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.

[Blood activation during long-term mechanical circulatory support]. / L'activation sanguine au cours de l'assistance circulatoire mécanique prolongée.

Mechanical circulatory support has become an approved treatment option for patients with cardiogenic shock or end-stage heart failure. However, recipients of heart assist devices are prone to high incidences of bleeding, thrombo-embolic and infectious complications. The occurrence of these complications is favoured by systemic alterations of coagulation and fibrinolysis, inflammation and immune responses. Several studies have evaluated these pathophysiological changes in patients undergoing long term circulatory support with pulsatile devices. However, the systemic consequences of the more recently introduced rotary blood pumps remain largely unknown. The present review focuses on the systemic consequences of long term circulatory support with pulsatile and non-pulsatile devices.

[Color M-mode Doppler for postoperative estimation of pulmonary capillary wedge pressure]. / Estimation postopératoire de la pression artérielle pulmonaire d'occlusion par étude Doppler, en mode M couleur, du flux transmitral.

OBJECTIVE: The aim of this study was to evaluate the accuracy of the combined index E/Vp (peak E velocity combined with color M-mode color Doppler flow propagation) for estimating pulmonary capillary wedge pressure, in post cardiac surgery patients. STUDY DESIGN: Prospective clinical trial. PATIENTS AND METHODS: In post cardiac surgery patients (D1), we have measured with transthoracic echocardiography peak early E transmitral pulsed Doppler velocities and color M-mode Doppler flow propagation velocity (Vp). The E/Vp ratio was compared with pulmonary capillary wedge pressure (PAPO) obtained simultaneously. RESULTS: Thirty eight patients were studied. The coefficient of correlation between PAPO and E/Vp was r = 0.71 (p < 0.0001). The sensitivity and the specificity of E/Vp > 1.5 for prediction of PAPO > 15 mmHg were 79% and 79% respectively. CONCLUSION: In post cardiac surgery patients, PAPO can be reasonably estimated by measuring the ratio E/Vp obtained with Doppler echocardiography.

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.

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.

[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.

Assessment of left ventricular regional wall motion by color kinesis technique: comparison with angiographic findings.

The analysis of segmental wall motion using two-dimensional (2-D) echocardiography is subjective with high interobserver variability. Color kinesis is a new technique providing a color-encoded map of endocardial motion. We evaluated the accuracy of color kinesis and 2-D for assessment of regional asynergy compared with left ventricular angiography as a reference method. Fifteen patients admitted for myocardial infarction were studied by echocardiography the day before left ventricular angiography. The left ventricle was divided into seven segments. Each segment was classified by two independent observers as normal or abnormal in 2-D and color kinesis. Accuracy of color kinesis and 2-D was evaluated and compared to left ventricular angiography. Color kinesis is significantly superior to 2-D for all seven segments (mean 0.80/0.68, P = 0.05), except for the septum (0.67/0.60, P = NS). Interobserver variability studied by chi-square statistic is lower with color kinesis (0.70) than with 2-D (0.57). We conclude that these data suggest that color kinesis is a useful method for assessing systolic wall motion in all segments, except the septum and for improving the accuracy of segmental ventricular function and interobserver variability.

[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.

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.

[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.

[Circulatory assistance while waiting for heart transplantation. Clinical course]. / L'assistance circulatoire en attente de transplantation. Evolution clinique.

OUTCOME: In most cases, mechanical circulatory assistance prior to transplantation can restore the main vital functions allowing a progressive physical rehabilitation during the period of assistance. According to several international registries, the transplantation rate ranges from 62% to 69% and the proportion of transplanted patients who had circulatory assistance and who were discharged ranges from 65% to 69%. COMPLICATIONS: Bleeding (42.5%), right heart failure (20-25%), air embolism and multiple organ failure are the main causes of early morbidity and mortality. Infection (28.5%), thromboembolic events and technical failures are the most frequent late complications. DURATION OF CIRCULATORY ASSISTANCE: The optimal time for transplantation is the moment when the incidence of complications and technical problems for transplantation are at their minima while the patient's vital functions are at their maxima.

[Circulatory assistance while waiting for heart transplantation. Outcome of heart transplantation after mechanical circulatory assistance]. / L'assistance circulatoire en attente de transplantation. Résultats de la transplantation cardiaque après assistance mécanique de la circulation.

SURVIVAL: In most of the published (uncontrolled) studies, survival after transplantation is similar for patients who required mechanical circulatory assistance and those who did not. Two controlled studies have reported a better survival rate in patients who had preoperative circulatory assistance. COMPLICATIONS: Infections are more frequent in transplanted patients who had a period of circulatory assistance preoperatively than in those who were transplanted after medical treatment. The effect of circulatory assistance on heart graft rejection is debated. The same is true for coronary grafts.