Results

There was no mortality and any related adverse events (follow-up 10 ± 3.5 months). New York Heart Association functional class improved in both groups from 2.3 ± 0.5 to 1.3 ± 0.5 (matrix, p = 0.0002) versus 2.4 ± 0.5 to 1.5 ± 0.5 (no matrix, p = 0.001). Left ventricular end-diastolic volume evolved from 142.4 ± 24.5 mL to 112.9 ± 27.3 mL (matrix, p = 0.02) versus 138.9 ± 36.1 mL to 148.7 ± 41 mL (no matrix, p = 0.57), left ventricular filling deceleration time improved significantly in the matrix group from 162 ± 7 ms to 198 ± 9 ms (p = 0.01) versus the no-matrix group (from 159 ± 5 ms to 167 ± 8 ms, p = 0.07). Scar area thickness progressed from 6 ± 1.4 to 9 mm ± 1.1 mm (matrix, p = 0.005) versus 5 ± 1.5 mm to 6 ± 0.8 mm (no matrix, p = 0.09). Ejection fraction improved in both groups, from 25.3% ± 7.3% to 32% ± 5.4% (matrix, p = 0.03) versus 27.2% ± 6.9% to 34.6% ± 7.3% (no matrix, p = 0.031).

Conclusions

This tissue-engineered approach is feasible and safe and appears to improve the efficiency of cellular cardiomyoplasty. The cell-seeded collagen matrix increases the thickness of the infarct scar with viable tissue and helps to normalize cardiac wall stress in injured regions, thus limiting ventricular remodeling and improving diastolic function.

Section snippets

Study Design

The study was a nonrandomized, controlled phase I clinical trial. Eligibility for inclusion was based on (1) systolic left ventricular (LV) dysfunction, as reflected by an echocardiographic LV ejection fraction (LVEF) of 35% or less; (2) a history of myocardial infarction with a residual akinetic and nonviable scar; and (3) an indication for concomitant single off-pump coronary artery bypass graft surgery (OP-CABG). These patients were free of angina symptoms, there was no indication of

Results

In this phase I nonrandomized trial, after consideration of inclusion and exclusion criteria, we enrolled 20 consecutive patients (90% male) presenting with chronic ischemic heart disease. The age of the infarcts was 8.2 ± 3.5 months (range, 3 to 25). The baseline characteristics were comparable in both groups (Table 1).

Bone marrow was aspirated from the posterior iliac crest during a brief general anesthesia with midazolam and etomidate; no bleeding complications at the harvest site were

Comment

This study attempts to demonstrate the feasibility and safety of simultaneous intramyocardial injection of BMC and fixation of a BMC-seeded matrix onto the epicardium of infarcted ventricles. The cardiac connective tissue is mainly composed of collagen, with smaller amounts of elastin, laminin, and fibronectin. There are two main types of collagen fibers in the normal adult heart, types I and III, produced by fibroblasts and myofibroblasts. Experimental observations have shown that in the

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