PubMed Health⌕ Search

Biomedical subjects

G Wieselthaler

Publications and source records attributed to G Wieselthaler.

At least 19 recordsLinked to original sources

Rapamycin as rescue therapy in a patient supported by biventricular assist device to heart transplantation with consecutive ongoing rejection.

Rapamycin is a new immunosuppressive agent that has been shown to be effective in acute heart allograft rejection. This case documents a patient suffering from cardiac sarcoidosis who was bridged to transplantation for 90 days with ongoing rejection after allograft implantation. Rejection did not abate despite treatment with antithymocyte globulin (ATG), FK506, a mycophenolate switch and courses of multiple apheresis. Initiation of rapamycin treatment resulted in a rapid resolution of cardiac rejection and reduction of concomitant immunosuppressive agents with few side-effects. Most notably was the reduction of panel reactive antibodies within a few weeks after the rapamycin initiation. This case illustrates that the utilization of rapamycin ceased ongoing rejection in a patient with a clear hyperimmune state despite prior extensive utilization of a variety of immunosuppressive strategies after heart transplantation.

Adult↗

Transitory immunologic response after implantation of the DeBakey VAD continuous-axial-flow pump.

BACKGROUND: The development of local and systemic infection is a significant risk factor associated with implantation of a ventricular assist device. The immunologic consequence of continuous-flow rotary blood pumps is not known. METHODS: Six male adult patients (mean age 47 plus minus 10.3) with end-stage left heart failure received a DeBakey VAD axial-flow pump for use as a bridge to transplantation. (Four patients underwent transplantation after a mean 115 plus minus 14 days; 2 patients are still waiting for the allograft.) RESULTS: We prospectively monitored T-cell populations and apoptosis-specific aberrant T-cell activation via CD95 triggering and annexin V binding to lymphocytes, identifying T cells undergoing early phases of apoptosis, within the first 10 weeks. Moreover, soluble death-inducing receptors soluble CD95 and soluble tumor necrosis factor-R1 were evaluated by enzyme-linked immunosorbent assay. CONCLUSION: Patients bridged to transplantation by a nonpulsatile ventricular assist device demonstrated an initial pronounced apoptosis-specific immune alteration by increased annexin V binding to CD3 T cells and death-inducing receptors soluble CD95/tumor necrosis factor-R1 (all P <.001). All parameters normalized after 7 weeks to baseline. No blood-borne sepsis was detected, as defined by blood culture, within the first 10 weeks of the cohort study. These results indicate a biphasic immunologic response in patients with end-stage heart failure treated with nonpulsatile ventricular assist devices.

Adult↗

Survival benefit of the implantable cardioverter-defibrillator in patients on the waiting list for cardiac transplantation.

BACKGROUND: The implantable cardioverter-defibrillator (ICD) effectively reduces sudden cardiac death in patients with severe LV dysfunction. Effect of ICD therapy on total mortality in patients on the waiting list for cardiac transplantation is still uncertain. METHODS AND RESULTS: We retrospectively analyzed 854 unselected consecutive patients (ICD therapy, n=102; 11.9%) on the waiting list for cardiac transplantation between January 1992 and March 2000. Actuarial 12-month total mortality rate on the waiting list was 24.2%; sudden cardiac death was the predominant mode of death (66.7% of total deaths). Kaplan-Meier analysis revealed improved survival for ICD (total mortality, 13.2%) compared with non-ICD (total mortality, 25.8%) patients (log rank, P=0.03). No event of sudden death occurred in ICD patients, whereas in non-ICD patients, 12-month sudden death rate was 20.1% (P=0.0001). Nonsudden death rates did not differ between ICD and non-ICD patients (P=0.16). A Cox proportional hazards model demonstrated that absence of an ICD was a powerful independent predictor of total mortality (P=0.02; relative risk, 2.22; 95% confidence interval, 1.16 to 4.17) and sudden cardiac death (P<0.0001; infinite relative risk) on the waiting list. CONCLUSIONS: ICD therapy, because it prevents sudden cardiac death, significantly improves survival on the waiting list for cardiac transplantation. The present study supports the use of ICDs as a bridge to transplantation in patients who are at risk of sudden cardiac death. Prospective randomized trials are needed to evaluate the potential benefit of prophylactic ICD therapy as a bridge to transplantation in all patients on cardiac transplant waiting lists.

Comorbidity↗

Late aortic dissection in a patient with a left ventricular assist device.

The limited availability of donor hearts means that an increasing number of transplantation candidates are temporarily or permanently supported by mechanical circulatory assist devices. We report a patient undergoing implantation of a Novacor left ventricular assist device who suffered fatal aortic dissection on postoperative day 11 after satisfactory recovery from multiple organ failure. The dissection of the aorta initially presented as an embolic peripheral ischemia. Early complete echocardiography is thus warranted to rule out dissection.

Aortic Dissection↗

Noninvasive monitoring of peak filling rate with acoustic quantification echocardiography accurately detects acute cardiac allograft rejection.

BACKGROUND: Acute cardiac allograft rejection is associated with early diastolic dysfunction. The development of chronic rejection is dependent on the frequency and severity of acute rejection episodes. Therefore, early diagnosis and therapy influence long-term survival significantly. For the first time, acoustic quantification, a new echocardiographic technology for on-line measurement of cardiac volumes and their changes, facilitates quantitative assessment of systolic and diastolic function noninvasively. METHODS: Since May 1996, all consecutive patients after cardiac transplantation (n = 94) underwent 475 endomyocardial biopsies and the same number of echocardiographic studies within 6 hours after biopsy before the histological results were available. RESULTS: Nineteen patients showed 23 episodes of acute rejection (ISHLT > or = 2). There was a significant decrease in left ventricular peak filling rate [PFR: end-diastolic volume (EDV)/ second) as a parameter of diastolic function during rejection (2.9 +/- 0.4, n = 23) as compared to PFR measured under nonrejection status (4.5 +/- 0.8; n = 452; p < 0.0001). Most importantly we found that in these 19 patients showing rejection, the PFR was normal in the last examination before rejection, but was significantly reduced during rejection (2.9 +/- 0.4 vs 4.5 +/- 0.7; n = 23, p < 0.0001). After successful rejection therapy, PFR again normalized in all patients, with the exception of 1 patient with steroid-refractory humoral rejection. We calculated sensitivity and specificity for several cutpoints for the event "first rejection" in 15 patients and plotted them in a receiver operating characteristic curve, showing that a PFR > or = 4.0 EDV/second is never associated with treatable rejection. A decrease of PFR of more than 18% from its prevalue of the last biopsy with no rejection increases the accuracy for the diagnosis of rejection significantly. CONCLUSIONS: We conclude that diastolic dysfunction during acute cardiac allograft rejection can be accurately detected by noninvasive measurement of peak filling rate with acoustic quantification echocardiography. Monitoring of this parameter provides reliable discrimination between treatable and nontreatable rejection.

Acute Disease↗

Post-transplant acute myeloid leukemia (PT-AML).

Acute myeloid leukemia following organ transplantation (PT-AML) is a rare event with only a few published cases in the literature. We present three patients who developed AML (FAB M1, M5, M4) after renal, double lung or liver transplantation. Molecular analysis detected a t(9;11) in one patient and documented the recipient origin of AML in a second patient. All patients were treated with chemotherapy. Immunosuppression was reduced to cyclosporin A (CsA) and prednisone in two patients and to prednisone alone in one patient. Two patients achieved a complete remission (CR), with a remission duration of 4.6 months in one patient, the other patient died from septicemia after 15.2 months in CR. One patient was refractory to chemotherapy and died from septicemia. This report together with the documented cases in the literature suggests that PT-AML (1) develops after a median interval of 5 years after transplantation with variable latency (range, <1-17 years); (2) is heterogeneous with respect to FAB classification; (3) shows chromosomal and molecular changes typical of therapy-related AML (t-AML: -7, +8, 11q23, inv16, t(15;17)); (4) standard chemotherapy is feasible after reduction of immunosuppression and produces a CR rate of 56% with a median remission duration of 4.6 months and an overall survival of 2.6 months; (5) the major complications are early death (25%), gram-negative septicemia, progressive disease or relapse. This review provides diagnostic and therapeutic experiences and guidelines for the management of this increasing group of post-transplant patients.

Acute Disease↗

High turnover bone disease following lung transplantation.

Recipients of lung transplants are at very high risk for significant bone loss. Nevertheless, data on bone disease after lung transplantation are still limited. We, therefore, retrospectively evaluated the data of 33 patients surviving at least 1 year after lung transplantation (LTx) who were seen in our outpatient clinic for osteologic evaluation. Results of clinical evaluations, radiographs, and dual-energy X-ray absorptiometry (DXA) were related to each other, to clinical variables, and to serum levels of osteocalcin, parathyroid hormone (PTH), and 25-hydroxyvitamin D: 14 of 33 patients (42%) had vertebral fractures, 9 of whom were diagnosed within 2 years after transplantation. Bone mineral density values (DXA) were markedly decreased and predictive of compression fractures. 25-Hydroxyvitamin D levels were low in 13 patients (39%) and PTH was elevated in 7 (21%). Despite corticosteroids and low 25-hydroxyvitamin D, serum osteocalcin was elevated in 12 patients (36%). This was only partially explained by hyperparathyroidism, low sex hormones, and impaired renal function, and may partly be caused by cyclosporin A. We thus conclude that severe symptomatic bone disease is common in lung transplant recipients and due to a complex situation including high turnover bone loss and hypovitaminosis D. DXA can be used to estimate fracture risk for individual patients.

Absorptiometry, Photon↗

Aerobic endurance training program improves exercise performance in lung transplant recipients.

STUDY OBJECTIVE: To determine whether an aerobic endurance training program (AET) in comparison to normal daily activities improves exercise capacity in lung transplant recipients. PATIENTS AND STUDY DESIGN: Nine lung transplant recipients (12+/-6 months after transplant) were examined. All patients underwent incremental bicycle ergometry with the work rate increased in increments of 20 W every 3 min. Identical exercise tests were performed after 11+/-5 weeks of normal daily activities and then after a 6-week AET. The weekly aerobic training time increased from 60 min at the beginning to 120 min during the last week. Training intensity ranged from 30 to 60% of the maximum heart rate reserve. RESULTS: Normal daily activities had no effect on exercise performance. The AET induced a significant decrease in resting minute ventilation from 14+/-5 to 11+/-3 L/min. At an identical, submaximal level of exercise, a significant decrease in minute ventilation from 47+/-14 L/min to 39+/-13 L/min and heart rate from 144+/-12 to 133+/-17 beats/min, before and after the AET, was noted. The increase in peak oxygen uptake after AET was statistically significant (1.13+/-0.32 to 1.26+/-0.27 L/min). CONCLUSIONS: These data demonstrate that normal daily activities do not affect exercise performance in lung transplant recipients > or = 6 months after lung transplantation. An AET improves submaximal and peak exercise performance significantly.

Activities of Daily Living↗

Flow measurement at the pump head of centrifugal pumps: comparison of ultrasonic transit time and ultrasonic Doppler systems.

Determination of blood flow is essential for monitoring rotary blood pumps. However, accurate measurement directly adjacent to the pump housing is difficult because of the highly irregular flow profiles near the fast spinning rotor. Therefore, a specially adapted flow probe based on the ultrasound transit time (USTT) principle was designed to evaluate the flow in centrifugal blood pumps. The probe can be directly mounted at the housing and creates 2 crossed measuring ultrasound beams. The mean value, Qm, of the 2 output signals corresponds to the blood flow and the difference, Qd, correlates to the vorticity of the flow profile in the pump outflow tract. In vitro measurements obtained an accuracy for mean flow values of better than +/-0.6 L/min in extreme working points and for vorticity values even as high as Qd = 3.5 L/min. Because of vorticity, however, the output signal contained considerable noise, and that required the application of a 10 Hz filter. Positioning of the ultrasound (US) beams parallel to the axial direction of the pump was superior to radial positioning. Additional measurement of the flow profile demonstrated that a large vorticity occurred (up to Qd equal to 3.5 L/min), and this vorticity was highly dependent upon the afterload of the pump. In vivo experiments demonstrated the reliability of the method. We concluded that USTT flow measurement can determine blood flow immediately adjacent to the pump housing with sufficient accuracy, and these measurements are superior to those from US-Doppler systems (which cannot handle the vorticity accurately enough) and electromagnetic devices (which lack zero stability).

Blood Flow Velocity↗

Pharmacologically induced heart failure for the evaluation of circulatory assistance.

For the evaluation of the hemodynamic interaction between the natural heart and an assist device, a reversible pharmacological model based on the channel blocker Verapamil under hyperkalemia, was developed for deterioration of left ventricular function. Four calves weighing 70-90 kg underwent standard implantation for left atrioaortal assist (BioMedicus, BP-80), pump anesthesia (oxygen/isoflurane [1%]; 8 mg/kg of BW/h ketamine), and of ventricular demand pacing at 120 bpm. Left atrial pressure (LAP), ventricular pressure (LVP), aortic pressure (AoP), pulmonary arterial (Qpulm) pressures, and graft flow (Qgraft) were monitored. The hemodynamic effects of anesthetic overdose (2% Isoflurane) were compared with those of Verapamil (Isoptin: 0.2 mg/kg BW/h 5 mmol/kg of BW/h of KCl) medication. Both regimens caused a decreased in AoP to < or = 50%. For Isoflurane, a slight reduction in cardiac output (CO) of 10% at a nearly constant LAP and a strong decrease of the peripheral resistance (Rperi) of 35% could be seen where Isoptin caused a significant reduction in CO of 40% at an increased LAP (+25%) and changes in Rperi of < 10%. Because the vascular tonus remains nearly constant, the hemodynamic effects are controllable and reversible (antagonized with calcium chloride); thus we conclude that Verapamil administration under hyperkalemia conditions is a proper model for mimicking congestive heart failure with low systemic side effects.

Anesthetics, Inhalation↗