[Atrial fibrillation and thromboprophylaxis in elderly patients]. / Vorhofflimmern und Thromboembolieprophylaxe bei älteren Patienten.

Chronic, nonvalvular atrial fibrillation occurs more frequently with increasing age, together with an increasing risk for ischemic stroke. Guidelines recommend oral anticoagulation with a vitamin K antagonist for patients >65 years without risk factors and patients <65 years with risk factors for cardiac diseases. Advancing age also increases the risk for bleeding complications under oral anticoagulants; thus, only a part of these patients receives anticoagulant therapy. The risk of falls in elderly patients is of advancing relevance for this therapeutic decision. Oral direct thrombin inhibitors like ximelagatran may be an alternative choice for therapy. Ischemic strokes and systemic embolism in the same frequency with 2x36 mg ximelagatran over 18 months (91/3664 patients: 1.6%/year, for study Sportif III and Sportif V) compared with warfarin (93/3665 patients: 1.6%/year for study Sportif III and Sportif V). All bleeding complications occurred less frequently under therapy with ximelagatran. This could be of importance for elderly patients with risk factors for bleeding or risk of falling.

[Heparin, thrombin and Factor Xa inhibitors]. / Heparine, thrombin- und faktor-Xa-inhibitoren.

Direct and indirect coagulation inhibitors are used to inhibit the activity of the serine proteases of the coagulation system. Indirect inhibitors act via antithrombin and heparin cofactor II. The main representatives are heparins, lowmolecular-weight heparins, fondaparinux, idraparinux and danaparoid. They bind to antithrombin and potentiate the inactivation of factor Xa and other serine proteases. Direct thrombin inhibitors bind reversibly to thrombin without cofactor. Anticoagulants are determined by global and specific anticoagulant methods. New anticoagulants are developed such as oral factor Xa inhibitors, oral thrombin inhibitors, antibody against activated factor VII, recombinant tissue pathway inhibitor to improve inhibition of blood coagulation or to induce nonanticoagulant effects (e. g. activated protein C in septicaemia). New anticoagulant methods are developed to improve and specify the anticoagulant effect of anticoagulants in thromboembolic diseases.

[Lepirudin for therapeutic use in heparin-induced thrombocytopenia]. / Lepirudin bei heparininduzierter Thrombozytopenie. Grundlagen und aktueller Erkenntnisstand zur klinischen Anwendung.

Heparin-induced thrombocytopenia (HIT) type II is an antibody mediated severe adverse event to heparin with a paradoxical decrease of platelet count and an increased risk for thromboembolic complications. The antibodies are directed against a neoepitop of platelet factor 4 after its binding to heparin. The incidence of HIT type II is lower with low-molecular-weight heparin compared to unfractionated heparin and lower in not operated patients compared to those after major surgery. In patients with HIT type II alternative anticoagulation has to be performed immediately due to the high thrombogenicity of the antibodies. The recombinant hirudin lepirudin (Refludan) is the anticoagulant drug of choice. A long-term anticoagulation has to be performed depending on the concomitant risk factors, intravenous administration followed by subcutaneous lepirudin overlapping with vitamin K antagonists.

Cardiac actinomycosis in a patient presenting with acute cardiac tamponade and a mass mimicking pericardial tumour.

A case of pericardial actinomycosis mimicking a pericardial tumour is reported. After the appearance of non-specific subpleural pulmonary nodules, a 48 year old woman presented with fever and clinical signs of pericardial tamponade. Subxiphoid pericardiotomy yielded a culture negative fluid and inflammatory reactive histopathology in the pericardial biopsy specimen. Because of suspected infection cefamandole was administered for 10 days and the patient became afebrile. The pericardial effusion recurred with no clinical signs two weeks later. Steroid medication resulted in rapid regression of the pericardial effusion. Subsequent echocardiography controls showed a tumour-like pericardial mass, confirmed by cardiac magnetic imaging. Surgical exploration led to the final histological diagnosis of actinomycosis. After high dose and long term penicillin G treatment the patient recovered fully with no recurrence during two years' follow up.

[Ximelagatran for treatment of venous thromboembolism]. / Ximelagatran zur Therapie thromboembolischer Erkrankungen.

Acute venous thromboembolism including asymptomatic and symptomatic pulmonary embolism without respiratory or cardiac failure is currently treated for 6 months, initially with subcutaneous low-molecular-weight heparin followed by oral anticoagulation. The main drawback of oral anticoagulation is caused by severe bleeding complications. Oral Ximelagatran has shown to be as effective and safe for the initial treatment of acute deep venous thrombosis compared to subcutaneous low-molecular-weight heparin followed by oral warfarin over a period of 4 weeks. Currently, oral ximelagatran is investigated versus subcutaneous low-molecular-weight heparin and oral warfarin over 6 months to demonstrate an almost equal efficacy and safety. The study is performed on a double blind and double dummy basis. Six months after oral anticoagulation of patients with acute deep venous thrombosis, recurrent venous thromboembolism may occur in up to 25% within 2 years. Ximelagatran is currently investigated versus placebo to demonstrate a reduced recurrence rate of venous thromboembolism over a period of 18 months.

Role of endothelin-1 in the development of a special type of cardiomyopathy.

The role of endothelin-1 (ET-1) in certain pathological states is still unclear. We have investigated the effect of anthracyclines (maximum dose, 450 mg/m(2) of body surface) on left ventricular systolic and diastolic function and how it influences the level of plasma ET-1 in 21 patients (12 female and nine male) with Hodgkin and non-Hodgkin lymphoma. We also studied the association between plasma ET-1 concentration and echocardiographic parameters. Serum ET-1 was measured by ELISA. Left ventricular function was analysed by echocardiography: ejection fraction (EF), velocity-time integral, E- and A-waves, E:A ratio, deceleration time (DT) and Doppler index were all measured. Statistical analysis was made by the Wilcoxon rank test. EF and serum ET-1 level decreased significantly (EF, 56.29+/-5.0% to 48.57+/-5.9%, P<0.0001; ET-1, 6.45+/-4.0 pg/ml to 2.9+/-1.0 pg/ml, P<0.0001). DT increased significantly (179.8+/-47.8 ms to 215.5+/-66.7 ms, P<0.01) after anthracycline therapy. There was no difference in other echocardiographic parameters before and after therapy. The decrease in serum ET-1 concentration might be a result of anthracycline's direct cytotoxic effect and the decreasing level of ET-1 can play a role in the reduction of EF. However, more studies are needed to evaluate the presence and severity of endothelial damage.

Anticoagulant-related skin reactions.

Cutaneous reactions have been reported during anticoagulant therapy with coumarin derivatives, unfractionated and low molecular weight heparins, heparinoids, danaparoid and hirudins. Anticoagulant-induced skin reactions vary from local allergic manifestations to skin necrosis. In patients with allergic reactions, diagnosis and crossreactions between anticoagulants can be confirmed by intracutaneous testing. Coumarin- and heparin-induced skin necrosis are rare, but are important side effects due to their high morbidity and occasional mortality. Cutaneous tests are contraindicated in these patients. In the future, anticoagulant strategies may include direct synthetic thrombin inhibitors (argatroban and melagatran/ximelagatran) and the Factor Xa inhibitor, pentasaccharide (fondaparinux).

Effect of phenprocoumon on monitoring of lepirudin, argatroban, melagatran and unfractionated heparin with the PiCT method.

Prothrombinase-induced clotting time (PiCT) is a clotting-time test for heparins and direct thrombin inhibitors to reduce drawbacks of aPTT. Effects of the direct thrombin inhibitors lepirudin, argatroban, melagatran and of unfractionated heparin (UFH) were investigated in normal and oral anticoagulant plasma samples. Lepirudin showed potentiating interferences with phenprocoumon effects. Melagatran, argatroban and UFH delivered distinct linear additive effects in both plasma sample groups. PiCT ratio reduces differences between both groups with UFH, and argatroban inhibitor-receptor-binding mode plays a role in interaction patterns.

Heparin-induced thrombocytopenia: pathophysiology and new treatment options.

Heparin induced thrombocytopenia (HIT) is a severe complication of heparin therapy. It is generally accompanied by a paradoxical decrease in platelets leading to activation of platelets and of the coagulation system. HIT type I is a mild, transient, non-immune disorder. HIT type II is an immune-mediated reaction towards neo-antigen on PF4, which is platelet factor 4 (PF4) that is exposed upon binding to heparins. A low sulfated octasaccharide is required for binding to PF4. The generated immunoglobulines bridge platelets by binding to the FcgRIIa-receptor. In patients with HIT type II heparin/LMW-heparin has to be discontinued immediately upon clinical suspicion. Diagnosis can be confirmed by laboratory tests. As patients are at high risk for or because they have developed thromboembolism, anticoagulation is mandatory, despite thrombocytopenia. Treatment options are danaparoid, r-hirudin, bivalirudin, argatroban, dextransulfate, and dermatansulfate. In future, fondaparinux and ximelagatran may be considered for treatment.

Angiotensin II type 1 receptor gene polymorphism and mitral valve prolapse syndrome.

BACKGROUND: Mitral valve prolapse syndrome (MVPS), a term applied to patients who have a variety of symptoms, has been associated with autonomic or neuroendocrine dysfunction. Recent evidence suggests that effects of angiotensin II mediated by the angiotensin II type 1 (AT(1)) receptor are involved in modulation of cardiovascular autonomic control in human beings. Association of a genetic polymorphism (A-C(1166)) of the AT(1) gene with abnormal vasomotion and low blood pressure related to autonomic control has been reported recently. Because the role of this genetic variant in MVPS has not been studied, we performed a case-control study of the A-C(1166) variant in a group of 76 white subjects with MVPS. METHODS AND RESULTS: All patients were genotyped by use of a mismatch polymerase chain reaction/Afl II restriction fragment length polymorphism analysis. Frequency of the C(1166) allele was 0.4 in patients with MVPS and 0.26 in control patients. The difference in genotype (chi square = 6.5; P <.05) and allele (chi square = 5.9; P =.02) frequencies between the groups was significant. The odds ratio in favor of carrying the C allele was 4 times greater for patients with MVP than for control patients (95% confidence interval 1.4 to 12.1). CONCLUSIONS: The current results indicate that the A-C(1166) polymorphism of the angiotensin II type 1 receptor gene is associated with MVPS in the white population.

Curing swallowing-induced arrhythmias with cimetidine.

A 57-year-old man with swallowing-induced arrhythmias is presented. The patient did not respond to conventional antiarrhythmic medication, but H2-receptor antagonist treatment proved effective.

The effects of probucol on QT/QS2 relation and systolic time intervals.

The QT, QTc, QS2 intervals, pre-ejection period-left ventricular ejection time ratios and serum lipoprotein levels were measured in 8 patients with primary hypercholesterolemia before and after a 3-month therapy with probucol, 1 g/day. Both QT and QTc intervals increased significantly, whereas no significant changes were observed between the pre- and post-treatment QT/QS2 and pre-ejection period-left ventricular ejection time ratios. These results help to explain why treatment with probucol, while effecting a prolongation of the QTc interval, does not result in serious arrhythmias in man.

A study of modulated ventricular parasystole by programmed stimulation.

To analyze the phase-dependent sensitivity of the parasystolic pacemaker to nonparasystolic beats, 11 patients with modulated ventricular parasystole were studied using the ventricular extrastimulus method. The intrinsic parasystolic cycle lengths ranged from 1,100 to 1,800 ms. Premature stimuli altered the duration of the parasystolic cycle lengths by amounts that depended on timing of the test impulses within the parasystolic cycles. Premature impulses delivered during the first part of the parasystolic cycles prolonged the parasystolic cycle lengths to 107 to 151% of the intrinsic parasystolic cycle lengths and impulses applied during the second part abbreviated them to 70 to 81% of the intrinsic parasystolic cycle lengths. In 10 patients the accelerating effects were of greater magnitude than the decelerating effects. Transition from the accelerating to slowing phases was progressive or unstable in 9 patients and abrupt in 2. Changes induced by individual stimuli were short-lived and the parasystolic pacemakers returned immediately to their original rates. In 1 patient the biphasic sensitivity of parasystole to premature stimuli was shown to sustain for 21 days.

Severe symptomatic atrioventricular block induced by pilocarpine eye drops.

An 89-year-old man with chronic glaucoma received hourly pilocarpine eye drops for seven hours, when he developed third-degree atrioventricular block with a slow idioventricular escape rate. After discontinuing the pilocarpine, the atrioventricular block gradually disappeared. The site of pilocarpine-related block was most likely within the His-Purkinje system.

Simple approach to an apparently chaotic arrhythmia.

Deciphering complex arrhythmias requires a strict, systematic approach. In a step-by-step analysis of an electrocardiogram recorded from a patient with severe metabolic disturbances, we present a few simple suggestions that may often be helpful in electrocardiographic interpretation.

The effects of overdrive pacing and lidocaine on atrioventricular junctional rhythm in man: the role of abnormal automaticity.

The effects of overdrive pacing and lidocaine were studied in 22 patients with atrioventricular (AV) junctional rhythms. Based on the responses to cardiac pacing and lidocaine, patients were divided into two groups. AV junctional rhythms in group I (17 patients) were suppressed by overdrive pacing, and their rates were decreased by lidocaine. Lidocaine also prolonged the junctional recovery time in these patients. AV junctional rhythms in group II (five patients) were not suppressed by overdrive pacing. In contrast, the rate increased after overdrive pacing. Lidocaine did not alter the basic cycle lengths or the recovery times of the AV junctional rhythms in this group of patients. The data suggest that AV junctional rhythms in group I were caused by normal automaticity, while those in group II were probably due to abnormal automaticity.

Electrophysiologic study of tachycardia-dependent paroxysmal His bundle block in man.

Electrophysiologic study was performed in a patient with tachycardia-dependent paroxysmal atrioventricular block. The site of block was within the His bundle. The effective refractory period of the His bundle was markedly prolonged and it was comparable to the critical atrial cycle length producing type II His bundle block. The most likely mechanism of paroxysmal atrioventricular block was repetitive concealed penetration of the blocking zone by nonconducted impulses that reached the proximal His bundle. Enhancing the blocking ratio at the atrioventricular nodal level resulted in improvement of overall atrioventricular conduction.