ECENT CLINICAL TRIALS SUGgest that bone marrowderived cell preparations, including mononuclear cells 1-5 and mesenchymal stem cells (MSCs), [6][7][8] can ameliorate left ventricular (LV) remodeling in patients with acute 1,3,8 and chronic 2,4,6,9 ischemic cardiomyopathy (ICM). An important issue in this new field is whether a certain cellular constituent Author Affiliations are listed at the end of this article.

Rationale Transcatheter, intramyocardial injections of bone marrow derived cell therapy produces reverse remodeling in large animal models of ischemic cardiomyopathy. Objective We used cardiac magnetic resonance imaging (CMR) in patients with LV dysfunction related to remote myocardial infarction (MI) to test the hypothesis that bone marrow progenitor cell injection cause functional recovery of scarred myocardium and reverse remodeling. Methods and Results Eight patients (age 57.2±13.3) received transendocardial, intramyocardial injection of autologous bone marrow progenitor cells (mononuclear or mesenchymal stem cells) in LV scar and border zone. All patients tolerated the procedure with no serious adverse events. CMR at 1-year demonstrated a decrease in end-diastolic volume (208.7±20.4 vs. 167.4±7.32mL; p=0.03), a trend towards decreased end-systolic volume (142.4±16.5 vs. 107.6±7.4mL; p=0.06), decreased infarct size (p<0.05), and improved regional LV function by peak Ecc in the treated infarct zone (-8.1±1.0 vs. -11.4±1.3; p=0.04). Improvements in regional function were evident at 3 months, while the changes in chamber dimensions were not significant until 6 months. Improved regional function in the infarct zone strongly correlated with reduction of EDV (r2=0.69, p=0.04) and ESV (r2=0.83, p=0.01). Conclusions These data suggest that transcatheter, intramyocardial injections of autologous bone marrow progenitor cells improve regional contractility of a chronic myocardial scar and these changes predict subsequent reverse remodeling. The findings support the potential clinical benefits of this new treatment strategy and ongoing randomized clinical trials.

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Rationale Transendocardial Stem Cell Injection (TESI) with mesenchymal stem cells improves remodeling in chronic ischemic cardiomyopathy, but the impact of the injection site remains unknown. Objective To address whether TESI exerts its effects at the site of injection only or also in remote areas, we hypothesized that segmental myocardial scar and segmental ejection fraction improve to a greater extent in injected than in non-injected segments. Methods and Results Biplane ventriculographic and endocardial tracings were recorded. TESI was guided to 10 sites in infarct-border zones. Sites were mapped according to the 17-myocardial segment model. As a result, 510 segments were analyzed in 30 patients before and 13-months after TESI. Segmental early enhancement defect (SEED, a measure of scar size) was reduced by TESI in both injected (−43.7±4.4%, n=95, p<0.01) and non-injected segments (−25.1±7.8%, n=148, p<0.001; between group comparison p<0.05). Conversely, segmental ejection fraction (SEF, a measure of contractility) improved in injected scar segments (19.9±3.3 to 26.3±3.5%, p=0.003) but not in non-injected scar segments (21.3±2.6 to 23.5±3.2%, p=0.20, between group comparison p<0.05). In the subgroup of scar segments with baseline SEF<20%, the SEF improvement was even greater in injected segments (12.1±1.2% to 19.9±2.7%, n=18, p=0.003) vs. non-injected segments (13.3±1.3% to 16.1±2.1%, n=15, p=0.05; between group comparison p<0.05). Conclusions These findings illustrate a dichotomy in regional responses to TESI. Although scar reduction was evident at the site of TESI and remotely, ventricular functional responses occurred preferentially at the sites of TESI. Furthermore, improvement was greatest when segmental left ventricular dysfunction was severe.

Objective While patients with cardiac implantable electronic devices could benefit from magnetic resonance (MR) imaging, the presence of such devices has been designated as an absolute contraindication to MR. Although scanning algorithms are proposed for cardiac implantable electronic devices, their safety remains uncertain. To address this issue, the safety of serial cardiac MR scans was evaluated in patients with implantable cardioverter defibrillators (ICDs). Methods Three serial cardiac MR scans were prospectively performed at 1.5 T on 10 patients (9 men) of median age 56 years (range 51–68) with ICDs. ICD interrogation was performed before and after the MR scan and at a follow-up of median 370 days (range 274–723). Image quality was also assessed. Results In all patients MR scanning occurred without complications. There were no differences between preand post-MR pacing capture threshold, pacing lead or high voltage lead impedance, or battery voltage values. During follow-up there were no occurrences of ICD dysfunction. Although most patients had image artifacts, the studies were generally diagnostic regarding left ventricular function and wall motion. Delayed enhancement imaging was of good quality for inferior wall and inferolateral infarcts, but ICD artifacts often affected the imaging of anterior wall infarcts. Conclusion Serial MR scans at 1.5 T in patients with ICDs, when carefully performed in a monitored setting, have no adverse effects on either patient or device. When required, single or multiple MR scans at 1.5 T may therefore be considered for clinical diagnostic purposes in these patients.