Adventitial delivery of an allogeneic bone marrow-derived adherent stem cell in acute myocardial infarction: phase I clinical study.

RATIONALE: MultiStem is an allogeneic bone marrow-derived adherent adult stem cell product that has shown efficacy in preclinical models of acute myocardial infarction (AMI). In this phase I clinical trial in patients with first ST-elevation-myocardial infarction (STEMI), we combine first-in-man delivery of MultiStem with a first-in-coronary adventitial delivery system to determine the effects of this system on left ventricular function at 4 months after AMI. OBJECTIVE: Test the effects of adventitial delivery of Multistem in the peri-infarct period in patients with first STEMI. METHODS AND RESULTS: This study was a phase I, open-label, dose-escalating registry control group study. Nineteen patients received MultiStem (20 million, n=6; 50 million, n=7; or 100 million, n=6) and 6 subjects were assigned to the registry control group. Two to 5 days after AMI, we delivered MultiStem to the adventitia of the infarct-related vessel in patients with first-time STEMI. All patients underwent primary percutaneous coronary intervention with resulting Thrombolysis In Myocardial Infarction grade 3 flow and with ejection fraction (EF) ≤45% as determined by echocardiogram or left ventriculogram within 12 hours of primary percutaneous coronary intervention. The cell product (20 million, 50 million, or 100 million) was well tolerated, and no serious adverse events were deemed related to MultiStem. There was no increase in creatine kinase-MB or troponin associated with the adventitial delivery of MultiStem. In patients with EF determined to be ≤45% by a core laboratory within 24 hours before the MultiStem injection, we observed a 0.9 (n=4), 3.9 (n=4), 13.5 (n=5), and 10.9 (n=2) percent absolute increases in EF in the registry, 20 million, 50 million, and 100 million dose groups, respectively. The increases in EF in the 50 million and 100 million groups were accompanied by 25.4 and 8.4 mL increases in left ventricular stroke volume. CONCLUSIONS: In this study, the delivery of MultiStem to the myocardium in patients with recent STEMI was well tolerated and safe. In patients who exhibited significant myocardial damage, the delivery of ≥50 million MultiStem resulted in improved EF and stroke volume 4 months later. These findings support further development of MultiStem in patients with AMI and they validate the potential of a system for delivery of adult stem cells at any time after primary percutaneous coronary intervention.

An integer based risk score for predicting 30-day major adverse cardiac or cerebrovascular events after percutaneous coronary intervention with drug-eluting stents: results from a large prospective multicentre registry, the STENT Group.

AIMS: Previous risk models predicting in-hospital major adverse cardiac or cerebrovascular events (MACCE) after percutaneous coronary interventions (PCI) may underestimate actual short-term post-procedure complications due to the trend toward early discharge of patients. METHODS AND RESULTS: Using a subset (N=10,679) from the STENT Group registry, a logistic regression model was developed to predict 30-day MACCE which includes death, myocardial infarction, target vessel revascularisation and stroke. An integer-based risk score was created from the model and validated in another subset (N=3,099). In the study subset, there was significant difference between in-hospital and 30-day MACCE N=443 (2.0%) vs. 131 (4.2), p<0.01, respectively. A final risk model included nine variables; absence of pre-procedural statin (odds ratio=1.3, 95% confidence interval=1.0-1.5), haemoglobin level (0.9/1 gm increase, 0.8-0.9), cardiogenic shock (4.4, 3.1-6.3), acute congestive heart failure (1.6, 1.2-2.3), left main disease (2.2, 1.3-3.7), left anterior descending artery lesion (1.3, 1.0-1.5), ostial lesion (1.6, 1.2-2.1), coronary thrombosis (2.0, 1.4-2.9) and ACC/AHA type C lesion (1.3, 1.1-1.6). The c-statistics of the final model were 0.653 and 0.692 in the study and validation subset, respectively. CONCLUSIONS: In this large real world registry of DES, in-hospital MACCE did not represent short-term post-procedure prognosis. The risk model consisting of nine variables predicted 30-day MACCE with modest discriminatory value.