Jean Pierre Villemot

Detection and prediction of acute heart transplant rejection with the myocardial T2 determination provided by a black-blood magnetic resonance imaging sequence

OBJECTIVES This study aimed to determine whether the myocardial T2 relaxation time, determined using a black-blood magnetic resonance imaging (MRI) sequence, could predict acute heart transplant rejection. BACKGROUND The use of black-blood MRI sequences allows suppression of the confusing influence of blood signal when myocardial T2 is calculated to detect myocardial edema. METHODS A total of 123 investigations, including cardiac MRI and myocardial biopsy, were performed 8 +/- 11 months after heart transplantation. Myocardial T2 was determined using an original inversion-recovery/spin-echo sequence. RESULTS A higher than normal T2 (> or = 56 ms) allowed an accurate detection of the moderate acute rejections evidenced at baseline biopsy (> or = International Society for Heart and Lung Transplantation grade 2): sensitivity, 89% and specificity, 70% (p < 0.0001). T2 was increased in grade 2 (n = 11) compared with grade 0 (n = 49, p < 0.05), grade 1A (n = 34, p < 0.05) and grade 1B (n = 21, p < 0.05); T2 was further increased in grade 3 (n = 8) compared with grade 2 (p < 0.05). In addition, in patients without rejection equal to or greater than grade 2 at baseline, a T2 higher than normal (> or = 56 ms) was correlated with the subsequent occurrence of equal or greater than grade 2 rejection within the next three months: sensitivity 63% (12/19) and specificity 78% (64/82) (p = 0.001). CONCLUSIONS Myocardial T2 determined using a black-blood MRI sequence, is sufficiently sensitive to identify most of the moderate acute rejections documented with biopsy at the same time, but is also a predictor of the subsequent occurrence of such biopsy-defined rejections.

Changes in hemodynamic and metabolic parameters following induced brain death in the pig.

Changes in hemodynamic and metabolic parameters (systemic oxygen delivery, [DO2], oxygen consumption [VO2], arterial lactate content) in brain-dead and control pigs in the absence of any inotropic or fluid support were studied. Brain death was induced by the inflation of a Foley catheter balloon placed into the subdural space of the animals. Serial atrial natriuretic peptide (ANP) determinations were performed to evaluate concomitant changes occurring in the endocrine function of the heart. Experiments were completed by a volume expansion protocol to provide a dynamic evaluation of these parameters. A significant increase in heart rate (from 113 +/- 5 to 176 +/- 11 beats/min), pulmonary capillary wedge pressure (from 7 +/- 1 to 12 +/- 3 mmHg), dP/dt (from 2040 +/- 340 to 4200 +/- 660 mmHg/sec-1), cardiac output (from 2.4 +/- 0.2 to 3.3 +/- 0.4 L/min), mean arterial pressure (from 66 +/- 8 to 93 +/- 14 mmHg), and systemic oxygen delivery (from 360 +/- 30 to 530 +/- 90 ml/min-1), was observed following brain death induction. These parameters returned below basal values within 60 min. On the contrary, serum lactate and VO2 remained unchanged. Following volume expansion, brain-dead pigs exhibited impaired hemodynamic response, with a significant decrease in dP/dt, MAP, and DO2. These changes were accompanied by a significant decrease in VO2 and a significant increase in lactate plasma levels. At the same time, a similar increase in ANP release was observed in both groups in response to volume expansion, suggesting that despite impaired myocardial contractility, endocrine function of the heart was preserved following brain death. We conclude that brain death leads to early impaired left ventricular contractility, which could be responsible for the changes observed in aerobic to anaerobic metabolism in response to rapid volume infusion. These results suggest that the use of fluid infusion to reduce the need in inotropic support in conventional therapeutic modalities should be used with care in the management of a brain-dead potential organ donor.

Microdialysis in the estimation of interstitial myocardial neuropeptide Y release

The purpose of this study was to investigate the feasibility of cardiac microdialysis for the in vivo estimation of cardiac interstitial peptide concentrations, and, to determine the changes in neuropeptide Y release in myocardial tissue during experimental brain death in pigs. Using a specifically designed concentric flexible probe, perfused with Ringer solution containing 0.5% of bovine serum albumin at a flow rate of 2 microliters/min, allowed us to obtain a 23 +/- 2% relative recovery rate in vitro. Based on these in vitro recovery data, a regional study of the kinetics of interstitial NPY levels following brain death was obtained by monitoring the changes in NPY dialysate levels recorded from dialysis probes implanted into the right and left ventricular walls of the beating heart in vivo. Basal dialysate NPY levels determined by radioimmunoassay were of 95.2 +/- 7.0 and 93.2 +/- 9.1 pmol/l in left and right ventricle, respectively. Brain death was followed by a sustained 2 h increase in NPY dialysate levels in both ventricles (peak levels: 173.2 +/- 30.9 pmol/l in left ventricle, and 149.7 +/- 23.9 pmol/l in right ventricle), which then returned to control levels. We conclude that cardiac microdialysis is a simple and promising new tool for evaluating the role of peptides in cardiovascular regulation.

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.

Activation of metalloproteinase-2, loss of matrix scleroprotein content and coronary artery calcification

Plaques from the coronary arteries of explanted hearts showed massive calcification (15-fold increase) with a loss of scleroproteins (-36%), an increase in the collagen to elastin ratio (twofold) and activation (+15%) of matrix metalloproteinase-2 (MMP-2). Plaque-free portions of the coronary artery gave results similar to those obtained with the internal mammary artery. There was a significant correlation between plaque calcification and MMP-2 activation, suggesting that the two processes may be linked.

Comparison of low and high initial tacrolimus dosing in primary Heart transplant recipients: A Prospective European Multicenter Study

Background. The purpose of this prospective, randomized, open-label, phase II, multicenter study was to optimize the initial oral dose of tacrolimus. Methods. A total of 113 patients were randomly assigned to initial low-dose (0.075 mg/kg/day, n=55) or high-dose (0.15 mg/kg/day, n=58) oral tacrolimus and followed for 3 months. Target whole-blood trough levels were 10 to 20 ng/mL. Prophylactic use of corticosteroids and azathioprine was identical in both groups, and antibody induction was mandatory. The primary endpoint was the time to and incidence of the initial oral tacrolimus dose adjustment because of toxicity or rejection, or withdrawal before initial dose change. Efficacy was assessed by the occurrence of biopsy-proven rejection (International Society for Heart and Lung Transplantation grade ≥1B). Results. In the primary endpoint, no significant difference was observed between the low- and high-dose groups. After 3 months, there was no difference in freedom from initial oral tacrolimus dose change because of rejection, toxicity, or withdrawal (89.0% vs. 87.6%; not significant [NS]). In both groups, dose adjustments were mainly required to achieve and maintain target blood levels (80.0% vs. 82.8%; NS). Patient survival was 92.7% and 98.3% (NS). There was no significant difference between groups regarding freedom from biopsy-proven acute rejection (57.1% vs. 66.3%; NS). The overall safety profiles indicated a tendency toward better tolerability in the low-dose group. Conclusions. Although low-dose and high-dose tacrolimus had similar efficacy, low-dose tacrolimus was associated with a more favorable safety profile. Therefore we recommend starting tacrolimus therapy after antibody induction at 0.075 mg/kg and adjust dose according to whole-blood trough levels.

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).

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.

Bilateral vs unilateral internal mammary revascularization in patients with left ventricular dysfunction

AIM To investigate the survival benefit of bilateral internal mammary artery (BIMA) grafts in patients with left ventricular dysfunction. METHODS Between 1996 and 2009, we performed elective, isolated, primary, multiple cardiac arterial bypass grafting in 430 consecutive patients with left ventricular ejection fraction ≤ 40%. The early and long-term results were compared between 167 patients undergoing BIMA grafting and 263 patients using left internal mammary artery (LIMA)-saphenous venous grafting (SVG). RESULTS The mean age of the overall population was 60.1 ± 15 years. In-hospital mortality was not different between the two groups (7.8% vs 10.3%, P = 0.49). Early postoperative morbidity included myocardial infarction (4.2% vs 3.8%, P = 0.80), stroke (1.2% vs 3.8%, P = 0.14), and mediastinitis (5.3% vs 2.3%, P = 0.11). At 8-year follow-up, Kaplan-Meier-estimated survival (74.2% vs 58.9%, P = 0.02) and Kaplan-Meier-estimated event-free survival (all cause deaths, myocardial infarction, stroke, target vessel revascularization, heart failure) (61.7% and 41.1%, P < 0.01) were significantly higher in the BIMA group compared with the LIMA-SVG group in univariate analysis. The propensity score matching analysis confirmed that BIMA grafting is a safe revascularization procedure but there was no long term survival (P = 0.40) and event-free survival (P = 0.13) in comparison with LIMA-SVG use. CONCLUSION Our longitudinal analysis suggests that BIMA grafting can be performed with acceptable perioperative mortality in patients with left ventricular dysfunction.

Ventricular Dysfunction in Patients with Acute Coronary Syndrome Undergoing Coronary Surgical Revascularization: Prognostic Impact on Long-Term Outcomes

Background Patients with non-ST elevation acute coronary syndrome complicated by left ventricular dysfunction (LVEF) are a poor prognosis group. The aim of our study was to assess the short and long term LEVF prognostic value in a cohort of NSTE-ACS patients undergoing surgical revascularization. Methods We performed elective and isolated CABG on a cohort of 206 consecutive patients with LVEF≤0.40 complicating acute coronary syndrome. The case cohort was compared with a cohort of controls (LVEF>0.40) randomly selected (2:1) among patients who underwent the procedure during this period. Results The Kaplan-Meier 5-year estimated survival rates for patients in the low and normal LVEF groups were 70.8% (95% confidence interval CI: 64.2–77.4) and 81.7% (95%CI: 77.8–85.6), respectively. A low LVEF was associated with both a higher all-cause (HR [95%CI] = 1.84[1.18–2.86]) and a higher cardiovascular mortality (HR = 2.07 [1.27–3.38]) during the first 12 months of follow-up. After adjustment for potential confounders, a low LVEF remained associated with a higher cardiovascular mortality only (1.87[1.03–3.38]) during the first 12 months of follow-up. After 12 months of follow-up, a low LVEF was no more associated with all-cause, nor cardiovascular mortality. Conclusion Patients with low LVEF might require more intensive care than patients with normal LVEF during the year after the surgical procedure, but once the first postoperative year over, the initial low LVEF was no more associated with long term mortality.