Summary Background c-kit-positive, lineage-negative cardiac stem cells (CSCs) improve post-infarction left ventricular (LV) dysfunction when administered to animals. We undertook a phase 1 trial ...(Stem Cell Infusion in Patients with Ischemic cardiOmyopathy SCIPIO) of autologous CSCs for the treatment of heart failure resulting from ischaemic heart disease. Methods In stage A of the SCIPIO trial, patients with post-infarction LV dysfunction (ejection fraction EF ≤40%) before coronary artery bypass grafting were consecutively enrolled in the treatment and control groups. In stage B, patients were randomly assigned to the treatment or control group in a 2:3 ratio by use of a computer-generated block randomisation scheme. 1 million autologous CSCs were administered by intracoronary infusion at a mean of 113 days (SE 4) after surgery; controls were not given any treatment. Although the study was open label, the echocardiographic analyses were masked to group assignment. The primary endpoint was short-term safety of CSCs and the secondary endpoint was efficacy. A per-protocol analysis was used. This study is registered with ClinicalTrials.gov , number NCT00474461. Findings This study is still in progress. 16 patients were assigned to the treatment group and seven to the control group; no CSC-related adverse effects were reported. In 14 CSC-treated patients who were analysed, LVEF increased from 30·3% (SE 1·9) before CSC infusion to 38·5% (2·8) at 4 months after infusion (p=0·001). By contrast, in seven control patients, during the corresponding time interval, LVEF did not change (30·1% 2·4 at 4 months after CABG vs 30·2% 2·5 at 8 months after CABG). Importantly, the salubrious effects of CSCs were even more pronounced at 1 year in eight patients (eg, LVEF increased by 12·3 ejection fraction units 2·1 vs baseline, p=0·0007). In the seven treated patients in whom cardiac MRI could be done, infarct size decreased from 32·6 g (6·3) by 7·8 g (1·7; 24%) at 4 months (p=0·004) and 9·8 g (3·5; 30%) at 1 year (p=0·04). Interpretation These initial results in patients are very encouraging. They suggest that intracoronary infusion of autologous CSCs is effective in improving LV systolic function and reducing infarct size in patients with heart failure after myocardial infarction, and warrant further, larger, phase 2 studies. Funding University of Louisville Research Foundation and National Institutes of Health.
Importantly a post hoc analysis of the long-term (10 years) follow-up data, recently collected, confirmed the safety of the protocol and showed that among patients treated with G-CSF, those receiving ...myocardial contrast echocardiography and the intravenous infusion of sulfur hexafluoride as a diagnostic tool had a significant benefit in left ventricular function compared with G-CSF alone or control group (Figure 1).
Endothelial progenitor cells (EPCs) are released from the bone marrow during cardiac ischemic events, potentially influencing vascular and myocardial repair. We assessed the clinical and angiographic ...correlates of EPC mobilization at the time of primary percutaneous coronary intervention in 78 patients with ST elevation myocardial infarction and the impact of both baseline and follow-up EPC levels on left ventricular (LV) remodeling. Blood samples were drawn from the aorta and the culprit coronary artery for cytofluorimetric EPC detection (CD34+CD45dimKDR+ cells, in percentage of cytofluorimetric counts). Area at risk was assessed by Bypass Angioplasty Revascularization Investigation myocardial jeopardy index, thrombotic burden as thrombus score and microvascular obstruction (MVO) as a combination of ST segment resolution and myocardial blush grade. Echocardiographic evaluation of LV remodeling was performed at 1-year follow-up in 54 patients, whereas peripheral EPC levels were reassessed in 40 patients. EPC levels during primary percutaneous coronary intervention were significantly higher in intracoronary than in aortic blood (0.043% vs 0.0006%, p <0.001). Both intracoronary and aortic EPC were related to area at risk extent, to intracoronary thrombus score (p <0.001), and inversely to MVO (p = 0.001). Peripheral EPC levels at 1-year follow-up were lower in patients with LV remodeling than in those without (0.001% 0.001 to 0.002 vs 0.003% 0.002 to 0.010; p = 0.01) and independently predicted absence of remodeling at multivariate analysis. In conclusion, a rapid intracoronary EPC recruitment takes place in the early phases of ST elevation myocardial infarction, possibly reflecting an attempted reparative response. The extent of this mobilization seems to be correlated to the area at risk and to the amount of MVO. Persistently low levels of EPC are associated to LV remodeling.
Abstract Objective We report our experience with use of LVAD as destination therapy for the management of patients with cardiac end-stage Distrophinopaties Methods From February 2011 to February ...2016, 7 patients with Distrophinopaties and dilated cardiomyopathy were assisted with LVAD at our Institution. Median age at surgery was 16.5 years (range 14,2-23,4). A ll patients were pre-operatively evaluated by multidisciplinary team approach. Results All patients survived to hospital discharge. The early post-operative course was characterized by abdominal bleeding (1 patient) and retropharyngeal bleeding (1 patient). Due to abdominal or retropharyngeal bleeding both required post-operative heparin infusion discontinuation for 35 and 33 days respectively. Amongst late complications, one child developed osteolysis and infection at the pedestal site of device which required surgical displacement; one patient required gastrostomy due to poor feeding and another suffered a cerebral stroke treated with percutaneous thrombus aspiration. The last 2 patients did not showed early or late complications. At median FU time of 21.7 months (range 3-45) we have 3 late deaths: one patient died after 45 months for lung infection, the second died for tracheal bleeding after 29 months and the last died for cerebral hemorrhage after 14 months. Conclusions Our experience indicate that the use of VAD as DT in Distrophinopaties patients with end stage DCM is feasible, suggesting that may be a palliative therapy for the treatment of these patients with otherwise no other therapeutic options.
Abstract This study evaluated the effect of three post surface treatments on quartz-fiber post (a) retention and (b) morphology. A control group was not treated. Different treatments were performed ...for the other posts: silanization; etching by hydrofluoric acid 9.5%; sandblasting with 50 μm Al2 O3 . Two specimens of each group were submitted to a qualitative scanning electron microscopy (SEM) analysis. Remaining specimens were luted in prepared root canals ( n = 10) and retentions were determined using a universal testing machine. Retentive post bond strengths were significantly enhanced with any tested post surface pretreatment. The increase in retentive strength was more remarkable in sandblasted and etched posts. Significant changes of post surfaces were SEM observed after different conditioning treatments.
Objectives This study sought to assess whether intracoronary adenosine or nitroprusside following thrombus aspiration (TA) is superior to TA alone for the prevention of microvascular obstruction ...(MVO) in ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). Background MVO, due to its multifactorial pathogenesis, still occurs after TA in a sizeable portion of patients. Methods We performed a placebo-controlled, randomized, open-label, blind-examination, multicenter trial. A total of 240 STEMI patients with Thrombolysis In Myocardial Infarction (TIMI) flow grade 0/1 were randomly allocated 1:1:1 to receive adenosine (n = 80), nitroprusside (n = 80), or saline (n = 80) given distal to the occluded site after TA. The primary endpoint was the incidence of ST-segment resolution (STR) >70% on surface electrocardiogram at 90 min after PCI. Secondary endpoints were angiographic MVO incidence (TIMI flow grade ≤2 or 3 with a myocardial blush grade <2) and major adverse cardiac event (MACE) rate at 30 days as a composite of cardiac death, myocardial infarction, target lesion revascularization, and heart failure requiring hospitalization. Results STR >70% occurred in in 71% of adenosine-treated patients, in 54% of nitroprusside-treated patients, and in 51% of saline-treated patients (p = 0.009 and p = 0.75, respectively, vs. saline). Angiographic MVO occurred in 18% of adenosine-treated patients, in 24% of nitroprusside-treated patients, and in 30% of saline-treated patients (p = 0.06 and p = 0.37, respectively, vs. saline). MACE occurred in 10%, 14%, and 20% of patients, respectively (p = 0.08 and p = 0.29 vs. saline). Conclusions In STEMI patients treated by PCI and TA, the additional intracoronary administration of adenosine, but not that of nitroprusside, results in a significant improvement of MVO, as assessed by STR.
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