Platelet-dependent thrombography gives a distinct pattern of in vitro thrombin generation after surgery with cardio-pulmonary bypass: potential implications.

BACKGROUND: Bleeding remains a potentially lethal complication of cardio-pulmonary bypass (CPB) surgery. The purpose of this study was to obtain a better insight into in vitro thrombin generation in the context of CPB. METHODS: We used Calibrated Automated Thrombography to assess blood coagulation of 10 low-risk patients operated for valve replacement with CPB, under 2 experimental conditions, one implicating platelets as platelet dysfunction has been described to occur during CPB. RESULTS: Our main finding was that CPB-induced coagulopathy was differently appreciated depending on the presence or absence of platelets: the decrease in thrombin generation was much less pronounced in their presence (mean endogenous thrombin potential change values before and after CPB were -3.9% in the presence of platelets and -39.6% in their absence). CONCLUSION: Our results show that experimental conditions have a profound effect in the study of in vitro thrombin generation in the context of CPB.

Cardiac surgery in cirrhotic patients: results and evaluation of risk factors.

OBJECTIVES: Liver cirrhosis increases mortality and morbidity following cardiac surgery. This study evaluated the results of cardiac surgery in cirrhotic patients and the relevance of EuroSCORE, Child-Turcotte-Pugh (CTP) class and model for end-stage liver disease (MELD) score in terms of prediction of surgical mortality and survival. METHODS: The study involved 34 patients with hepatic cirrhosis who underwent cardiac surgery between January 1996 and January 2010. RESULTS: The in-hospital mortality was 26%. Postoperative mortality of patients with CTP class A, B or C was 18, 40 and 100%, respectively. In univariate analysis, a history of cerebrovascular disease and hypoalbuminaemia was predictive of operative mortality. Multivariate exact logistic regression revealed that hypoalbuminaemia was an independent factor. Long-term survival was 63 ± 0.08% at 1 year and 40.2 ± 0.12% at 5 years. The 1-year survival for CTP A, B and C was 76.7 ± 0.09, 60 ± 15.4 and 0%, respectively, and the 5-year survival was 60 ± 15.4, 25 ± 0.19 and 0%, respectively. The EuroSCORE was not a discriminant [area under the curve (AUC): 0.57 ± 0.15]. The performance of CTP class and MELD score was better, but neither provided optimal discrimination: AUC was 0.691 ± 0.110 for MELD and 0.658 ± 0.10 for CTP class. CONCLUSIONS: Cardiac surgery can be performed safely in CTP class A patients. In CTP C patients, surgery is hazardous, and an alternative treatment must be considered. In CTP B, the MELD score could be helpful in deciding whether surgical intervention is a reasonable option.

Modified Bentall procedure using two short grafts for coronary reimplantation: long-term results.

BACKGROUND: The modified Bentall procedure remains a gold standard of aortic root surgery. We present in this study the early and late outcomes of a particular modification using 2 separated grafts for the coronary reimplantation. METHODS: From 1995 to 2009, 153 patients aged 57±12 (mean±standard deviation [SD]) underwent elective (n=113) or urgent (n=40) aortic root replacement with a composite mechanical valve conduit reconstruction using 2 short, separated 8-mm Dacron grafts for the coronary reimplantation and were retrospectively reviewed. RESULTS: Aortic disease etiologies were annuloaortic ectasia (n=108), type A aortic dissection (n=38), aortic false aneurysm, or Valsalva aneurysm evolution after previous cardiac surgery (n=7). The overall early mortality was 8.5% (20% for urgent procedure and 4.4% for elective procedure). For the whole group, actuarial survival at 5 and 10 years was 86.3%±2.78 and 73.7%±4.23, respectively. Among the 23 late deaths, 9 were valve-related deaths (stroke, n=3; endocarditis, n=1; unknown, n=5). During the follow-up, linearized rates of major bleeding, thromboembolism, and endocarditic evolution were, respectively, 1.3 %/patient-years, 0.42 %/patient-years, and 0.22 %/patient-years. One patient presented a nonseptic false aneurysm of the right coronary anastomosis and no structural valve dysfunction has been diagnosed. In total, only 2 patients required an aortic root reoperation. CONCLUSIONS: The modified Bentall procedure using 2 separated grafts for the coronary reimplantation is a feasible, safe, easy, and reproducible operative technique for aortic root surgery.

Off-label use of recombinant activated factor VII in intractable haemorrhage after cardiovascular surgery: an observational study of practices in 23 French cardiac centres (2005-7).

OBJECTIVES: The study aimed to describe French off-label use of rFVIIa for intractable bleeding in major cardiovascular surgery. METHODS: Retrospective observational analysis of data from 2005 to October 2007 (no formal guidelines were available) was employed. The collect request form was elaborated by a multidisciplinary committee. RESULTS: Data on 109 patients--37 mechanical cardiac assist devices--were collected, with repeated injection for 24%. Bleeding stopped, decreased or continued in 43%, 37% and 20% of the cases, respectively. For patients treated in the intensive care unit (ICU), hourly bleeding decreased from 365 ± 212 to 115 ± 106 ml h(-1) (p<0.001). The median number of transfused products was 25 (2-90) before and 6 (0-48) after rFVIIa (p<0.001). Most patients had been well compensated with fibrinogen (>1g.l(-1)) and platelets (>50 G.l(-1)) before rFVIIa. The bleeding outcome (cessation, decrease or no change) was associated with the infused dose (81 ± 31, 71 ± 24, 64 ± 23 µg.kg(-1); p = 0.044) and did not differ whether rFVIIa was administered in the operating room (49%) or ICU (51%). Thrombotic events occurred in 13% of patients without assist devices and in 27% of those with them (but without obvious intra-device clotting). The overall 28-day survival rate was 60% and associated with bleeding outcome (p = 0.002). CONCLUSIONS: rFVIIa rescue therapy was followed by control of bleeding in a substantial number of the patients with seemingly acceptable safety; however, thrombotic risk remains a matter of concern. Our observational study suggests that the dose to be tested prospectively is at least 80 µg.kg(-1).

Recombinant activated factor VII attenuates major arterial bleeding in noncoagulopathic rabbits.

BACKGROUND AND OBJECTIVE: Recombinant activated factor VII (rFVIIa), which is used off-label as an adjuvant therapy for uncontrolled and life-threatening bleeding, might also attenuate intractable bleeding related to macrovascular arterial lesions. Here we evaluated the efficacy of rFVIIa in sealing a large arterial wound in haemostatically competent rabbits. METHODS: Sixty male New Zealand rabbits were randomly divided into vehicle control and 80 and 200 µg kg⁻¹ rFVIIa groups (n = 20 animals each). A standardized wound of the isolated right carotid artery was made in all rabbits with an 18-G catheter. Bleeding, which was limited by mild compression, was assessed every minute. At 5 min, an intravenous bolus of vehicle or human rFVIIa was given and the animals were further observed for 1 h. Efficacy was assessed from the bleeding duration and blood mass lost. Statistical significance was defined as P less than 0.05. All investigators were blinded to the treatment the animals received. RESULTS: The bleeding duration and blood mass lost were significantly reduced in both rFVIIa dosage groups as compared with the vehicle control group. For the vehicle, 80 and 200 µg kg⁻¹ rFVIIa groups, the median bleeding durations were 56 min (range 7-60 min), 15 min (range 5-60 min) and 10 min (range 5-60 min), respectively; and the median blood mass losses were 22.5 g (range 1-58 g), 12 g (range 0-36 g) and 5 g (range 0-31 g), respectively. The prothrombin time was shorter in the rFVIIa groups. Visual inspection of the carotid artery and microscopic analysis of the liver and kidney revealed neither gross thrombi nor entrapped microthrombi in any rabbit. CONCLUSION: Recombinant FVIIa at 80 or 200 µg kg⁻¹ promoted the sealing of a large and slightly compressed arterial wound in rabbits. These results suggest a potential role for the drug in the management of massive bleeds due to an arterial lesion when surgical intervention is not immediately and readily available. Safety should remain a matter of concern.

Left main coronary disease treated by direct surgical angioplasty: long-term results.

BACKGROUND: Left main coronary artery (LMCA) disease is currently treated by coronary artery bypass grafting or, more recently, by percutaneous coronary intervention. Occasionally, direct surgical patch angioplasty of the LMCA can be proposed as an alternative treatment. The aim of this study was to analyze, on a long-term basis, the safety and efficacy of this technique. METHODS: This retrospective analysis was obtained from clinical data between April 1995 and December 2008: 91 consecutive patients (67 men, 24 women; mean age: 58+/-10 years) underwent surgical angioplasty of the LMCA with an autologous pericardial patch. Among them, 80 (87.9%) presented an isolated LMCA disease. Mean logistic European system for cardiac operative risk evaluation of this series was 3.9+/-2.9. Concomitant surgical procedures included coronary artery bypass grafting (n=11; 12%), valve procedure (n=5; 5.5%), and carotid endarterectomy (n=1; 1.1%). We analyzed the early and late mortality, major adverse cardiac or cerebral event rate, and repeat revascularization rate. RESULTS: The mean follow-up was 7.22+/-3.60 years (maximum 13.8 years, minimum 180 days). Perioperative mortality was 1.1%. Five and ten-year global survival was 95+/-4.5% and 80+/-8.3%, respectively. Major adverse cardiac or cerebral event rates at five and ten years were, respectively, 21+/-8.4% and 31+/-9.6%. First repeat postoperative revascularization rate was 12+/-6.8% at five and 17+/-7.8% at ten years (n=10 patients). Among them, repeat target lesion revascularization concerned four patients. CONCLUSIONS: Similar to other series, our study shows satisfactory long-term outcomes with the surgical patch-plasty of LMCA. This technique can be proposed as an efficient and safe alternative to selected patients, particularly in case of isolated LMCA disease without extended calcification.

Clinical and microbiologic features of multivalvular endocarditis.

Multivalvular endocarditis accounts for 15% of all endocarditis. The mechanisms of spread of the infection differs whether endocarditis is only left-sided (involving both the mitral and aortic valves) or bilateral. In left-sided bivalvular endocarditis, it is often a secondary mitral lesion following a primary aortic endocarditis. Multivalvular endocarditis often results in severe and extensive cardiac lesions, well described at echocardiography and frequently responsible for severe heart failure. Patients often need surgery, which consists of radical debridement of all the infected tissue with reconstruction using different types of prostheses; therefore, the surgery may be very complex. The goal should be an early diagnosis of endocarditis to avoid spread of the infection to more than one valve, to improve the prognosis for those patients.

Aortic valve replacement for active infective endocarditis: 5-year survival comparison of bioprostheses, homografts and mechanical prostheses.

OBJECTIVE: In the surgical treatment of acute aortic valve infective endocarditis (IE), the long-term outcome depending on the choice of valve replacement remains uncertain. We aimed to compare the impact on 5-year mortality of use of three types of implanted valves: bioprosthesis (heterograft), mechanical prosthesis and homograft. METHODS: A total of 167 patients with a definite aortic valve IE who underwent aortic replacement were selected from a prospective observational population-based study. Association between the type of implanted valve and 5-year mortality was examined by the use of an adjusted Cox model. RESULTS: Bioprostheses were implanted in 31 patients (18.6%), homograft in 27 (16.2%) and mechanical valves in 109 (65.2%). Patients with bioprothesis had a higher 5-year mortality risk than patients with mechanical prosthesis (adjusted hazard ratio (HR) 2.39, 95% confidence interval (95% CI), 1.09-5.21; p=0.029), particularly in patients < or =65 years old (adjusted HR 4.14 (1.27-13.45), p=0.018) but not in patients >65 years old (adjusted HR: 1.45 (0.35-5.97), p=0.60). Five-year mortality risk did not differ between patients with homografts and those with mechanical prostheses (HR 0.46, 95% CI (0.15-1.42), p=0.18). CONCLUSIONS: A bioprosthetic valve used for aortic valve IE replacement may be associated with lower overall 5-year survival than the use of a mechanical valve in patients up to 65 years old. Further studies are needed to explain these results.

Left atrial radiofrequency ablation during mitral valve surgery: a prospective randomized multicentre study (SAFIR).

BACKGROUND: Randomized studies evaluating left atrial radiofrequency ablation (RFA) in patients with persistent atrial fibrillation undergoing mitral valve surgery are scarce and monocentric. AIM: To evaluate the efficacy of left atrial RFA concomitant with mitral valve surgery to restore and maintain sinus rhythm. METHODS: The SAFIR is a multicentre, double-blinded, centrally randomized study involving four university hospitals. Between December 2002 and September 2005, 43 patients with mitral valve disease and long-standing, persistent atrial fibrillation (duration>6 months) were included. We compared valvular surgery alone (n=22) or with left atrial RFA (n=21). The main endpoint was sinus rhythm at 12 months without recurrence of arrhythmia during follow-up. Secondary endpoints were surgical adverse events, atrial fibrillation relapses, stroke and echocardiographic measurements after three and 12 months' follow-up. Analyses of the efficacy criteria were performed on an intention-to-treat basis. RESULTS: The primary endpoint occurred significantly more often in the RFA group than in the control group (respectively, 12/21 patients [57%] vs 1/22 patients [4%]; p=0.004). There were more patients with sinus rhythm in the RFA group than in the control group at discharge (72.7% vs 4.8%; p<0.005), 3-month follow-up (85.7% vs 23.8%; p<0.01) and 12-month follow-up (95.2% vs 33.3%; p<0.005). The patients in the RFA group had similar rates of postoperative complications and stroke during follow-up as those in the control group. CONCLUSIONS: This multicentre study suggests that left atrial RFA is effective and safe in patients with chronic atrial fibrillation and mitral valve disease.

Comparison of two-year outcomes in patients undergoing isolated coronary artery bypass grafting with and without peripheral artery disease.

We aimed to evaluate the long-term clinical outcomes among patients with peripheral arterial disease (PAD) after coronary artery bypass grafting. We studied 589 consecutive patients who had undergone isolated coronary artery bypass grafting from January 2003 to June 2005 at our university hospital. The effect of PAD was assessed by comparing the 2-year follow-up data from 2 groups of patients: 243 patients with and 346 without PAD. A large systematic atherosclerosis screening was performed, including cerebrovascular disease, lower extremity artery disease, and abdominal aorta disease and its branches. PAD was defined as a history of treated atherosclerotic disease and significant atherosclerotic stenosis on screening. Patients with PAD were significantly older (70 +/- 9 vs 64 +/- 11 years, p <0.001) and were more often men (p = 0.04) than those without PAD. They had a greater incidence of hypertension (p = 0.002), chronic renal dysfunction (p <0.01), chronic pulmonary disease (p = 0.005), and a history of coronary artery disease (p = 0.03). No significant difference was noted between the 2 groups with regard to the left ventricular ejection fraction. The 2-year cumulative survival rate was 76.6% for patients with PAD and 94.1% for those with isolated coronary disease (p <0.001). In conclusion, after adjusting all significant variables, the presence of PAD appeared as an independent predictive factor for all-cause mortality (adjusted hazard ratio 3.2, 95% confidence interval 1.8 to 5.7, p = 0.001).

Refractory anaphylactic cardiac arrest after succinylcholine administration.

Refractory shock from anaphylaxis can occur after induction of general anesthesia. We report two cases of fatal cardiac arrest with increased blood tryptase and immunoglobulin E values after succinylcholine administration. Tryptase and immunoglobulin E assays may help to identify anaphylactic reactions when cardiac arrest occurs at induction of anesthesia.

Heparin-induced thrombocytopenia and cardiopulmonary bypass: anticoagulation with unfractionated heparin and the GPIIb/IIIa inhibitor tirofiban and successful use of rFVIIa for post-protamine bleeding due to persistent platelet blockade.

Heparin-induced thrombocytopenia was diagnosed in a 50-year-old man on day 5 after cardiac surgery (aorto-coronary bypass and mitral valve replacement). He required redo (para-prosthesis leak) on day 13. The cardiopulmonary bypass (CPB) was performed with unfractionated heparin (UFH) and the platelet glycoprotein (GP) IIb/IIIa inhibitor tirofiban. Post-protamine bleeding likely due to documented persistent platelet blockade by tirofiban was successfully treated with one dose of recombinant activated factor VII (rFVIIa, 60 microg/kg). No thrombotic complications were detected. The management of CPB with UHF and tirofiban is a convenient option and rFVIIa seems appropriate to handle bleeding issues.

Nine-year routine clinical experience of aortic valve replacement with ATS mechanical valves.

BACKGROUND AND AIM OF THE STUDY: The study aim was to update the authors' experience with aortic valve replacement (AVR) using the ATS mechanical prosthesis in terms of early and long-term outcome in routine practice. METHODS: This retrospective analysis was extracted from clinical data available between April 1996 and February 2005, of AVR with the ATS Medical prosthesis in 510 consecutive patients (345 men, 165 women; mean age 62 +/- 12 years), of whom 296 underwent isolated AVR (iAVR). Concomitant surgical procedures included coronary artery bypass grafting (AVR+CABG, n = 47), mitral valve procedure (AVR+MVP, n = 59), ascending aortic replacement (AVR+AAR, n = 74) and other procedures (AVR+Miscellaneous, n = 34). Early and late morbidity/mortality were analyzed for the entire group in case of emergency surgery, preoperative low left ventricular ejection fraction (LVEF <50%) and in elderly people (age > or = 70 years). RESULTS: The overall 30-day mortality was 7.2% (iAVR 4.7%; AVR+CABG 4%; AVR+MVP 8.5%; AVR+AAR 2.9%; AVR+Miscellaneous 14.7%). The five- and nine-year global survival rates were respectively 81.14 +/- 2.4% and 67.02 +/- 10.4%. Long-term survival was lower in case of emergency surgery (p = 0.001), when the preoperative LVEF was <50% (p = 0.03), and when patients were aged > or = 70 years (p = 0.0005). Linearized postoperative valve-related death was 1.1% per patient-year (pt-yr). However, nine years' freedom from valve-related death and valve-related morbidity were not significantly different when the patient age was > or = 70 years. The linearized rate for postoperative thromboembolism complication was 0.4% per pt-yr, and that for postoperative bleeding complication 0.63% per pt-yr. There were two perivalvular leaks (0.05%/pt-yr). Neither valve thrombosis, structural dysfunction nor endocarditis were observed. CONCLUSION: The findings of this retrospective study point to a globally very good performance of the ATS valve, and essentially similar to previously reported results with these and other available mechanical valves.

Prevention of biliary lesions that may occur during radiofrequency ablation of the liver: study on the pig.

OBJECTIVE: To prevent bile duct injury by using a cold 5% glucose isotonic solution cooling in the bile ducts when radiofrequency (RF) is performed in a porcine model. SUMMARY BACKGROUND DATA: Complications that may arise during liver RF ablation include biliary stenosis and abscesses. METHODS: The RITA 1500 generator was used for the experiments. Two lesions were performed in the left liver. The pigs were killed 1 or 3 weeks after the procedure. An ex vivo cholangiogram was obtained by direct injection into the main bile duct. Samples of RF lesions, of liver parenchyma near and at a distance from the RF lesions, underwent pathologic studies. Two groups of 20 pigs each were treated: one without perfusion of the bile ducts and the other with perfusion of cold 5% glucose isotonic solution into the bile ducts. The Pringle maneuver was used in 50% of the RF procedures. Radiologic lesions were classified as biliary stenosis, complete interruption of the bile duct, or extravasation of the radiologic contrast liquid. RESULTS: Histologic lesions of the bile ducts were observed near the ablated RF lesion site and at a distance from the RF lesions when a Pringle maneuver was performed. Radiologic and histologic lesions of the bile ducts were significantly reduced (P < 0.0001) when the bile ducts were cooled. CONCLUSIONS: Cooling of the bile ducts with a cold 5% glucose isotonic solution significantly protects the intrahepatic bile ducts from damages caused by the heat generated by RF when performed close to the bile ducts.

Practical approach to the diagnosis and management of thrombocytopenia associated with tirofiban treatment.

Anti-GPIIb/IIIa associated thrombocytopenia has been reported in most large trials, but very little data is available regarding tirofiban. We report three cases of thrombocytopenia, most likely attributed to tirofiban (two moderate and one severe). For each patient, laboratory investigation has allowed us to exclude another cause of thrombocytopenia, particularly heparin-induced thrombocytopenia. Platelet count recovery could be earlier with tirofiban than with abciximab. Some suggestions are proposed for practical management of these patients with persistent thrombotic risk, who are sometimes candidates for cardiopulmonary bypass surgery.

Postoperative ventricular arrhythmias after cardiac surgery: immediate- and long-term significance.

AF is frequent after cardiac surgery. However, ventricular arrhythmias are less known. The purpose of the study was to evaluate the causes and the prognostic significance of severe ventricular arrhythmias occurring after cardiac surgery. For 10 years, among 2,100 cardiac surgeries, 16 (0.8%) patients (13 men, 3 women; age 49-71 years, mean 62 +/- 9 years) without previous ventricular arrhythmias, with preserved left ventricular ejection fraction, and without acute cause of ventricular arrhythmias, developed VF (n = 4) or a sustained VT between 3 days and 3 weeks after cardiac surgery (coronary artery bypass grafting [n = 6], valve replacement [n = 10]). Rapid AF (n = 5) or slow AF (n = 1) were present at the time of VT/VF. Programmed ventricular stimulation occurred after up to three extrastimuli in the basal state and after infusion of 20-30 micrograms of isoproterenol. An echocardiogram, coronary angiography, Holter monitoring with heart rate variability (HRV) study were performed. Ventricular stimulation was negative in six patients (with AF); sustained and clinical VT was induced in 10 patients with a left ventricular ejection fraction > 0.40, except in one patient. Valvular prothesis and coronary bypass graftings were normal. In all patients, HRV was normal before surgery and decreased after cardiac surgery; before versus after surgery, respectively, HR 69 +/- 9 and 89 +/- 30 beats/min (P < 0.01), SDNN 117 +/- 31 and 50 +/- 11 ms (P < 0.001), low frequency (LF) 474 +/- 658 and 51 +/- 40 ms2 (P < 0.05), high frequency (HF) 115 +/- 23 and 33 +/- 32 ms2 (P < 0.05), LF:HF 4 +/- 3 and 1 +/- 0.6 (P < 0.01). Follow-up lasted from 6 months to 10 years (mean 3 +/- 2 years). In patients without induced VT, 1 patient died from asystole, 1 had an ICD but no subsequent events, and the other 4 untreated patients are free of events. Patients with induced VT were treated with amiodarone and beta-blockers except in one patient who died from extracardiac complications. Six of nine patients had no inducible VT with this treatment and are alive; 3 patients had inducible VT, 1 died suddenly before implantation of ICD, and 2 patients are alive with an ICD; recurrent VTs were noted in one patient and received an ICD. In conclusion, recent heart surgery may increase the risk of ventricular arrhythmias. The reduction of indexes reflecting sympathetic and parasympathetic tone could facilitate the occurrence of atrial arrhythmias (and then VT) in patients without ventricular arrhythmogenic substrate or the development of VT/VF in patients with a latent previous ventricular arrhythmogenic substrate. In patients without inducible VT, the prognosis is excellent and an ICD is not recommended in these patients. In those with inducible VT, there is a high incidence of responders to antiarrhythmic drugs with a favorable prognosis.

Platelet activation induced by human antibodies to interleukin-8.

Some cases of heparin-induced thrombocytopenia (HIT) have been reported to be associated with antibodies against interleukin-8 (IL-8), a chemokine related to platelet factor 4. We found that sera from 5 HIT patients containing immunoglobulin G (IgG) or IgM antibodies to IL-8, as evidenced using surface plasmon resonance spectroscopy, were able to trigger IL-8-dependent activation of washed platelets, leading to procoagulant activity. This activation occurred at IL-8 concentrations achievable in vivo and was facilitated by heparin (0.1 U/mL). Activation was also induced by affinity-purified anti-IL-8 IgG and involved FcgammaRIIa. In the 2 patients who could be followed up, antibodies were no longer detectable 4 months after heparin withdrawal. One additional patient with paraneoplastic recurrent thrombosis without thrombocytopenia was found to have platelet-activating anti-IL-8 IgM, but in this case heparin was inhibitory. This is another example of potentially pathogenic platelet activation by antibodies.

Autologous cell transplantation and cardiac tissue engineering: potential applications in heart failure.

The promising concept of cell transplantation and cardiac tissue engineering has been developed in the last few years and focused on strategies attempting to replace dysfunctional, necrotic, and/or apoptotic cardiomyocytes with new cells of mesodermal origin. Transplantation of autologous cells minimizes the risk of neoplasia and avoids immune rejection associated with allogenic or xenogenic cells and recent data hold enormous hopes for short term clinical practices. Tissue engineering represents another promising approach that makes possible the creation of new functional tissues to replace the lost or failing one. Three-dimensional polymeric scaffolds provide the mechanical support for the candidate cells until the formation of cardiac-like tissue prior to surgical repair of the infarcted myocardium. For ultimate clinical applications, further investigations have to select the appropriate cell types, to determine the sufficient number of grafted cells and to provide the long term evaluation of these strategies in the global improvements of cardiac function (neoangiogenesis, synchronous contraction and extracellular matrix remodelling).