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.

Successful long-term outcome of the first combined heart and kidney transplant in a patient with systemic Al amyloidosis.

Simultaneous cardiac and renal involvement is associated with a particularly poor prognosis in patients with AL amyloidosis (AL-A). We report the first case of a successful long-term outcome of combined heart and kidney transplantation not followed by autologous stem cell transplantation in a patient with systemic AL-A. The recipient was a 46-year-old man with end-stage renal failure associated with serious cardiac involvement in the context of AL-A. Before transplantation, two courses of oral melphalan plus prednisone induced partial hematologic remission, as shown by the decrease in circulating free light chain with no improvement of renal or heart function. The patient underwent combined heart and kidney transplantation as a rescue treatment. During the follow-up period (36 months), plasma cell dyscrasia remains in complete remission, with normal free lambda light chain levels and no recurrence of amyloid deposition on heart and kidney grafts. This case report demonstrates that combined heart and kidney transplantation not systematically associated with stem cell transplantation may be considered an additional therapeutic option in AL-A patients with severe organ dysfunction and partial hematologic remission.

[Four years of circulatory support with the INCOR axial pump from Berlin Heart]. / Quatre ans d'assistance circulatoire avec la pompe axiale INCOR Berlin Heart.

Implantation of definitive left ventricular support is now a therapeutic option for certain patients in refractory heart failure who are not candidates for transplantation. Here we report the case of a patient assisted for more than 4 years with an INCOR axial pump from Berlin Heart. This case shows the feasibility of long term assistance with a continuous flow pump, and an innovative anti-thrombotic strategy relying on the combination of low molecular weight heparin with platelet anti-aggregants.

Tumor necrosis factor alpha and glutathione interplay in chronic heart failure.

The pro-inflammatory cytokine, tumor necrosis factor alpha (TNF alpha), in concert with neurohormones, contributes to chronic heart failure (CHF) progression. This implies that TNF a antagonism may constitute an important target for CHF therapy. However, clinical trials in CHF patients using compounds that trap TNF alpha, comprising infliximab, an antibody directed to TNF alpha, and etanercept, a soluble recombinant receptor of TNF alpha, gave disappointing results bringing back to light the dual, short-term beneficial and long-term harmful effect of TNF alpha. This review focuses on the dual, concentration- and time-related effects of TNF alpha, the yin and yang action of TNF alpha in cardiac ischemia/reperfusion and contraction. Importantly, the harmful effects of TNF a are related to glutathione deficiency, a common hallmark to several other chronic inflammatory diseases. Recently, in rat models of CHF, oral administration of the glutathione precursor, N-acetylcysteine (NAC), was shown to hinder pathways of TNF alpha harmful signalling and to rescue cardiac structure and function. These results suggest that glutathione deficiency in association with TNF alpha activation may play a role in the pathophysiology of CHF and that NAC may represent a potential therapy in CHF.

Immunologic events and long-term survival after combined heart and kidney transplantation: a 12-year single-center experience.

BACKGROUND: In this study we compare the incidence of cardiac rejection and long-term survival after combined heart and kidney transplantation (HK) and single heart transplantation (H). Combined HK transplantation is a surgical option for patients with irreversible cardiac and renal failure. However, long-term results of combined HK transplantation on immunologic events and patient survival remain unknown. METHODS: Between 1988 and 1997, 12 consecutive patients underwent combined HK transplantation (HK group) at a single institution. A control group (H group) of 24 single heart transplant recipients operated on within the same period was matched for age, pre-operative pulmonary vascular resistance, hepatic insufficiency and gender mismatch. Recipients and donors were ABO compatible without HLA antigen matching. All patients received immediate triple immunosuppression that included cyclosporine. Because of early renal dysfunction, cyclosporine was switched to anti-thymocyte globulin in 5 patients from the HK group and in 1 patient from the H group (p = 0.01). RESULTS: Actuarial freedom from heart rejection at 6 months and at 1 year following transplantation averaged 90 +/- 9% and 70 +/- 14% in the HK group, and 65 +/- 10% and 49 +/- 11% in the H group, respectively (p = 0.023). Actuarial survival at 1, 5 and 12 years was not significantly different between groups, at 66%, 55% and 28% in the HK group, and 66%, 44% and 32% in the H group, respectively (p = 0.66). CONCLUSION: The incidence of cardiac rejection was significantly lower. Long-term survival in the HK group was similar to that in the H group. Putative mechanisms of decreased cardiac rejection in the HK group include allogeneic stimulation, donor-derived dendritic cells and induction by anti-thymocyte globulins. The need for long-term immunosuppression may be reduced after combined heart and kidney transplantation.

Doppler tissue imaging to predict myocardial recovery during mechanical circulatory support.

Bridge to recovery is a possibility for patients receiving mechanical circulatory support. However, no reliable factors exist to predict a sustained myocardial recovery. We report the use of a new technique of Doppler tissue imaging to document myocardial recovery in two cases with promising results.

Cardiac troponin I release after open heart surgery: a marker of myocardial protection?

BACKGROUND: Unlike creatine kinase MB isoenzyme, cardiac troponin I (cTnI) is a highly specific marker of myocardial injury. Its release has recently been studied after coronary artery bypass grafting operation. However, its significance after open heart surgery (OHS) remains to be determined. This protein release could be a marker of myocardial protection. We sought to study cTnI release after OHS in patients with normal coronary arteries and to compare it with cTnI release in patients after coronary artery bypass graft (CABG) surgery. METHODS: Eighty-five patients undergoing OHS and 86 patients undergoing CABG were enrolled in the study. CTnI concentrations were measured in serial venous blood samples drawn before surgery and immediately, 12 hours, 24 hours, 48 hours, and 5 days after aortic unclamping. RESULTS: In the OHS group and in the CABG group without acute myocardial infarction (AMI), cTnI peaked at 12 hours postoperatively (6.35 +/- 6.5 and 5.38 +/- 8.55 ng/mL, respectively) and normalized on day 5 postoperatively (0.57 +/- 2 and 0.72 +/- 1.62 ng/mL, respectively). CTnI concentration did not differ significantly between the OHS group and the CABG group in the absence of AMI for any samples considered. In the CABG group, 2 patients had AMI. In the OHS group, cTnI levels at 12 hours postoperatively were found to correlate closely with CPB and aortic cross-clamping (ACC) times, contrary to the CABG group, which correlated only with occurrence of AMI. CTnI release was independent of age and ejection fraction in either group. CONCLUSIONS: cTnI release in patients after OHS with normal coronary arteries has the same profile as cTnI release in patients after CABG in the absence of AMI. However, its peak at 12 hours postoperatively is only correlated to ACC and CPB times, which is contrary to cTnI release after CABG surgery. This observation suggests that cTnI could be a marker of myocardial ischemia after OHS.

Myocardial recovery after mechanical support for acute myocarditis: is sustained recovery predictable?

BACKGROUND: At present, myocardial recovery with mechanical support for acute myocarditis is a more frequently observed issue. However, predictive parameters of a sustained myocardial recovery are still under investigation. METHODS: Two recent cases of mechanical support for acute lymphocytic myocarditis with two different outcomes are reported. Literature about this disease and predictability of a sustainable myocardial recovery are reviewed. RESULTS: Acute lymphocytic myocarditis is an individual entity whose outcome is associated with the importance of healed cell damage. Unfortunately, there are no available means of quantifying the fibrotic scar and endomyocardial biopsy has a high percentage of false-negative results. Echocardiographic assessment of systolic and diastolic cardiac function is difficult while under mechanical support and its significance is not obvious. Forthcoming development of Doppler could better correlate myocardial contractility and histology to be predictive of a sustained recovery after acute myocarditis under mechanical support. CONCLUSIONS: Long-lasting recovery after mechanical support for acute myocarditis remains unpredictable in our experience. More predictive factors are needed.

Preliminary experience with Silzone-coated St. Jude medical valves in acute infective endocarditis.

BACKGROUND AND AIM OF THE STUDY: The rate of recurrent postoperative endocarditis after valve replacement in early-stage acute infective endocarditis is extremely high. Metallic silver coating of the sewing ring may improve the short- and long-term outcome after valve implantation. This report details our experience with the St. Jude Medical Silzone prosthesis in early surgical treatment of acute infective endocarditis. METHODS: Ten patients (mean age 66.4 years) referred for native valve or prosthetic valve endocarditis were operated on between April 1998 and June 1999. The microorganisms responsible for the acute infection were Staphylococcus (n = 1), Streptococcus (n = 1) and Pseudomonas aeruginosa (n = 1); blood cultures remained negative in two cases. The indication for surgical treatment was related to hemodynamic condition (n = 5), a major cerebral event (stroke; n = 1), annulus abscess (n = 1), and echocardiographic evidence of large cuspal vegetations (n = 3). All patients had received preoperative intravenous antibiotics (mean 7.8 days). Four mitral, five aortic valve replacements, and one double mitral-aortic valve replacement, were performed after extensive debridement of the infected and necrotic tissues. Mean duration of postoperative antibiotic treatment was 32.3 days. Postoperative follow up (mean 6 months; range: 2-14.2 months) was 100% complete, and included prospective repeated transthoracic echocardiography at one week, and one, six and 12 months postoperatively. RESULTS: One patient died early in the immediate postoperative period from pneumonia and major hypoxemia. All other patients are symptom-free, without evidence of recurrent infection and perivalvular leak. CONCLUSION: Although these early results with the St. Jude Medical Silzone prosthesis require confirmation by more extensive studies, they infer that silver coating of the sewing ring may dramatically improve management of patients with active endocarditis.

The freestyle stentless aortic bioprosthesis: more about the subcoronary technique.

Two years after aortic valve replacement with a Freestyle stentless aortic xenograft using the partial scallop inclusion technique, late prosthetic valve endocarditis developed with abscess formation in the space between the porcine and native human aortic wall. The presence of such a periprosthetic dead space exposes the patient to increased postoperative pressure gradients and the risk of superinfection.

Early effect of cyclophosphamide on oncogene expression in vivo.

Cyclophosphamide (CP) is a widely used chemotherapeutic drug, with proven carcinogenic effects. Secondary tumours induced by CP are kidney tumours in humans and haemopoietic malignancies in rodents. Previous experiments have shown its effect on H-ras, c-myc and p53 gene expression in long term in vivo experiments. Our model was developed to analyse the events in the first 24 hours after the administration of CP in short term experiments. The expression of Ha -ras, c-myc and p53 was investigated in the target organs during and up to 24 hours after the administration, at 0.25, 0.5, 1, 6, 12 and 24 h. Since the majority of CP-induced tumours are leukemias and lymphomas in the CBA/Ca mouse model, RNA was obtained from the thymus and the spleen. The results show that p53 is strongly expressed in the thymus during the focused period. On the other hand, the samples were subjected to in situ hybridisation and compared with the results of in situ hybridisation of lung and liver samples. Comparing the results of total RNA and in situ hybridisation should prove useful if the total RNA signal is too weak or not detectable at all. The in situ hybridisation picture showed many positive cells without high expression of oncogenes. Further flow-cytometric studies are necessary to provide a full explanation of the mechanism of CP induced changes.

[External ventricular support in primary cardiogenic shock]. / Dérivations ventriculaires externes dans le choc cardiogénique primaire.

Primary cardiogenic shock is a common condition with a high mortality rate. In this indication, mechanical assist plays an important part and has improved a lot over the last decade. The authors report their experience with the same assist device in patients with primary cardiogenic shock. Nineteen patients (9 dilated cardiomyopathies, 7 myocardial infarctions, 2 myocardities, 1 undetermined) were treated with an external mechanical ventricular assist device (Thoratec, Berkeley, U.S.). Fourteen patients received a biventricular assist and 5 had a uni-left ventricular assist device. Four of the 19 patients were completely weaned off their ventricular assist after 13, 27, 36 and 94 days, respectively. Ten patients underwent transplantation after an average of 43 days (range 8-95 days). Of the 19 patients, 7 had a portable console allowing autonomous ambulation. Five patients died under mechanical assistance (26.9%) and 3 patients died after transplantation. Three patients required temporary haemodialysis; 4 suffered embolic complications; 4 had mediastinal haemorrhages; 4 had bleeding from other sites, and 6 suffered from late tamponnade. Fourteen patients had at least one infectious episode. The authors conclude that, in patients referred for severe primary cardiogenic shock, the implantation of an external biventricular assist is a reliable option, allowing sequential weaning or being a bridge to transplantation in non-dependent patients, providing they are severely selected.

[Left ventricular kinetics studied by the color kinesis method. Comparison of bidimensional echographic and angiographic data]. / Etude de la cinétique ventriculaire gauche par la technique du color kinesis. Comparaison aux données échographiques bidimensionnelles et angiographiques.

The object of this study was to assess the value of CK in the evaluation of left ventricular wall motion. Fifteen coronary patients aged 56 +/- 12 years were included: 8 patients were examined after acute myocardial infarction and 7 after unstable angina with a history of myocardial information. The left ventricle was divided into 7 segments after a modified Heger model, excluding the basal septal and basal lateral segments not seen on angiography. The left ventricular wall motion was assessed in two-dimensional echocardiography (2DE) and colour kinesis (CK) by two observers and compared with the results of left ventriculography, considered the reference method. Over all the 105 segments studied (7 segments for each of the 15 patients), CK was significantly better than 2DE (80% of segments correctly evaluated by CK vs 68% by 2DE, p < 0.05). Colour kinesis significantly improved the study of all segments except the interventricular septum (67% vs 60%, p = NS). The inter-observer variability in 2DE and CK evaluated over 135 segments (9 per patient) by the kappa was improved by colour kinesis (0.57 in 2DE, 0.7 in CK). The authors conclude that CK enables evaluation of left ventricular wall motion with greater precision and less inter-observer variability.

[Myocardial infarction in a pregnant woman during salbutamol therapy]. / Infarctus du myocarde chez une femme enceinte au cours d'un traitement par salbutamol.

The authors report the case of a 31 year old woman at 30 weeks' gestation who developed a non-Q wave postero-lateral myocardial infarction during treatment with salbutamol. There were no complications and delivery took place at term normally. Coronary angiography was performed 3 months post-partum and was normal: the Methergin test was negative. Myocardial ischaemia occurring during treatment with a beta-2 mimetic in pregnancy is rare and hardly ever progresses to myocardial infarction. The usual mechanism of ischaemia is an imbalance of myocardial oxygen demand and supply. Myocardial oxygen consumption is naturally increased during pregnancy and excess intracellular calcium secondary to the beta-1 stimulation occurring with the use of beta-2 mimetic drugs further aggravates matters. This hypothesis raises the question of the value of calcium inhibitors in these forms of myocardial ischaemia.

[Pulmonary embolism and thrombus trapped in a patent foramen ovale. Cure by heparin therapy]. / Embolie pulmonaire et thrombus enclavé dans un foramen ovale perméable. Guérison sous héparinothérapie.

The authors report the case of a 84-year old patient admitted to hospital for pulmonary embolism. The diagnosis was made by ventilation and perfusion pulmonary scintigraphy. Transthoracic echocardiography was performed routinely and showed a thrombus wedged across a patient foramen ovale, confirmed at transoesophageal echocardiography. Spiral thoracic computerised tomography showed thrombus in the two main pulmonary arteries and the inferior vena cava. Thrombolysis or thrombectomy under cardiopulmonary bypass, was thought to carry an excessive risk at that age and with the left-sided position of the thrombus. The alternative was therefore anticoagulation which led to dissolution of the thrombus without recurrence of pulmonary embolism or cerebrovascular accident.

[Spontaneous reduction of late chronic atrial fibrillation after mitral valvuloplasty. Echocardiographic evidence of the restoration of mechanical atrial activity]. / Réduction spontanée d'une fibrillation auriculaire ancienne à distance d'une valvuloplastie mitrale, Evidence ultrasonographique de la reprise d'une activité auriculaire mécanique.

Spontaneous, long lasting reduction of chronic permanent atrial fibrillation, usually complicating rheumatic valvular heart disease, has rarely been described in the literature. Its mechanism is unclear. In practice, the question is to determine whether the electrical activation coincides with restoration of a mechanical atrial contraction. The authors report the case of a woman with mixed rheumatic aortic and mitral valve disease (essentially mitral stenosis), in whom reversion to sinus rhythm was observed after 9 years of atrial fibrillation and which was long lasting (at least 9 months), and, above all, accompanied by atrial contraction documented for the first time to the best of the authors' knowledge, by Doppler echocardiography.

[Validation of the measurement of cardiac output by acoustic quantification in patients with severe congestive heart failure]. / Validation de la mesure du débit cardiaque par la méthode de quantification acoustique chez le patient insuffisant cardiaque sévère.

The technique of acoustic quantification (AQ), because of its automatic detection of the contours, enables left ventricular volumes to be calculated in real time using the technique of disk summation. The objective of the study was to evaluate the reliability of cardiac output (CO) measurements obtained with AQ based on left ventricle volumes in patients with severe congestive heart failure. Seventeen patients, mean age 68 +/- 11 years, NYHA stage IV, in sinus rhythm and without significant valve regurgitation were enrolled prospectively. CO, measured simultaneously by 2-dimensional echocardiography (2DE), pulsed Doppler echocardiography (DOP) and AQ, was compared to the thermodilution technique (TD) data. CO, measured by AQ, was highly correlated with TD (r = 0.875; p < 0.001) with a small bias (-0.05 l/min). DOP and 2DE were also well correlated with TD (r = 0.835 and r = 0.701, respectively). Concerning ventricular volume measurement, AQ was well correlated with 2DE (for telediastolic, r = 0.892, and telesystolic volumes, r = 0.874). However, telesystolic (bias, +36.6 +/- 35 ml) and telediastolic volumes (bias, +35.6 +/- 35 ml) were overestimated. We conclude that AQ is a reliable technique, able to estimate CO precisely in patients with severe congestive heart failure. On the other hand, both telesystolic and telediastolic volumes were overestimated.

[Therapeutic strategy of the management of acute heart failure]. / Stratégie thérapeutique de la prise en charge de l'insuffisance cardiaque aiguë.

Acute cardiac failure should be approached clinically and paraclinically as an emergency and precipitation is not always what is required. Consequently, strict clinical and paraclinical strategy leads to decisive action to improve the prognosis. The authors describe the principles of management of acute cardiac failure. The different stages which are carried out simultaneously in clinical practice are discussed: physiopathological basis, clinical and paraclinical investigations, symptomatic and aetiological treatment. The description and indications of circulatory assistance are considered. This constitutes a major therapeutic advance of the last decade and has changed the treatment of the most severe clinical forms of acute cardiac failure.

[Diagnostic value of echocardiography and thoracic spiral CT angiography in the diagnosis of acute pulmonary embolism]. / Valeur diagnostique de l'échographie cardiaque et de l'angioscanner thoracique hélicoïdal pour le diagnostic de l'embolie pulmonaire aiguë.

The objective of this study was to define the limits of echocardiography and to evaluate thoracic spiral CT angiography (TSCTA) for the diagnosis of pulmonary embolism (PE). One hundred twelve consecutive patients, hospitalised for suspected PE, were included in this prospective study. All were investigated by pulmonary ventilation-perfusion scintigraphy (Sc) and 50 had a high probability of PE on this examination. Sc was normal in 22 patients. Forty patients were excluded because of an intermediate probability. In 50 patients with PE confirmed on Sc, transthoracic echocardiography (TTE) showed only indirect evidence of PE (intracavitary thrombus in 4% of cases). TSCTA demonstrated PE in 82% of cases and did not show any thrombus image when Sc was normal. Its negative predictive value was therefore 70% and its positive predictive value was 100%. Its sensitivity varied according to degree of perfusion defect (96% in the case of lobar lesion, 66% in the case of segmental lesion and 16% for a subsegmental lesion). Multidimensional transoesophageal echocardiography (TOE), performed in 37 of the 50 patients with PE, only revealed thrombi in the pulmonary tree in 3 patients (8%), all presenting severe PE. No thrombus was visualized on TOE in patients with non-serious PE. All thrombi observed on TOE were also demonstrated by TSCTA. In conclusion, TTE usually provides only indirect signs of PE. TOE has a poor diagnostic sensitivity for PE. TSCTA has a better sensitivity than TOE for the detection of thrombi in the pulmonary artery trunk and proximal centimetres of its two branches, but normal CT angiography cannot exclude a distal PE.

[Circulatory assistance while waiting for heart transplantation. Patient selection and choice of the assist system]. / L'assistance circulatoire en attente de transplantation. Sélection des patients et choix du système d'assistance.

TWO CLINICAL SITUATIONS: Mechanical circulatory assistance can be indicated in two clinical situations: i) patients on the waiting list for heart transplantation who have chronic heart failure unresponsive to drug therapy and whose clinical status worsens; ii) patients with acute heart failure. INDICATIONS: The exact indications for mechanical circulatory assistance are difficult to establish. Hemodynamic criteria are no longer sufficient. Circulatory assistance may be proposed for chronic heart failure patients with a high risk of death or in a situation of acute deterioration. Among these patients, several risk factors can be used to establish scores that have a better predictive value than risk factors taken alone. Two predictive models have been recently established. The first one takes into account 7 independent variables: etiology, heart rate at rest, left ventricle ejection fraction, mean blood pressure, intraventricular rhythm disorder, VO2max and serum sodium). In addition to these variables, the second model also includes pulmonary wedge pressure. In selected patients with acute heart failure, circulatory assistance is needed as early as possible to avoid irreversible multiple organ failure. The crucial problem is rapid assessment of the feasibility of heart transplantation. PREOPERATIVE MORTALITY RISK FACTORS: Several variables can be used to predict survival in candidates for mechanical circulatory assistance on the heart transplantation waiting list. They include hemodynamic criteria, renal function, liver function, preoperative infection and the emergency nature of the need for circulatory assistance. CHOICE OF THE ASSIST SYSTEM: The choice depends both on the patient (surface area is important) and the underlying disease.