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Background: Stem cell therapy is investigated as a treatment option for patients with ischemic heart disease. In this study, long-term safety and efficacy of autologous intra-myocardial injections of adipose-derived stromal cells (ASCs) was studied in patients with refractory angina., Methods: Sixty patients with coronary artery stenosis and preserved left ventricular ejection fraction were 2:1 randomised to intramyocardial injections of ASCs or saline and followed for 3 years., Results: For patients in the ASC group, the bicycle exercise time and the exercise performance in watt were un-changed (383 ± 30 s to 370 ± 44 s, P = 0.052 and 81 ± 6 to 78 ± 10, P = 0.123, respectively), but the performance in METs was reduced significantly (4.2 ± 0.3 to 4.0 ± 0.4, P = 0.027) during the follow-up period. However, in the same period, there was in the placebo group a significant decline in bicycle exercise time (437 ± 53 s to 383 ± 58 s, P = 0.001), the exercise performance measured in watt (87 ± 12 W to 80 ± 12 W, P = 0.019) and in METs (4.5 ± 0.4 to 4.1 ± 0.4, P = 0.002). Moreover, angina measured as CCS class was significantly reduced in the ASC group but not in the placebo group (2.5 ± 0.9 to 1.8 ± 1.2, P = 0.002 and 2.5 ± 0.8 to 2.1 ± 1.3, P = 0.186, respectively). However, no significant change was observed between the two groups., Conclusions: Patients receiving ASCs had improved cardiac symptoms and unchanged exercise capacity, in opposition to deterioration in the placebo group. Trial registration ClinicalTrials.gov Identifier: NCT01449032. Registered 7 October 2011-Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT01449032?term=jens+kastrup&rank=7.

Background: The study assessed long-term safety and efficacy of intramyocardial injection of autologous bone-marrow derived mesenchymal stromal cells (BMMSCs) in patients with severe stable coronary artery disease (CAD) and refractory angina., Methods: Thirty-one patients with severe stable CAD and refractory angina were included. Patients had reversible myocardial ischemia and no further revascularization options. Autologous BMMSCs were isolated, culture expanded and stimulated with vascular endothelial growth-factor to facilitate endothelial differentiation. BMMSCs were injected into an ischemic, viable region of the myocardium. Patients were followed for 3 years., Results: We found significant clinical improvements in exercise time (p=0.0016), angina class (CCS) (p<0.0001), weekly number of angina attacks (p<0.0001) and use of nitroglycerine from (p=0.0017). In the Seattle Angina Questionnaire there were significant improvements in physical limitation score, angina stability score, angina frequency score and quality of life score (all p<0.0001). When comparing all hospital admissions from 3 years before to 3 years after treatment, we observed highly reduced admission rates for stable angina (p<0.0001), revascularization (p=0.003) and overall cardiovascular disease (p<0.0001). No early or late side-effects of the treatment were observed., Conclusions: The final 3-year follow-up data after intramyocardial injection of autologous BMMSCs, in patients with severe CAD and refractory angina, demonstrated sustained clinical effects, reduced hospital admissions for cardiovascular disease and excellent long-term safety. The results indicate that autotransplantation of BMMSCs to the heart does not only improve symptoms but also slows down disease progression., (© 2013.)

In patients with stable coronary artery disease (CAD) and refractory angina, we performed direct intramyocardial injections of autologous mesenchymal stromal cells (MSC) and followed the safety and efficacy of the treatment for 12 months. A total of 31 patients with stable CAD, moderate to severe angina, normal left ventricular ejection fraction, and no further revascularization options were included. Bone marrow MSCs were isolated and culture expanded for 6-8 weeks and then stimulated with vascular endothelial growth factor (VEGF) for 1 week. The 12-month follow-up demonstrated that it was safe to culture expand MSCs and use the cells for clinical treatment. The patients' maximal metabolic equivalent (MET) during exercise increased from 4.23 MET at baseline to 4.72 MET at 12-month follow-up (p < 0.001), Canadian Cardiovascular Society Class (CCS) was reduced from 3.0 to 0.8 (p < 0.001), angina attacks per week from 13.8 to 3.2 (p < 0.001), and nitroglycerin consumption from 10.7 to 3.4 per week (p < 0.001). In addition, Seattle Angina Questionnaire (SAQ) evaluations demonstrated highly significant improvements in physical limitation, angina stability, angina frequency, and quality of life (p < 0.001 for all). It is safe in the intermediate/long term to treat patients with stable CAD using autologous culture expanded MSCs. Previously reported, early and highly significant improvements in exercise capacity and clinical symptoms persist after 12 months. The results are encouraging, and a larger controlled study is warranted.

Background: In patients with ST-segment elevation myocardial infarction (STEMI) pre-infarction angina, pre-procedural TIMI flow and collateral flow to the myocardium supplied by the infarct related artery are suggested to be cardioprotective. We evaluated the effect of these factors on myocardial salvage index (MSI) and infarct size adjusting for area at risk in patients with STEMI treated with primary percutaneous coronary intervention., Methods and Results: Cardiac magnetic resonance (CMR) was used to measure myocardial area at risk within 1-7 days and final infarct size 90 ± 21 days after the STEMI in 200 patients. MSI was calculated as (area-at-risk infarct size) / area-at-risk. Patients with pre-infarction angina had a median MSI of 0.80 (IQR 0.67 to 0.86) versus 0.72 (0.61 to 0.80) in those without pre-infarction angina, P = 0.004). In a regression analysis of the infarct size plotted against the area-at-risk there was a strong trend that the line for the pre-infarction angina group was below the one for the non-angina group (P = 0.05). Patients with pre-procedural TIMI flow 0/1, 2 and 3 had a median MSI of (0.69 (IQR 0.59 to 0.76), 0.78 (0.68 to 0.86) and 0.85 (0.77 to 0.91), respectively (P<0.001). Collateral flow did not change MSI (P = 0.45) nor area-at-risk (P = 0.40) and no significant difference in infarct size adjusted for area at risk (P = 0.25) was observed., Conclusions: Pre-infarction angina increases MSI in patients with STEMI supporting the theory that pre-infarction angina leads to ischemic preconditioning. As opposed to the presence of angiographically visible collateral flow to the infarct area pre-procedural TIMI flow is strongly associated with MSI.

Aims: We evaluated the feasibility, safety and efficacy of intra-myocardial injection of autologous mesenchymal stromal cells derived endothelial progenitor cell (MSC) in patients with stable coronary artery disease (CAD) and refractory angina in this first in man trial., Methods and Results: A total of 31 patients with stable CAD, moderate to severe angina and no further revascularization options, were included. Bone marrow MSC were isolated and culture expanded for 6-8 weeks. It was feasible and safe to establish in-hospital culture expansion of autologous MSC and perform intra-myocardial injection of MSC. After six months follow-up myocardial perfusion was unaltered, but the patients increased exercise capacity (p < 0.001), reduction in CCS Class (p < 0.001), angina attacks (p < 0.001) and nitroglycerin consumption (p < 0.001), and improved Seattle Angina Questionnaire (SAQ) evaluations (p < 0.001). For all parameters there was a tendency towards improved outcome with increasing numbers of cells injected. In the MRI substudy: ejection fraction (p < 0.001), systolic wall thickness (p = 0.03) and wall thickening (p = 0.03) all improved., Conclusions: The study demonstrated that it was safe to treat patients with stable CAD with autologous culture expanded MSC. Moreover, MSC treated patients had significant improvement in left ventricular function and exercise capacity, in addition to an improvement in clinical symptoms and SAQ evaluations.

Objectives: In the Euroinject One phase II randomized double-blind trial, therapeutic angiogenesis of percutaneous intramyocardial plasmid gene transfer of vascular endothelial growth factor (phVEGF-A(165)) on myocardial perfusion, left ventricular function, and clinical symptoms was assessed., Background: Evidence for safety and treatment efficacy have been presented in phase I therapeutic angiogenesis trials., Methods: Eighty "no-option" patients with severe stable ischemic heart disease, Canadian Cardiovascular Society functional class 3 to 4, were assigned randomly to receive, via the NOGA-MyoStar system (Cordis Corp., Miami Lakes, Florida), either 0.5 mg of phVEGF-A(165) (n = 40) or placebo plasmid (n = 40) in the myocardial region showing stress-induced myocardial perfusion defects on (99m)Tc sestamibi/tetrofosmin single-photon emission computed tomography., Results: No differences among the groups were recorded at baseline with respect to clinical, perfusion, and wall motion characteristics. After three months, myocardial stress perfusion defects did not differ significantly between the VEGF gene transfer and placebo groups (38 +/- 3% and 44 +/- 2%, respectively). Similarly, semiquantitative analysis of the change in perfusion in the treated region of interest did not differ significantly between the two groups. Compared with placebo, VEGF gene transfer improved the local wall motion disturbances, assessed both by NOGA (p = 0.04) and contrast ventriculography (p = 0.03). Canadian Cardiovascular Society functional class classification of angina pectoris improved significantly in both groups but without difference between the groups. No phVEGF-A(165)-related adverse events were observed; however, NOGA procedure-related adverse events occurred in five patients., Conclusions: The VEGF gene transfer did not significantly improve stress-induced myocardial perfusion abnormalities compared with placebo; however, improved regional wall motion, as assessed both by NOGA and by ventriculography, may indicate a favorable anti-ischemic effect. This result should encourage more studies within the field. Transient VEGF overexpression seems to be safe.

The purpose of this study was to compare the angiographic outcome of implantation of the coil-design Crossflex stent with the tubular NIR stent for treatment of coronary artery stenoses. Two hundred twenty-three patients with one genuine coronary artery lesion were randomized to implantation with a 15 mm Crossflex stent (n = 112) or a 16 mm NIR stent (n = 111). The patients had angiographic follow-up after 6 months. Primary endpoint was minimal luminal diameter (MLD) after 6 months. There was a similar clinical outcome in the two groups. At 6-month follow-up, the MLD was significantly lower in the Crossflex group (1.94 +/- 0.79 mm) than in the NIR group (2.37 +/- 0.84 mm; P < 0.001). Early gain was the same in the two groups. Late loss and percent diameter stenoses were significantly higher in the Crossflex group. The binary restenoses rate was 26% and 17% in the Crossflex and the NIR groups, respectively (P = NS). The coil-design Crossflex stent was found to be inferior to the tubular NIR stent concerning late loss and MLD at 6-month follow-up., (Copyright 2003 Wiley-Liss, Inc.)

Background In patients with ST-segment elevation myocardial infarction (STEMI) pre-infarction angina, pre-procedural TIMI flow and collateral flow to the myocardium supplied by the infarct related artery are suggested to be cardioprotective. We evaluated the effect of these factors on myocardial salvage index (MSI) and infarct size adjusting for area at risk in patients with STEMI treated with primary percutaneous coronary intervention. Methods and Results Cardiac magnetic resonance (CMR) was used to measure myocardial area at risk within 1-7 days and final infarct size 90±21 days after the STEMI in 200 patients. MSI was calculated as (area-at-risk infarct size) / area-at-risk. Patients with pre-infarction angina had a median MSI of 0.80 (IQR 0.67 to 0.86) versus 0.72 (0.61 to 0.80) in those without pre-infarction angina, P = 0.004). In a regression analysis of the infarct size plotted against the area-at-risk there was a strong trend that the line for the pre-infarction angina group was below the one for the non-angina group (P = 0.05). Patients with pre-procedural TIMI flow 0/1, 2 and 3 had a median MSI of (0.69 (IQR 0.59 to 0.76), 0.78 (0.68 to 0.86) and 0.85 (0.77 to 0.91), respectively (P<0.001). Collateral flow did not change MSI (P = 0.45) nor area-at-risk (P = 0.40) and no significant difference in infarct size adjusted for area at risk (P = 0.25) was observed. Conclusions Pre-infarction angina increases MSI in patients with STEMI supporting the theory that pre-infarction angina leads to ischemic preconditioning. As opposed to the presence of angiographically visible collateral flow to the infarct area pre-procedural TIMI flow is strongly associated with MSI. [ABSTRACT FROM AUTHOR]

Aim: Analyze clinical, temporal and procedural characteristics from 7,528 consecutive percutaneous coronary intervention (PCI) patients in one of the largest published contemporary European PCI-database during a 6-year period. Method: Retrospective study design. Period: 1998–2004. Temporal and referral changes in a Danish PCI-registry were analyzed. Demographic and angiographic variables were compared with data from randomized clinical trials, US-registries and current guidelines. Results: 22,214 patients were examined with coronary angiography and 7,528 patients were treated with PCI. The annual number of PCI’s increased by 15%. Over time, the fraction of patients with risk factors increased, median age increased from 61 to 64 years and the coronary pathology was significantly worsened. ST-elevation myocardial infarction patients primarily admitted to hospitals without facilities for primary angioplasty, were less likely to receive primary PCI. Baseline-data were in general in par with randomized clinical trial study populations and large-scale US data-registries. Interestingly, 14% of all PCI-procedures were performed on patients with a clinical presentation, for which coronary artery bypass grafting would be recommended by guidelines. Conclusion: PCI is performed in an increasingly sicker population, but generally in accordance with randomized trials and similar to US tradition. However, 14% were treated with PCI even though coronary artery bypass grafting was recommended by guidelines. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: In the Euroinject One phase II randomized double-blind trial, therapeutic angiogenesis of percutaneous intramyocardial plasmid gene transfer of vascular endothelial growth factor (phVEGF-A165) on myocardial perfusion, left ventricular function, and clinical symptoms was assessed. Background: Evidence for safety and treatment efficacy have been presented in phase I therapeutic angiogenesis trials. Methods: Eighty “no-option” patients with severe stable ischemic heart disease, Canadian Cardiovascular Society functional class 3 to 4, were assigned randomly to receive, via the NOGA-MyoStar system (Cordis Corp., Miami Lakes, Florida), either 0.5 mg of phVEGF-A165 (n = 40) or placebo plasmid (n = 40) in the myocardial region showing stress-induced myocardial perfusion defects on 99mTc sestamibi/tetrofosmin single-photon emission computed tomography. Results: No differences among the groups were recorded at baseline with respect to clinical, perfusion, and wall motion characteristics. After three months, myocardial stress perfusion defects did not differ significantly between the VEGF gene transfer and placebo groups (38 ± 3% and 44 ± 2%, respectively). Similarly, semiquantitative analysis of the change in perfusion in the treated region of interest did not differ significantly between the two groups. Compared with placebo, VEGF gene transfer improved the local wall motion disturbances, assessed both by NOGA (p = 0.04) and contrast ventriculography (p = 0.03). Canadian Cardiovascular Society functional class classification of angina pectoris improved significantly in both groups but without difference between the groups. No phVEGF-A165-related adverse events were observed; however, NOGA procedure-related adverse events occurred in five patients. Conclusions: The VEGF gene transfer did not significantly improve stress-induced myocardial perfusion abnormalities compared with placebo; however, improved regional wall motion, as assessed both by NOGA and by ventriculography, may indicate a favorable anti-ischemic effect. This result should encourage more studies within the field. Transient VEGF overexpression seems to be safe. [Copyright &y& Elsevier]