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E Wolner

Publications and source records attributed to E Wolner.

At least 37 records · Page 2Linked to original sources
PubMed2002

The impact of diabetes mellitus at the time of heart transplantation on long-term survival.

AIMS/HYPOTHESIS: To analyse the impact of diabetes mellitus (DM) at the time of heart transplantation on long-term survival and incidence of transplant coronary artery disease (TxCAD). METHODS: We analysed 773 consecutive adult heart transplant recipients who underwent primary heart transplantation from May 1986 until December 2000. The cohort consisted of 140 patients with diabetes mellitus (with DM, men 82%) and 633 patients without (wo DM, men 84%) diabetes mellitus at the time of transplantation. The patients were documented as to survival and incidence of TxCAD. RESULTS: Patients with diabetes mellitus were older compared to those without diabetes mellitus (with DM 54.9+/-6.8a vs wo DM 49.7+/-10.8a; p=0.0001), they had a higher incidence of ischaemic cardiomyopathy prior to transplantation (with DM 52% vs wo DM 30%; p=0.0001), but reduced long-term survival (10 year survival: with DM 40% vs wo DM 58%; log-rank=0.025). Surprisingly, the incidence of transplant coronary artery disease (TxCAD) was comparable at 10 years (with DM 28% vs wo DM 22%; log-rank=0.625). In multivariate Cox proportional hazard analysis, diabetes mellitus present at the time of heart transplantation (HR 1.594; 95%CI 1.009-2.518; p=0.045), but not age (HR 0.990; 95%CI 0.965-1.014; p=0.404) was an independent predictor affecting long-term survival. CONCLUSION/INTERPRETATION: The presence of diabetes mellitus at the time of heart transplantation adversely affects long-term patient survival, but does not predict the occurrence of transplant coronary artery disease. The definite mechanisms of adverse survival primarily seem to relate to generally impaired global organ function. Despite a less favourable long-term outcome, our data still justify heart transplantation in end-stage heart failure patients with diabetes mellitus.

Adult↗
PubMed2002

Endoluminal stent-graft placement in patients with acute aortic dissection type B.

OBJECTIVES: This study was performed to evaluate the feasibility, safety and effectiveness of endovascular stent-grafting in treating Stanford type B acute aortic dissection. We describe our first clinical experiences and initial results with stent-grafting across the primary entry tear in patients with acute aortic dissection type B. METHODS: Between March 2000 and August 2001, nine patients with acute type B dissection were treated endoluminally by stent-graft implantation. There were seven male and two female patients with a mean age of 63 years (between 48 and 85 years). In all nine patients aortic dissection was diagnosed by multislice computed tomography (CT) angiography. All nine patients had a maximal aortic diameter of 5.5 cm or more and recurrent pain, one patient showed hemoptysis. This patient with signs of a contained rupture was treated under emergency condition, the eight remaining patients were in hemodynamic stabile condition at the time of intervention. The GORE Excluder stent-graft system was used in eight patients (mean 1.8 stents/patient) and the TALENT stent-graft system in one patient, which were introduced transfemorally. RESULTS: The primary entry tear could be sealed successfully in all nine patients. Complete thrombosis of the false thoracic aortic lumen was obtained in two patients, in the remaining seven patients the false lumen was obliterated in the area of the thoracic aorta but perfused via re-entries in the abdominal region. No severe intraoperative complications occurred. One patient developed bilateral incomplete paraplegia with motor and sensory deficits affecting completely the right leg and partially the left leg, 14 h after intervention. A cerebrospinal fluid drainage was initiated by inserting a lumbar catheter. All nine patients, including the patient with the transient paraplegia, could be discharged from the hospital in excellent condition and without remaining neurologic deficits. Control CT scans showed a reduction of the false lumen from 2.34+/-0.58 to 0.7+/-0.44 cm and an increase of the true lumen from 1.56+/-0.5 to 4.10+/-0.6 cm in the thoracic aortic region. Mean ICU stay was 1.8 days, mean postoperative hospital stay was 7.6 days. CONCLUSIONS: Stent-grafting of acute type B dissections may represent a very effective and promising new method by closure of the primary entry tear, thereby minimizing the risk of rupture of the thoracic aorta and optimizing distal perfusion by decompression of the true lumen.

Aged↗
PubMed2002

Death-inducing receptors and apoptotic changes in lymphocytes of patients with heart transplant vasculopathy.

The specific role of lymphocyte apoptosis and transplant-associated atherosclerosis is not well understood. The aim of our study was to investigate the impact of T cell apoptotic pathways in patients with heart transplant vasculopathy. Amongst 40 patients with cardiac heart failure class IV who have undergone heart transplantation, 20 recipients with transplant-associated coronary artery disease (TACAD) and 20 with non-TACAD were investigated one year postoperative. Expression of CD95 and CD45RO, and annexin V binding were measured by FACS. Soluble CD95, sCD95 ligand (sCD95L), tumour necrosis factor receptor type 1 (sTNFR1), and histones were measured in the sera by ELISA. The percentage of cells expressing CD3 and CD4 was significantly reduced in TACAD as well as in non-TACAD patients as compared with control volunteers. Interestingly, the proportion of CD19+ (B cells) and CD56+ (NK) cells was increased in TACAD groups (versus non-TACAD; P < 0.01, and P < 0.001, respectively). In contrast to sCD95, the expression of CD95 (APO-1/Fas) and CD45RO (memory T cells), and sCD95L were significantly increased in non-TACAD and TACAD patients. T cell activation via CD95 with consecutive apoptosis was increased in both groups. The concentration of sTNFR1, IL-10 and histones was significantly elevated in sera from TACAD than non-TACAD patients, and in both groups than in healthy controls. These observations indicate that the allograft may induce a pronounced susceptibility of CD4+ T cells to undergo apoptosis and antibody-driven activation-induced cell death. This data may suggest a paradox immune response similar to that seen in patients with autoimmune diseases.

Aged↗
PubMed2002

Activation-induced T cell death, and aberrant T cell activation via TNFR1 and CD95-CD95 ligand pathway in stable cardiac transplant recipients.

Specific blockade by antibodies (Abs) utilized in induction therapy may cause activation-induced cell death (AICD) in lymphocytes of transplant recipients, preactivated via CD95 and tumour necrosis factor-alpha receptor type 1 (TNFR1), and reduce allograft rejection frequency. Amongst 618 heart transplant (HTX) patients receiving antithymocytes globulin (ATG) therapy, 14 recipients with IVUS-verified freedom of transplant vasculopathy were studied. The control group contained 14 patients awaiting transplantation, classified by the New York Hearth Association heart failure as class IV. From 618 HTX patients 89% were free of rejection grade ISHLT > or =2-3 within 3-month post transplantation and 86% after one year. The death inducing receptors (DIR) such as CD95, CD95L and soluble TNFR1 were significantly increased in HTX recipients versus controls, as demonstrated by FACS, immunoblotting or ELISA (P < 0.001). The presence of increased DIR and in vivo apoptosis in HTX recipients, indicated by annexin-V binding, was further confirmed by the presence of high concentration of histones in the sera of patients. ATG, anti-IL-2R and OKT-3 Abs inhibited cell proliferation in a dose-dependent manner. The induction of apoptosis and/or necrosis was demonstrated in cells cultured with these Abs by annexin-V and 7-aminoactinomycin staining, respectively. Our findings demonstrate that T cells from HTX recipients express high level of CD95, CD95L and soluble TNFR1, and undergo apoptosis and AICD. These cells recognizing donor alloantigens may be selectively eliminated in vivo, and should be responsible for the observed immunological unresponsiveness, indicated by low rejection rates in our patient cohort treated by conventional triple therapy.

Adult↗
PubMed2002

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↗
PubMed2002

Depletion of intracellular GTP results in nuclear factor-kappaB activation and intercellular adhesion molecule-1 expression in human endothelial cells.

The expression of the intercellular adhesion molecule 1 (ICAM-1) on the surface of endothelial cells plays an important role in immune-mediated processes. The induction by the proinflammatory cytokine interleukin (IL)-1beta is regulated by nuclear transcription factor kappaB (NF-kappaB). We studied the effect of an inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitor, mycophenolic acid (MPA), on constitutive and IL-1beta-induced expression of ICAM-1 in human umbilical vein endothelial cells (HUVECs). Unexpectedly, pretreatment with MPA enhanced the constitutive expression and potentiated the induction of ICAM-1 by IL-1beta, as detected by flow cytometry. Northern blot analysis revealed an increase in ICAM-1 mRNA levels in cells treated with MPA. This was associated with an increase in phosphorylation of IkappaB-alpha (an inhibitor of NF-kappaB), nuclear translocation of the NF-kappaB subunits p50 and p65 and their binding to DNA as detected by Western blotting, confocal microscopy, and electrophoretic mobility shift assay. The up-regulation of ICAM-1 by MPA was prevented by high doses (100 microM) of guanine or guanosine but not by physiological doses (0.1 microM), indicating that guanylates are involved in endothelial responses to IL-1beta. Cultivation of HUVECs in the absence of guanine enhanced further ICAM-1 expression during IMPDH inhibition. These results demonstrate that cytokine-mediated endothelial ICAM-1 expression can be modulated by IMPDH inhibition. We believe this represents a novel interaction between endothelial guanylate metabolism, NF-kappaB activation, and adhesion molecule expression.

Cells, Cultured↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

Target vessel revascularization without cardiopulmonary bypass in elderly high-risk patients.

BACKGROUND: Coronary artery bypass grafting in patients over 75 years is associated with high operative risk. Target vessel revascularization without cardiopulmonary bypass is a promising option for highly selected, older patients. However, the outcome remains uncertain. METHODS: We investigated 44 patients over 75 years, matched for preoperative risk and left ventricular function, who underwent coronary artery bypass grafting either with or without cardiopulmonary bypass (CPB). We analyzed patients characteristics, Parsonnet score, EuroSCORE, short as well as midterm outcome and quality of life (freedom from recurrence of angina, anti-anginal therapy, sf36 test). RESULTS: Perioperative mortality was higher in the patient group operated with CPB (15.9) as compared to patients operated without CPB (4.5%, p = 0.0226). Patients operated with cardiopulmonary bypass received more grafts (3.1 +/- 0.1) than patients operated without cardiopulmonary bypass (1.6 +/- 0.1, p = 0.0001) and and were more likely to undergo complete revascularization (with CPB 100%, without CPB 63.6%, p = 0.0010). Perioperative complications were more frequent and midterm survival was worse in the patient group operated with CPB (log rank p = 0.0228). Quality of life was comparable in both groups. CONCLUSIONS: The concept of incomplete target vessel revascularization of the culprit lesion seems to be a promising option for selected high-risk patients, predominantly due to lower perioperative mortality.

Aged↗
PubMed2001

Complete revascularization in coronary artery bypass grafting with and without cardiopulmonary bypass.

BACKGROUND: The feasibility of complete revascularization on the beating heart without cardiopulmonary bypass (CPB) as compared with the standard operation with CPB in elective low-risk patients with multivessel disease has not been clearly demonstrated in a prospective trial. METHODS: Eighty selected low-risk patients were enrolled. In preoperative study with coronary angiography, the decision was made whether complete revascularization without CPB could be performed. Patients were randomly assigned to receive CABG either with (n = 40) or without CPB (n = 40). Randomization criteria were age, sex, and left ventricular ejection fraction. Completeness of revascularization as well as short- and mid-term clinical outcome in a 13.4 +/- 6.5 month follow-up period were monitored. RESULTS: Twenty-six of 40 (65%) patients undergoing CABG without CPB underwent complete revascularization. In 5 of these patients (12.5%) suitable vessels were discarded for technical reasons and 9 patients (22.5%) were switched to CABG with CPB owing to the deeply intramyocardial course of target vessels (n = 5) or to hemodynamic instability (n = 4). In the group of patients operated on with CPB, 34 of 40 patients (85%) received complete revascularization. In 6 patients (15%) suitable vessels were discarded for technical reasons. Mean number of bypass grafts was 3.1 +/- 0.8 with CPB and 2.6 +/- 0.5 without CPB (p = 0.043). Clinical outcome and hospital stay were comparable in both groups. No patient died during the study period. No myocardial infarction was observed. Three patients undergoing CABG without CPB underwent successful PTCA 3 months after surgery. CONCLUSIONS: CABG without the use of CPB is effective for complete revascularization in the majority of selected low-risk patients. Nevertheless, it has to be stated that the rate of incomplete revascularization in this early series of CABG without CPB is higher, and compromises the basic principle of complete revascularization.

Aged↗
PubMed2001

Lessons learned from the first clinical implants of the DeBakey ventricular assist device axial pump: a single center report.

BACKGROUND: The bridge to transplantation with pulsatile mechanical assist devices became a standard procedure for patients deteriorating on the waiting list. Recently, continuous flow axial impeller pumps were introduced to clinical application offering new advantages. METHODS: From November 1998 till September 2000, 6 male patients (mean age 53 plus or minus 11 years) with end-stage left heart failure were implanted with a DeBakey ventricular assist device (VAD) axial-flow pump for bridge to transplantation. RESULTS: Three patients were successfully transplanted after 74, 115, and 117 days, respectively. Two other patients died after 25 and 133 days. One patient is still on the device after 108 days. Because of modification of the implantation technique after the first 2 patients, mean pump-flow within the first 3 weeks was increased from 4.3 +/- 0.6 L/min to 6.7 +/- 0.3 L/min. Patients were put on regular bicycle-ergometer training and improved their exercise capacities up to a mean maximum oxygen consumption of 20.2 mL/kg/min. CONCLUSIONS: Initial implants of the DeBakey VAD demonstrated support properties comparable to pulsatile pumps but without significant restrictions for extended use.

Equipment Design↗
PubMed2001

Cardiopulmonary bypass affects cognitive brain function after coronary artery bypass grafting.

BACKGROUND: The causes for cognitive impairment after coronary artery bypass grafting (CABG) have long been a topic for debate. METHODS: We prospectively followed 308 consecutive, unselected survivors of CABG at our institution. In addition to determination of clinical measurements, cognitive brain function was measured objectively by P300 auditory-evoked potentials before CABG, at 7-day and at 4-month follow-up. Standard psychometric tests (Trail Making Test A, Mini Mental State Examination) were also performed. RESULTS: At 7-day follow-up cognitive P300 auditory-evoked potentials were significantly impaired compared with preoperative levels (peak latencies: 376 +/- 40 ms versus 366 +/- 37 ms, p = 0.0001). P300 measurements were almost normalized at 4-month follow-up (peak latencies: 369 +/- 33 ms, p = NS versus preoperative). Standard psychometric tests failed to detect this subclinical cognitive impairment. Multiple regression analysis revealed that use of cardiopulmonary bypass was the only independent predictor of impaired cognitive brain function at 7-day (p < 0.0001) and 4-month follow-up (p = 0.0008). The presence of diabetes mellitus (p = 0.0135) or concomitant repair of significant carotid artery stenosis (p = 0.0049) was predictive of late improvement of cognitive brain function at 4-month follow-up. CONCLUSIONS: Objective cognitive P300 auditory-evoked potential measurements demonstrate that the use of cardiopulmonary bypass is the only predictor of short- and long-term cognitive brain dysfunction after CABG. Interestingly, the presence of diabetes mellitus and concomitant repair of a significant carotid artery stenosis were predictive for long-term cognitive benefit.

Aged↗