Pablo Maureira

Short-term heart retention and distribution of intramyocardial delivered mesenchymal cells within necrotic or intact myocardium.

Cell therapy with bone marrow mesenchymal stem cells (BMSCs) is a new strategy for treating ischemic heart failure, but data concerning the distribution and retention of transplanted cells remain poor. We investigated the short-term myocardial retention of BMSCs when these cells are directly injected within necrotic or intact myocardium. 111Indium-oxine-labeled autologous BMSCs were injected within either 1-month-old infarction (n = 6) or normal myocardium (n = 6) from rats. Serial in vivo pinhole scintigraphy was scheduled during 1 week in order to track the implanted cells. The myocardial retention of BMSCs was definitely higher in myocardial infarction than in normal myocardial area (estimated percent retention at 2 h: 63 ± 3% vs. 25 ± 4%, p < 0.001) and the estimated cardiac retention values were unchanged in both groups along the 7 days of follow-up. On heart sections at day 7, labeled BMSCs were still around the injection site and appeared confined to the scarred tissue corresponding either to the infarct area or to the myocardium damaged by needle insertion. BMSCs have a higher retention when they are injected in necrotic than in normal myocardial areas and these cells appear to stay around the injection site for at least a 7-day period.

Repairing chronic myocardial infarction with autologous mesenchymal stem cells engineered tissue in rat promotes angiogenesis and limits ventricular remodeling.

BackgroundTissue engineering scaffold constitutes a new strategy of myocardial repair. Here, we studied the contribution of a patch using autologous mesenchymal stem cells (MSCs) seeded on collagen-1 scaffold on the cardiac reconstruction in rat model of chronic myocardial infarction (MI).MethodsPatches were cultured with controlled MSCs (growth, phenotype and potentiality). Twenty coronary ligated rats with tomoscingraphy (SPECT)-authenticated transmural chronic MI were referred into a control group (n = 10) and a treated group (n = 10) which beneficiated an epicardial MSC-patch engraftment. Contribution of MSC-patch was tested 1-mo after using non-invasive SPECT cardiac imaging, invasive hemodynamic assessment and immunohistochemistry.Results3D-collagen environment affected the cell growth but not the cell phenotype and potentiality. MSC-patch integrates well the epicardial side of chronic MI scar. In treated rats, one-month SPECT data have documented an improvement of perfusion in MI segments compared to control (64 ± 4% vs 49 ± 3% p = 0.02) and a reduced infarction. Contractile parameter dp/dtmax and dp/dtmin were improved (p & 0.01). Histology showed an increase of ventricular wall thickness (1.75 ± 0.24 vs 1.35 ± 0.32 mm, p &0.05) and immunochemistry of the repaired tissue displayed enhanced angiogenesis and myofibroblast-like tissue.Conclusion3D-MSC-collagen epicardial patch engraftment contributes to reverse remodeling of chronic MI.

Residual viability is a predictor of the perfusion enhancement obtained with the cell therapy of chronic myocardial infarction: a pilot multimodal imaging study.

Purpose Up to now, there has been limited investigation into cell therapy in the chronic phase of severe myocardial infarction (MI), and many questions remain concerning the contribution of the engrafted cells and especially their impact on the reperfusion of MI areas, when assessed by objective quantitative imaging techniques. This randomized pilot SPECT, PET, and MRI study was aimed at assessing the effects of bone marrow mononuclear cells (BMNCs) when implanted in areas of severe and chronic MI. Materials and Methods Fourteen patients, who were referred for coronary artery bypass grafting (CABG) and in whom a screening MIBI-SPECT revealed severely damaged myocardium (<50% uptake under nitrate), were randomized between a cell therapy group (n = 7; CABG and injection of BMNCs within MI areas) and a control group (n = 7; CABG alone). Results The MI areas exhibited a posttherapeutic enhancement in the rest–uptake of MIBI in the cell therapy group [difference between 6-month control and baseline: +6.8% (5.4%), P = 0.03] but not in the control group [+1.0% (4.3%)]. However, in a per-patient analysis, this improvement was significant (> +9%) in only 3 cell therapy patients, whose MI areas before therapy had a higher FDG uptake [59% (9%) vs 38% (8%), P = 0.03] and a lower transmural extent at MRI [40% (6%) vs 73% (18%), P = 0.03] when compared with the other cell therapy patients. Conclusions Perfusion enhancement, obtained with BMNCs in areas of chronic MI, might require an intermediate level of viability documented with FDG-PET and MRI and that totally necrotic MI seems refractory to this cell therapy technique.

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.

Use of the model for end-stage liver disease score for guiding clinical decision-making in the selection of patients for emergency cardiac transplantation

OBJECTIVES The outcomes of emergency cardiac transplantation remain controversial, but recipient selection is essential for success. With a shortage of organs, it is essential to determine an objective method, such as a risk score, for choosing patients who are at too great a risk to undergo cardiac transplantation. In this study, we analysed the model for end-stage liver disease in terms of predicting operative mortality after emergency cardiac transplantation. METHODS We analysed the Nancy University database of heart transplantation and selected all patients who underwent emergency heart transplantation between January 2005 and January 2012. The calibration and discriminatory power were evaluated to determine the model for end-stage liver disease (MELD) score. Preoperative and peri-operative variables regarding the prediction of operative mortality were analysed by univariate and multivariate logistic regression models. RESULTS Forty-three patients underwent emergency cardiac transplantation. The operative mortality was 20.9% (n = 9). The Hosmer-Lemeshow test demonstrated a calibrated model for predicting operative mortality (P = 0.15), and the MELD score presented an excellent discrimination between survivors and non-survivors (AUC: 0.89 ± 0.05; 95% CI: 0.79-0.99). In the univariate analysis, an MELD score of ≥ 16 and bilirubin concentration were predictive markers of operative mortality. Multivariate logistic regression tested the contribution of the univariate risk predictors (P < 0.15) and confirmed that an MELD score of ≥ 16 was predictive of operative mortality. CONCLUSIONS The MELD score appears to be adequate for predicting operative mortality among patients who undergo heart transplantation. The MELD score could therefore be used to guide clinical decision-making for emergency transplantation.

Surgery for Acute Type A Aortic Dissection in Octogenarians

Abstract  Background and aim: Emergency surgery for type A aortic dissection (AAD) is associated with high mortality rates. The published outcomes of such surgery in aging patients are controversial and the optimal management for elderly patients has not been established. Our study aimed to evaluate the outcomes of surgery for AAD in patients over the age of 80 years. Materials and Methods: Between January 1996 and January 2010, 236 patients underwent surgery for AAD, of which 15 patients were older than 80 years. We evaluated the operative mortality in the whole cohort compared to the outcomes in the elderly subgroup. We assessed the preoperative risks factors and quality of life after surgery by performance status and the patients’ ability to return home. Results: Operative mortality was higher in patients aged >80 years (40% vs. 18%, p = 0.04). The survival rate for patients >80 years at one, three, and five years was 53.3%± 0.12%, 42.6%± 0.14%, and 42.6%± 0.12%, respectively. Of the survivors, six patients were able to return home (40%) and the postoperative performance status was “3” in one patient, “2” in six patients, and “1” in two patients. A preoperative level of 2 or greater was found to be a significant risk factor (p = 0.04). Conclusion: Survival in octogenarians undergoing surgery for AAD is possible, and some patients were able to return home with a reasonable level of autonomy. Larger series will be needed to define the optimal management for octogenarians presenting with AAD.
(J Card Surg 2012;27:65–69)

Bilateral internal mammary artery bypass grafting: long-term clinical benefits in a series of 1000 patients

Objective Bilateral internal mammary arteries (BIMA) remain widely underused in coronary artery bypass grafting (CABG). In this study, we aim to investigate the early and long-term outcomes of BIMA grafts in isolated CABGs. Design Single-centre retrospective observational study. Setting University Hospital, Nancy. Patients 1000 consecutive patients undergoing elective, isolated, primary, multiple CABGs using BIMA grafts and supplemental venous grafts for multi-vessel coronary disease. Main outcome measures In-hospital mortality and major morbidity, and long-term all-cause mortality. Results Mean age of the overall population was 60±15 years. A left ventricular ejection fraction (LVEF) ≤45% was found in 28% of the patients and 27.1% of the patients were diabetics. Comorbidities were represented by chronic renal failure, chronic obstructive pulmonary disease and peripheral artery disease in 11, 11.7 and 27.3% of the cases, respectively. The in-hospital mortality rate was 2.8%. Early postoperative morbidity included myocardial infarction (2.2%), stroke (0.9%), mesenteric ischaemia (0.7%) and mediastinitis (2.2%). The Kaplan–Meier 8-year survival rates for patients less than 65 and between 65 and 74 years of age were 88% and 66%, respectively (p<0.01). Multiple regression analysis showed that patients’ age 65 years or greater at baseline (OR 2.3; 95% CI 1.3 to 4, p<0.001), acute coronary syndrome (OR 1.9; 95% CI 1.1 to 3.4, p=0.02), chronic renal failure (OR 2.7; 95% CI 1.4 to 5.2, p<0.001), peripheral artery disease (OR 3.1; 95% CI 1.8 to 5.5, p<0.001) and LVEF ≤45% (OR 2.6; 95% CI 1.4 to 4.5, p<0.001) were independent predictors of long-term cardiovascular mortality. Conclusions Our longitudinal analysis presents encouraging data concerning operative risk of BIMA grafting and provides excellent long-term survival in appropriately selected patients.

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.

Robotic total endoscopic sutureless aortic valve replacement: proof of concept for a future surgical setting

Sutureless valves have recently enabled closed chest aortic valve replacement. This paper evaluates the feasibility of a robotic telemanipulation during thoracoscopic sutureless aortic valve implantation in cadavers.