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Biomedical subjects

M C Deng

Publications and source records attributed to M C Deng.

At least 37 records · Page 2Linked to original sources

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↗

Ambulatory care of patients with left ventricular assist devices.

BACKGROUND: Left ventricular assist devices (LVAD) have revolutionized the treatment of patients with acute and chronic heart failure as they provide a high quality of life. We report on our experience with patients receiving ambulatory care after LVAD implantation. METHODS AND RESULTS: Since July 1995, 46 patients with a mean age of 45+/-11 years underwent implantation of an electrically driven LVAD with portable controller and batteries. Sixteen (35%) patients bridged >30 days were treated in part on an outpatient basis. After LVAD implantation, they were treated in the hospital for 86+/-32 days (range 40 to 153 days). Afterward, they received ambulatory care for 74+/-76 days (range 2 to 301 days, total experience 1206 days). In 13 cases, the outpatient treatment was interrupted by 1.7+/-1.7 readmissions, for a total of 32+/-42 days (median 19 days). Reasons for readmission included systemic or drive line infections (incidence 0.0066 per outpatient day), suspected or true thromboembolic events (incidence 0.0066 per outpatient day), and suspected malfunction of the LVAD. One patient supported as alternative to transplantation died after cerebral bleeding after 244 days, 1 patient with a history of acute myocarditis had ventricular fibrillation during LVAD assist while being at home for 177 days and died in a low output state, 10 patients were given transplantation after a mean support interval of 206+/-88 days, and 4 patients currently await heart transplantation. CONCLUSIONS: Outpatient treatment after LVAD implantation is feasible, and severe complications are uncommon.

Adult↗

Combining nonpharmacologic therapies for advanced heart failure: the Münster experience with the assist device-defibrillator combination.

Implantable cardioverter defibrillators (ICDs) and ventricular assist devices (VADs) have been used as a bridge to cardiac transplantation. In selected patients, the combined implantation may be required. This study was motivated by a case of a 33-year-old female patient with giant cell myocarditis who died of ventricular tachyarrhythmias after having been placed on a VAD with which she had been treated on an out-of-hospital basis for a prolonged period of time. A subsequent retrospective analysis of our data showed that, of 73 patients who had to be bridged mechanically (54 Novacor, 12 TCI Heartmate, 4 Thoratec, 3 Medos) in our institution between 1993 and 1998, 10 patients had undergone defibrillator implantation either before (n = 8) or after (n = 2) implantation of a VAD. The cases are presented, and the feasibility of the combination therapy discussed.

Adult↗

Impact of local donor and regionalization on a German transplantation center. UNI NRW. Universities of North Rhine Westfalia.

Optimal allocation of donor organs is an ongoing matter of debate. We report on the impact of the foundation of UNI NRW, a close transplant collaboration of seven university centers with the intention of improving donor organ allocation, on the heart transplant program in Münster. All donor organs retrieved were offered first to the patients within this region before going into the Eurotransplant (ET) Foundation pool. The heart transplant program data were prospectively (for 1997) and retrospectively (for 1996) analyzed with regard to donor organ availability and allocation. There was a slight decrease in the number of donor hearts offered and accepted within the UNI NRW region in 1997 as compared to in 1996. However, due to the significantly lower organ export rate, the number of heart transplantations performed in UNI NRW rose from 47 to 72 procedures. In Münster, only six donor organs (16%) were procured from outside UNI NRW in 1997, and these were, in part, due to special urgency requests. In conclusion, the institutionalization of UNI NRW within the framework of ET offers more flexibility, decreases total ischemic time, and may help to lower costs.

Europe↗

On the contractile function of protein phosphatases in isolated human coronary arteries.

It is unknown whether protein phosphatases types 1 and 2A are present in and can regulate the tone of human vascular tissue. The expression and possible function of serine/threonine protein phosphatases (PP) type 1 (PP1) and type 2A (PP2A) were studied in isolated human coronary arteries. Catalytic subunits of PPI and PP2A were identified by means of phosphatase activity measurement in tissue homogenates, by separation of enriched extracts through affinity column chromatography, by immunoblotting with specific antibodies, by hybridization of mRNA with specific DNA probes and PCR of reverse transcribed mRNA. Based on these methods, the catalytic subunits of PP1(alpha,beta,gamma) and PP2A(alpha,beta) were identified. Appropriately, cantharidin, an inhibitor of PP1 and PP2A, increased basal tone of human isolated coronary artery rings with an EC50 of about 16 micromol/l by increasing the phosphorylation state of the regulatory light chains of myosin. In summary, PP1 and PP2A are expressed in human coronary arteries and they can alter vascular tone.

Chromatography, Affinity↗

Heart transplants--assessment of dental procedures.

The object of this study was to evaluate the effects of dental foci on survival rates and rejection episodes in heart transplant recipients. Therefore, in a retrospective longitudinal study we studied 74 heart transplant recipients at the Department of Maxillofacial Surgery and Department of Thoracic and Cardiovascular Surgery, University of Münster. Study patients were divided into groups: those in which dental foci had been verified (n = 31) and those without dental foci (n = 43). Statistical analysis was performed using the chi-square test, Kaplan-Meier life table analysis, and the log-rank test. Before heart transplantation, patients were screened clinically and radiographically to determine the extent of dental foci. Postoperatively, patients were evaluated dentally and medically to identify the impact of dental foci on the incidence of systemic and oral infections, frequency and severity of rejection episodes, mortality, and complications arising during dental treatment. By comparing the mortality, infection and rejection rates in the various groups no statistically significant differences (P > 0.05) were found between patients. Despite immunosuppression, extended inflammatory processes such as abscess formation or viral stomatitis were not found in the oral cavity. We therefore suggest that patients suffering from the symptoms of severe heart failure need not be subjected to rigorous preoperative dental treatment.

Bacteremia↗

Metallothionein: localization in human transplant endomyocardium, relation to cytokines and allograft function.

BACKGROUND: The aim of this study was to investigate the role of metallothionein in cardiac transplants in relation to cytokines and allograft function. Recent studies have revealed an association of allograft dysfunction with elevated proinflammatory cytokines independent of cellular rejection. In animal experiments, cytokines induced overexpression of metallothionein, a low-molecular-weight protein implicated in cellular stress response. METHODS: In 105 consecutive biopsies from 15 patients during the first 3 months after heart transplantation, metallothionein expression was investigated immunohistochemically. Its relation to serum interleukin-6, tumor necrosis factor-alpha, interleukin-2 (IL-2), soluble interleukin-2 receptor rejection, and echocardiographic parameters was determined. Forty-three biopsies of 12 patients with idiopathic ventricular tachycardia served as controls. RESULTS: Metallothionein expression was demonstrated in small vessels, cardiomyocytes, fibrocytes, and interstitial round cells. A positive relation between interleukin-6 levels and the number of metallothionein-positive small vessels (p < 0.028) was observed. Patients with lower serum IL-2 levels showed significantly higher numbers of metallothionein-positive small vessels (p < 0.043). Grafts with prolonged ischemic time (>150 minutes) showed a significantly higher myocardial metallothionein score (p < 0.021). Metallothionein expression was associated with lower fractional shortening, larger left ventricular end-systolic diameter, and lower mean arterial pressure but not with acute cellular rejection. CONCLUSIONS: Metallothionein expression is associated with elevated interleukin-6 and decreased interleukin-2 serum levels and left ventricular allograft dysfunction in the absence of rejection.

Acute Disease↗

Evolving short-term and long-term mechanical assist for cardiac-failure -- a decade of experience in Münster.

Technological advances and growing expertise has lead to referral of much sicker patients with a greater incidence of heart failure prior to and after cardiac surgical procedures. The diversity of the heart failure patient cohort mandates a differentiated protocol for mechanical support adapted to the clinical requirements. It is desirable to have appropriate mechanical support available for different circumstances of heart failure. In this paper, we review the first decade of the Muenster University Hospital experience with the use of intra-aortic ballon pump, extracorporal membrane oxygenators, short term uni- and biventricular assist systems such as Thoratec and Medos devices, as well as long term left ventricular assist systems such as the TCI Heartmate and the Novacor system. The patient profiles, indications, contraindications, and future trends are reviewed within the framework of a contemporary university hospital Servive.

Assisted Circulation↗