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Biomedical subjects

M C Deng

Publications and source records attributed to M C Deng.

At least 19 recordsLinked to original sources

Mechanical circulatory support for advanced heart failure: effect of patient selection on outcome.

BACKGROUND: Use of wearable left ventricular assist systems (LVAS) in the treatment of advanced heart failure has steadily increased since 1993, when these devices became generally available in Europe. The aim of this study was to identify in an unselected cohort of LVAS recipients those aspects of patient selection that have an impact on postimplant survival. METHODS AND RESULTS: Data were obtained from the Novacor European Registry. Between 1993 and 1999, 464 patients were implanted with the Novacor LVAS. The majority had idiopathic (60%) or ischemic (27%) cardiomyopathy; the median age at implant was 49 (16 to 75) years. The median support time was 100 days (4.1 years maximum). Forty-nine percent of the recipients were discharged from the hospital on LVAS; they spent 75% of their time out of the hospital. For a subset of 366 recipients, for whom a complete set of data was available, multivariate analysis revealed that the following preimplant conditions were independent risk factors for survival after LVAS implantation: respiratory failure associated with septicemia (odds ratio 11.2), right heart failure (odds ratio 3.2), age >65 years (odds ratio 3.01), acute postcardiotomy (odds ratio 1.8), and acute infarction (odds ratio 1.7). For patients without any of these factors, the 1-year survival after LVAS implantation including the posttransplantation period was 60%; for the combined group with at least 1 risk factor, it was 24%. CONCLUSIONS: Careful selection, specifically implantation before patients become moribund, and improvement of management may result in improved outcomes of LVAS treatment for advanced heart failure.

Adolescent↗

The impact of anti-endotoxin core antibodies on endotoxin and cytokine release and ventilation time after cardiac surgery.

OBJECTIVES: We hypothesized that a temporary cardiopulmonary bypass (CPB)-induced reduction of endotoxin antibody levels contributes to elevated endotoxin levels and the associated inflammatory consequences, with a significant influence on the postoperative ventilation time period. BACKGROUND: Cardiac surgery using CPB induces a systemic inflammatory response syndrome with an associated risk of increased postoperative morbidity and mortality. METHODS: A total of 100 consecutive patients undergoing elective coronary artery bypass graft surgery using CPB were prospectively investigated. Endotoxin core antibodies (immunoglobulin [Ig] M/IgG against lipid A and lipopolysaccharide), endotoxin, interleukin (IL)-1-beta, IL-6, IL-8 and tumor necrosis factor-alpha were measured serially from 24 h preoperatively until 72 h postoperatively. RESULTS: Eighty-five patients had no complications (group 1), whereas 15 patients required prolonged ventilation (group 2). In both groups, there was a decrease of all antibodies 5 min after CPB onset, compared with baseline values (p < 0.001), an increase of endotoxin and IL-8 peaking at 30 min postoperatively (p < 0.001) and an increase of IL-6 peaking 3 h postoperatively (p < 0.001). In group 2, preoperative antibody levels were lower (p < 0.01)--specifically, the decrease in IgM was significantly stronger and of longer duration (p < 0.002)--and levels of endotoxin (p < 0.001) and IL-8 (p < 0.001) were higher at 30 min postoperatively. CONCLUSIONS: We conclude that an CPB-associated temporary reduction of anti-endotoxin core antibody levels contributes to elevated endotoxin and IL-8 release. Furthermore, lower levels of IgM anti-endotoxin core antibodies were associated with a greater rise in endotoxin and IL-8, as well as prolonged respirator dependence.

Adult↗

Activation of the cardiac interleukin-6 system in advanced heart failure.

OBJECTIVES: The study objective was to assess the cardiac expression of interleukin-6 (IL6) and its receptor (IL6R) in advanced heart failure. BACKGROUND: While IL6 plasma levels are elevated and associated with an impaired prognosis in advanced heart failure, little is known about the intracardiac expression of the IL6 system. METHODS: Heart tissue was obtained from 20 patients (n=10, idiopathic dilated cardiomyopathy, age 44+/-15 years; n=10, ischemic cardiomyopathy, age 55+/-8 years) at the time of transplantation. Left and right ventricular tissue was subjected to in situ hybridization, Northern blot analysis, and RT-PCR. Signals were quantified by densitometric scanning and corrected for G3PDH-mRNA levels. Right ventricular biopsy specimens (n=11) of patients with arrhythmias and normal cardiac function served as controls. In addition, data were correlated with cardiac catheterization and echocardiography data obtained at transplant evaluation. RESULTS: Ventricular IL6 and IL6R transcripts were detected in all explant specimens examined. Expression of both mRNA species was higher than in controls (P=0.001). Left ventricular IL6 mRNA levels correlated positively with heart rate (r=0.77; P=0.009), pulmonary capillary wedge pressure (r=0.53; P=0.03), right atrial pressure (r=0.77; P=0.003), and inversely with left ventricular ejection fraction (r=-0.61; P=0.03). Right ventricular IL6 mRNA levels correlated inversely with cardiac index (r=-0.48; P=0.05). IL6R expression did not correlate with hemodynamic data. CONCLUSIONS: In advanced heart failure, cardiac IL6/IL6R mRNA expression is increased and may play a role in the pathophysiology of advanced heart failure.

Adult↗

Medical liability disputes involving thoracic and cardiovascular surgeons.

BACKGROUND: Medical malpractice claims against surgeons are increasing. In Germany, as in most other European countries, there is no central registry of medical malpractice claims. It is not known at which rate medical liability claims are decided in favor of the physician or the patient. METHODS: All cases of reproaches of medical malpractice in which our clinic was involved within the 10-year period between 1989 to 1999 were reviewed. To compare our results with the general experience in the field of thoracic and cardiovascular surgery, we reviewed the data of the regional medical society in the same time period. RESULTS: From 1989 to 1999, our Clinic was involved in 74 medical liability disputes. There were 28 reproaches of medical malpractice against our department (0.1% of cases performed). Malpractice was detected in only 7 of 74 claims (9.5%). Most reproaches were made for incorrectly performed operations (80%), but only 4 (6.8%) of 59 claims were regarded as medical malpractice. CONCLUSIONS: Reliable data on reproaches of medical malpractice are virtually absent. Only 10% of all reproaches in our study were finally regarded as medical malpractice. A central registry of medical malpractice cases would allow analysis of the areas in which we have to improve performance, and how unjustified reproaches of medical malpractice can be avoided.

Cardiac Surgical Procedures↗

Heart transplantation indicated only in the most severely ill patient: perspectives from the German heart transplant experience.

The COCPIT study, performed in a complete national cohort of adult patients consecutively listed for cardiac transplantation in Germany in 1997, found a beneficial effect only in the group that was at high risk of dying from heart failure without transplantation. If these results can be reproduced in other countries, the discussion on the respective roles of pharmacological and organ-saving surgical therapies for advanced heart failure, medical urgency and waiting time as heart transplantation allocation criteria, and the feasibility of a randomized clinical trial testing the survival benefit of transplantation must be reopened.

Adult↗

Prediction of clinical outcome after cardiac surgery: the role of cytokines, endotoxin, and anti-endotoxin core antibodies.

Coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) can lead to a systemic inflammatory response syndrome with organ failure and increased morbidity and mortality. The mechanisms of these findings are still under discussion. We investigated whether anti-endotoxin core antibodies, endotoxin, and proinflammatory cytokines influence the clinical course after cardiac surgery. Seventy-eight patients undergoing CABG using CPB were investigated. Anti-endotoxin core antibodies, endotoxin, interleukin (IL)-6, IL-8, IL-1beta, and TNF-alpha were measured 24 h preoperatively and up to 72 h postoperatively. Patients with a postoperative mechanical ventilation time below 24 h (n = 65; Group A) were compared to patients with prolonged respirator therapy (>24 h; n = 13; Group B). Preoperative antibody levels were significantly lower in Group B (P < 0.001). In this group, antibody levels remained decreased during the observation period (P < 0.001). Endotoxin significantly increased 30' postoperatively in both groups (P < 0.002). The increase in Group B was 3-fold higher (P< 0.001). IL-8 increased postoperatively in both groups, peaking 3 h after surgery (P < 0.001). In Group B, the IL-8 release was significantly higher than in Group A (P < 0.001). IL-6 significantly increased in both groups, reaching its maximum 24 h postoperatively (P < 0.001). No differences between groups were observed. No significant changes of IL-1beta and TNF-alpha were observed. We conclude that anti-endotoxin core antibodies may be predictive of adverse outcome after cardiac surgery. The imbalance between antibodies and endotoxin results in an exaggerated increase in endotoxin and IL-8 with an impact on clinical outcome.

Aged↗

Effect of receiving a heart transplant: analysis of a national cohort entered on to a waiting list, stratified by heart failure severity. Comparative Outcome and Clinical Profiles in Transplantation (COCPIT) Study Group.

OBJECTIVE: To determine whether there is a survival benefit associated with cardiac transplantation in Germany. DESIGN: Prospective observational cohort study. SETTING: All 889 adult patients listed for a first heart transplant in Germany in 1997. MAIN OUTCOME MEASURE: Mortality, stratified by heart failure severity. RESULTS: Within 1 year after listing, patients with a predicted high risk had the highest global death rate (51% v 32% and 29% for medium and low risk patients respectively; P<0.0001), had the highest risk of dying on the waiting list (32% v 20% and 20%; P=0.0003), and were more likely to receive a transplant (48% v 45% and 41%; P=0.01). Differences between the risk groups in outcome after transplantation did not reach significance (P=0.2). Transplantation was not associated with a reduction in mortality risk for the total cohort, but it did provide a survival benefit for the high risk group. CONCLUSION: Cardiac transplantation in Germany is currently associated with a survival benefit only in patients with a predicted high risk of dying on the waiting list. Patients with a predicted low or medium risk have no reduction in mortality risk associated with transplantation; they should be managed with organ saving approaches rather than transplantation.

Acute Disease↗

Transplant vasculopathy: a model for coronary artery disease?

Although transplant vasculopathy and native atherosclerosis are clinically and pathologically different entities, the pathogenesis of both diseases exhibits some common mechanisms. Both may be regarded as responses to injury within a broadened concept of the immune system. Alloantigens (e.g. on donor endothelial cells) or autoantigens (e.g. oxydized LDL cholesterol) are presented by antigen presenting cells to the T cells of the body's immune system. With the appropriate costimulatory signal, this signal pattern generates a differentiated T cell, B cell, and inflammatory cell response whereas without the second signal, the immune cells undergo apoptosis. In case of immune cell proliferation and differentiation, a coordinated pattern of cytokine release is initiated. Monocyte-derived macrophages are also involved in this process which culminates in rolling, sticking, and diapedesis through the coronary vascular endothelium and phenotype switch of medial smooth muscle cells mediated by generation of growth-promoting cytokines. Thus, viewed within a broadened paradigm of the immune system's role both disease entities may represent different vignettes of an integrated pathophysiological response to an endothelial injury.

Animals↗

[Long-term management after heart transplantation--an assessment of current status].

Due to an improvement of results after heart transplantation, there is a continuously growing number of long-term surviving patients. Aimed at a characterization of established diagnostic and therapeutic protocols, the Working Group of Thoracic Organ Transplantation within the German Society of Cardiology performed a survey among all German heart transplantation centers. Based on the experience of 1,500 patients, the clinical relevance as well as approaches for prevention and treatment of rejection, infection, cardiac allograft vasculopathy, malignancy, hypertension, renal insufficiency, and quality of life were assessed by a questionnaire. As a result, a time dependency of expected complications could clearly be shown. While early after HTX acute rejection and infection episodes were judged as clinically important, later on cardiac allograft vasculopathy, malignancy, and renal insufficiency predominate as relevant complications. This spectrum was reflected by a differentiated diagnostic protocol (early after HTX more frequent diagnostic procedures for rejection and infection, later intensified examinations to identify cardiac allograft vascular disease and malignancy) as well as by different intensities of immunosuppression and concomittant medication. Regarding further improvement of survival rates and quality of life, future clinical and scientific activities should be focused on the prevention of late complications after heart transplantation.

Aftercare↗

Effect of high dose platelet inhibitor treatment on thromboembolism in Novacor patients.

BACKGROUND: Thromboembolism and bleeding are among the most hazardous complications following implantation of long-term left ventricular support systems. This report focuses on the effect of high dose platelet inhibitor treatment in patients with the Novacor system to prevent thromboembolic events. METHODS: Thirty-eight (out of 58) Novacor patients (43+/-11 years old) were studied in a non-randomized manner. Postimplantation: 20 patients were treated with heparin only (control group), whereas in the other 18 patients aspirin (3x330 mg/day) and dipyridamol (3x75 mg/day) were added to the treatment protocol (aspirin group). RESULTS: Age, body size, underlying heart disease and support interval were comparable among both groups, however, patients in the aspirin group were much sicker with regard to urgency status, postoperative right heart failure and hematologic disorders. Cerebral thromboembolic complications were lower in the aspirin group (33% of patients, 0.4+/-0.7 events) as compared to the control group (55% (P=0.18), 1.4+/-2.3 events (P=0. 048)). Non-cerebral thromboembolism of surgical relevance was rare. The incidence of bleeding complications was mildly increased in the aspirin group. CONCLUSION: The addition of high dose platelet inhibitors seems to lower the incidence of thromboembolism in Novacor patients.

Adult↗

Reversal of metallothionein expression is different throughout the human myocardium after prolonged left-ventricular mechanical support.

OBJECTIVES: We examined the distribution of metallothionein (MT), a stress-inducible protein, and the cardiomyocyte diameter in human hearts after left-ventricular assist device (LVAD) support. BACKGROUND: Remodeling in end-stage heart failure is characterized by myocyte hypertrophy and alterations of several inducible proteins. LVADs used as a bridge to cardiac transplantation unload the left ventricle and may lead to a reversal of the remodeling, but little is known about the pathophysiology of this process. METHODS: The immunoreactivity for MT and the cardiomyocyte diameter was analyzed in left-ventricular tissue specimens of 17 patients with end-stage heart failure before and after LVAD support. RESULTS: MT positive cells were mainly located sub-endocardially in vacuolized cardiomyocytes and in small vessels throughout the myocardium. During LVAD support, MT-positive myocytes decreased in the sub-endocardial (p < 0.008) and sub-epicardial region (p < 0.003), MT-positive vessels decreased similarly (p < 0.003). Cardiomyocyte diameter decreased significantly only in the sub-endocardium (p < 0.03). Hearts of patients supported longer than 88 days (= median) showed substantially lower MT reactivity at the time of LVAD explantation as compared to patients supported less than 88 days. CONCLUSION: Our results suggest that unloading of the left ventricle during prolonged LVAD support leads to regression of cellular hypertrophy and a decrease of MT expression. The preferential reduction of MT-positive vacuolized cardiomyocytes in the sub-endocardium is comparable with the concept of greatest reduction of wall stress in this area of the myocardium and may be due to the improvement of myocardial blood flow and the energy balance.

Adult↗

Selection and management of ventricular assist device patients: the Muenster experience.

BACKGROUND: Because of the growing discrepancy between the availability of donor organs and the number of patients with end-stage heart disease who need heart transplantation, a larger proportion of patients waiting for a suitable donor heart require pre-operative mechanical circulatory assistance. The criteria for the selection and management of these patients as applied at Muenster University Hospital are reviewed. METHODS: The study population consists of 631 patients referred to our center for transplantation between January 1, 1990, and December 31, 1996. Two hundred ninety-seven patients were listed for transplantation and 157 were transplanted. Of 41 patients who underwent implantation of a ventricular assist device (n = 34, Novacor; n = 6, TCI HeartMate; n = 1, Medos), 39 received the device as a bridge to transplantation and 2 as permanent support. For the purpose of the analysis, the study population was divided into 3 groups (elective bridging, urgent bridging, emergency bridging) and compared with heart transplant candidates who did not require mechanical circulatory assistance. RESULTS: Patients who underwent elective or urgent assist-device implantation were younger and had greater hemodynamic compromise than the remainder of patients waiting for heart transplantation, as suggested by a higher functional class and lower mean arterial pressure, cardiac index, serum sodium, and pulmonary artery wedge pressure. Survival of patients who electively underwent implantation of an assist device was better than that of patients who were stable on the waiting list and did not undergo heart transplantation during follow-up. CONCLUSIONS: This finding suggests that earlier implantation of assist devices may facilitate resolution of organ dysfunction before heart transplantation.

Adult↗

Implantable left ventricular assist systems (LVAS): recent results. A report from a series of meetings sponsored by the Study Group on Advanced Heart Failure of the Working Group on Heart Failure.

Implantable left ventricular assist systems (LVAS) consist of implantable pumps with small control consoles and power sources that can be worn externally. These systems provide far greater patient mobility and independence than external pumps with bulky control consoles. Patients with implantable LVAS can be discharged from hospital and are able to return to work and resume active sports. Most patients have received these systems as a bridge to heart transplantation. Clinical status and quality of life improve dramatically after device implantation and survival on support (60-70% after approx. 100 days of support) is acceptable compared with transplant candidates on medical therapy. Patient selection and adverse events, primarily bleeding, thromboembolism and infection, are important issues with LVAS. In the future, long-term support and bridging to myocardial recovery may become important indications for LVAS.

Adolescent↗

The bad ventricle--revascularization versus transplantation.

BACKGROUND: The proportion of patients with left-ventricular dysfunction (LVD) undergoing high risk revascularization is increasing. In this patient group, the perioperative risk is elevated because of the pre-existing pathophysiology. Detailed evaluation and interdisciplinary differential therapeutic considerations on the basis of the comparative benefit rationale, with cardiac transplantation alternative, is mandatory. METHODS: Among 7275 patients who underwent coronary artery bypass grafting between 1990 and 1998 in our institution, we found 51 patients who had had an ejection fraction <20%, and thus were candidates for transplantation (group CABG); these were compared with 163 patients who were listed for cardiac transplantation because of ischemic cardiomyopathy (group HTX). The survival analysis was performed on the basis of the intention-to-treat principle independent of subsequent transplantation. RESULTS: Both groups were comparable with regard to left-ventricular ejection fraction; pulmonary capillary wedge pressure and serum creatinine, but patients in the CAGB group were older (63+/-11 vs 56+/-8; p = 0.001) and included a higher percentage of women (m/f: 42/9 vs 152/11; p = 0.03). Nevertheless, there was a similar 1-year survival in both groups (group BP 71.9% vs group HTX 66.3%; p = ns). Looking at the CABG group, the internal thoracic artery was used in 36/51 patients, an intra-aortic balloon pump was used preoperatively in 26 patients, and intraoperatively in 6. Left-ventricular assist devices had to be inserted in three patients, extracorporeal membrane oxygenation once. Perioperative (30 day) survival was 88.2 %. An elevated preoperative serum creatinine and the nonusage of the internal thoracic artery predicted an adverse outcome. In the long-term course, the NYHA functional class improved in most cases from III preoperatively to I after 26 (2-66) months. CONCLUSION: We conclude that patients with ischemic cardiomyopathy, viable myocardium, and graftable vessels can be revascularized with acceptable risk. Since for these patients a standby of mechanical circulatory support must be anticipated perioperatively, this infrastructure should be established within the center.

Aged↗

Arrhythmias in heart failure: current concepts of mechanisms and therapy.

About one half of deaths in patients with heart failure are sudden, mostly due to ventricular tachycardia (VT) degenerating to ventricular fibrillation or immediate ventricular fibrillation. In severe heart failure, sudden cardiac death also may occur due to bradyarrhythmias. Other dysrhythmias complicating heart failure include atrial and ventricular extrasystoles, atrial fibrillation (AF), and sustained and nonsustained ventricular tachyarrhythmias. The exact mechanism of the increased vulnerability to arrhythmias is not known. Depending on the etiology of heart failure, different preconditions, including ischemia or structural alterations such as fibrosis or myocardial scarring, may be prominent. Reentrant mechanisms around scar tissue, afterdepolarizations, and triggered activity due to changes in calcium metabolism significantly contribute to arrhythmogenesis. Furthermore, alterations in potassium currents leading to action potential prolongation and an increase in dispersion of repolarization play a significant role. Treatment of arrhythmias is necessary either because patients are symptomatic or to reduce the risk for sudden cardiac death. The individual history, left ventricular function, electrophysiologic testing, and the signal-averaged ECG give useful information for identifying patients at risk for sudden cardiac death. The implantable cardioverter defibrillator (ICD) has evolved as a promising therapy for life-threatening arrhythmias. A potential role may exist for antiarrhythmic drugs, mainly amiodarone. There is growing evidence that patients with sustained VT or a history of resuscitation have the best outcome with ICD therapy regardless of the degree of heart failure. Many of these patients require additional antiarrhythmic therapy because of AF or nonsustained VTs that may activate the device. Catheter ablation or map-guided endocardial resection are additional options in selected patients but seldom represent the only therapeutic strategy.

Anti-Arrhythmia Agents↗