Effect of timing of clopidogrel administration on 30-day clinical outcomes: 300-mg loading dose immediately after coronary stenting versus pretreatment 6 to 24 hours before stenting in a large unselected patient cohort.

BACKGROUND: The aim of our prospective multicenter Clopidogrel Registry was to evaluate the efficacy and safety of a 300-mg loading dose of clopidogrel at the time of ad hoc stenting in patients with suspected coronary artery disease who were not pretreated with clopidogrel for any reason, and to compare the 30-day clinical event rates with the outcome of patients pretreated with a loading dose of clopidogrel 6 to 24 hours before stenting. METHODS: Between March 2002 and February 2004, 4160 consecutively included patients received a 300-mg loading dose of clopidogrel immediately after (group 1, n = 2679) or 6 to 24 hours before stenting (group 2, n = 1481). RESULTS: The primary end point (triple composite end point of acute myocardial infarction, all-cause death, and urgent repeat target vessel revascularization) at 30 days occurred in 4.74% versus 2.77% in groups 1 and 2, respectively (P = .002). The secondary end point events, the stent thrombosis, occurred significantly more frequently in group 1, with a trend toward increase in incidence of death, target vessel revascularization, or need for glycoprotein IIb/IIIa antagonists during percutaneous coronary intervention. Pretreatment with clopidogrel was associated with more major bleeding (secondary safety end point) (0.41% vs 1.35% in groups 1 and 2, respectively; P = .001). CONCLUSIONS: The results of our multicenter prospective Clopidogrel Registry demonstrate lower efficacy of a 300-mg loading dose of clopidogrel at the time of stenting compared with pretreatment 6 to 24 hours before percutaneous coronary intervention on the 30-day composite clinical end point in the large unselected patient cohort, which suggests the benefit of clopidogrel pretreatment in all incoming patients with suspected significant coronary artery disease scheduled for coronary angiography.

[Effects of autologous bone marrow derived CD34+ stem cells on the left ventricular function following myocardial infarction]. / A csontvelo eredetu CD34+ ossejtek hatása a bal kamra funkciójára akut miokardiális infarktust követoen.

Both experimental and human clinical studies executed in the last 5 years suggested that bone marrow derived cells may participate in the healing process after myocardial infarction. A number of small clinical trials indicated mild or moderate beneficial effect of intracoronary administration of bone marrow derived stem cells after myocardial infarction. Most of the studies used mononuclear cell fraction; due to the cellular heterogeneity of this cell population the type of the effective subpopulation was not known. We investigated the safety and functional effects of the autologous bone marrow CD34+ stem cells after intracoronary administration in patients with recent myocardial infarction. 8 patients with impaired left ventricular function were transplanted with CD34+ bone marrow stem cells 12 +/- 1 day after the acute coronary event. 2D-echocardiography, FDG-PET and MIBI-SPECT were performed before transplantation and 6 month later. During the 6-month follow-up the global left ventricular function (basal EF 37.3 +/- 2.9%, after cell therapy 44.8 +/- 4.1%) and regional viability / metabolism increased significantly (17.6 +/- 13.5%). The increase of myocardial perfusion in the infarct region was tendentious but not significant. Our results demonstrate for the first time that the CD34+ subpopulation of bone marrow derived stem cells improves left ventricular function and viability after myocardial infarction.

[Molecular pathology and clinical manifestations of Fabry disease]. / A Fabry-kór molekuláris patológiája és klinikai megjelenési formái.

Fabry disease is a rare, progressive lysosomal storage disorder caused by mutation in the GAL gene and an impaired function of the alpha-galactosidase A enzyme. The enzymatic defect results in the progressive accumulation of glycosphingolipids in endothelial cells, smooth muscle cells, leucocytes and fibroblasts leading to organ damage in the skin, eye, nervous system, kidney and heart. Major clinical manifestations include acroparesthesis, angiokeratoma, corneal opacities, vascular diseases of the heart, kidney, and the central nervous system. Enzyme replacement therapy has recently become available for the treatment of Fabry patients. In this review the authors describe clinical features of Fabry disease in 31 Hungarian patients. At the time of this analysis the database consisted of 31 cases (15 males, 16 females) of whom 5 have died (4 males, 1 female). The most common disease-specific manifestation was angiokeratoma in males, and eye symptoms in females. 25% of female subjects were symptom free. Genotyping was performed in all cases and disease-causing mutations were found in all families. Three new mutations were identified. Twelve patients (8 males and 4 females) are currently receiving enzyme replacement therapy.

[Current practice and future perspectives of myocardial stem cell therapy]. / A myocardialis ossejt kezelés jelenlegi gyakorlata és távlatai.

Myocardial infarction became more frequent mainly in the developed countries in the past decades. Beside the pharmacological (thrombolysis, beta-blockers, ACE-inhibitors, antiplatelet- and lipid-lowering drugs, etc.) and interventional (percutaneous coronary intervention, intraaortic balloon pump, resynchronization therapy, left ventricular assist devices etc.) procedures the quality of life of patients and the morbidity and mortality data were improved. However we experience development of heart failure following myocardial infarction because of significant cell loss and left ventricular remodeling. Until now there was not any therapeutic procedure affecting via cardiomyocyte renewal, but in the last 5 years the myocardial stem cell therapy was introduced to human clinical phase. In this review the authors summarized the general features of stem cells, why these cells are in the focus of the interest and their preclinical and clinical applications in myocardial infarction. Promising issues suggests, that intramyocardial implantation of autologous bone marrow derived stem cells become a new therapeutic modality in treatment of myocardial infarction. The stem cell therapy and regenerative medicine would open new perspectives in cardiology. However it is very important to remark, that this, as every medical procedure can be dangerous and can cause side effects. A lot of molecular and cellular mechanism of cell therapy is not clear at present, that's why we should be careful with this opportunity holding in our hands. We have to plan multicenter clinical trials to evaluate the long term safety and efficacy of the procedure.

Effects of long-term transdermal nitrate treatment on left ventricular function in patients following myocardial infarction.

BACKGROUND: [corrected] Nitrates are widely used for the treatment of myocardial infarction (MI). The large megatrials (GISSI-3 and ISIS-4) did not in fact demonstrate a significant decrease in mortality in the nitrate-treated group. However, examination of the number of postinfarction angina episodes and the occurrence of cardiogenic shock in the GISSI-3 study did reveal significant decreases. HYPOTHESIS: It was hypothesized that chronic nitrate treatment after an MI preserves left ventricular systolic and/or diastolic functions. METHODS: Patients were divided into two groups: those receiving chronic nitrate treatment for 6 months after an MI (n = 30), and those without such treatment (n = 29). Echocardiography was performed 3, 14, 42, and 180 days after the infarction. The changes in early diastolic and atrial contraction-related mitral valve inflow pattern and deceleration time were assayed. Alterations in systolic, diastolic, and atrial reverse flow velocities in the pulmonary vein were measured, as were ejection fraction (EF), the number of registered angina episodes, and the maximal ST-segment depression in response to the stress test. RESULTS: During the 6-month study period, the increase in systolic pulmonary venous flow velocity was significantly larger in the nitrate group than in the controls. The decreases in the velocities of the diastolic and the atrial reverse flow were also more pronounced in the nitrate group than in the controls. The EF was improved only in the nitrate group. Examination of the maximal ST-segment depression in response to the stress test revealed a significant decrease in the nitrate group only. There were no significant differences between the two groups in the number of registered angina episodes or mitral inflow pattern. CONCLUSIONS: The study showed that prolonged nitrate treatment after an MI may help preserve diastolic left ventricular function.

Comparison of the new cardioselective beta-blocker nebivolol with bisoprolol in hypertension: the Nebivolol, Bisoprolol Multicenter Study (NEBIS).

OBJECTIVES: The aim of the present study was to evaluate the antihypertensive efficacy of the highly beta(1)-selective adrenergic antagonist nebivolol in comparison with bisoprolol in the treatment of mild to moderate essential hypertension. METHODS: This multicenter, single-blind, randomized, parallel-group 16-week study involved a 4-week placebo run-in, followed by a 12-week treatment period (5 mg nebivolol or 5 mg bisoprolol). Patients (n = 273) eligible for the study had a sitting diastolic blood pressure (DBP) between 95 and 110 mm Hg and a systolic blood pressure (SBP)