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Biomedical subjects

A Wasler

Publications and source records attributed to A Wasler.

At least 19 recordsLinked to original sources

Late acute cardiac allograft rejection: new therapeutic options?

BACKGROUND: Late acute cellular rejection is associated with decreased survival and the development of CAV. Among new immunosuppressive drugs introduced into clinical practice, everolimus, has been shown to be safe in cardiac transplantation. We report our experience with everolimus in heart transplant recipients who developed late acute cellular cardiac rejection. METHODS: Patients with a history of previous rejection episodes who experienced cardiac rejection were switched to an everolimus, cyclosporine, and steroid immunosuppressive regimen. All patients had already received statins and antihypertensive medications. Everolimus, cyclosporine trough levels, and laboratory values were controlled monthly. Drug administration was adapted to an everolimus trough level between 3 and 8 ng/mL, mean maintenance dosage was 0.25 to 1.5 mg twice a day. Death, safety, side effects, biopsy-proven acute rejection episodes, laboratory values, and blood levels were evaluated retrospectively. RESULTS: Four cardiac allograft recipients (two male, two female), at a median of 1473.25 days post-orthotopic heart transplantation (oHTx) (range = 65 to 3045), received 1 to 1.5 mg everolimus per day. Over a follow-up period of at least 2 month (range = 2 to 10) the mortality was 0%. The drug was well tolerated; no acute cellular rejection greater than grade 1a (ISHLT grading) was observed after 2 months. In one patient increased cholesterol values and in two others, elevated triglyceride levels were seen, but were controlled with increased statin therapy. No obvious increased creatinine values were seen with everolimus. CONCLUSION: In conclusion, conversion to an everolimus-based immunosuppressive regimen after late cardiac rejection is safe and effective; no major side effects were observed.

Acute Disease↗

Improving the rate of organ donation.

BACKGROUND: Organ shortage is a major problem in transplantation. Many potential donors are still lost due to a lack of information and communication. Many transplantation centers report a major donor increase after introducing new donor policies. The aim of this study was to evaluate in retrospective fashion a new donor policy in our region. METHODS: For the past 10 years all reported donors from intensive care units (ICUs) in our region were evaluated. Our new policy had 2 main steps: accepting more marginal grafts and using a transplantation representative. The goal was the improved communication with ICUs to support physicians involved in donor care. A public information program was also implemented. RESULTS: In the first year, numbers of donors obviously improved (+60.5%) and remained stable the following year. The mean donor age increased to 41.56 years. The donor pool showed mainly an improved kidney-donation rate (+53%) with also an increase in multiorgan donation (+37%). One year posttransplantation survival was not negatively influenced by this donor pool. As expected, transplantation activities increased notably, particularly liver transplantation (+31.11%) but also kidney transplantation (+26.73%). DISCUSSION: Many donors are lost because physicians in charge of brain dead patients are not fully informed about modified donation criteria. The reason for this is a lack of information and communication by transplantation units. Improved surgical techniques and better preoperative, intraoperative, and postoperative treatment have yielded better results with marginal grafts. Immediate graft function in recipients of suboptimal grafts may be delayed, but without a significantly negative impact on patient and graft survival. Because the age of organ recipients is steadily increasing with fewer contraindications for transplants, more organs will be needed.

Brain Death↗

Mild chronic anemia following heart transplantation: a syndrome with prognostic relevance?

The clinical relevance of mild chronic anemia in patients after heart transplantation (HTX) has not yet been demonstrated. Forty-five outpatients who had undergone HTX 2-99 months prior to investigation and who had not received blood transfusions or erythropoietin (EPO) before data acquisition were observed over a period of 37 months. Anemia was found in 36 of the 45 patients and was normocytic, normochromic, and slightly anisocytotic (coefficient of variation = 16 +/- 2, normal 11.5-14.5). Anemic patients showed elevated EPO levels, whereas in nonanemic patients EPO levels were normal. Survival after HTX differed significantly in anemic and nonanemic patients (P < 0.02), with 100% survival in the nonanemic and 85% in the anemic group. Chronic anemia in patients after HTX shows a typical pattern. Even when mild, anemia in patients after HTX seems to be of prognostic value and thus might be an indicator of chronic disorders.

Adolescent↗

Intramyocardial electrograms for non-invasive rejection monitoring: initial experience with an infection-specific parameter.

Non-invasive rejection monitoring based on the analysis of paced intramyocardial electrograms enables repeated or even daily graft surveillance. The rejection-sensitive parameter is calculated from the maximum slope of the descending part of the t wave. Biopsy-proven rejection grade 2 or higher (ISHLT classification) can safely be detected. Nevertheless, infection influences the rejection-sensitive parameter in the same manner as does rejection (99% negative predictive value for rejection grade 2 or higher, 17% positive predictive value). We defined the infection-specific parameter as the time on the O line between the pacemaker stimulus and the crossover with the maximum slope of the descending part of the t wave. Patients were classified prospectively according to infection status: patients without infection and those with clinically apparent infection. Patients with clinically apparent infections had a significantly longer infection-specific parameter. A simultaneous decrease of the rejection-sensitive parameter and an increase in the infection-specific parameter was observed during clinical infection: a decrease in the rejection-sensitive parameter and no changes in the infection-specific parameter were observed during rejection. This preliminary analysis revealed that discrimination of rejection and infection might be possible by the analysis of intramyocardial electrograms.

Diagnosis, Differential↗

Intramyocardial electrogram variability in the monitoring of graft rejection after heart transplantation.

The ventricular evoked response is a well-standardized electrophysiological signal that can be used for noninvasive, long-term cardiac transplant monitoring. Rejection-sensitive and infection-specific parameters extracted from intramyocardial electrograms correlate with clinical results. The influences of pacing rate, transition from intrinsic to paced rhythm and positional changes on the diagnostic parameters were studied. Increasing the pacing rate shortened the ventricular evoked response and directly influenced the infection specific parameter. The rejection-sensitive parameter remained stable at pacing rates between 100 and 120 beats/min. Measurements made immediately after the patient assumed a supine position and after switching to paced rhythm showed a decrease in the rejection-sensitive parameter. A change in position from supine to upright did not influence the rejection-sensitive parameter, but higher values were measured after returning to the supine position. In conclusion, noninvasive recordings of the ventricular evoked response for monitoring of cardiac allograft should be done at the same time of day, at the same pacing rate, and with the patient resting for at least 5 minutes before measurements are made.

Adolescent↗

[Mechanical circulatory support in heart failure].

Heart transplantation is an established therapy for end-stage cardiac disease. The number of organ donors is limited, and the mortality on the waiting list is increasing. To give these patients a chance to survive their waiting time, chronic mechanical circulatory support, especially left ventricular assist devices have been clinically established. The results with this therapy are encouraging. Because of these results trials using these devices as an alternative for cardiac transplantation are initiated. Due to the further development and miniaturization of such devices this indication will become more important. The most interesting patients are the one, in which devices could be explanted after chronic support, because their myocard has recovered. If we can find a way to identify such patients a new form of therapy for end-stage heart disease could be established.

Equipment Design↗

Evoked epimyocardial electrogram for rejection diagnosis after heart transplantation.

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.

Adult↗

Donor heart quality control. Analysis of echocardiographic (EC) findings and patient outcome.

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.

Adolescent↗

Definitions of cytomegalovirus disease after heart transplantation: antigenemia as a marker for antiviral therapy.

In this prospective study, cytomegalovirus (CMV) antigenemia was defined as the marker for initiation and episodes of antigenemia as the indicator for the duration of antiviral therapy (CMV hyperimmune globulin and ganciclovir). The CMV antigenemia assay and CMV-specific IgM and IgG antibody tests were used to monitor CMV infection in 22 heart transplant recipients who, between October 1992 and July 1994, were followed up for 6 months. A total of 178 out of 627 antigenemia assays tested positive. The highest number of positive cells was greater after primary infection than after either reactivation (43.3 vs 0.3; P < 0.01) or reinfection (43.3 vs 9.3; P = NS). Sixty episodes of antigenemia were observed. More episodes of antigenemia were seen after primary infection than after either reactivation (4.6 vs 0.2; P < 0.01) or reinfection (4.6 vs 2.2; P = NS). The detection of antigenemia indicated the initiation of antiviral therapy within 24 h after the blood sample was harvested. Therapy was stopped immediately after a subsequent negative result became available. Our experience indicates that antigenemia directed antiviral therapy prevents CMV disease after primary and secondary infection in heart transplant recipients.

Adolescent↗

Paced epimyocardial electrograms for noninvasive rejection monitoring after heart transplantation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: This sensitive noninvasive method for rejection monitoring with a high level of reliability provides the possibility of reducing the number of endomyocardial biopsies.

Biopsy↗