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Competing Interests: Conflict of interest: GP and AM declare no conflict of interest. DLC reports Speaker Bureau and Scientific Advisor for Roche, Astra Zeneca, Amgen, Novartis, BMS, MSD, and Boehringer Ingelheim. DI is the CEO of ISHEO srl and has received grants from Abbvie, Merck Serono, Bristol Myers Squibb, Pierre Fabre, Eli Lylli, Boehringer Ingelheim, Angelini, Fidia Pharma, and AlfaSigma.

Recent advances in coronary revascularization techniques have improved the outcomes of ischemic heart disease in both acute and chronic settings. As a drawback, an increase in patients with an advanced stage of ischemic cardiomyopathy refractory to optimal medical treatment has been observed. Among the therapeutic alternatives under investigation, cell therapy showed considerable anti-ischemic potential. Although several types of cells have been used, bone marrow-derived endothelial progenitor cells are among the most appealing therapeutic agents due to their angiogenic properties. In particular, endothelial progenitors expressing the transmembrane protein CD133 have been in vitro and in vivo extensively characterized and clinically tested. The aim of this paper is to discuss the translational process that allowed the clinical application of CD133+ endothelial progenitor cells in the context of ischemic cardiomyopathy.

Background: 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., Methods: 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., Results: 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.

A national study group has been established by the Italian Federation of Cardiology to investigate the role of stem/progenitor cell therapy in the treatment of cardiovascular diseases. This article is aimed to point out the challenges and debated issues in the conduction of clinical trials, focusing on the Italian clinical and regulatory existing situation.

Myocardial cell therapy is a new promising therapeutic option for patients with heart failure. In this paper, we review the main experimental evidences and the first clinical researches in this field. Moreover, a comment on the theoretical and practical aspects for a pilot clinical use and a glance to the future are also provided.

Background: This study was undertaken to assess our experience of the evolution, over time, of beating heart surgery in the Cardiologic Center Foundation Monzino., Methods: From March 1995 to June 2000, 506 patients underwent myocardial revascularization on beating heart: 313 until May 1999, and 193 between June 1999 and June 2000, after the advent of coronary artery stabilizers and shunts, to keep the surgical field bloodless, with minimal motion and continuous myocardial perfusion. Surgical accesss was via a median sternotomy for 408 cases and via a left anterior thoracotomy for 98 cases., Results: The indications by choice increased, from I to II period, from 61% to 83% with special situations in which patients had three-vessel coronary artery disease raised from 33% to 50%, concerning also bypass grafts performed on circumflex artery and right coronary increased. Postoperative mortality in hospital decreased from 1.3% to 0.5% and perioperative IMA (acute myocardial infarction) from 3.8% to 0.5% in patients undertaken to median thoracotomy. Hospital stay decreased from 8 to 7 days about [no significant differences with patients who underwent CPB (cardiopulmonary bypass)]; in patients who underwent to MTS (left anterior minithoracotomy) there was no deaths, IMA decreased from 3.9% to 0% and hospital stay from 6 to 5 days. Grafts patency increased from 92.3% to 100%., Conclusions: To perform completed revascularisations is possible now even on the beating heart, and also to make precise anastomosis as on pump CABG, in a reproducible and easy way. The beating heart procedure, that is also more economical, might be expanded to all patients, not only high risk patients.

We define as Banking of the tissues all the procedures that include the finding, preparation, conservation and distribution of the homograft. The vascular homografts are taken and put into a solution of transportation at +4 degrees C and kept at this temperature till their arrival at the Bank. The following step is the dissection of the homograft which will have to be performed as quickly as possible at most 24 hours after the taking in conditions of maximum sterility. At the Italian Homograft Bank at Centro Cardiologico, the vascular homografts are kept at +4 degrees C for 96 hours on average with antibiotics. After a phase of sterilization at +4 degrees C the tissue is frozen according to a homogeneous and controlled thermic decrease and stored at -150 degrees C/-180 degrees C in fumes of liquid nitrogen till the moment of their employment allowing a long term conservation. The aim of all these procedures of cryopreservation is to keep the structural and functional integrity of cells and tissues. The thermic decrease of the tissues must occur so that to avoid all the damages of the cellular vitality and functionality and especially of the tissue structure in toto. In order to limitate these events some cryoprotector agents are employed because they reduce the concentration of the solutes, the cellular dehydration, the formation of micro-macro crystals. Another step to establish if the homograft is proper is the study of bacteriological and viral aspects. The viral screenings are performed on the donor's blood and the bacteriological tests are performed on the tissue and on the liquids. For each phase of the banking a series of information about the donor and about the tissues are recorded and filed both on paper and database so that to grant always a right conduct of the material.

Background: This study was conducted to assess the impact of coronary bypass surgery (CABG) without cardiopulmonary bypass (CPB) on high-risk patients., Methods: From February 1997 to July 1998, 71 patients considered at high-risk underwent a CABG off-pump. Using the "Higgins score", eleven preoperative risk factors were identified and stratified in this group of patients. Among 1271 patients who underwent CABG with CPB in the same period, using a computer-based matched comparison, a second identical group of patients was selected according to the 11 risk variables and the number with coronary disease, so that complete preoperative matching included the year of operation, score index and coronary target. Moreover, among seven other preoperative variables that were not included in the matching comparison, the two groups differed only in mean age (64 +/- 10.9 vs 61.6 +/- 7.3 in groups off and on-pump, respectively, p < 0.05). Postoperative outcome and complications and blood requirement were compared. Myocardial cell injury and left ventricular performance were also assessed in the two groups., Results: The global incidence of neurologic complications in the off-pump group was significantly lower (9.8 vs 0%, in on and off-pump groups, respectively; p = 0.02). Patients undergoing CABG off-pump required blood far less often (% of transfused patients: 26.7% for the patients with CPB and 11.2% for the patients without CPB; p = 0.032). Three patients from the on-pump group (4.2%) had a perioperative myocardial infarction (AMI), versus 0% of the off-pump cases (p = ns). Postoperative atrial fibrillation accounted for 14.1% in off-pump patients and 30.9% in on-pump patients (p = 0.027). One patient in both groups (1.4%) suffered from postoperative heart failure. Mean ventilation time and ICU stay did not differ significantly between the two groups. However, hospital discharge occurred earlier in the off-pump group (9.3 +/- 3 vs 12.6 +/- 8, p = 0.007). In-hospital death occurred in one case from the on-pump group (1.4%) versus 0% of patients operated off-pump. CPK-MB release in patients without perioperative AMI was significantly lower in off-pump patients 6 and 12 hours after the operation (36.6 +/- 17 IU/l vs 69.8 +/- 23 IU/l after 6 hours, p < 0.05; and 36.7 +/- 19 IU/l vs 67.3 +/- 26 IU/l after 12 hours, p < 0.05, in off and on-pump groups, respectively) and LVSWI turned out to be better in off-pump patients 6 hours postoperatively (34.2 +/- 2 g*m/m2 vs 27.2 +/- 3 g*m/m2, p < 0.01)., Conclusions: CABG without CPB seems to be a promising technique for high-risk patients. It offers better neurologic and cardiac protection, shortens postoperative hospital stay and reduces the need for blood transfusion.

Background: Long-term durability of homograft valves is related to cellular viability and immunological compatibility. In this paper, we carry out a critical update of the relationship between cellular viability and immunology of cryopreserved homograft valves., Biological Issue: In the first section, we review the theoretical background of the superior durability of cryopreserved valves with high cellular viability, with respect to the "fresh" antibiotic-stored valves, with lower viability rates. Afterwards, a brief review of the principal factors influencing the homograft valve viability rate during harvesting, preparation, sterilization and cryopreservation phases, is performed., Cellular Viability: In the second paragraph, we analyze the problem of cellular viability in cryopreserved valves, both for matrix cells--fibroblast--and for endothelium. In particular, we report the current methods of quantifications of viability and more recent biological researches. Correlations between biological and clinical data are also discussed., Immunological Issue: Finally, the immunological issue and its relationships with cellular viability is analyzed, with particular regard to experimental evidence and clinical implications. Moreover, we have described the recent hypothesis on the influence of cryopreservation on the antigenicity of tissues, and the laboratory researches on the long-term antibody response in humans after homograft valve implantation.

It has been well established that the internal thoracic artery (ITA) is a good alternative to the saphenous vein as conduit for coronary artery bypass grafting because of superior early and late patency. Many surgeons now commonly use both ITAs for CABG and many have adopted complex grafting methods such as free ITA graft and sequential anastomosis; despite these techniques, it's not always possible to achieve complete revascularization with arterial conduits. More recently the right gastroepiploic artery (rGEA) and the inferior epigastric artery (IEA) have been used as alternative arterial conduits. The authors report the experience of a case of myocardial revascularization in a patient with angina not responsive to medical therapy, severe tri-vessel coronary artery disease, which had a previous total bilateral saphenectomy; the patient was also found to have a right fibrothorax. In the surgical strategy the authors considered that the bilateral use of mammary artery could have been the cause of the depressed respiratory function and that it was important to leave intact the left hemithorax; they therefore employed the rITA in the revascularization of the anterior descending (AD). To complete the revascularization they used the IEA for a marginal branch of the circumflex artery and the rGEA for the interventricular posterior artery, branch of the right coronary artery. In this fashion good early results were obtained with absence of perioperative complications with a good life expectancy.

There are still controversies about the surgical results of myocardial revascularization in aged population, in terms of cardiac and non-cardiac morbidity and mortality. This issue prompted us to study retrospectively 71 patients older than 75 years electively operated of coronary artery bypass grafting (CABG) from June 1990 to June 1993 (Group A). Elderly population was compared with a contemporaneous and concurrent control group of patients younger than 75 years (Group B). Patients > 75 years have been divided in successive subgroups according to the severity of coronary artery disease (3 vessel disease 67.7%, 2 vessel disease 26.7%, 1 vessel disease 5.6%), echocardiographic ejection fraction (EF > 50%: 40.8%; 50-30%: 42.2%; < 30%: 16.9%) and preoperative risk factors. Left internal thoracic artery (LITA) utilization rate was 97.1% in Group B and 57.7% in Group A (p < 0.001). Cardiopulmonary bypass circulation, aortic cross-clamping time and number of coronary anastomoses were similar in the 2 groups (2.87 +/- 0.9 versus 2.8 +/- 0.8, NS). Operative mortality rate of aged population was 4.2% while no patient of Group B died (NS). Concerning the cardiac morbidity, there were no significantly differences between the 2 groups: myocardial infarction occurred in 3 patients of Group B (4.2%) and in 5 patients of Group A (7%; NS). Atrioventricular block was also similar in the 2 groups. Non-cardiac complications occurred more frequently in the aged population group: neurologic complications in 11.2% versus 1.4% (p < 0.04), renal insufficiency in 12.6% versus 1.4% (p < 0.03) and respiratory failure in 9.8% versus 1.4% (p = 0.06). (ABSTRACT TRUNCATED AT 250 WORDS)

When complete revascularization can not be obtained with the internal mammary artery and saphenous veins, the inferior epigastric artery may be an excellent alternative conduit. We describe our experience with this conduit, review the anatomy of this artery, and present the evolution of our harvesting technique through a pararettal approach. Proximal anastomoses were made first with the aid of an oval cuff of the common femoral artery (5 cases, Group A). Two patients (40%) of this group studied postoperatively revealed a graft occlusion. In the last 13 cases (Group B) we tailored the proximal anastomoses directly to the aorta. All patients studied postoperatively showed patent inferior epigastric artery grafts. There were no hernias and no deaths. Inferior epigastric artery can be considered a good alternative conduit in myocardial revascularization.