Practical use of dabigatran etexilate for stroke prevention in atrial fibrillation.

Atrial fibrillation (AF) is associated with an increased risk of thromboembolism, and is the most prevalent factor for cardioembolic stroke. Vitamin K antagonists (VKAs) have been the standard of care for stroke prevention in patients with AF since the early 1990s. They are very effective for the prevention of cardioembolic stroke, but are limited by factors such as drug-drug interactions, food interactions, slow onset and offset of action, haemorrhage and need for routine anticoagulation monitoring to maintain a therapeutic international normalised ratio (INR). Multiple new oral anticoagulants have been developed as potential replacements for VKAs for stroke prevention in AF. Most are small synthetic molecules that target thrombin (e.g. dabigatran etexilate) or factor Xa (e.g. rivaroxaban, apixaban, edoxaban, betrixaban, YM150). These drugs have predictable pharmacokinetics that allow fixed dosing without routine laboratory monitoring. Dabigatran etexilate, the first of these new oral anticoagulants to be approved by the United States Food and Drug Administration and the European Medicines Agency for stroke prevention in patients with non-valvular AF, represents an effective and safe alternative to VKAs. Under the auspices of the Regional Anticoagulation Working Group, a multidisciplinary group of experts in thrombosis and haemostasis from Central and Eastern Europe, an expert panel with expertise in AF convened to discuss practical, clinically important issues related to the long-term use of dabigatran for stroke prevention in non-valvular AF. The practical information reviewed in this article will help clinicians make appropriate use of this new therapeutic option in daily clinical practice.

Pheochromocytoma-related 'classic' takotsubo cardiomyopathy.

We report a case of a 53-year-old hypertensive male with takotsubo cardiomyopathy in the setting of pheochromocytoma. Pheochromocytoma presenting as takotsubo cardiomyopathy is a recognized but uncommon occurrence with recently increasing number of published cases. We present typical apical ballooning syndrome, with transient left ventricular apical ballooning in contrast to several reports, in which patients with pheochromocytoma-induced cardiomyopathy had so called 'inverted'takotsubo cardiomyopathy. In patients being diagnosed with acute coronary syndrome symptoms without coronary artery stenosis or spasm, and pronounced blood pressure variability, pheochromocytoma-induced takotsubo or 'inverted' takotsubo cardiomyopathy should be kept in mind.

Geographic variability in outcomes within an international trial of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes. Results from PURSUIT.

AIMS: Variations in outcome of patients from different geographic regions have been observed in many large international trials. We analysed the factors that might contribute to the geographic variations in patient outcome and treatment effect as observed in the PURSUIT trial. METHODS: In PURSUIT, 9461 patients with acute coronary syndromes without persistent ST-elevation were randomized to the platelet inhibitor eptifibatide or placebo for 72 h in 27 countries in four geographic regions: Western (n=3697) and Eastern Europe (n=1541) as well as North (n=3827) and Latin America (n=396). The primary end-point was the 30-day composite of death or myocardial infarction. In the initial univariate analysis, the treatment effect appeared greater in N. America than in W. Europe, while no benefit was apparent in L. America and E. Europe. However, the confidence intervals were wide and overlapping. To study these differences, a subdivision in an early and late patient outcome and treatment effect was made. Accordingly, we analysed the rate of death or infarction at 72 h censored for percutaneous coronary intervention and the rate between 3 and 30 days, respectively. Additional analyses were performed with different definitions of myocardial infarction using progressively higher thresholds of CK(-MB) elevation. Multivariable analysis was used to evaluate the relation between region and outcome and to determine the adjusted odds ratios for the eptifibatide treatment effect. RESULTS: Major differences in baseline demographics were apparent among the four regions; in particular, more patients from E. Europe had characteristics associated with impaired outcome. Interventional treatment also varied considerably, with more patients from N. America undergoing revascularization. Despite differences in the 72 h event rate, eptifibatide showed a consistent trend towards a reduction in the composite end-point among all four regions and for all definitions of infarction. Relative reductions ranged from 17-42% in W. Europe, 23-35% in N. America, 0-33% in E. Europe, and 55-82% in L. America. After multivariable adjustment, the pattern of benefit with eptifibatide was consistent among the regions. In patients undergoing percutaneous coronary intervention during study drug infusion in W. Europe (n=266) and N. America (n=931), the relative reduction in myocardial infarction during medical therapy ranged from 56-75% in W. Europe and 14-67% in N. America, while the reduction in procedure-related events ranged from 12-44% and 25-61% for different definitions of infarction. After multivariable adjustment neither benefit nor rebound were apparent after study drug discontinuation, or after 3 days in all regions, except in L. America. In general, the differences in outcome and treatment effect were greatest when the protocol definition of myocardial infarction (CK(-MB) >1 upper normal limit) was applied. Under stricter definitions, these differences became smaller and disappeared with the investigator's assessment. CONCLUSION: The analysis suggests that the apparent differences in patient outcome and eptifibatide treatment effect can be explained largely by differences in baseline demographics and adjunctive treatment strategies as well as by the methodology of myocardial infarction definition and the adjudication process.

Prior aspirin use predicts worse outcomes in patients with non-ST-elevation acute coronary syndromes. PURSUIT Investigators. Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy.

Aspirin is beneficial in the prevention and treatment of cardiovascular events, but patients who have events while taking aspirin may have worse outcomes than those not on aspirin. We investigated the association between prior aspirin use and clinical outcomes in 9,461 patients with non-ST-elevation acute coronary syndromes enrolled in the Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, before and after adjustment for baseline factors. We also examined whether eptifibatide has a differential treatment effect in prior aspirin users. Prior aspirin users were less likely to have an enrollment myocardial infarction (MI) (vs unstable angina) (43.9% vs 48.8%, p = 0.001) but more likely to have death or MI at 30 days (16.1% vs 13.0%, p = 0.001) and at 6 months (19.9% vs 15.9%, p = 0.001). After adjustment, prior aspirin users remained less likely to have an enrollment MI (odds ratio 0.88, 95% confidence interval 0.79 to 0.97) and more likely to have death or MI at 30 days (odds ratio 1.16, 95% confidence interval 1.00 to 1.33) but not at 6 months (odds ratio 1.14, 95% confidence interval 0.98 to 1.33). In a multivariable model, eptifibatide did not have a different treatment effect in prior aspirin users compared with nonusers (p = 0.534). Prior aspirin users had fewer enrollment MIs but worse long-term outcomes than nonusers. We found no evidence for a different treatment effect of eptifibatide in prior aspirin users.

Neuropathological changes within the brain of rabbits with experimental model of antiphospholipid syndrome in different time after immunization.

The post-mortem neuropathological investigations were carried out on 20 female New Zealand rabbits. Two main types of changes were found: inflammatory, including meningeal and perivascular infiltrates, and thrombotic within the nervous tissue. The findings revealed that active process within the CNS persists at least 3 months after APS was evoked, however its intensity, especially necrotic changes and vessel wall thickening evidently diminish. The active APS after experiment had been finished was also confirmed in blood samples.

Central nervous system involvement in pregnant rabbits with experimental model of antiphospholipid syndrome.

A postmortem neuropathological investigations were carried out on 23 female rabbits divided into 3 groups; pregnant animals with experimental antiphospholipid syndrome (APS), nonpregnant rabbits with antiphospholipid syndrome and nonpregnant animals without antiphospholipid syndrome. The aim of study was to analyze the CNS changes related to experimental model of APS in rabbits and to answer, whether pregnancy influences the intensity of CNS changes related to APS. The findings suggest that the experimental model of APS used in our study appeared to be effective in the development of the CNS involvement in rabbits. The extent thickening of CNS vessel wall is the most common feature of vasculopathy related to APS. In rabbits, pregnancy seems to be a factor facilitating the CNS damage related to APS.

[A case of dilated cardiomyopathy caused by myocardial microinfarcts in the course of polycythemia vera]. / Przypadek kardiomiopatii rozstrzeniowej spowodowanej mikrozawalami serca w przebiegu czerwienicy parawdziwej.

This article presents a case of 45-year-old man with polycythemia vera non diagnosed before. The first symptom of polycythemia vera was acute congestive heart failure which suggested diagnosis of myocarditis. Polycythemia vera was confirmed by raised hematocrit, significantly increased platelet count, normal oxygen saturation, score for leukocyte alkaline phosphatase (LAP)-130 and splemomegaly. Echocardiography revealed left ventricular histological. Coronary arteriography showed normal coronary arteries. Finding of histological examination of the endomyocardial biopsy were described as necrosis of myocytes and abnormal blood flow in very small coronary vessels. It was the main reason of dilated cardiomyopathy caused by microinfarcts in polycythemia vera. Hematological parameters were reduced to normal levels after hydroxyurea treatment. Digitalis and ACE-inhibitor therapy quickly improved cardiovascular status from III to II NYHA class.

[Difficulties with pharmacologic treatment of a patient with atrioventricular nodal reentrant tachycardia]. / Trudnosci w leczeniu farmakologicznym u chorej z nawrotnym czestoskurczem wezlowym.

A case history of a 38 year old teacher with AVNRT is described. She had been treated for 11 years with 11 antiarrhythmic drugs in various combinations. No treatment prevented recurrence of arrhythmia. During long term treatment with class IA, IC, II, III and IV antiarrhythmic drugs, various side effects occurred. There was also suspicion of proarrhythmic effect, especially of prajmaline. Some of the drugs terminated tachycardia while administered intravenously. But often deep hypotonia, heart automatism disturbances and even asystole occurred, MAS syndrome occurred 5 times. The patient was referred to our laboratory to perform percutaneous radiofrequency ablation of the slow pathway. The procedure was performed without any complications. Efficacy of the ablation was proved by electrophysiologic study before and after intravenous atropine administration. During the 11 months follow-up the patient had no tachycardia. She is on no antiarrhythmic medication and continues her normal activity.

[Selective catheter ablation of the slow pathway in a patient with recurrent atrioventricular nodal reentrant tachycardia]. / Wybiórcza ablacja drogi wolnego przewodzenia usunela napady nawrotnego czestoskurczu wezlowego.

The case of a 35 year-old patient with recurrent, sustained atrioventricular nodal reentry tachycardia (AVNRT)--type slow/fast--refractory to group IA, IC, II, IV antiarrhythmic agents is presented. The maximum rate of the tachycardia was 280/min. During the antiarrhythmic treatment with group IA, IC and IV agents the tachycardia rate was 230/min. The effective refractory period (ERP) of the slow pathway was 200 ms in antegrade direction. ERP of the fast pathway was 260 ms in antegrade and 210 ms in retrograde direction. Ablation of the slow pathway was performed with radiofrequency energy (device HAT 200 S manufactured by Osypka GMBH, catheter Cereblate No 6). The total ablation time was 96 s, maximal temperature of the effective ablation time was 51 centrigrades. Total energy delivered was 2316 J. The ablation caused neither atrioventricular conduction block nor any damage to the heart structure other than the slow conduction pathway. After the ablation there are no evidence of conduction through the slow pathway. Conduction in anterograde and retrograde direction occurs through the fast pathway. No AVNRT were observed. After ablation the patient has no antiarrhythmic treatment.

[Electrical ablation with high frequency (radiofrequency) in patients with recurrent atrioventricular nodal reentrant tachycardia--introductory information]. / Ablacja pradem wysokiej czestotliwosci (radiofrequency) u chorych z nawrotnym czestoskurczem wezlowym--doniesienie wstepne.

In 10 patients (pts) with atrioventricular nodal reentrant tachycardia type slow/fast (AVNRT) refractory to the antiarrhythmic treatment, radiofrequency current catheter ablation was performed. Adult pts (mean age 31 years) suffered from paroxysms of AVNRT for 2 to 18 years (mean 8 years). Episodes of arrhythmia recurred from 2-3 times a week to 1 for several months during antiarrhythmic therapy. The mean rate of the tachycardia was 243/min. 3 pts had syncope and 5 fainted during the tachycardia. In 2 females mitral valve prolapse was diagnosed. Programmed stimulation of the right atrium on the basic rate 130/min revealed ERP of the slow pathway mean 238 ms and ERP of the fast one mean 346 ms. The tachycardia has been induced with right atrium stimulation--most often programmed or burst stimulation--200 and 220/min, sometimes with incremental pacing. Successful radiofrequency energy ablation was performed in all 10 pts. Average number of the impulses for one pt was 7.7 (from 1 to 18 impulses). The total average time of the ablation was 216 s. The temperature of effective ablation was average 65 centigrade. The effect of the ablation was evaluated during repeated electrophysiological study before and after intravenous injection of atropine. Ablation was considered successful when no tachycardia was induced. P-R interval did not change and no episodes of AVNRT was observed in the 1-3 months follow-up. No complications were observed during the ablation and after the procedure, especially no thromboembolism was noticed. The echocardiographic evaluation revealed no damage to the heart structure. The pts receive no antiarrhythmic treatment and they are systematically controlled.

[Emergency epicardial dissection of the accessory pathway in a patient with atrioventricular nodal reentrant tachycardia]. / Przeciecie dodatkowego szlaku przewodzenia w trybie pilnym u chorego z uporczywym czestoskurczem przedsionkowo-komorowym.

Diagnostic and therapeutic problems in 14 year old patient with concealed WPW syndrome were presented. Paroxysms of atrio-ventricular reentrant tachycardia 180-220/min were frequently recurring, usually with normal QRS pattern. Tachycardias often had to be terminated by intravenous administration of antiarrhythmic drugs. Long term treatment with various antiarrhythmic agents did not prevent recurrence of tachycardias but they became sustained and were recurring more often. Their other side effects manifested with sinus node disfunction and depression of the heart muscle. The electrophysiologic study revealed right anterior septal accessory pathway. Epicardial dissection of the accessory pathway was urgently performed. The control electrophysiologic study revealed no evidence of conduction through the accessory pathway. The patient did not require antiarrhythmic treatment. During the 12 months follow up no tachycardia occurred.

[Indications for emergency cardiovascular surgery at the Institute of Cardiology]. / Operacje kardiochirurgiczne ze wskazan zyciowych w materiale Instytutu Kardiologii.

Between 1981 and 1989 73 patients (46 males, 27 females aged 15-69; mean 42) underwent emergency cardiac operation in the I Clinic of Cardiosurgery. There were 39 (53%) patients with valvular disease, 18 (25%) with prosthetic valve dysfunction and endocarditis, 9 (12%) with acute aortic dissection (2 of them had Marfan's syndrome), 5 (7%) with atrial myxoma and 2 (3%) with malignant pericardial mesothelioma. All of them were treated in C.C.U. before surgery. 27 urgent operations were performed within the first 24 hours after the admission to C.C.U. 30 of 73 patients died (41%). The IV NYHA functional class was stated as the most significant predictive factor for in-hospital mortality. The greatest mortality was observed in the group of patients with valvular disease (53%). In hospital survival rate reached 50% after reoperations as a procedure of choice in prosthetic valve dysfunction. Good early results were observed in patients with aortic dissection (survival rate--66%). The presence of Marfan's syndrome was associated with a poor surgical prognosis. There were no deaths after atrial myxoma removal, but all patients with malignant mesothelioma died. The most common cause of all deaths was congestive heart failure.

[Indications for emergency surgical treatment of ectopic atrial tachycardia]. / Chirurgiczne leczenie ektopowego czestoskurczu przedsionkowego--ze wskazan pilnych.

Recurrent automatic atrial tachycardia can induce dilated cardiomyopathy. We present clinical and therapeutic problems of 16 years old male with ectopic left atrial tachycardia refractory to pharmacological therapy. In this patient long periods of atrial tachycardia 200-240/min due to lack of effective medication caused cardiac failure. Uncontrolled taking of various antiarrhythmic drugs and persistent tachycardia led to cardiogenic shock. The electrophysiologic study revealed focus of the tachycardia localized in the area of left cardiac auricle. The rate of the tachycardia was changing from 84 to 240/min, with periods of Mobitz I block in the AV node. In periods of 1:1 AV conduction the tachycardia had sometimes LBBB QRS morphology. The atrial tachycardia provoked unsustained ventricular one. The patient was operated. Resection of left auricle and mitral valvuloplasty were performed. After the operation the patient regained undisturbed sinus rhythm and symptoms of heart failure disappeared.

[Dissection of the accessory conduction pathways with simultaneous mitral valve surgery]. / Przeciecie dodatkowych szlaków przewodzenia z jednoczasowa operacja wady mitralnej.

The case of surgical treatment of a 44-years old female with a double atrio-ventricular accessory pathway and mitral stenosis was described. Fast ventricular rates due to conduction through the accessory pathways during atrial fibrillation in course of mitral stenosis caused severe heart failure, occasionally with deep hypotonia. Combined treatment with prajmaline and propafenone blocked conduction through accessory pathways. The ventricular rate slowed from approx. 200/min to 150/min. Addition of digoxin slowed the ventricular rate down to approx 80-100/min. There were no signs of preexcitation. Treatment with diuretics and vasodilators was continued. The state of patient improved. Echocardiographic and hemodynamic evaluation revealed: mitral stenosis (orifice - 75 mm2) with moderate regurgitation, small aortic and tricuspid regurgitation. The coronary arteries were normal. On the base of the ECG recordings during atrial fibrillation both accessory pathways were localized on lateral and posterior parts of the left free wall. The patient was operated on. Both atrio-ventricular by-pass tracts were dissected using Sealy's method in Cox modification and then mitral valve prosthesis Medtronic-Hall 27 mm was implanted. Prajmaline and propafenone were discontinued and preexcitation did not recovered. The sinus rhythm was restored by electroversion. The patient had no overt heart failure on discharge from the Institute.

[Captopril-induced attacks of bronchial asthma]. / Napad astmy oskrzelowej wywolany kaptoprylem.

There was presented the case of a bronchial asthma attack in 29 years old patient with congestive heart failure and a history of atopic bronchial asthma in 30th minute after 12.5 mg of captopril administration.