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Mario C Deng

Publications and source records attributed to Mario C Deng.

At least 37 records · Page 2Linked to original sources
PubMed2003

The heart-allocation simulation model: a tool for comparison of transplantation allocation policies.

BACKGROUND: Numerous studies have investigated prognostic factors for the survival of transplant candidates waiting for a donor organ, but little is known about the impact of allocation policies on waiting list outcome. Simulation models would allow a comparison of different policies for allocating donor hearts on pretransplant outcome. METHODS: A model was built for the Eurotransplant waiting list for heart transplantation. Survival and delisting distributions were estimated from the Eurotransplant transplant candidate inflow between 1995 and 2000 (n=7,142). Other characteristics were obtained directly from the transplant candidate inflow of 1999 and 2000 (n=2,097) and the donor organs of 1998 and 1999 (n=1,520). Overall and subgroup waiting list mortality were estimated for allocation policies differing by ABO blood group, border, and clinical profile rules. RESULTS: The model estimated that international organ exchange reduces waiting list mortality in the different countries by 1.9% to 12.4%. An allocation policy incorporating the initial clinical profile of the transplant candidates further reduced waiting list mortality by 1.7%. Changing ABO rules toward identical matching yielded a slightly more equitable survival for the different groups, without an overall effect on mortality. The best possible allocation policy is the policy where organs are allocated to patients that are at highest risk of dying, and withholding organs from patients that would eventually delist because of improvement. CONCLUSIONS: Patients benefit from international organ exchange and by a heart allocation scheme based on clinical profiles. Timely delisting of patients who are-temporarily-too well for transplantation is the best waiting list policy.

Computer Simulation↗
PubMed2003

A prognostic model for predicting waiting-list mortality for a total national cohort of adult heart-transplant candidates.

BACKGROUND: Current trends in medical management of advanced heart failure and transplant medicine and the enactment of a national transplant law forced a change toward allocation driven by disease severity. OBJECTIVE: The aim of this study was to create a model for predicting waiting-list survival on the basis of simple clinical parameters. METHODS: The clinical profiles of all patients registered for heart transplantation in Germany in 1997 (n=889) were used as a derivation set, and the total German 1998 cohort (n=897) was used as a validation set. The model was validated by the c statistic and by comparison of risk stratified mortality rates. The validated model was fine tuned by the appropriate calibration procedures. The data were first classified into physiologic subscores: an urgency score, a left ventricular heart failure score, a right ventricular heart failure score, and a systemic heart failure score. A stepwise modeling procedure was undertaken using these subscores as factors as well as the recipient's age, ABO blood group, and body surface area. RESULTS: The urgency and the left ventricular subscore were found to be significantly associated with waiting-list mortality. A summary index termed German Transplant Society (GTS) score was then calculated on the basis of seven parameters contained in these two subscores. The GTS score was able to predict waiting-list mortality risks for the 1998 cohort: 1-year mortality before transplantation was 71%, 34%, 11% for the high, medium, and low risk groups, respectively. CONCLUSION: The use of this continuous disease severity index may improve the selection of cardiac transplant candidates.

Adult↗
PubMed2003

Vascular collagens: spotlight on the role of type VIII collagen in atherogenesis.

Collagens play a central role in maintaining the integrity and stability of the undiseased as well as of the atherosclerotic vessel wall. An imbalanced metabolism may lead to uncontrolled collagen accumulation reducing vessel wall velocity, frequently resulting in arterial occlusion or thrombosis. A reduced production of collagen and its uncontrolled degradation may affect the stability of the vessel wall and especially of the atherosclerotic plaques by making them prone to rupture and aneurysm. This review presents an overview on the four groups of vascular collagens and on their role in atherogenesis. The major focus was to highlight the extraordinary role and importance of the short chain network forming type VIII collagen in the extracellular matrix of undiseased arteries and of atherosclerotic plaques. The molecular structure of type VIII collagen, its cellular origin, its implication in atherogenesis, its temporal and spatial expression patterns in human and experimental models of atherogenesis, the factors modulating its expression, and--not at least--its potential function is discussed.

Arteriosclerosis↗
PubMed2003

Proposition: the benefit of cardiac transplantation in stable outpatients with heart failure should be tested in a randomized trial.

Recent data suggest that cardiac transplantation is associated with a survival benefit only in patients at high risk for dying of advanced heart failure without this procedure. To test the hypothesis that survival and quality of life advantages associated with cardiac transplantation exist in stable outpatients, a 3-stage approach is proposed: 1). to establish a database within the International Society for Heart and Lung Transplantation/United Network for Organ Sharing/Eurotransplant infrastructure that will provide an estimate of the survival benefit of heart transplantation in various heart failure risk strata by prospectively following cohorts of patients listed for heart transplantation; 2). to organize an international consensus conference that will define, based on the review of the Stage 1 data, the feasibility of a prospective randomized trial; and 3). pending consensus, to perform a clinical trial, perhaps with an augmented, randomized design that allocates cardiac transplantation to all patients at high risk for dying of heart failure while randomizing patients at low risk to either conventional treatment or cardiac transplantation. Generating such scientific evidence is important in light of today's donor organ crisis and the associated difficulties of equitable resource allocation.

Cohort Studies↗
PubMed2003

Mechanical Circulatory Support device database of the International Society for Heart and Lung Transplantation: first annual report--2003.

Over the last 2 decades, mechanical circulatory support devices have been developed with the goal of supporting patients with advanced heart failure as a bridge to cardiac transplantation, a bridge to recovery, and an alternative to transplantation (also called chronic or destination therapy). The current generation of devices provides a differentiated spectrum of circulatory support. The major limitations of mechanical circulatory support devices are infection, coagulopathies and device dysfunction. The Scientific Council on Mechanical Circulatory Support of the International Society for Heart and Lung Transplantation has established an international database to generate critical data to advance knowledge about the effectiveness of mechanical circulatory support device therapy for one of the most difficult and costly contemporary medical problems, the malignant syndrome of advanced heart failure.

Adolescent↗
PubMed2003

Reversible pulmonary hypertension in heart transplant candidates--pretransplant evaluation and outcome after orthotopic heart transplantation.

BACKGROUND: Heart transplantation is the most effective treatment for well-selected patients with endstage heart failure. Unfortunately, transplant candidates with pulmonary hypertension (PHT) are often not considered for heart transplantation. This study was performed to assess the value of prostaglandin E(1) (PG-E(1)) for reduction of PHT and to predict the postoperative outcome, compared to patients without PHT. PATIENTS AND METHODS: We studied a group of 151 consecutive heart transplant candidates using right heart catheterization. In patients with PHT (pulmonary vascular resistance, PVR> or =2.5 Wood-Units (WU) and/or transpulmonary gradient (TPG)> or =12 mmHg) a short-term treatment protocol with PG-E(1) was performed, to achieve PVR<2.5 WU and TPG<12 mmHg. RESULTS: 61 patients (40%) had PHT according to our criteria. Reduction of PHT was successful in 71% of patients (n=43), of these, 18 patients underwent cardiac transplantation and the 1-year mortality rate was 22% (n=4). The 1-year mortality rate in transplanted patients without PHT was 14% (n=3). There was no statistical difference in survival between the PHT and the non-PHT group. Outcome in patients without heart transplantation was similar in both groups, except for patients with non-reducible PHT (1-year mortality 50%). CONCLUSIONS: Our study demonstrates the efficacy and safety of PG-E(1) in lowering PHT in heart transplant candidates, as well as the need for aggressive evaluation and treatment in these patients. Patients with reversible PHT have comparable post-transplant outcomes and no tendency to higher acute right ventricular failure.

Alprostadil↗
PubMed2003

Mechanical circulatory support device database of the International Society for Heart and Lung Transplantation.

Over the last 2 decades, mechanical circulatory support devices have been developed at a rapid pace with the goal of supporting patients with advanced heart failure as a bridge to cardiac transplantation, a bridge to recovery, and an alternative to transplantation, also called chronic or destination therapy. The current generation of devices provides a differentiated spectrum of circulatory support. The major limitations are infection, coagulopathies, and device dysfunction. The Scientific Council on Mechanical Circulatory Support of the International Society for Heart and Lung Transplantation has established an international database (http://www.ishlt.org/regist_mcsd_main.htm) to generate critical data to advance knowledge about effectiveness of mechanical circulatory support device therapy for one of the most difficult and costly contemporary medical problems, the malignant syndrome of advanced heart failure.

Databases, Factual↗
PubMed2002

The interleukin-6/interleukin-6-receptor system is activated in donor hearts.

OBJECTIVES: To assess the potential of the donor heart to respond to interleukin-6 (IL6), the present study investigated the expression of IL6 receptor components in the myocardium of donor hearts before transplantation. BACKGROUND: Donor heart dysfunction early after transplantation has been associated with the cytokine storm after donor brain death. Proinflammatory cytokines are thought to play a central role in this process. Interleukin-6 is of specific interest because it has been associated with cardiac allograft dysfunction and is related to an impaired prognosis. Its action requires expression of the specific IL6 receptor (IL6R), and the common signal transducer of the IL6 family glycoprotein 130 (gp130) in the donor heart. METHODS: The activation of IL6, IL6R and gp130 messenger ribonucleic acid (mRNA) and protein was studied via reverse transcription-polymerase chain reaction (RT-PCR) and immunohistology in donor hearts (n = 6) and compared with patients undergoing evaluation of ventricular arrhythmias (control, n = 9) or with advanced heart failure (n = 20). RESULTS: Messenger RNA of IL6, IL6R and gp130 was strongly expressed in all chambers of donor hearts, whereas right ventricles of control patients did not show any expression (donor vs. control: p < 0.005). Right ventricles of failing hearts showed IL6, IL6R and gp130 mRNA levels comparable with those found in donor hearts. Immunohistochemistry paralleled the RT-PCR data on the protein level. While IL6 was mainly expressed by myocytes, both receptor components were preferentially found mainly on interstitial cells. CONCLUSIONS: The expression of the IL6 receptor components in the donor heart before transplantation establishes the condition sine qua non for the response of the donor heart to circulating IL6. This mechanism may explain the close association of elevated IL6 serum levels to acute cardiac allograft dysfunction in the early perioperative period.

Antigens, CD↗
PubMed2002

Reduction of hypoxia-inducible heme oxygenase-1 in the myocardium after left ventricular mechanical support.

Left ventricular assist devices (LVAD) may improve cardiac function. The pathogenesis of this phenomenon, called 'reverse remodelling', is not completely elucidated. To examine the hypothesis that LVAD support eliminates tissue stress by reducing local hypoxia, the distribution of heme oxygenase-1 (HO-1), a stress protein inducible by hypoxia, was examined in vivo and in vitro. The immunoreactivity for HO-1 was semi-quantitatively analysed in left ventricular tissue of 23 patients (14 dilated cardiomyopathy (DCM), six ischaemic heart disease (IHD), three myocarditis/congenital heart disease) with end-stage heart failure before and after LVAD support, while two unused donor hearts served as controls. Control hearts stained almost negative for HO-1, while failing hearts showed immunoreactivity mainly in cardiomyocytes, but also in endothelial cells, some smooth muscle cells and fibroblasts. Hearts with IHD showed significantly higher HO-1 immunoreactivity than hearts with DCM or myocarditis/congenital heart disease. After LVAD support, the HO-1 content decreased significantly in the DCM and IHD group and was significantly higher in the subendocardium than in the subepicardium. In vitro, under hypoxic conditions, neonatal rat cardiomyocytes showed an increase of HO-1 protein content up to sixfold above the normal level, which returned to normal values after normoxic cultivation. Mechanical support reduces the HO-1 content of the failing heart and HO-1 is inducible in vitro under hypoxia and is reversible under normoxia. This supports the concept that restoration of cardiac normoxia by mechanical unloading, particularly in the subendocardium, may be in part responsible for the phenomenon of 'reverse remodelling'.

Adult↗
PubMed2002

Reversible activation of nuclear factor-kappaB in human end-stage heart failure after left ventricular mechanical support.

OBJECTIVE: Left ventricular assist devices (LVAD) have been used to 'bridge' patients with end-stage heart failure to transplantation. Although several reports have suggested that the native ventricular function recovers after long-term LVAD support, a process called 'reverse remodeling', the underlying biological mechanisms are still unknown. As the transcription factor nuclear factor-kappaB (NF-kappaB) has been shown to be active in the failing human heart, we examined whether its activity is altered under LVAD support, and may thus contribute to the dynamic process of 'reverse remodeling'. METHODS: The activity of NF-kappaB was studied in 16 patients with end-stage heart failure (eight with dilated cardiomyopathy, six with ischemic heart disease, one with myocarditis, and one with congenital heart disease) before and after LVAD support by immunohistochemistry using an antibody against active NF-kappaB. Gel-shifts for NF-kappaB DNA-binding activity were performed with paired human myocardial tissue from four patients. The mean cardiomyocyte diameter before and after mechanical unloading was measured with an image analyzer system. RESULTS: 15 patients out of 16 showed a significant decrease in the number of NF-kappaB positive cardiomyocyte nuclei after LVAD support in the left ventricular myocardium. The NF-kappaB DNA-binding activity also decreased after LVAD support as measured by gel-shift analysis. While the number of positive cardiomyocytes was significantly higher in the subendocardium than in the subepicardium at the time of LVAD implantation, this difference was no longer present at the time of LVAD explantation. The diameter of cardiomyocytes in the left ventricle decreased significantly as a parameter of structural reverse remodeling. CONCLUSION: LVAD support decreases the extent of NF-kappaB activation in failing human hearts, suggesting that NF-kappaB may be involved in the process of 'reverse remodeling'.

Adult↗
PubMed2002

Microvascular prothrombogenicity and transplant coronary artery disease.

A major impediment for the long-term success of heart transplantation is the development of transplant coronary artery disease (CAD). Several risk factors for the development of transplant CAD are associated with the transformation of a normal thromboresistant microvasculature into a prothrombogenic microvasculature. Prothrombogenicity is characterized by loss of anticoagulation (i.e. loss of antithrombin), loss of fibrinolytic activity (i.e., loss of tissue plasminogen activator) and presence of endothelial activation (i.e. upregulation of endothelial intercellular adhesion molecule-1 and major histocompatibility class II antigen human leukocyte antigen-DR) in the arterial allograft microvasculature. Microvascular prothrombogenicity during the first trimester after transplantation is directly associated with subsequent development of transplant CAD. Although the mechanisms responsible for the loss of thromboresistant endothelium are unclear, the fact that changes in the anticoagulant, fibrinolytic, and activational status of endothelial cells may occur early after transplantation suggests a peritransplant phenomenon as an initiating event. Reducing prothrombogenicity of the cardiac microvasculature early after transplantation could slow the development of transplant CAD and significantly improve allograft survival.

Animals↗
PubMed2002

Therapeutic options and heart failure survival score predictability in an academic heart failure center: an analysis of 120 consecutive patients during a 1-year period.

BACKGROUND: the incidence and prevalence of patients with advanced heart failure is increasing worldwide and the number of cardiac transplantations remains limited. AIMS: it was the aim of the study to describe our experience with the increasing number of available medical, interventional and cardiac surgery options, and to assess heart failure survival score predictability in an academic heart failure center within a 1-year follow-up. METHODS AND RESULTS: in all patients who were referred for cardiac transplant evaluation within a 12-month period between April 1998 and March 1999 at our Interdisciplinary Heart Failure and Transplant Program, our team assessed all medical interventions as well as interventional and surgical treatment options that were available, based on the clinical profile on initial presentation. In 92% of the 120 patients referred for cardiac transplantation evaluation, drug therapy could be optimized. A considerable number of patients could be subjected to an organ-preserving intervention or surgery, either PTCA (n=11), CABG (n=4), valve repair (n=7), multisite pacing (n=7), or partial ventricular resection (n=5). Only a small group of patients with the worst heart failure survival score were listed for heart transplantation (n=17) or received a ventricular assist device (n=3). CONCLUSIONS: within a contemporary cohort of advanced heart failure patients, only a small number of patients will undergo cardiac transplantation, which is predictable by the heart failure survival score. Most patients will undergo optimized medical therapy and a considerable number will be subjected to interventional or surgical treatment options.

Adrenergic beta-Antagonists↗