Reduced levels of both circulating CD4+ CD25+ CD127(low/neg) and CD4+ CD8(neg) invariant natural killer regulatory T cells in stable heart transplant recipients.

A cross-regulation between two regulatory T cell (T(reg) ) subsets [CD4(+) CD25(+) and invariant natural killer (NK) T - iNK T] has been described to be important for allograft tolerance induction. However, few studies have evaluated these cellular subsets in stable recipients as correlates of favourable clinical outcome after heart transplantation. T(reg) and iNK T cell levels were assayed by flow cytometry in peripheral blood samples from 44 heart transplant recipients at a 2-year interval in 38 patients, and related to clinical outcome. Multi-parameter flow cytometry used CD4/CD25/CD127 labelling to best identify T(reg) , and a standard CD3/CD4/CD8/Vα24/Vß11 labelling strategy to appreciate the proportions of iNK T cells. Both subtypes of potentially tolerogenic cells were found to be decreased in stable heart transplant recipients, with similar or further decreased levels after 2 years. Interestingly, the patient who presented with several rejection-suggesting incidents over this period displayed a greater than twofold increase of both cell subsets. These results suggest that CD4(+) CD25(+) CD127(low/neg) T(reg) and iNK T cells could be involved in the local control of organ rejection, by modulating immune responses in situ, in clinically stable patients. The measurement of these cell subsets in peripheral blood could be useful for non-invasive monitoring of heart transplant recipients, especially in the growing context of tolerance-induction trials.

Lower incidence of cytomegalovirus infection with everolimus versus mycophenolate mofetil in de novo cardiac transplant recipients: a randomized, multicenter study.

Cytomegalovirus (CMV) is a major cause of infectious complications following cardiac transplantation, severely affecting short- and long-term outcomes. A 12-month, multicenter, randomized, open-label study in de novo cardiac transplant patients was undertaken to compare the efficacy, renal function, and safety of everolimus plus reduced cyclosporine versus mycophenolate mofetil (MMF) plus standard cyclosporine (ClinicalTrials.gov NCT00150046). CMV-specific data was prospectively collected on infections, laboratory evidence, CMV syndrome, and CMV disease. In total, 176 patients were randomized (everolimus 92; MMF 84). Use of CMV prophylaxis was similar between groups (everolimus 20.8%; MMF 24.0%). Patients in the everolimus arm had a significantly lower incidence of any CMV event (8.8% versus 32.5% with MMF, P<0.001), CMV infection as an adverse event (4.4% versus 16.9%, P=0.011), laboratory evidence of CMV (antigenemia 7.7% versus 27.7%, P<0.001; polymerase chain reaction assay 2.2% versus 12.0%, P=0.015), and CMV syndrome (1.1% versus 8.4%, P=0.028). In the donor (D)+/recipient (R)+and D-/R+ subgroups, even after adjusting for use of prophylaxis, the CMV event rate remained significantly lower with everolimus than with MMF (P=0.0015 and P=0.0381, respectively). In conclusion, de novo cardiac transplant recipients experienced lower rates of CMV infection, CMV syndrome, or organ involvement on an everolimus-based immunosuppressant regimen compared with MMF.

[Paediatric cardiac surgery and autoevaluation: risk score, complexity score and graphic analysis]. / Chirurgie cardiaque pédiatrique et auto-évaluation: score de risque, score de complexité et analyses graphiques.

The creation of a paediatric surgical unit requires autoevaluation in order to: assess the quality of the results with respect to recognised international standards, answer the family's questions about the results obtained and adhere to criteria of accreditation Between January 2003 and December 2004, 201 consecutive patients, children (N= 164) or operated for adult congenital heart disease (N= 37) were treated. No patient was excluded. The RACHS-1 risk score, the ARISTOTLE scores of complexity and performance and the CUSUM and VLAD graphic analyses were applied to the study of hospital mortality. An original "variable performance-adjusted display" (VPAD) graphic analysis was performed to show up any possible variations of performance. Paediatric hospital survival was 97.56% (95% CI: 93.9 - 99.1). The paediatric complexity and performance scores were 6.79 +/- 0.22 and 6.62 respectively. In the absence of statistical significance in this field of autoevaluation, graphic analyses indicated the performance of our unit with no "learning" curves. Graphic scores and analyses allow assessment of the function of a paediatric cardiac surgical unit and the variations of complexity with respect to time, before the appearance of statistical significance. The ARISTOTLE complexity and performance scores and their adaptation in VPAD seem to be more reliable and discriminating than the RACHS-1 score.

[Late presentation of type A aortic arch blockage with a large type I aortopulmonary window]. / Présentation tardive d'une interruption de l'arche aortique de type A avec large fenêtre aorto-pulmonaire de type I.

We report the case of a 39 day old infant, hospitalised for congenital cardiopathy associated with type A blockage of the aortic arch with a large type I aortopulmonary window. The infant was in cardiogenic shock with pulmonary systemic hypertension and a tightly stenosed arterial canal (< 2 mm). With no possibility of re-opening the arterial canal under PGE1 at this stage, complete repair was performed as an emergency. After section of the aortopulmonary window, it was closed on the pulmonary side with a patch of autologous pericardium. Repair of the aortic arch was performed without prosthetic material, under selective cerebral perfusion to protect the brain parenchyma, after mobilisation of the descending thoracic aorta, which was anastomosed directly with the distal part of the window and aortic arch. Recovery was uncomplicated, with no residual lesion at 6 month post-operative follow up. The late clinical presentation of this patient shows the effect of medical management without prior catheterisation, with operative techniques minimising peri-operative tissular ischaemia and conserving aortic and pulmonary growth potential.

[Advanced cardiac failure. New surgical approaches]. / L'insuffisance cardiaque avancée. Approches chirurgicales actuelles.

THERAPEUTIC OPTIONS: Prognosis of advanced heart failure is ominous since survival rate is less than 65% one year after an acute and severe cardiac episode. Medical therapy has proven to be efficient in reducing fatal complications and in delaying critical evolution. Depending on the etiology and the myocardial status, new surgical approaches can also be proposed for repair or substitution. SURGICAL REPAIR: The beneficial effect of myocardial revascularization on severe ischemic cardiomyopathy, the relevance of mitral valve repair in dilated cardiomyopathy, and the advantage of ventricular remodeling in patients with major ventricular dyskinesia has been clearly demonstrated. All these surgical techniques improve ventricular function and enhance survival rate by about 70% after three years. SUBSTITUTION PROCEDURES: The best therapeutic option to recover heart function for normal life and reduced mortality remains, when possible, cardiac transplantation. Ventricular cardiac assist devices are planned as a temporary option to bridge the waiting period to transplantation or for myocardial recovery but can also be proposed as a chronic implantation in an outpatient care scheme. Cardiomyoplasty for therapeutic management of advanced cardiac failure is still a controversial surgical approach. Other clinical strategies such as transmyocardial laser revascularization, myocardial angiogenesis and myocardial cell therapy are being investigated or developed. ADAPTED TREATMENT: Optimal management of each patient with advanced heart failure requires an adequate treatment selected among a wide range of medical and/or surgical strategies.

[Reflections on external circulatory assistance. Apropos of 8 patients treated with the MEDOS system]. / Réflexions sur les assistances ventriculaires externes. A propos de huit patients traités par système MEDOS.

Mechanical circulatory support is required when cardiogenic shock is unresponsive to well conducted medical therapy. In this hemodynamic situation, when the patient's life is in danger, within hours, several questions should be answered quickly. These questions take into consideration the etiologies of cardiogenic shock and are related to the possibility of improvement of myocardial function, cardiac transplantation, the choice of uni- or biventricular support and surgical techniques of left ventricular assistance (left atrium to aorta or left ventricular apex to aorta). The follow-up of patients with circulatory support is complex. It requires to take into consideration hemodynamic, mechanical and hemobiological parameters as well as the peripheric organ function. We report in this article our clinical experience with eight patients that underwent circulatory support with Medos external ventricular assist device.

[Uni- or biventricular circulatory assist devices. Selection criteria and patients' follow-up, choice of device]. / Assistances uni- ou biventriculaires. Critères de sélection et de surveillance des patients, choix du dispositif.

Therapy of patients presenting with cardiogenic shock refractory to medical treatment can be undertaken with uni or biventricular circulatory assist devices. Pre implantation evaluation of patients is aimed at defining the etiology as well as the extent of uni versus biventricular heart failure, the possibility of recovery of myocardial function improvement of vital organ function and the possibility of cardiac transplantation. Circulatory assist devices must provide efficient support of the failing ventricles, allow recovery of myocardial function or cardiac transplantation under optimal circumstances. The choice of uni-biventricular support of total artificial heart is discussed as well as criteria useful in defining a therapeutic strategy.

[Bleomycin in Kaposi disease in a patient with heart transplantation]. / Bléomycine dans la maladie de Kaposi chez un transplanté cardiaque.

INTRODUCTION: Kaposi's disease is increasingly frequent in transplant recipients. The therapeutic approach in heart transplantation is not fully established. CASE REPORT: A 61-year-old male transplant recipient (June 1992) presented Kaposi's disease on the legs. Immunosuppressive therapy was reduced, cyclosporin by 20 p. 100, withdrawal of azathioprine and 40 p. 100 reduction in prednisone was insufficient to control the disease. Due to the extension of the lesions and the major functional handicap, bleomycin was given and led to complete regression of the lesions within 6 months. DISCUSSION: This case illustrates the difficult therapeutic situation encountered in heart transplant recipients. The situation may be life-threatening with organ rejection. The first step is to reduce immunosuppressive therapy. If this is insufficient or the Kaposi is particularly aggressive, bleomycin may be used. The efficacy of bleomycin observed in our case requires confirmation in multicenter studies.

[Viral pneumopathies after heart transplantation. Radioclinical analysis]. / Pneumopathies virales après transplantation cardiaque. Analyse radioclinique.

From a retrospective study of 80 cases of heart transplantation, the contribution of chest X-rays to the diagnosis of viral pneumonia was studied. Among 66 episodes of pneumonia, a viral cause was proved in 16 cases (CMV: 9, Herpes: 7), with 13 cases during the first 4 months. CMV pneumonia was revealed in 3 cases by a diffuse pulmonary infiltrate with a rapidity fatal outcome and in 6 cases by focal infiltrates that disappeared within 1 and 7 weeks. Herpes pneumonia was immediately revealed, in 5 cases, by a diffuse infiltrate. In 11 out of 16 cases, the viral pneumonia improved but its course was complicated by the development of another pneumonia.

[Herpes simplex virus pneumonia following transplantation]. / Pneumopathies à herpès simplex virus (HSV) chez les transplantés.

The HSV (1 or 2) is the cause of serious pulmonary infections among patients who have had a transplantation. This study in retrospect is based on the analysis of 145 patients who underwent a cardiothoracic transplant at the CHU. in Nancy. Confronted with clinical signs calling to mind breathing difficulties, the analysis of the broncho alveolar lavage (or of the bronchial brushing) revealed the viral aetiological agent. The answer from the laboratory is quickly available by immunofluorescence or by immunoperoxidase with viral anti-protein monoclonal antibodies and by the multiplication in vitro of the virus into cell cultures. The HSV 1 was responsible for 8 herpetic lung infections. The specific Acyclovir treatment was used 6 times successfully. When such a direction of treatment was impossible (in 2 cases) the outcome was fatal. The carry HSV is highly frequent and recurrences under immuno-suppressor treatment require an Acyclovir prophylaxis among patients admittedly carrying the virus in a pre-transplanted serum assessment.

[Atrial natriuretic factor after heart-lung transplantation. Consequences of cardiac denervation]. / Facteur atrial natriurétique après transplantation cardio-pulmonaire. Conséquences de la dénervation cardiaque.

Due to the discovery and elaboration of alpha ANP, the heart can be considered a veritable endocrine gland involved in fluid and electrolyte homeostasis as well as blood pressure regulation. Nevertheless, the mechanisms regulating the synthesis and release of this new hormone are far from being understood. Heart-lung transplantation provides an interesting research model for evaluating the consequences of allograft denervation on alpha ANP synthesis and release, without the disadvantage of significantly increasing the overall atrial tissue mass, as observed in orthotopic heart transplantation. To appreciate better these consequences, we studied the changes in alpha ANP release following heart-lung transplantation. Five patients were included in the study. It began during the immediate postoperative period and went on to the 8th postoperative day. Alpha ANP levels were determined using radioimmunoassay. The postoperative course was characterized by a rapid significant increase in hormone levels as of the 6th postoperative day (45.6 +/- 5.5 fmol/ml). These findings were comparable to those found in a previous study involving orthotopic heart transplantation alone. Thus, the heart-lung group was also capable of high levels of alpha ANP release from the onset. However, this rapidly increasing release was not found to be correlated with the changes in hemodynamic parameters observed postoperatively (blood and cardiac filling pressures). Moreover, we observed no episodes of rejection which might explain the increased release of this hormone. Finally, the fact that increased alpha ANP release occurs despite a smaller increase in the overall tissue mass is more than noteworthy. In conclusion, as we found in our initial study involving heart transplant recipients, the sustained high levels of alpha ANP observed following heart-lung transplantation are in favour of a possible modulating role played by cardiac innervation on the release of this hormone.

Short-term effects of human orthotopic heart transplantation on hormones regulating fluid and electrolyte balance.

Hormonal regulation of fluid and electrolyte homeostasis and blood pressure is under the auspices of three organs: the heart, the brain, and the kidneys. Their regulatory roles are fulfilled by the actions of atrial natriuretic peptide (ANP), vasopressin, and the renin-angiotensin-aldosterone system (RAAS), respectively. The aim of this study was to appreciate the short-term effects of orthotopic human heart transplantation on the release of these hormones. Alpha-ANP, renin, aldosterone, and vasopressin serum levels were assessed by radioimmunoassay before and during the 10 days after grafting in a series of 10 patients. On day 1, alpha-ANP levels dropped from 42.4 +/- 6.5 to 25.1 +/- 2.2 fmol/ml before returning to levels comparable with those found before transplantation. This decrease in alpha-ANP levels was associated with a peak in vasopressin and aldosterone levels. With the exception of the peak in vasopressin levels seen on day 1, preoperative and postoperative levels of this hormone were near normal. Increased preoperative renin levels dropped significantly as of day 5 (from 268 +/- 99 to 122 +/- 66 ng/L). This decrease was related to improved patient hemodynamic status. No significant correlation was found between the changes in alpha-ANP levels, RAAS or vasopressin levels, patient hemodynamic status, or administered drugs. In conclusion, grafted heart tissue was capable of high alpha-ANP release early on. The drop in alpha-ANP serum levels, compared with the peaks in vasopressin and aldosterone on day 1, might have been caused by the ability of the graft to play a role in the hormonal regulation of fluid and electrolyte balance.(ABSTRACT TRUNCATED AT 250 WORDS)

[Value of continuous venous blood oxygen measurement during external circulatory assistance]. / Intérêt de la mesure en continu de la SvO2 pendant une assistance circulatoire externe.

A case is reported of a 40 year-old man, on the waiting-list for heart transplantation, who developed terminal heart failure. Using an Opticath catheter and a radial artery catheter, SV(-)O2 was monitored continuously, and cardiac output, pulmonary arterial and wedged pressures, and right atrial pressure were repeatedly measured. Despite appropriate treatment (adrenaline, dobutamine, glyceryl trinitrate), the patient remained in anuria and cardiogenic shock. External circulatory support (ECS) (BVS 5000 Abiomed) was therefore used as a bridge to cardiac transplantation. The resultant increase in systemic blood flow led to an early and fast rise in SV(-)O2, from 40% to 73%, with a decrease in the oxygen extraction ratio (ERO2) from 50 to 30%. Serum lactate concentrations returned to normal within the first six hours of ECS (less than 120 mg.l-1). During the first 24 h of ECS, SV(-)O2 decreased and ERO2 rose significantly on two occasions: during an episode of shivering, and another of restlessness during nursing. An attempt at weaning the patient from the ventilator at the 39th h also led to a sudden decrease in SV(-)O2, with a rise in ERO2. The Opticath catheter was finally removed after 150 h of ECS because of a decrease in reflected light intensity.

Prevalence and causes of long-lasting hepatic dysfunction after heart transplantation: a series of 80 patients.

The long-term follow-up of 80 heart transplant patients (70 men, 10 women) from January 1982 to July 1985 who had received cyclosporine (CsA) showed a high incidence of mild to severe liver dysfunction. Fifty patients (62.5%) had long-lasting postoperative biological disturbances (alanine amino transferase greater than 2N and/or alkaline phosphatase greater than 1.5N for 3 months or more). Most patients were asymptomatic; eight were icteric, and one had arthralgia. The most common biological feature consisted of isolated elevation of ALAT (27 cases). Assessment of causes led to a definite etiology in 42 patients: 7 cardiac failure, 13 HBsAg-positive liver disease (26%) (chronic persistent hepatitis 8, chronic active hepatitis 2, subacute necrosis 2). Fourteen patients (28%) sustained non-A, non-B (NANB) hepatitis (chronic persistent hepatitis 5, chronic active hepatitis 1, cirrhosis 1), and 7 (14%) sustained a drug-related hepatitis. Liver biopsy and complete virus screening was contributive to the diagnosis in nearly all patients. Additionally, prolonged impairment of liver function tests occurred in 62% of heart transplant recipients, mostly during the first 6 postoperative months. Hepatitis B virus (HBV) and NANB hepatitis accounted for 26% and 28% of the cases of liver dysfunction, respectively; drug-induced hepatitis may have been involved in 14% of the cases. Complete hepatitis virus screening should be performed before heart transplant and in any case of abnormal liver function posttransplantation. HBV vaccination prior to heart transplant is recommended in HBsAg- and HBcAb-negative candidates for heart replacement. Long-term follow-up of these patients is mandatory to assess the severity of these liver dysfunctions.

Early and late hemodynamic evaluation after cardiac transplantation: a study of 28 cases.

Right heart catheterization was performed in 28 patients 1 week and 6 to 24 months after orthotopic cardiac transplantation. All patients were receiving cyclosporine and methylprednisolone orally. At early catheterization, right heart pressures as well as pulmonary capillary wedge pressure still remained above normal values in the majority of patients. Systemic arterial hypertension was already present in 29% of the patients and cardiac index was usually in the normal range, without any inotropic support. Results of late catheterization showed continuing improvement with return of right heart pressures to normal values in most but not all patients. Systemic arterial hypertension was noted in nearly all patients and is likely to be the result of hypervolemia secondary to cyclosporine-induced sodium retention. The increase in cardiac index, which was above normal values in 39% of the patients, was also consistent with hypervolemia in the setting of cardiac denervation. Thus, cardiac function at rest is satisfactory at short- and long-term assessment after cardiac transplantation, but the development and persistence of systemic arterial hypertension associated with cyclosporine use are a matter of concern in such patients.

Endarterectomy of the left main coronary artery stenosis by a 'transpulmonary artery approach'.

For better visualization of the left main coronary artery, a new technique involving transection of the main pulmonary artery is described. With this new method it was possible to perform endarterectomy of the left main coronary artery in 35 patients from February 1981 to July 1987. The endarterectomy incision was closed with a pericardial or venous patch. We had no mortality, and 91% are free from angina at a mean follow-up of 31 months. Angiographic evaluation was performed in 19 patients revealing good patency of the left main artery. This procedure is safe, and we recommend it in isolated left main coronary artery stenosis without distal involvement and with good left ventricular function.