Search PubMed⌕ Search

Biomedical subjects

W Kiowski

Publications and source records attributed to W Kiowski.

At least 55 records · Page 3Linked to original sources

Identification of patients not requiring endomyocardial biopsies late after cardiac transplantation.

BACKGROUND: The risk for rejection is highest early, but graft rejection requiring intensified immunosuppression may be present even late after transplantation. Nonetheless, a considerable number of patients are absolutely free of rejection requiring intensified immunosuppression (Rej) late after transplantation. Therefore, we tried to identify patients who do not need endomyocardial biopsies > or = 2 years after transplantation and those who may benefit from long-term follow-up with routine endomyocardial biopsies. METHODS: A total of 112 patients (age 45+/-12 years) had a follow-up with regular endomyocardial biopsies of > or = 3 years. A total of 4194 endomyocardial biopsies were performed (1364 > or = 2 years after transplantation). They were divided into three categories: rejection score=0, Texas 0-2 or International Society for Heart and Lung Transplantation (ISHLT) 0 or 1A; rejection score=1, Texas 3-4 or ISHLT 1B or 2; rejection score=2, Texas > or = 5 or ISHLT > or = 3A. RESULTS: During the third and subsequent posttransplantation years, 31 of 112 (28%) patients had < or = 1 further Rej (total 51). Independent predictors identifying patients with Rej in multivariate analysis were age [odds ratio (OR)=0.96 per year, P<0.05], the sum of rejection score (OR=1.07 per score point, P<0.005) and the mean cyclosporine level in the first 2 years (OR=1.07 per % of upper therapeutic range, P<0.01). Fifty-eight (52%) patients with age >25 years, sum of rejection score < or = 17, and mean cyclosporine level <90th percentile during the first 2 years would not have needed biopsies in the third and subsequent years, whereas the other 48% had a risk of 54% to develop further Rej. In addition to predictors identifying patients with rejection, time after transplantation (OR=0.73 per year, P<0.005), cyclosporine level below therapeutic range (OR=2.15, P<0.05), and reduction of prednisone (OR=2.64, P<0.05) were independent predictors at each endomyocardial biopsy. CONCLUSIONS: Risk of Rej remained considerably high in approximately one third of our patients late after transplantation. In these, further surveillance biopsies appear justified, whereas half of the patients had no risk of Rej as long as immunosuppressive therapy was sufficient.

ABO Blood-Group System↗

Cardiac allograft rejection late after transplantation is a risk factor for graft coronary artery disease.

BACKGROUND: Graft coronary artery disease (CAD) is an increasingly important problem during long-term survival after heart transplantation, but the importance of cellular rejection, in particular late after transplantation, remains undetermined. METHODS AND RESULTS: We analyzed 492 coronary angiographies (967+/-705 days after transplantation; range, 49 days to 9.4 years) and 5201 endomyocardial biopsies (518+/-648 days after transplantation) from 156 patients (age, 47+/-11 years). Patients with angiographically detectable graft CAD had significantly more episodes of rejection requiring augmentation of immunosuppressive therapy (i.e., International Society of Heart and Lung Transplantation score > or = 3A) than those without graft CAD during the first (3.7+/-2.6 vs. 2.2+/-2.0, P<0.001) as well as subsequent years after transplantation (1.2+/-1.9 vs. 0.4+/-0.9, P<0.01). Multivariate logistic regression analysis including established risk factors for CAD, ischemic time, gender and age of donors and recipients, number of mismatches, cytomegalovirus infection, and drug therapy showed that the number of rejections during the first [odds ratio (OR)=1.39, P<0.005] as well as subsequent years (OR=1.49, P<0.05), previous cytomegalovirus infection (OR=3.21, P<0.05), donor age >40 years (OR=2.97, P<0.05), and current or former smoker status (OR=2.76, P<0.05) were independent predictors of graft CAD. In patients without angiographically detectable graft CAD 1 year after transplantation, the number of rejections after the first year was even more strongly related to graft coronary artery disease than in the total patient population, underlining the importance of late cellular rejection (OR=1.74, P<0.005). CONCLUSION: Rejection requiring augmentation of immunosuppression early and late after transplantation is an independent risk factor for the development of angiographically detectable graft CAD. Hence, the search for and treatment of moderate or severe rejection seems to be prudent even late after transplantation.

Adolescent↗

[Influence of various antithrombotic therapy methods on the incidence of subacute coronary stent occlusions, hemorrhagic complications and length of hospitalization].

BACKGROUND: The clinical benefit of coronary stenting is reduced by the risk of thrombotic stent occlusion as well as hemorrhagic complications of intensive antithrombotic therapy. We compared the influence of different antithrombotic therapies on the incidence of post-interventional complications and in-hospital stay duration. METHODS: After successful placement of a coronary stent, 334 consecutive patients were given different antithrombotic treatments in addition to aspirin 100 mg/d indefinitely: (1) phenprocoumon for 3 months (n = 47), (2) low molecular weight heparin 2 x 100 U/kg/d s.c. for 4 weeks (n = 90), (3) ticlopidine 2 x 250 mg/d and low molecular weight heparin 2 x 100 U/kg/d s.c. for 4 weeks (n = 72) and (4) ticlopidine 2 x 250 mg/d for 4 weeks (n = 125). RESULTS: Major events were subacute stent thrombosis in 17 patients (5%), and severe hemorrhagic complication in 20 patients (5.9%). The incidence of subacute stent thrombosis in groups 1 to 4 was 10.6%, 11%, 1.4% and 0.8% respectively. The use of ticlopidine was associated with a significant lowering of stent occlusions in univariate and multivariate analysis (p = 0.0013). Additional uni- and multivariate predictors were stent placement as a "bail-out" procedure (p = 0.033) and in patients with acute coronary syndrome (p = 0.049). Anticoagulant therapy was associated with a higher incidence of severe hemorrhagic complications (p < 0.01) and a prolonged in-hospital stay (p = 0.01). CONCLUSIONS: These results confirm that anti-thrombotic therapy with aspirin and ticlopidine combines low rates of subacute stent occlusion and hemorrhagic complications. Treatment with phenprocoumon and low molecular weight heparin does not improve the rate of subacute stent occlusion but increases hemorrhagic complications. Very low rates of stent occlusion permit short in-hospital stays with concomitant reduction in cost.

Acute Disease↗

Cryopreserved arterial allografts in the treatment of major vascular infection: a comparison with conventional surgical techniques.

OBJECTIVE: Recent findings with cryopreserved heart valve allografts in the treatment of infectious endocarditis suggest that the use of cryopreserved arterial allografts may improve the outcome in patients with vascular infections. METHODS: Seventy-two patients with mycotic aneurysms (n = 29) or infected vascular prostheses (n = 43) of the thoracic (n = 26) or abdominal aorta (n = 46) were treated with in situ repair and extra-anatomic reconstruction using prosthetic material (n = 38) or implantation of a cryopreserved arterial allograft (n = 34). Disease-related survival and survival free of reoperation were assessed. Morbidity, cumulative lengths of intensive care, hospitalization, antibiotic treatment, and costs were calculated per year of follow-up. RESULTS: The use of cryopreserved arterial allografts was superior to conventional surgery in terms of disease-related survival (P =.008), disease-related survival free of reoperation (P =.0001), duration of intensive care per year of follow-up (median 1 vs 11 days; range 1 to 42 vs 2 to 120 days; P =.001), hospitalization (14 vs 30 days; range 7 to 150 vs 15 to 240 days; P =.002), duration of postoperative antibiotic therapy (21 vs 40 days; range 21 to 90 vs 60 to 365 days; P =.002), incidence of complications (24% vs 63%; P =.005), and elimination of infection (91% vs 53%; P =.001). In addition, costs were 40% lower in the group treated by allografts (P =.005). CONCLUSIONS: The use of cryopreserved arterial allografts is a more effective treatment for mycotic aneurysms and infected vascular prostheses than conventional surgical techniques.

Adult↗

Acute cardiovascular effects of insulin-like growth factor I in patients with chronic heart failure.

Insulin-like growth factor I (IGF-I) enhances myofibrillar development in cardiomyocytes of rats in culture and in vivo. In addition, IGF-I has vasodilatory effects and improves cardiac function in healthy volunteers. This study was conducted to evaluate the acute hemodynamic effects of IGF-I in patients with chronic heart failure Eight patients with chronic heart failure were randomized to receive recombinant human IGF-I (60 micrograms/kg) or placebo, i.v., over 4 h in a cross-over, double blind study on 2 consecutive days. Electrocardiogram as well as systemic hemodynamics were continuously monitored over 7 h by flow-guided thermodilution and radial artery catheters. IGF-I was well tolerated by all patients, and no pathological changes on electrocardiogram were recorded. Compared with placebo, IGF-I increased the cardiac index by 27 +/- 3.7% (+/- SE; P < 0.0005) and the stroke volume index by 21 +/- 5.6% (P < 0.05), and decreased systemic vascular resistance by 28 +/- 4.4% (P < 0.0002), right atrial pressure by 33 +/- 9.0% (P < 0.003), and pulmonary artery wedge pressure by 25 +/- 6.1% (P < 0.03). Mean systemic and pulmonary artery pressure as well as heart rate and pulmonary vascular resistance were not significantly influenced by IGF-I treatment. Insulin and C peptide levels were decreased by IGF-I, whereas glucose and electrolyte levels remained unchanged. Urinary levels of norepinephrine decreased significantly (P < 0.05) during IGF-I infusion. Thus, acute administration of IGF-I in patients with chronic heart failure is safe and improves cardiac performance by afterload reduction and possibly by positive inotropic effects. Further investigations to establish whether the observed acute effects of IGF-I are maintained during chronic therapy appear to be warranted.

Adult↗

Relative frequency of functional sympathetic and parasympathetic reinnervation after heart transplantation.

Although there is evidence of partial sympathetic reinnervation late after transplantation, little is known about the relative frequency of sympathetic and, in particular, parasympathetic reinnervation. We examined the heart rate response to various maneuvers (standing up, handgrip exercise, phase 2 of Valsalva maneuver for sympathetic function, carotid sinus massage, phase 4 of Valsalva maneuver, and atropine for parasympathetic function) in 65 patients 3 to 110 months after transplantation and in 16 healthy volunteers and defined reinnervation as either one normal (>50% of control group) and at least one partial (>33% of control group) heart rate response or partial responses in all three tests of the respective part of the autonomic nervous system. Thirty-five (54%) patients had sympathetic reinnervation, but only 16 (25%) had parasympathetic reinnervation (p < 0.001); earliest reinnervation was found 11 months after transplantation, and all but one patient with parasympathetic reinnervation also had sympathetic reinnervation. Signs of sympathetic but not parasympathetic reinnervation were common late (>5 years) after transplantation (74% vs 30%).

Heart↗

Endothelial control of vascular tone in chronic heart failure.

Patients with chronic heart failure (CHF) are hemodynamically characterized by increased vasoconstriction and a reduced vasodilator response to exercise. In addition to various compensatory neurohumoral mechanisms, there is evidence that the endothelium plays an important role in the abnormal vasodilator response. This evidence comes from studies investigating the microvascular response to regional, intra-arterial administration of the endothelium-dependent vasodilator acetylcholine, which found that the vasodilator response and therefore the bioavailability of nitric oxide (NO) was impaired in the microcirculation of the leg, forearm, and myocardium of patients with CHF. The mechanisms underlying this abnormal response are not entirely clear but may reflect a muscarinic receptor abnormality. Because conduit artery vasodilatation during hyperemic blood flow is also impaired and because this response is not dependent on muscarinic receptor activation, this possibility appears to be unlikely. However, impaired smooth muscle responsiveness to NO stimulation, impaired L-arginine availability or utilization, endothelial release of vasoconstricting prostanoids, increased NO degradation and reduced NO synthase activity have all been implicated in this impaired response. In addition, the vasoconstrictor activity of endothelin (ET)-1 appears to play an important role in the regulation of tone in CHF, although the importance of different ET receptors is not yet clear.

Chronic Disease↗

[Pharmacologic therapy of severe heart failure].

Improvement of symptoms and, accordingly, quality of life, as well as prolongation of life, are the objectives of drug therapy in congestive heart failure patients. Diuretics are most effective in relieving symptoms related to congestion, and angiotensin converting enzyme inhibitors improve exercise capacity, reduce the incidence of decompensations and hence hospitalizations, and prolong life. Angiotensin type-1 receptor antagonists also seem to improve survival, while digoxin improves symptoms and morbidity but not survival in patients in sinus rhythm. The value of prophylactic antiarrhythmic therapy with amiodarone and oral anticoagulation in the presence of sinus rhythm is not established, and the role of newer dihydropyridine calcium antagonists and betablockers is also not precisely defined. These agents should only be considered in selected cases after careful consideration of potential advantages and risks, and should usually be used as an addition to established therapy. Better understanding of the pathophysiology of congestive heart failure will lead to the development of new treatment concepts, the clinical relevance of which will have to be tested in appropriately designed clinical trials.

Adrenergic beta-Antagonists↗

[After-care of the patient with myocardial infarct].

Patients after myocardial infarction are at a substantial risk for recurrent cardiac events; therefore, an optimal patient care is of great importance. Early revascularisation is one important contributor to the prognosis after myocardial infarction. Antithrombotic agents, betablockers, and ACE-inhibitors also contribute significantly to the improved outcome after myocardial infarction. Reduction of risk factors, in particular cessation of smoking and lowering of lipids are of highest importance to improve the prognosis after myocardial infarction.

Adrenergic beta-Antagonists↗

[Cost effectiveness of ACE inhibition in therapy of chronic heart failure in Switzerland: evaluation based on the SOLVD study].

BACKGROUND AND OBJECTIVES: Morbidity and mortality data in Switzerland underline the socioeconomic importance of heart failure. In the SOLVD study (Study on Left Ventricular Dysfunction), cardiovascular morbidity and mortality were reduced with the ACE inhibitor enalapril in patients with heart failure. The economic implications of this treatment were analyzed in a retrospective economic analysis from the perspective of Swiss third party payers. PATIENTS AND METHODS: Source of the economic analysis was the SOLVD study data. This prospective study was placebo-controlled, double-blind and had a mean follow-up of 3.45 years (41.4 months), involving 2569 patients with heart failure, mainly in NYHA classes II and III. Costing data for treatment with enalapril, the per diem charges for hospitalization and the average length of hospital stay were retrieved from published national sources. The costs of in- and output were calculated and compared for the two treatment groups in a cost-efficacy analysis. RESULTS: Additional treatment with enalapril resulted in an additional cost of 2.5 million Swiss francs. These incremental costs were, however, offset by reduced hospital costs (CHF 6.45 million savings) in the enalapril group. For the complete treatment cohort of the SOLVD study, the net savings were approximately 4.26 million Swiss francs. CONCLUSIONS: From the clinical point of view, treatment with ACE inhibitors leads to a reduction in the progression of heart failure and reduced cardiovascular morbidity and mortality. With respect to health economics, it can be demonstrated that treatment with enalapril does not only offer clinical benefits, but that these also translate into impressive economic savings of CHF 3315 per patient.

Adult↗

Atrioventricular block after administration of atropine in patients following cardiac transplantation.

BACKGROUND: Atropine is widely used as a parasympatholytic agent during diagnostic and therapeutic procedures. We observed an unexpected paradoxical response to atropine after cardiac transplantation. METHODS: In a study investigating the occurrence of autonomic reinnervation after cardiac transplantation, atropine, at 0.015 mg/kg body weight, was given intravenously to 23 patients (mean age, 56+/-8 years) 98 days to 6.4 years after transplantation. RESULTS: Two patients experienced a witnessed syncope 40 and 150 min after administration of atropine. Second-degree atrioventricular (AV) block was documented in the first patient immediately afterward, and third-degree AV block was seen on 24-hr electrocardiogram monitoring in the second patient. A third patient developed documented AV block 15 min after atropine but experienced no sequelae because of a previously implanted pacemaker. CONCLUSIONS: Although the underlying mechanism is not clear, these findings suggest that atropine may paradoxically cause high-degree AV block in patients after transplantation. Accordingly, it should be used with caution and appropriate monitoring in these patients.

Adult↗

[Regional differences in referral for heart transplantation].

UNLABELLED: Although cardiac transplantation is a well established means of treating end-stage heart disease, only selected patients receive this therapy. The aim of this study was, therefore, to investigate the frequency of referrals for and performed cardiac transplantations and to assess the prognosis of patients from the different regions of German-speaking Switzerland. From the beginning of 1989 to October 1995, 401 patients, aged 49 +/- 12 years, were referred to the University Hospital of Zurich for evaluation of the possibility of cardiac transplantation. 149 (37%) of them were transplanted. Transplanted patients had greater cardiac impairment than those who were not transplanted. There was no differences in age or underlying diseases. More patients from the south-eastern part of Switzerland were referred than from the north-eastern part. In contrast to this, the frequency of transplanted patients was similar to all parts of Switzerland. Survival rate was not related to the origin of transplanted patients (1-year survival 80%, 5-year survival 73%) whereas overall survival in patients who were not transplanted was significantly worse (1-year survival 64%, 5-year survival 45%) and differed between the various parts of our catchment area. Patients from regions with a high referral rate had better survival. Patients who lived in or near big cities were less frequently referred and had worse survival. Also, survival was related to the number of follow-up controls in the specialized clinic for heart failure and heart transplantation. In 1989 and 1994, years in which more than 30 patients were transplanted at our institute, only 4 of 69 (5.8%) died while waiting for transplantation, whereas during the other years 25 of 132 (18.9%) died (odds ratio = 0.26; p = 0.01). Moreover, the time from listing to transplantation was significantly shorter in 1989 and 1994 (50 +/- 66 vs. 95 +/- 134 days, p = 0.001). CONCLUSIONS: Patients from the different parts of our catchment area were not equally referred for heart transplantation. The better survival of non-transplanted patients from regions with a high referral rate suggests that the possibility of transplantation is taken into account earlier and more frequently. Follow-up controls of these patients in a specialized centre seem to be useful since these patients have a better outcome. Nevertheless, the recruitment of donors remains the unsolved problem.

Adult↗

Reduced coronary flow reserve during exercise in cardiac transplant recipients.

BACKGROUND: Coronary flow reserve (CFR) is reduced in a majority of patients after heart transplantation (HTx). Pharmacological interventions, however, provide only limited information on CFR under physiological conditions. Thus, CFR during exercise was evaluated in the present study. METHODS AND RESULTS: Coronary angiography was performed at rest and during supine bicycle exercise in 35 patients early (2 to 3 months; n = 10) or late (1 to 6 years; mean, 2.5 years; n = 25) after HTx and in 8 controls (C). CFR was determined by parametric imaging after administration of 10 mg intracoronary papaverine, during exercise, and after 1.6 mg sublingual nitroglycerin. Epicardial coronary artery size was measured by quantitative coronary angiography. CFR after papaverine was normal early (3.6 +/- 0.5 versus C, 3.6 +/- 0.7; P = NS) and late (3.8 +/- 1.3 P = NS) after HTx. During exercise, CFR was normal early (3.1 +/- 0.6 versus C, 3.9 +/- 0.9; P = NS) but decreased late (2.3 +/- 0.6; P < .01) after HTx. The increase in coronary cross-sectional area during exercise was also diminished late after HTx (14 +/- 10% versus C, 22 +/- 10%; P < .05). Both exercise-induced CFR (r = -.39, P < .05) and coronary vasodilation (r = -.44, P < .01) were inversely correlated with time after HTx. CONCLUSIONS: CFR during exercise is normal early but reduced late after HTx, whereas CFR after papaverine administration is maintained. This difference between physiological and pharmacological vasodilation suggests progressive endothelial dysfunction after HTx.

Adult↗

Acute and short-term effects of the nonpeptide endothelin-1 receptor antagonist bosentan in humans.

In recent years, evidence from various animals experiments has accumulated that emphasizes the role of endothelin-1 in the pathophysiology of several cardiovascular diseases, including congestive heart failure. The recent advent of potent antagonists of this system now allows the assessment of the involvement of endothelin-1 in the maintenance of vascular tone in animals and humans. We report hemodynamic data from two trails in patients with chronic severe congestive heart failure (i.e., reduced left ventricular ejection fraction of < 30%, elevated resting pulmonary capillary wedged pressure > 15 mmHg, and/or reduced cardiac index of 2.5 L/min/m2 or less) who were treated with the mixed endothelin-type A and type B-receptor antagonist bosentan. In the first study, the acute effect of bosentan (300 mg, intravenous) on hemodynamics and neurohormones was investigated. Bosentan was well tolerated and significantly improved impaired hemodynamics due to systemic and venous vasodilation. In the second, trial, bosentan was given orally (0.5 g bid) for 14 days, in addition to conventional triple treatment for congestive heart failure, including digitalis, angiotensin-converting enzyme inhibitors, and diuretics. Cardiac hemodynamics were monitored during the first 24 hours of treatment, and measurements were repeated during the last day of bosentan therapy. Bosentan was well tolerated in these patients as well, and hemodynamic measures were compatible with an additional effect of bosentan after 2 weeks. However, there was a slight increase in heart rate as well. Our result underline the importance of endogenously generated endothelin-1 in congestive heart failure and suggest a potential benefit of endothelin antagonism in such patients. However, long-term studies are needed to establish whether chronic endothelin antagonism has beneficial clinical effects and is capable of improving survival and/or symptoms in severe heart failure patients who remain symptomatic despite standard triple therapy.

Administration, Oral↗