Heart transplant for the failing ischaemic ventricle.

Clinical application of heart transplantation goes beyond 28 years experience. Ischaemic heart diseases remain, with idiopathic cardiomyopathies, the main indications for cardiac transplant. A combination of haemodynamic, contractile and viability measurements may be useful to choose between transplant and coronary revascularization for the failing ischaemic ventricle. Advances in the detection of early rejection, improved organ preservation procedures, and the introduction of new immunosuppressive therapy protocols have produced dramatic results in heart transplantation. Late graft atherosclerosis remains a serious threat despite retransplantation and, in some cases, mechanical circulatory support.

Cyclosporin A-mediated cholestasis in patients with chronic hepatitis after heart transplantation.

Viral chronic hepatitis often occurs in heart transplant recipients receiving cyclosporin. This essential immunosuppressive drug may induce cholestasis. We investigated the effect of treatment with cyclosporin on serum conjugated bile acids in patients with chronic hepatitis developing after heart transplantation. Fifty-nine patients were studied: 17 with chronic hepatitis, 15 heart transplant patients with normal alanine aminotransferase activity, and 27 heart transplant patients with chronic hepatitis, the last two groups receiving cyclosporin. Hepatic biochemical tests and total bile acid concentration were determined on fasting blood samples. The individual glyco- and tauroconjugated bile acids were quantified by high-performance liquid chromatography and direct spectrometry. In patients taking cyclosporin the bilirubin concentration and the alkaline phosphatase activity were increased only when hepatitis was present, in association with a slight increase in cholic acid level (5.13 microM vs. 0.68 microM; P < 0.01). Conjugated lithocholate concentration was dramatically higher when hepatitis and immunosuppression with cyclosporin were associated (1.17 microM vs. 0.03 and 0.04 microM; P < 0.01). Chenodeoxycholate was the main circulating bile acid only in the heart transplant patients treated with cyclosporin but without hepatitis. These results suggest that the mechanisms which explain the cyclosporin-associated modifications of the bile acid pool are different according to the presence or absence of hepatitis. The occurrence of hepatitis in patients on cyclosporin led to an increase in serum lithocholate and primary bile acid concentrations. Further studies are required to assess the effect of ursodeoxycholic acid for this cholestasis.

Coronary artery vasomotion in cardiac transplant patients with normal coronary angiograms.

In 18 consecutive transplant patients with normal coronary angiograms and without calcium blocker therapy, and in 20 controls, we measured the diameters of the left anterior descending artery using quantitative coronary angiography. Measurements were effected on the frames recorded 5 min or more after intravenous administration of 0.4 mg methylergometrine, and 2 min after subsequent 2 mg bolus intracoronary isosorbide dinitrate administration. The arterial vasodilatory capacity was defined as the ratio of the difference of the largest and smallest arterial diameters and the smallest diameter. We observed normal vasoconstriction of the different coronary arterial segments. Coronary arterial diameter decrease from basal state was about 8% and was more pronounced at the distal segments of the left anterior descending artery. There was no difference of vasodilatory capacity between transplant patients and controls for the proximal and middle portion of the left anterior descending artery, while the difference was highly significant for the distal portion. In eight patients, the decrease of the vasodilatory capacity was beyond the lower limit of the normal range of values. The significance of those quantitative angiographic abnormalities is still unproven. They could be due to early vasomotor capacity blunting after transplantation and to late structural alterations of distal coronary vessels in cardiac transplant patients.

Implications of de novo ELAM-1 and VCAM-1 expression in human cardiac allograft rejection.

Both cytokines produced by activated monocytes and T cells and direct cell-to-cell contact with antigen-primed T cells during inflammatory reactions are known to induce the expression of several adhesion proteins on endothelial cells. In this prospective longitudinal study, we analyzed the expression of ELAM-1, VCAM-1, and ICAM-1 on myocardial allograft biopsy specimens taken from 16 cardiac allograft recipients either for routine monitoring or for the investigation of suspected rejection. Infiltrating T cells were identified using anti-CD3 antibodies. Three to six sequential biopsies taken at one-week intervals were analyzed by means of conventional histology and immunohistochemistry. Seven patients did not develop rejection during the study; their biopsies were negative for VCAM-1 and ELAM-1, although faint ICAM-1 staining was present on capillaries, reflecting constitutive expression. Three patients entered the study with clear-cut clinical and histologic signs of acute rejection. Intense VCAM-1 and ICAM-1 expression was detected on capillary and postcapillary venules, together with a heavy CD3+ T cell infiltrate; VCAM-1 was also expressed on arteriolar endothelial cells. ELAM-1 was undetectable in all three cases. Six patients developed acute rejection during the course of the study. In four, ELAM-1 and VCAM-1 were expressed on both capillary and postcapillary venules one or two weeks before the histological diagnosis of rejection (heavy CD3+ cell infiltrate). Importantly, ELAM-1 expression was short-lived and had disappeared by the time CD3+ cellular infiltrate was detected, thus extending in vivo the finding that ELAM-1 expression is usually transient in vitro. Only VCAM-1 expression was observed in the other two patients, one week prior to the histological diagnosis of rejection. These results suggest that ELAM-1 and VCAM-1 might represent early predictive markers of acute cardiac allograft rejection. ELAM-1 expression is, however, usually transient, necessitating frequent testing.

[Rheumatologic manifestations in heart transplant recipients. A cross-sectional study of 365 patients]. / Manifestations rhumatologiques chez les transplantés cardiaques. Etude transversale de 365 patients.

Rheumatological complications are sometimes disabling in heart transplant recipients and may negate the good results obtained with transplantation. The objective of this study was to evaluate the incidence of these complications. 365 consecutive heart transplant recipients (292 males and 73 females) were systematically interviewed and examined according to a standardized protocol. The mean age of the patients was 45.9 +/- 12.0 years (range: 11-68). The mean duration from transplantation to time of the study was 35.8 +/- 25.6 months (range: 1-115). The rheumatological disorders most frequently encountered were: gout, osteoporosis, osteonecrosis and myalgias. Early-onset polyarticular gout was diagnosed in 63/365 patients (17.3%). This diagnosis was significantly associated with patient's age, time since transplant, male sex, serum uric acid, serum creatinine, diuretics intake and inversely associated with the serum cyclosporin levels. Hyperuricemia was observed in 75.9% of transplant recipients with a mean of 507.5 +/- 132.5 mumol/l (range: 97-965). An osteoporotic fracture was present in 18/365 patients (4.9%) and was significantly associated with the patient's age, but not with the dose of corticosteroids. Osteonecrosis was detected in 10/365 patients (2.7%), always affected the hip, and was significantly associated with the patient's age, but not with the high doses of steroids. Myalgias were reported by 14/365 patients (3.8%). Laboratory, electromyographic and histological analysis were negative. Rheumatological complications are frequent in heart transplant recipients and justify preventive and therapeutic management.

Chronic administration of cyclosporin A induces a decrease in hepatic excretory function in man.

Chronic administration of cyclosporin A may induce cholestasis in a few patients. The purpose of this study was to examine the effect of chronic administration of cyclosporin A on serum bile acid levels, serum bilirubin concentration, and bromosulfophthalein plasmatic fractional clearance. Twenty heart-transplanted patients with normal serum alanine aminotransferase activity receiving cyclosporine A during a mean duration of 33 months (range 7-54) were compared to 20 matched kidney-transplanted patients with normal serum alanine aminotransferase receiving azathioprine for a mean duration of 34 months (range 6-72). As compared to azathioprine-treated patients, patients treated with cyclosporin A had an increase in serum bile acid levels of 32% (P < 0.01), an increase in serum bilirubin concentration of 100% (P < 0.001), and a decrease in bromosulfophthalein plasmatic fractional clearance of 60% (P < 0.001). These results suggest that cyclosporin A induces a decrease in hepatic excretory function in man.

[Acute cardiac graft rejection after orthotopic cardiac transplantation. Elements of diagnosis and monitoring, therapeutic attitude]. / Le rejet aigu de greffon cardiaque après transplantation cardiaque orthotopique. Eléments de diagnostic et de surveillance, attitude thérapeutique.

The diagnosis of acute rejection in heart allograft recipients receiving cyclosporine is still an important challenge. The poor diagnostic value of clinical signs and the ECG means that regular endomyocardial biopsies must be performed. Despite their diagnostic value during the first year after transplantation, endomyocardial biopsies are less sensitive there after and currently suffer from the lack of a universally accepted histological classification. Doppler echocardiography can be used for routine surveillance and has proven reliable for the diagnosis of acute rejection with various clinical presentations when used in conjunction with endomyocardial biopsies. Immunohistological examination of myocardial specimens can further increase the sensitivity of histological diagnosis. Similarly, immunoscintigraphy with indium 111-labelled antimyosin antibodies is of value for the prediction of acute rejection after the first year. Therapeutic approaches have been standardized, but must still be tailored to the individual patient according to the severity of the rejection and the presence of associated infection and/or metabolic disturbances.

Heart-lung transplantation in situs inversus. A case report in a patient with Kartagener's syndrome.

After a long history of recurrent chronic pulmonary infections in a 25-year-old woman with Kartagener's syndrome, a heart-lung transplantation was performed. A modified surgical procedure was needed to perform transplantation because of the presence of a situs inversus, which is usually associated with bronchiectasis and sinusitis in this congenital syndrome. A large single atrium was created with both the right and left recipient atria used to facilitate anastomosis with the donor's right atrium. The patient was discharged after resolution of early ventilatory complications and is in good condition 8 months after transplantation.

Heart transplantation: update.

Clinical application of heart transplantation goes beyond 25 years experience. The main indications for cardiac transplantation remain idiopathic cardiomyopathies and ischemic diseases. To obtain a suitable donor has become progressively more difficult due to the increase of transplants performed and the shortage of donors. Advances in the detection of early rejection, improved organ preservation procedures, and the introduction of new immunosuppressive therapy protocols have produced dramatic results in heart transplantation. Late graft atherosclerosis remains a serious threat despite retransplantation and, in some cases, mechanical cardiac support.

Heart and heart-lung transplantation in the 1990s.

After 22 years of clinical application in our unit, heart transplantation is now an accepted therapeutic method. Its indications are well established, its surgical technique and post-operative control and treatment well defined, mostly due to better diagnosis of the rejection episodes with the aid of echocardiography and endomyocardial biopsy and the use of cyclosporin. The results are remarkable with a survival rate of 70% at 5 years, and a full rehabilitation into family, social and often professional life for almost all the survivors. Its use has dramatically changed the prognosis of patients with irreversible cardiac failure but underlines the lack of a sufficient number of donors' hearts. The heart-lung transplantation, making use of the progress of heart transplantation, has been used successfully since 1982 and for the first time in Europe by our group. Improvement in the selection of recipients, lung preservation, surgical technique and post-operative management have brought a new and real hope to patients not only irreversible cardiopulmonary lesions but also terminal pulmonary disease.

[Infectious complications of heart-lung transplantation]. / Les complications infectieuses des transplantations coeur poumons.

This study describes the infectious complications in 68 heart-lung transplant patients. We focused interest on early post-transplant infections so called nosocomial pulmonary infections, their exacerbating cofactors their clinical expression, and elements of diagnosis and treatment. Furthermore we describe the principal infections seen during long-term followup, which are opportunist infections caused most often by immunosuppression: Cytomegalovirus infections have a high incidence with serious clinical consequences in heart-lung transplant patients. As well as pneumocystis carinii infections and fungal infections, such as aspergillosis.

Chronic liver dysfunction in heart transplant recipients, with special reference to viral B, C, and non-A, non-B, non-C hepatitis. A retrospective study in 80 patients with follow-up of 60 months.

In order to assess the prevalence, causes, and severity of chronic liver dysfunction (LD) in heart transplant patients, 80 transplanted patients followed for 60 months (median; range, 1.5-98 months) were reviewed. Sustained liver dysfunction was found in 50 patients, occurring during the first year after heart transplantation in 42 (84%) of them. Most patients were asymptomatic (80%). Causes for the liver dysfunction included non-A, non-B hepatitis in 16 cases (32%), viral B hepatitis in 13 (26%), delta hepatitis in one (2%), drug-induced hepatitis in six (12%), and cardiac failure in seven (14%). Anti-HCV antibodies were found in 56.2% of patients with non-A, non-B hepatitis and in 22% of patients with HBV hepatitis. It was found neither in patients with drug-induced hepatitis cardiac failure nor in patients with normal liver tests. This study outlines a high prevalence of LD (62.5%) in heart transplant patients, the high frequency of viral-related chronic LD (usually of moderate severity), and high incidence of HCV and HBV hepatitis.

[Heart transplantations: impact on female fertility]. / Transplantations cardiaques: répercussions sur la fécondité féminine.

Improvements in the management of patients with cardiac transplantation make it possible for these patients in the child-bearing age to expect a pregnancy. In fact, since 1987, several cases of pregnancy after cardiac transplantation have been reported. We report here two cases of successful pregnancy two years after cardiac transplantation. First Case. Pregnancy was uneventful until 36 weeks of gestation with no evidence of transplant rejection. At 38 weeks of gestation, a cesarean section was performed for increasing blood pressure, cholestatic pruritus and cephalopelvic disproportion. Cesarean section was performed under regional anesthesia and a healthy baby boy of 2680 gr was delivered. The patient was discharged one week after. Eighteen months after, both the mother and the baby are in good condition. Second case. Pregnancy was complicated by severe maternal anemia and fetal hypotrophia. Because of increasing renal insufficiency and pre eclampsia, a cesarean section was performed under regional anesthesia at 36 weeks of gestation. Delivery of a healthy baby girl of 1700 g. Five other cases have been reported. Cesarean section performed in september 1984 for a patient who underwent cardiac transplantation in 1980. Delivery of a healthy baby of 3280 gr. Death of the mother five months after following heart transplant rejection. Vaginal delivery performed in august 1986 for a patient who underwent cardiac transplantation in 1984. Delivery of a preterm baby at 31 weeks of gestation who survived without any sequelae. Vaginal delivery performed in august 1987 for a patient who underwent cardiac transplantation in april 1985. Delivery of a healthy baby of 2550 gr at 38 weeks of gestation. Vaginal delivery of twins (baby girl of 1200 and 1100 gr) in april 1988 of a patient who underwent cardiac transplantation in 1986. Vaginal delivery at 38 weeks of gestation performed in november 1990 for a patient who underwent cardiac transplantation in 1986. All the cases reported showed that: The foetus is not affected by the immuno-suppressive treatment of the mother. This was already known for pregnant patients with renal transplant. The cardiovascular changes associated with pregnancy are well tolerated by the heart transplant. Preexisting hypertension is increased, particularly during the third trimester of pregnancy and during labour. The incidence of preterm labor is increased in patients with heart transplant. Transplant rejection never occurred during pregnancy.