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Sirolimus is an m-TOR inhibitor without renal side effects and potentially protects against the development of malignancy. Due to a higher incidence of complications in two trials and an official warning in the drug information, the use of Sirolimus in liver transplantation is limited. The participants of this consensus meeting had to analyse and evaluate the literature with respect to the potential role of Sirolimus in liver transplantation. This consensus statement follows the scheme normally employed for the presentation of guidelines including the grading of evidence (1a-5) and the extent of recommendation (A-C). Moreover, the consensus included the experience of the authors with respect to the handling of Sirolimus after liver transplantation.

The subjective global assessment (SGA) or the body mass index (BMI) is used to determine the nutritional state after LTX. Bioelectrical impedance analysis (BIA) is used as tool to determine body composition by nutritional care professionals.BIA, SGA, BMI, and serum albumin (SA) levels were performed to assess malnutrition following liver transplantation. BIA measurement was used as reference standard to determine existing malnutrition. A phase angle (PA)5 was used to define potentially existing chronic disease-related malnutrition as a standard. All other measured parameters were compared with respect to their prognostic accuracy regarding the prediction of malnutrition as compared to the mentioned standard.Seventy-one recipients (51 men, 20 women) were included. Median age was 58, weight 77 kg, BMI 26 kg/m(2) , PA 4.1°, and SA 4.3 g/dL. According to the Nutritional Risk Screening 2002, 9.4% (6/71), to BMI 15.4% (11/71), to SA 30.9% (22/71), and to BIA 36.5% (28/71) of the patients were malnourished. PA did not correlate with BMI or NA, there was a significant correlation with SA (p = 0.001). Univariate analysis revealed SA as independent predictor for malnutrition. ROC analysis for all parameters revealed a significantly (p0.05) better area under the receiver operating characteristic curve for SA (0.812) than for BMI (0.603) for the prediction of malnutrition.SGA or BMI calculation alone does not suffice to evaluate the nutritional status. SA seems to play a crucial role in the prediction of severe disease-related malnutrition in this special patient cohort.

Sirolimus is an m-TOR inhibitor without renal side effects and potentially protects against the development of malignancy. Due to a higher incidence of complications in two trials and an official warning in the drug information, the use of Sirolimus in liver transplantation is limited. The participants of this consensus meeting had to analyse and evaluate the literature with respect to the potential role of Sirolimus in liver transplantation. This consensus statement follows the scheme normally employed for the presentation of guidelines including the grading of evidence (1a-5) and the extent of recommendation (A-C). Moreover, the consensus included the experience of the authors with respect to the handling of Sirolimus after liver transplantation.

In 10 heart transplant patients different hemodynamic states have been forced by randomized changes of pacing rate (PR) and postural variations (overall 40, 4/spl plusmn/1 per patient). Cardiac output assessed with thermodilution technique was compared to the ventricular evoked response (VER) recorded with telemetric pacemakers from epimyocardial leads. Linear regression analysis between the negative extremum during the depolarization phase of the VER (R/sub amp/) and the stroke volume (SV=CO/PR) resulted in the equation: R/sub amp/[%]=140-0.4*SV[%] with r=0.89 and p

Intramyocardial electrograms from the spontaneously beating and the paced heart were recorded in 8 heart transplants for rejection monitoring, using telemetric dual chamber pacemakers and two epimyocardial leads, located at two different right ventricular positions. Linear regression analysis of the rejection sensitive parameters showed that the correlation between the two electrodes was significantly higher for the paced than for the spontaneous heart beats.

Paced epicardial electrograms from heart transplants were recorded via implanted telemetric pacemakers. Signals were processed automatically and extracted parameters from the ventricular evoked response are compared to the degree of acute rejection according to histological findings from endomyocardial biopsy. Statistical analysis and an estimation of the diagnostic quality of this noninvasive method for detection of acute cardiac rejection are presented. >

Intramyocardial electrograms have been recorded noninvasively via telemetric pacemakers from spontaneously beating heart transplants. The amplitudes of premature QRS complexes have been compared to those of normal QRS complexes. Linear regression analysis revealed increased amplitudes, which are assumed to be due to the reduced filling pattern of the premature beats. Hence, intramyocardial electrograms contain haemodynamic information.

Intramyocardial electrograms were recorded noninvasively in 20 heart transplants using telemetric pacemakers and two epimyocardial leads, located at two different ventricular positions. One electrode was used to stimulate and the other electrode was used to sense the electrical activity of the heart and vice versa. Linear regression analysis of the time from the stimulus to the steepest negative slope of the electrograms revealed increasing values with increasing anatomical distance and a symmetrical behavior with respect to the two leads. This indicates the close relationship of this parameter to ventricular conduction velocity.

A system for non-invasive rejection monitoring after heart transplantation is presented. This system is based on the recording of intramyocardial electrograms via pacemaker telemetry and remote analysis of these electrograms with an Internet accessible workstation. The qualification of the system to support a multicenter study has been assessed.

Aim The aim of this study was to examine the relation between cardiac haemodynamics and parameters extracted from the intracardiac electrogram obtained during pacing, i.e. ventricular evoked response. Methods and results In the course of routinely scheduled right heart catheterization, intracardiac electrograms and cardiac haemodynamics were monitored simultaneously in ten heart transplant patients (two females, aged 4812 (18–59) years), using pacemaker telemetry and Swan–Ganz thermodilution techniques. Different haemodynamic states were induced by pacemaker programming (pacing rate changes) and table tilting (postural changes). Forty different haemodynamic states were assessed, with an average of three (2–4) haemodynamic variations in each patient. Linear regression analysis between relative stroke volume changes and relative changes in the R wave slew rate as extracted from the evoked responses revealed a strong, inverse, and highly significant correlation (r=0·93, P

Der goldene Standard der Abstosungsdiagnostik bei Patienten nach Herztransplantation ist trotz intensiver Forschungen nach wie vor die invasive und kostenintensive EMB (Endomyokardbiopsie) [11]. Mit den Computerized Heart Allograft Recipient Monitoring (CHARM) konnte eine neue nichtinvasive Methode entwickelt werden, basierend auf der Analyse von intramyokardialen Elektrogrammen. Mit Hilfe eines telemetriefahigen Herzschrittmachers konnen zur Abstosungsdiagnostik bei Patienten nach Herztransplantation beliebig oft Sequenzen aufgezeichnet und analysiert werden. Die hohe Korrelation dieser Signale mit den klinischen Ergebnissen konnte bereits in verschiedenen monozentrischen Studien sehr gut dargestellt werden [1, 3, 4, 6, 10, 12, 13].

Telemetric recording and subsequent analysis of intramyocardial electrograms offer a noninvasive method for patient monitoring after heart transplantation. Decreasing electrical activity indicates both episodes of rejection and infection. Analysis of the duration of the ventricular evoked response recorded during pacing reveals a significant increase of this parameter only during infection. In many cases, this additional information can be used to differentiate between the two pathological effects and to enhance the specificity of the method.

Diagnosis of acute heart rejection after transplantation with the help of epimyocardial electrograms has been reported as a sensitive and practicable method. Long-term follow-up has been limited, however, by variations o signal, which can be avoided by using pacemaker-induced signals.For stimulation and detection of the ventricular evoked response, a new type of electrode with fractal surface structure was used. Seventeen patients undergoing heart transplantation were included in the study. Amplitudes of the depolarization and repolarization parts of ventricular evoked response signals were analyzed and related to the degree of acute rejection according to histologic findings from endomyocardial biopsy.In cases of focal moderate rejection (grade 2, International Society for Heart and Lung Transplantation grading) and higher degrees of rejection, significant amplitude decreases were found.This sensitive noninvasive method for rejection monitoring with a high level of reliability provides the possibility of reducing the number of endomyocardial biopsies.

Modern pacemakers and electrodes are equipped with supplementary features that can be utilized for many problems related to cardiac diagnosis and therapy management. Especially the recording and computer-assisted analysis of intramyocardial electrograms (IEGM), particularly of ventricular evoked responses (VER), supplies important information. The IEGMs are transmitted with large bandwidth from the implanted pacemaker to an extracorporeal receiver and from there via Internet to a central data processing station, where a specially designed software for IEGM processing is available. An individual password secured account is installed for each user. After signal processing is completed, a comprehensive patient report including trend courses and relevant clinical data is provided and can be utilized by the user for further decisions. Using this basic structure, CHARM (Computerized Heart Acute Rejection Monitoring), a system for non-invasive rejection monitoring after heart transplantation, has been developed and successfully evaluated in a clinical environment.

In a retrospective analysis, 149 echocardiographic (EC) evaluations were compared with conventional clinical parameters for donor heart selection. Of these cases, 12% were found with severe impairment of ventricular wall motion or with morphological abnormalities. Nearly half of the echocardiographically diagnosed pathological findings in donor hearts were not detected by conventional standards for heart screening. Analysis of EC-screened donor heart outcome showed a primary graft nonfunction rate of 3.1%. We suggest EC as an additional screening instrument for further dynamic and morphological information about donor heart condition. Potential donors can be saved for transplantation and severe complications can be avoided by detecting occult cardiac dysfunction. Early detection of cardiac dysfunction may have an impact on donor therapy and can avoid unnecessary and expensive transportation of the surgical team to the harvest site.

An endomyocardial electrogram (ECG) was reported to be a sensitive and practicable method for rejection monitoring after heart transplantation. Long-term follow up was limited, however, by variations of signals. The repolarization part of ECG signals vary with changes of heart rate. Both can be avoided by using pacemaker-induced signals. For stimulation and sensing of the ventricular-evoked response, a new type of electrode with fractal surface structure was used. Twenty patients undergoing heart transplantation were evaluated. Amplitudes of the depolarization and repolarization part of the ventricular-evoked response signals were analyzed and related to the degree of acute rejection according to histological findings from endomyocardial biopsy. Signals were transferred by Internet and analyzed automatically. In the case of focal moderate rejection (grade 2, International Society for Heart Transplantation grading) and higher degrees of rejection, a significant amplitude decrease was found. This sensitive non-invasive method for rejection monitoring with a high level of reliability provides the possibility of reducing the number of endomyocardial biopsies.

Besides the current classification of cytomegalovirus (CMV) infection and disease we defined "CMV antigenaemia" as the marker for initiation of antiviral therapy (CMV hyperimmune globulin 2 ml/kg/d and ganciclovir 1000 mg/d), and "episodes of CMV antigenaemia"(the time from detection of antigenaemia until a subsequent antigenaemia assay tested negative again) indicated the time period of antiviral treatment. Patients were at highest risk for antigenaemia at day 38.2 +/- 20.9 after heart transplantation. We observed 50 episodes of antigenaemia in 18 patients. The mean duration was 7.3 +/- 6.4 days. No antigenaemia associated symptoms and no anti-CMV IgM was observed without preceding evidence of antigenaemia. Antigenaemia-associated symptoms and antigenaemia disappeared after antiviral therapy was initiated. Our therapy did not prevent CMV infection, but despite the repeated evidence of active CMV infection, no patient suffered CMV disease.

During CMV viremia, the CMV specific lower matrix protein CMV pp65 can be detected in the nucleus of polymorphonuclear cells. A relationship has been found between the number of CMV pp65 positive cells, the clinical course and the effect of antiviral treatment on CMV disease. From 1990, heart recipients (triple drug therapy) were screened for CMV pp65 (antigenemia, according to the method described by The et al.), anti-CMV-IgM and -IgG. Tests were repeated at least every 4 weeks. Group 1 consisted of 23 patients who had been transplanted at least one year before the introduction of CMV testing as described. Between 1990 and 1992 26 patients were followed up during the first year after transplantation and represent group 2. In group 1, 1184 antigenemia assays were performed and 13 tested positive. In group 2 (1195 tests, 261 positive results), 20 out of the 26 recipients tested positive for CMV pp65. Without preceding evidence of a positive CMV pp65, no rise of IgM or IgG antibodies was observed. The time until the first antigenemia (time from detection until a subsequent test remains negative); 13 were found in group 1, 84 in group 2. In group 2, 46 episodes of antigenemia (mean duration 24.5 +/- 27.1 days) consisted of more than 1 consecutive positive result of the antigenemia assay (4.8 +/- 4.1). During these episodes the white blood cell count was 3460 +/- 1790/mm3. After the episodes, the mean leucocyte count was 6320 +/- 1870/mm3. The detection of CMV antigenemia indicated the initiation of antiviral treatment (hyperimmune globulin and ganciclovir). Therapy was stopped again when the antigenemia assay tested negative again. Antigenemia disappeared in all patients after initiation of antiviral treatment, CMV disease was not observed. CMV antigenemia mainly cumulates within the first year after heart transplantation. Antigenemia directed antiviral therapy does not prevent infection or repeated antigenemia but prevents CMV disease after heart transplantation.

During the first year after orthotopic heart transplantation 39 recipients (given prophylactic immunosuppression with antithymocyte globulin for 7 days after orthotopic heart transplantation and triple drug maintenance therapy) were screened for cytomegalovirus antigenemia and anti-cytomegalovirus immunoglobulin M (index) and immunoglobulin G levels (antibody units) by MEIA-method. Until day 14, all recipients received cytomegalovirus hyperimmunoglobulin at a dosage of 2 ml/kg/day. Four patient groups were defined: group 1 (n = 15) seropositive recipient/seropositive donor, group 2 (n = 9) seronegative recipient/seropositive donor, group 3 (n = 8) seropositive recipient/seronegative donor and group 4 (n = 7) seronegative recipient/seronegative donor. Twenty-four donors and 23 recipients were seropositive for anti-cytomegalovirus immunoglobulin G. After transplantation, 31 recipients tested positive for cytomegalovirus antigenemia before immunoglobulin M elevation and at least 7 days before the onset of clinical symptoms of cytomegalovirus. In group 2, episodes of cytomegalovirus antigenemia appeared earlier, were more frequent, and lasted longer than in groups 1 and 3. Without previous evidence of positive cytomegalovirus antigenemia testing, no sign of cytomegalovirus disease was seen. When cytomegalovirus antigenemia was positive, cytomegalovirus hyperimmunoglobulin was readministered at the same dosage and gancyclovir (1000 mg/day) was given until cytomegalovirus antigenemia disappeared. However, episodes of recurrent cytomegalovirus were observed (2.6 +/- 1.9, 4.3 +/- 1.0, and 2.3 +/- 1.2 in groups 1, 2 and 3, respectively). In groups 1 and 3, the anti-cytomegalovirus immunoglobulin G antibody level remained high during the observation period. In groups 2 and 4 anti-cytomegalovirus immunoglobulin G antibodies were positive because of hyperimmunoglobulin prophylaxis but immunoglobulin G decreased again after discontinuation of the prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

This study describes clinical experience with a rapid method for diagnosis of cytomegalovirus infection in organ-transplanted patients, based on the detection of CMV-specific antigens in peripheral polymorphonuclear cells with a mixture of monoclonal antibodies. This CMV-pp65 assay was formerly called the "CMV immediate early antigen assay." A group of 180 organ-transplanted patients were examined with this assay; 75 of them could be observed from the date of transplantation. These 75 patients consisted of two groups: 59 kidney transplant patients receiving no CMV hyperimmunoglobulin prophylaxis (group I), 13 heart-transplanted patients, and 3 liver transplanted patients receiving prophylaxis (group II). Group III consisted of 105 patients who had been transplanted ca. 2 years before starting this study. In group I, 26 (44%) were CMV-pp65-positive (13 primary and 13 secondary infections). Fifteen of these 26 (58%) positive patients showed clinical symptoms of CMV infection. Eleven of these 15 (73%) were primary infections. Symptomatic patients had significantly more CMV-pp65-positive cells than asymptomatic patients; 12 patients showed a high number of positive cells and 11 of them developed severe CMV illness. Thirty-three patients were CMV-pp-65-negative (22 CMV IgG-sero-positive, 11 CMV IgG-seronegative). None of them had symptoms of CMV infection. In all patients of group I there were 36 periods of graft dysfunction in which CMV infection had to be differentiated from transplant rejection. In 10 out of 36 there was a CMV-pp65-positive test result and subsequent seroconversion. Treatment of viral infection resulted in improvement of clinical problems. In the remaining 26 episodes no CMV-pp65-positive cells were detected: in 17 cases graft dysfunction was caused by rejection, in 9 cases by other complications. In group II, 13 of 16 patients (81%) were positive in the CMV-pp65 assay (6 primary infections, 7 secondary infections). However, none of them showed clinical signs of CMV infection, regardless of the number of positive cells. No CMV-related graft dysfunction was observed. In group III, CMV infections did not play an important role. The experiences described suggest that this test is a valuable tool in early CMV diagnosis and in differentiating CMV-dependent graft dysfunction from other graft dysfunctions. It allows prompt therapeutic intervention.

Hearts from brain dead victims of carbon monoxide poisoning have been reported to be unsuitable for heart transplantation. We present the case of a 30-year-old male donor who was the victim of carbon monoxide poisoning. He was on ventilation for 16 days before the organs were offered for harvesting. A liver biopsy indicated focal liver cell necrosis. The liver graft was not used. Heart transplantation was performed successfully. No evidence of ischemic areas or myocardial cell necrosis could be found in all heart biopsy specimens. Four months after transplantation, graft function remains excellent.

Forty-three consecutive patients who were being treated with digitalis, angiotensin converting enzyme inhibitors, and diuretics were evaluated for orthotopic heart transplantation. After right heart catheterization in patients with more than 3 Wood units or with a mean pulmonary artery pressure higher than 30 mm Hg (n = 13; group 1), prostaglandin E1 (PGE1) therapy was initiated at a dosage of 5 ng/kg/min and was increased stepwise (mean maintenance dosage, 35 ng/kg/min) until side effects (joint pain, digital edema) occurred. After 6 days of PGE1 administration, dosage decreased stepwise. One week after PGE1 was stopped, right heart recatheterization was performed, and the patients were listed on the waiting list. Hemodynamic data significantly improved in PGE1-treated patients. Patients without pulmonary hypertension (group 2, n = 30) were put directly on the waiting list. No oversized or local donor was required for transplantation. Eight of 13 patients in group 1 underwent transplantation. The other five patients died while on the waiting list. In group 2, 15 patients underwent transplantation, and 15 patients died while on the waiting list. A prolonged mean survival time on the waiting list (6.0 versus 3.1 months, p0.005) was noticed in group 1. PGE1 was administered after orthotopic heart transplantation whenever indicated; no death was related to right ventricular failure in group 1. The results after orthotopic heart transplantation in patients treated with PGE1 were comparable to the control group. PGE1 therapy enabled us to perform orthotopic heart transplantation on patients with pulmonary hypertension at a comparable risk with normal heart transplant recipients.

This retrospective study was carried out to evaluate the effect of prostaglandin E1 on the frequency of rejection in 36 heart transplant recipients who survived orthotopic heart transplantation for 60 days or longer. The therapy for both groups was the same except group 1 (n = 12) was given PGE1 for 6 to 14 days. Indication for the PGE1 was right ventricular mismatch or failure. The prostaglandin administration started during the transplantation procedure. The dosage was 28 to 64 ng/kg/min and was tapered down from 14.7 to 32 ng later. No major side effects related to PGE1 have been observed. During the first 60 days after heart transplantation, in the group treated with prostaglandin, rejection grade 2 or higher was evident in 0.91 biopsies/patient versus 2.2 in nontreated patients, (p less than 0.05). A prolonged interval free from rejection (p less than 0.05) was observed in the patients treated with prostaglandin.

The manufacturers of nuclear magnetic resonance (NMR) scanners [1], as well as the manufacturers of pacemakers, emphasize that NMR tomography of pacemaker patients is contraindicated. However, NMR results, required for planning oncologic and surgical procedures, cannot be obtained by other methods. Nevertheless, the possible risk of pacemaker malfunction due to NMR has to be taken into consideration.

Elevated pulmonary vascular resistance (PVR) and pulmonary hypertension (PH) are high risk factors for early graft failure in orthotopic heart transplantation (oHTx). The need for an oversized donor in patients with elevated PVR aggravates the shortage of suitable donor organs. To decrease the elevated PVR to values suitable for orthotopic heart transplantation prostaglandin E1 (PGE1) was administered in 11 patients (11 male, mean age 49.2 years, mean dosage 35 ng/kg per min over 6-8 days). Ten days after the discontinuation of the PGE1 therapy, recatheterization was done. All haemodynamic data were determined by right heart catheterization using a Swan Ganz catheter and thermodilution technique before, and 10 days after, PGE1 treatment. The Wilcoxon signed ranks test was used for statistics. PVR significantly decreased in all patients (5.5 to 2.8 Wood units, P0.005). All patients were considered to be suitable for oHTX and put on the waiting list. At the time of writing, in eight of these patients (eight male, mean age 49.6 years; four ischemic, four dilatative CMP) oHTX had been successfully performed. No right ventricular failure occurred in the postoperative phase. These results sugest that long-term moderation of elevated PVR by PGE1 therapy weeks or months before transplantation enables oHTX in patients with elevated PVR.

In view of the numerous techniques known for noninvasive rejection monitoring for heart transplant recipients, it is important, especially for small transplant centres, to select suitable parameters for routine monitoring. We verified the methods for rejection monitoring and on the basis of the good results after orthotopic heart transplantation in our unit (33 patients, 78% overall survival, no death later than 6 months after transplantation), consider the following parameters useful for small transplant centres: heart/thorax ratio, echocardiography and neopterin. The Fast-Fourier analysis should prove of great value for small transplant units, given the availability of suitable apparatuses.

Results: At listing, no significant differences were noted between the 2 groups (HIV+ vs HIV−) for sex ratio, viral etiology, number of nodule(s) (1.6±0.9 vs 2.3±2.4, p = 0.8), maximal diameter of nodule(s) (27±8mm vs 25±12mm, p = 0.9), and AFP level. Rate of patients in each group that exceeded Milan criteria were similar (2/20 (10%) vs 11/61 (18%)). HIV+ patients were younger (49±5 years vs 56±5 years, p = 0.001). The rate of patients treated by chemoembolization (mean number of cure: 1.5±0.5 vs 1.4±1, p = 0.86) was similar but the rate of radiofrequency was higher in HIV+ patients (8/20 (40%) vs 11/61 (18%), p = 0.04). Drop-out (DO) of HIV+ patients were significantly higher (7/20 (35%) vs 6/61 (9%), p = 0.007). Tumoral progression (n = 5) and HIV evolution (n = 2) were responsible of DO in HIV+. With a similar waiting-time (7±8 months vs 4±5 months, p = 0.13), 13 HIV+ and 55 HIV− were transplanted with one post-operative death in each group. On the explanted liver, no significant differences were noted concerning the number of nodule(s) (2.3±1.6 vs 2.6±3.2, p = 0.70), with a maximal diameter of (27±13mm vs 28±14mm, p = 0.82), presence of satellite nodules (4/13 vs 21/49, p = 0.39), vascular invasion (6/13 vs 22/48, p = 0.98) but Edmonson grade was higher in HIV+ (3.1±1.1 vs 2.5±1.1, p = 0.04). After a mean follow-up of 16±18 months and 24±16 months for HIV+ and HIV− patients (p = 0.11), respectively, a tumoral recurrence was noted in 4/13 (30%) HIV+ patients at 2, 3, 11 and 37 months vs 2/49 (4%) in HIV− patients at 20 and 28 months after LT (p< 0.001). Conclusion: In our series, because of high drop-out (35%) and recurrence after LT (30%) in HIV+ patients, a better selection in this kind indication must be performed.

We report on a 14-years old boy with isolated interruption of the aortic arch (type B). By the use of extracorporal circulation complete relief could be achieved by interposing a large Dacron tube. Follow up restudy demonstrated a normotensive patient without residual gradient of the systemic blood pressure.