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.

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.

[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.

Surgical correction of chronic postembolic obstructions of the pulmonary arteries.

Following episodes of pulmonary embolism, the presence of thrombi in the pulmonary arteries leads to severe respiratory insufficiency and chronic right heart failure. We have operated upon 16 such patients, nine men and seven women from 23 to 68 years of age. All had severe dyspnea, 14 had chronic cor pulmonale, six had mental disturbances with syncope, and four had severe cardiac failure. The presence of clots was demonstrated by pulmonary angiography, and the permeability of the distal arterial bed was ascertained by selective injection of the bronchial arteries. In all cases but two a lateral thoracotomy was used so that the obstructed arterial branches could be approached distally. The inferior vena cava was always ligated to prevent recurrences. There were six operative deaths, three from cardiac failure, one from acute pulmonary edema, one from hemothorax, and one following a pyothorax. Ten patients are surviving after 6 months to 10 years. One is still limited because of significant pleuropulmonary sequelae. Six are enjoying good results with marked improvement in their functional limitations, a significant drop in the pulmonary artery pressure, and radiological permeability of previously obstructed arteries. Three are excellent condition--completely asymptomatic.

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)

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.

Surgical treatment of acute dissection of the aorta superimposed on pre-existing aneurysm of the ascending aorta. Total replacement of the ascending aorta with reimplantation of the coronary arteries. A report on five cases.

Five cases of acute dissection of the ascending aorta superimposed on a pre-existing aneurysm, including two with propagation of the dissection into the coronary arteries, were treated by total replacement of the ascending aorta utilizing a valve containing tube graft and reimplantation of the coronary arteries. Diverse techniques such as the use of an intermediate tube for reconnecting the coronary arteries, correction of the coronary dissection by reapproximation of the two layers or with bypass grafting, support of the distal aortic suture line with Teflon felt and fistulization of the periprosthetic space to the right atrium, greatly simplified the treatment of these lesions, permitting survival of four out of five patients, who are in excellent health one, four, and seven years respectively after surgery.

[Aneurysm of Valsalva's sinus, apropos of 7 surgical cases[]. / Anévrismes du sinus de Valsalva, à propos de 7 cas opérés.

The authors describe 7 cases of rupture of the Valsalva sinus. Until rupture the aneurysm is silent. Aortic insufficiency and left to right shunt are major components of this syndrome. Surgical treatment under extra-corporal circulation needs aortotomy and an approach of the ruptured extremity to close the defect and maintaining the integrity of the valvular structures.

[Surgical result of 48 Bigelow myotomies for obstructive myocardiopathy]. / Résultat chirurgical de 48 myotomies de Bigelow pour myocardiopathie obstructive.

Bigelow's myotomy is one of the surgical options available for the treatment of hypertrophic obstructive cardiomyopathy (HOCM). The results of this operation were analysed in 48 cases operated between 1965 and May 1983. The average age of the patients was relatively low (38 years) but preoperative symptoms were severe (34 patients in Class III and 6 patients in Class IV of the NYHA Classification). The diagnosis was confirmed in all cases by echocardiography, carotid pulse tracings and cardiac catheterisation. 28 patients had associated lesions including 21 cases of mitral regurgitation (minimal in II cases, moderate in 6 cases and severe in 4 cases). All patients underwent Bigelow myotomy which was associated with a complementary procedure in 9 cases (including 2 mitral valve replacements and 2 semi-circular annuloplasties). The hospital mortality was 6 patients; surgical morbidity resulted from permanent intraventricular conduction defects (27 cases). At long-term, 3 more patients died, 2 from cardiac causes. Of the remaining 39 patients followed-up for an average of 32 months, functional improvement was marked, except in very advanced stages of the disease (Class IV) or forms with severe or uncorrected mitral regurgitation. The indications for Bigelow myotomy are discussed with reference to three parameters of HOCM (intraventricular pressure gradient, mitral regurgitation, decreased left ventricular compliance). This procedure has a beneficial effect on the subaortic stenosis and left ventricular compliance. It should be completed by mitral valve surgery in patients with significant regurgitation.

[Value of C-reactive protein in the cardiac postoperative period]. / Intérêt de la CRP en postopératoire cardiaque.

Twenty patients underwent special clinical and biological monitoring during their period of hospitalisation in the Department of cardiovascular surgery. The clinical monitoring concentrated on the patient's temperature and the search for postoperative complications; the biological part of the study was concerned with monitoring the levels of serum C-Reactive protein (CRP) as assessed by an immuno-nephelometric method. In 10 patients with a normal postoperative course the levels of this protein, an indicator of an inflammatory or infective process, were similar, giving an identical graph in all patients. On the other hand, in the 10 patients with inflammatory or infective postoperative complications, the levels of CRP were abnormal, parallel with the clinical state, sometimes rising even before the complication manifested itself clinically. It therefore seems useful and justified to measure CRP systematically, once before surgery and at least once daily in the postoperative period. The frequency of this investigation could be increased in patients with difficult or complex postoperative courses. A high CRP, even with a normal temperature, should alert the surgeon to a complication or to the inefficacy of anti-inflammatory or anti-infective therapy. These results confirm those published by other surgical teams, both in cardiovascular surgery and traumatology.

[Heart transplantation. Experience at La Pitié hospital. Apropos of 82 cases]. / La transplantation cardiaque. L'expérience de La Pitié. A propos de 82 cas.

Since 1968, 320 patients with severe irreversible myocardial failure, have been referred to our department for transplantation; 78 p. 100 had dilated cardiomyopathies; 14 p. 100 had ischaemic heart disease and 8 p. 100 had valvular heart disease. One hundred and five patients had absolute contra-indications and were excluded (pulmonary hypertension, diabetes, gastro-duodenal ulcer, age, or other major organic disease). Of the remaining 215 patients, only 82 were transplanted because of the limited number of available donor hearts. The most commonly used technique was orthotopic grafting as described by Lower and Shumway; Barnard's method of heterotopic grafting was used in 1 case and a block heart and lung transplantation by Reitz and Shumway's method was performed in 3 cases. The main postoperative complications, apart from technical problems (7 deaths), were related to rejection (107 episodes, 27 deaths), infection (82 episodes, 13 deaths), atherosclerosis of the graft (4 cases, 2 deaths, 1 retransplantation) and malignant tumours (3 deaths). After transplantation, 82 p. 100 of patients were discharged after an average hospital stay of 2 months; 47 p. 100 survived the first year and lead almost normal socio-professional activities. Thirty patients are still alive, the longest postoperative survival being 9 years. Significant advances have been made in the last 3 years. Classical immuno-suppressor therapy (steroids, azathioprine, horse antilymphocytic serum) has given way to more effective antilymphocytic sera and more powerful immuno-suppressor drugs (cyclosporine A). This treatment has greatly changed the postoperative course of events. Rejection phenomena, though still as common, are much less serious and, above all, more insidious.(ABSTRACT TRUNCATED AT 250 WORDS)

[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.

[Pseudoaneuysms of the heart after myocardial infarct. Apropos of 5 operated cases]. / Les faux anévrysmes du coeur après infarctus du myocarde. A propos de 5 cas opérés.

The authors base themselves on 5 personal cases and a review of the literature to summarise the clinical and paraclinical features of false aneurysms of the heart. The clinical features differ from those of true aneurysms only slightly. It is only arteriography, which shows up the collar and the slow evacuation of the cavity, which makes the real distinction and argues in favour of operation. The results of surgical treatment have been satisfactory, especially considering the natural outcome, which is always death from rupture.

[Value of hemodynamic surveillance by radiocardiography in human heart transplants]. / Intérêt de la surveillance hémodynamique par radiocardiographie dans les transplantations cardiaques humaines.

Eighteen cases of cardiac transplantation have been carried out for 16 recipients since October 1973, there being 8 survivors at present. The importance of screening in such a treatment is vital. It is a simple method, easy to control, can be carried out at the bedside, is reproducible, reliable, and completely harmless, and by allowing the haemodynamic function of the graft to be seen at all times, helps in the marching of the donor and the recipient, in following the function of the graft in the immediate post-operative period, and in discovering rejection crises, and evaluating the long-term fate of the transplant.

[Results of open heart mitral commissurotomy in 85 patients]. / Commissurotomie mitrale à coeur ouvert. Résultats chez 85 opérés.

Open heart mitral commissurotomy was performed in 85 patients between January 1973 and January 1976. This series comprised 38 patients with pure mitral stenosis and 47 patients with associated mitral and aortic or tricuspid lesions. Mitral commissurotomy, always complete, was associated with correction of mitral incompetence, either preexisting or peroperative, in 19 cases; in 44 cases with correction of an aortic lesion and in 10 cases with correction of a tricuspid lesion. The surgical mortality was 2.3 p. 100 (2 deaths); one post-operative myocardial infarction and one spontaneously regressive post-operative jaudice was observed. No cases of post-operative systemic embolism was observed. A short apical systolic murmur was detected in 12 cases. The results of this series together with those already published suggest that the indications of this operation should be widened and that it should be employed whenever the best immediate anatomical result and long-term prognosis are desired.

[The low-profile Liotta valve. Mid-term results]. / La valve de Liotta "bas-profil". Résultats à moyen terme.

We report the mid-term results obtained with 279 "low profile" Liotta xenografts implanted at the Hôpital de la Pitié, Paris, in 257 patients between February, 1981 and November, 1984. There were 86 aortic, 138 mitral, 11 triscupid and 22 mitral-aortic valve replacements. The wavy suture ring of the prosthesis makes it "low profile". The Liotta valve is of particular interest in certain anatomical situations such as aortic annulus more dilated than the supra-coronary aorta, or small right and left ventricular cavities. The overall operative mortality rate was 8.6%. The 236 survivors were followed up for 3 to 48 months, a total of 374.3 patients-years. The overall actuarial survival rate at 3 years is 92.2%. Although there were few thromboembolic accidents, about one-third of the patients remain under anticoagulant therapy (0.86 episodes for 100 patients-years). Globally, 98.1% of the patients are free of any thromboembolic accident. Deterioration occurred 29 and 44 months respectively after implantation in two patients aged 9 and 20 years (0.57 episodes for 100 patients-years). Three cases of endocarditis on prosthesis were observed. Altogether, almost 91.2% of the patients have had no complication for 3 years, and indeed they functionally improved, most of them now being in class I or II (aortic valve 97%, mitral valve 87.2%). Thirty-eight patients underwent repeated catheterization at rest and during exercise. Mean transvalvular gradient was 12.4 mmHg in aortic valve patients and 5.9 mmHg in mitral valve patients. Mean functional valve area was 1.6 cm in aortic valve patients and 2.1 cm in mitral valve patients, and it clearly increased during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

[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.

[Recurrence of mitral disease after commissurotomy. Criteria influencing operative mortality during reintervention using extracorporeal circulation]. / Récidive mitrale après commissurotomie. Critères influençant la mortalité opératoire lors de la réintervention sous circulation extra-corporelle.

Reoperation for secondary deterioration after mitral commissurotomy is associated with a higher immediate postoperative mortality than other open heart operations. We analysed the factors responsible for this increased mortality. A total of 232 patients reported for clinical deterioration after closed heart mitral commissurotomy were reviewed. Mitral valve prostheses were implanted in 202 cases; open heart commissurotomy was possible in 30 cases. Associated procedures included 14 tricuspid valve replacements, 53 tricuspid annuloplasties and 30 aortic valve replacements. The global mortality was 12 p. cent (30 deaths). The causes of death were myocardial failure (19 cases), cerebrovascular accidents (4 cases), prosthetic valve thrombosis (4 cases), infection (2 cases), section of the mitral annulus (1 case). The clinical hemodynamic and anatomical criteria influencing the operative prognosis were analysed: 1. Operative mortality was related to the clinical stage (zero mortality at Stage II, 10,3 p. cent at Stage III, 38 p. cent at Stage IV, p less than 0,001); 2. There was a significant correlation with cardiothoracic ratio: 23 p. cent mortality when greater than 0,60; 9,8 p. cent mortality when less than 0,60 (p less than 0,02); 3. There was a significant correlation with cardiac index: 19 p. cent mortality when less than 21; only 9 p. cent mortality when greater than 21 (p less than 0,04); 4. There was a significant correlation with systolic pulmonary arterial pressure: mortality of 11 p. cent when less than 60 mmHg; mortality of 22 p. cent when greater than 60 mmHg (p less than 0,06). 5. The presence of tricuspid regurgitation increased the operative risk (mortality rose from 12 to 22 p. cent, p less than 0,05) when the surgeon detected moderate or severe tricuspid regurgitation. These results show that the clinical, radiological and hemodynamic aggravation of these patients has a bad influence on operative mortality. This aggravation is not related to the delay between the initial commissurotomy and reoperation but to the delay between the recurrence of symptoms after the first operation and reoperation. Operative mortality was 12 p. cent when this delay was less than 10 years but 23 p. cent when the delay was over 10 years (p less than 0,02). Our findings suggest that these patients should be reoperated earlier if the prognosis of this type of surgery is to be improved.

[Aorto-coronary bypass. 1. Immediate results evaluated in a sample of 357 operated patients]. / Pontages aorto-coronariens. 1. Résultats immédiats appréciés sur un matériel de 357 patients opérés consécutivement.

Over a period of 36 months, 357 patients have had one or several aorto-coronary bypass graft operations, either alone (305 patients) or in combination with another surgical procedure. 230 (66.4%) of these patients had acute coronary insufficiency: unstable angina or "menance syndrome" in 177, Printzmetal's angina in 34, threatened extension of an infarction in 14, and post-cannulation stenosis in 5. 75 patients had chronic coronary insufficiency, and in the 52 others the coronary lesions were associated with valvular or myocardial lesions. A total of 489 grafts were carried out, 261 of which (53.4%) were on the anterior descending artery. Of the 305 patients with grafting and no other surgical procedure, 190 (62,3%) had one single graft, 104 (34.1%) had 2 grafts, and 11 (3.6%) had 3 grafts. For theses 305 patients, the mortality during the first month (6.9%, or 4.5% for the last six months of the series) was influenced by age (a mean of 52.1 in the survivors and 57.1 in the deceased, p less than 0.001), a preoperative infarction less than 8 days old (p less than 0.001), significant changes in left ventricular function (a mean ejection fraction of 44.9% +/- 0.20 in the deceased, and 61.5% +/- 0.19 in the survivors, p less than 0.001), a mean end-diastolic volume of 252 ml +/- 98 in the former and of 136 ml +/- 51 in the latter, p less than 0.001). The advent of a postoperative infarct thus increases the mortality. An infarct complicated the progress of 11.1% of patients. The probability of such a complication occuring depends upon the state of the vascular bed distal to the bypassed artery and on the duration of the extracorporeal circulation.