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Cardiac cell therapy is still restricted to experimental studies and clinical trials. This investigation is an analytic overview of worldwide ongoing trials and is aimed to show useful findings for planning new clinical trials.Based on the online searching engine of the National Library of Medicine database for clinical trials (www.clinicaltrials.gov), all the ongoing studies registered were analyzed and classified.On May 30, 2009, 95 studies were registered worldwide: 40 of these were conducted in Europe and 4 in Italy. Phase 1, 2, 3 and 4 studies were 28%, 57%, 14% and 1%, respectively; observational and randomized studies were 22% and 78%, respectively. The clinical setting of enrolled patients was acute coronary syndrome in 43 studies (46%), heart failure in 29 studies (30%), chronic heart disease in 23 studies (24%). The treatment strategies investigated are cytokine-induced cell mobilization in 8% and cell implantation in 92%. The cell types used for direct implantation are mononuclear cells in 81%, endothelial precursor cells CD34+ in 11%, endothelial precursor cells CD133+ in 5%, myoblasts in 2% and adipoblasts in 1% of cases. CONCLUSIONS; The present snapshot of worldwide ongoing clinical trials provides useful information for planning an experimental clinical program on cardiac cell therapy.

The aim of the study was to validate a novel formula for aortic valve area (AVA) based on the principle of continuity equation, that substitutes Doppler-derived stroke volume (SV) by SV directly measured with real time simultaneous triplane three-dimensional echocardiography (RT3P). RT3P has proved accuracy for left ventricular volume calculation. So far, however, neither this potential has been applied to hemodynamic assessment, nor RT3P has succeeded in the evaluation of aortic valve disease.AVA was measured in 21 patients with aortic stenosis using Gorlin's equation, Doppler continuity equation (two-dimensional echocardiography), the novel RT3P method, and by substituting Doppler-derived SV by SV measured with two-dimensional stroke volume (2DSV). RT3P has the best linear association (R(2)= 0.61) and the best correlation with Gorlin of all noninvasive methods (even if not statistically significant). RT3P carries significantly lower mean differences with catheterization, as compared with 2D and 2DSV (Table 4). Standard deviations of mean differences between RT3P and catheterization and between the other echocardiographic methods are not statistically different, even if RT3P seems to be nearer to catheterization. Inter- and intraobserver variability were, respectively, 0.03 +/- 0.11 cm(2) and 0.02 +/- 0.03 cm(2), better than 2D and 2DSV.RT3P has revealed to be more accurate than two-dimensional method in AVA quantification, with a better intraobserver agreement. In addition, it allows simple and fast image acquisition.

To verify feasibility and safety of bone marrow stem cells (BMC) mobilization in patients (pts) with acute myocardial infarction (AMI) and to monitor the clinical effects of BMC mobilization in terms of myocardial perfusion and function.Eight male pts (median age: 50.5 years) treated with a primary PTCA were enrolled. The mobilization regimen consisted of G-CSF 5 microg/kg/12 h from day 0 to day +2 and GM-CSF 2.5 microg/kg/24 h. All pts underwent coronary angiography, intracoronary doppler flow study, echocardiography, and nuclear thallium scan before treatment and at 6 months. All pts showed increased values of WBC and circulating CD34+ following cytokine administration. No patient died. All patients completed a 6-months follow-up: target lesion revascularization rate was 12,5%, target vessel revascularization rate was 37.5%, angiographic mean ejection fraction increased from 49.8+/-11.9 to 55.4+/-8.7 (p=NS), mean coronary flow reserve from 1.63+/-0.42 to 2.5+/-0.4 (p=0.001), mean Thallium uptake raised from 55.56+/-16.42% to 67.56+/-13.66% (p=0.01), and normally perfused segments from 16% to 52% (p=0.01).Cytokine-induced BMC mobilization is feasible in AMI pts. Improvements of myocardial perfusion can be expected after PTCA associated with G-CSF and GM-CSF induced mobilization. Further studies are required to define the role of BMC-mobilization and the most effective cytokine combination.

Mobilization of endothelial progenitor cells has been suggested to contribute to neo-vascularization of ischemic organs. Aim of this study was to investigate whether the combination of granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage (GM)-CSF may influence the expansion of circulating KDR+ cells in patients with acute myocardial infarction (AMI). KDR+ cells significantly increased in peripheral blood of AMI patients treated with G-CSF and GM-CSF compared to untreated patients. This KDR+ cells population was CD14+ but not CD34+ or CD133+. CD14+/KDR+ cells were also obtained in vitro by culturing mononuclear cells from healthy donors in a Rotary Cell Culture System in the presence of G-CSF + GM-CSF, but not of the individual growth factors. CD14+/KDR+ cells, obtained from patients or from in vitro culture, co-expressed hematopoietic (CD45, CD14) and endothelial markers (CD31, CD105, and VE-cadherin). CD14+/KDR+, but not CD14+/KDR- cells, stimulated the organization of human microvascular endothelial cells into capillary-like structures on Matrigel both in vitro and in vivo. The combination of G-CSF and GM-CSF induced a CD14+/KDR+ cell population with potential pro-angiogenic properties.

A unidirectional clinical pathway for acute myocardial infarction from out-of-hospital setting to the coronary care unit and catheterization laboratory could lead to mortality reduction. The ongoing "Progetto Torino Network. Gestione globale dell'infarto miocardico acuto prime ore dal territorio all'ospedale" is based on this statement and described in the three-structural, diagnostic-therapeutical, multimedial issues. This project represents the historical evolution of our involvement in out-of-hospital cardiac emergency management.

Introduction. Intracoronary or intramyocardiac injection of bone marrow stem cells or growth factor-mobilized peripheral blood stem cells (PBSC) may contribute to myocardial regeneration and neovascularization of the ischemic myocardium either in animal models or in human. This effect is probably due to a selective colonization of the ischemic area by PBSC. Very few studies were done in the acute setting of ischemic heart disease, with controversial results. Aims of this pilot study were: i) to verify feasibility and safety of PBSC mobilization in patients with acute myocardial infarction (AMI); ii) to monitor clinical effects of PBSC mobilization in terms of global and segmental myocardial perfusion and function. Patients and methods. Eight male patients (mean age: 51,7±5,6 years) were enrolled. All were treated with a primary percutaneous transluminal coronary angioplasty (PTCA) for an anterior (5 patients) or an inferior (3 patients) AMI. The mobilization regimen consisted of G-CSF 5 μg/kg/12h from day 1 to day 3 and GM-CSF 2.5 μg/kg/24h from day 1 to day 5 (starting within 24 hours from PTCA). Since transient severe hypotension was noticed in the first three patients, the protocol was amended by reducing and tapering GM-CSF administration (2.5 μg/kg/24h at days 3, 5, 7). All patients underwent coronary angiography, intracoronary doppler flow study, echocardiography, and nuclear Thallium scan before treatment and at 6 months apart. Results. WBC and PBSC peaked during the 3th day of mobilization. Mean WBC and PBSC peaks were 34960± 10794 leukocytes/μL and 29.71± 30.8 CD34+/μL. Five in hospital adverse events were recorded: severe hypotension in 3 patients (as previously mentioned), atrial fybrillation in 1 patient, recurrent ischemia in 1 patients. No death was observed. At present 7 patients completed a 6-months follow-up evaluation: target lesion revascularization rate was 14,3% (1 patient) and target vessel revascularization rate was 42,8% (3 patients). Angiographic mean ejection fraction increased from 49,8±11,9 to57,1±8,9 (p=NS), and mean coronary flow reserve raised from 1,63±0,42 to 2,45±0,36 (p=0,005). Perfusion improvement was observed by nuclear study in 66% of patients. Conclusions. We conclude that: a) cytokine-induced stem cell mobilization is feasible in AMI patients with adequate GM-CSF administration; b) myocardial perfusion appears to improve within the first six months of follow-up; c) the 3 cases of progressive coronary disease give a concern about a potential negative effect of hematopoietic cytokines (particularly GM-CSF) on silent coronary lesions. However, PBSC mobilization using G-CSF only is worthwhile of further investigation.