[The efficacy and safety of moxonidine in patients with metabolic syndrome (the O.B.E.Z.I.T.A. trial)]. / Ucinnost a bezpecnost podávání moxonidinu u pacientu s metabolickým syndromem (klinické hodnocení O.B.E.Z.I.T.A.).

INTRODUCTION: Treatment with agents neutral to lipid metabolism but with a positive effect on glucose metabolism might significantly improve the long-term prognosis of patients with metabolic syndrome and hypertension. The aim of our non-interventional observational clinical study was to evaluate the safety of treatment with moxonidine and to assess changes to the metabolic syndrome-related laboratory parameters. MATERIALS AND METHODS: A total of 748 patients over 18 years of age (22-87; mean 59; median 60) were included in a 6-month evaluation (two 3-monthly study visits). There were slightly more female patients (n = 401, 54%) with metabolic syndrome (> or = 3 NCE ATP III risk factors) and poorly controlled hypertension. A standardized data collection form was used, blood pressure measurement was standardized as per the guidelines and laboratory samples were assessed in a certified laboratory. The study medication (moxonidine, Cynt) was prescribed to patients with newly diagnosed hypertension and/or patients with hypertension poorly controlled at an initial visit. RESULTS: The majority of patients (98.8%) completed the study. No adverse effects were reported during the study. Moxonidine was mostly prescribed as an add-on treatment to other antihypertensives (81.1% patients) due to the lack of efficacy of the present antihypertensive treatment. The most frequent dose was 0.4 mg/day as monotherapy (44.9% of patients) as well as add on treatment (59.8% of patients). A change to the treatment was performed in 142 (19.2%) of patients during the follow up visit and in 57 (7.7%) of patients during the last study visit. All parameters (blood pressure, body weight, waist circumference, total cholesterol, LDL- and HDL-cholesterol, triglycerides, glycaemia and pulse) have changed highly significantly (p < 0.001). CONCLUSION: Over the 6-month follow up, a highly significant change was observed to all monitored parameters. An addition of monoxidine (Cynt) to an existing treatment resulted not only in a reduction to blood pressure but also in highly significant changes to metabolic parameters without any significant modifications of the treatment. Treatment with monoxidine can be considered as metabolically neutral with an added value of positive effect on metabolic parameters. This is in line with the results of other studies.

[Combination therapy of hypertension in general clinical practice. The results of the KOHYBA study]. / Kombinainí Iécba hypertenze v bezné klinické praxi. Výsledky studie KOHYBA.

INTRODUCTION: The aim of hypertension treatment is to achieve blood pressure target values; in the majority of patients this is achieved with combination therapy. ACE inhibitors and imidazoline receptor agonists have neutral effect on lipid metabolism and positive effect on glucose metabolism. They thus may significantly improve long-term prognosis of patients with hypertension and metabolic syndrome or hypertension and diabetes mellitus. The aim of our research was to evaluate physicians' approach to hypertension treatment and to ascertain the proportion of patients in general clinical practice who require combination treatment to control their hypertension. The study also aimed to assess the knowledge of the type and frequency of adverse events associated with the administered agents. MATERIALS AND METHODOLOGY: The 12-week evaluation (two 6-week visits) included 993 patients with mild to moderate hypertension above 18 years of age (20-92; mean 57; median 56) with proportional distribution of men and women (48% and 51%, respectively). Data were collected using a standard instrument and blood pressure measured in a standard manner according to guidelines. Hypertension was newly identified in 609 patients (61%), insufficiently controlled hypertension in 363 patients (37%) and data on hypertension were missing in 21 patients (2%). The initial therapy was imidapril (Tanatril) 10 mg. On the first follow up visit, it was on the physician's discretion to increase the dose (increase--imidapril 20 mg) or to prescribe a combination of lower doses [low dose combination--imidapril 10 mg + moxonidin (Cynt) 0.2 or 0.3 mg, respectively]. The second visit, scheduled at 12 weeks post study entry, was attended by 965 patients (97%). RESULTS: Eleven (1.1%) patients discontinued the treatment prematurely. Dry irritant cough, occurring in 4, i.e., only 0.4%, patients was the most frequent cause of treatment discontinuation. Over the 12 weeks oftreatment, systolic blood pressure declined from 154 mm Hg to 132 mm Hg (p < 0.001); diastolic blood pressure declined from 92 mm Hg to 80 mm Hg (p < 0.001). By the second visit, normal blood pressure was achieved by 718 (74%) patients. Overweight and obese patients have profited from the treatment significantly more than patients with BMI < 25. This held true for the reduction of systolic blood pressure (p = 0.022 at the first follow up and p = 0.037 at the second follow up, respectively) as well as the reduction of diastolic blood pressure (p = 0.003 at the first follow up and p = 0.001 at the second follow up, respectively). After the first follow up visit, the majority of patients continued to take 10 mg of imidapril (610; 61%). At the second follow up visit, 808 (84%) patients continued on the study medication, 79% of patients were on imidapril (5, 10 or 20 mg) and 21% on imidapril + moxonidin combination. Imidapril monotherapy (no other antihypertensive) was prescribed to 258 (27%) patients. CONCLUSION: Imidapril is an ACE inhibitor with one ofthe lowest incidences (less than 1% of patients) of dry irritant cough. It thus may become an alternative treatment modality in patients who experienced cough while taking other ACE inhibitors. A significant reduction of blood pressure can be expected in the majority of patients at a dose as low as 10 mg.

Effect of short-term maximal exercise on BNP plasma levels in healthy individuals.

Many studies documented the relationship between elevated plasma concentrations of natriuretic peptides and cardiovascular diseases, especially heart failure. However, it is still uncertain whether physical exercise leads to a significant release of natriuretic peptide in healthy subjects. The aim of this study was to determine the effect of maximal physical activity on plasma BNP concentrations in healthy individuals within 3 hours after the short-term exercise. BNP plasma concentrations were measured in 15 healthy volunteers before, immediately after as well as 1 hour and 3 hours after bicycle spiroergometry. Maximal workload and exercise capacity were assessed in watts, watt-seconds, metabolic equivalents and VO(2max). Mean BNP plasma levels before, immediately after, 1 hour and 3 hours post-exercise were 19.4+/-2.5; 30.6+/-4.7; 17.9+/-2.5 and 18.7+/-3.1 pg/ml, respectively. The increase of BNP concentrations immediately after exercise was statistically significant (p=0.0017) compared to baseline values. We did not find any correlation between the post-exercise increase of BNP levels and age, body mass index, maximal workload or exercise capacity. In conclusion, short-term maximal physical exercise in healthy individuals led to a fast and transient rise of plasma BNP concentrations, which remained well within normal range and far below the cut-off value for heart failure (100 pg/ml).

[Will the therapy of chronic heart failure be guided by plasma levels of natriuretic peptides?]. / Budeme lécit srdecní selhání podle plazmatické koncentrace natriuretických peptidu?

Natriuretic peptides, especially BNP and NT-proBNP became useful tool for both, the diagnostics and the estimation of prognosis in chronic heart failure. As the plasma levels of natriuretic peptides copy changes in clinical status, an attractive hypothesis was formed saying that BNP/NT-proBNP guided therapy could have better clinical outcomes than therapy guided by patients' clinical status (symptoms). In past few years this hypothesis was tested in several randomized controlled clinical trials (STARS-BNP, TIME-CHF, PRIMA). However, results of these trials are very controversial. There are preliminary results of clinical trial OPTIMA referred in this paper, too. This one-centre study was performed at the authors' institution. Altogether 52 patients with chronic heart failure were randomized to one of the above mentioned treatment strategies. The rate of cardiovascular events was lower in the patients in whom the treatment was guided by BNP values compared to the patients in whom the treatment was guided by their clinical status. However, the difference was not statistically significant.

Natriuretic peptides - physiology, pathophysiology and clinical use in heart failure.

The natriuretic peptides - atrial, brain and C-type - were discovered during the last twenty years. Their effects on cardiovascular, renal, cerebral and other tissues through guanylyl cyclase were uncovered. Over the past decade natriuretic peptides (NPs) became a very useful tool in the management of heart failure patients. Results of many clinical trials have shown that BNP and NT-proBNP are helpful for diagnosis of heart failure. They are also independent markers of prognosis not only in heart failure patients but also in patients with other cardiovascular diseases. Recently published data document the utility of NPs in guiding treatment of heart failure patients. In this article, we focus on basic biochemical and physiological characteristics of NPs as well as on their significance in management of heart failure patients. Some limitations and pitfalls of NPs levels interpretation in diagnosing heart failure are also discussed.

[The safety of long-term administration of losartan in current clinical practice: a non-intervention NCT-CZ 14/04/LOZ study]. / Bezpecnost dlouhodobého podávání losartanu v bezné klinické praxi: neintervencní studie NCT-CZ 14/04/LOZ.

INTRODUCTION: Losartan is the longest used angiotensin II receptor blocker in clinical practice. It is one of the first-line drugs for the treatment of hypertensive disease and there is enough data available today about its use in the treatment of the disease, including some specific situations (left ventricular hypertrophy, cerebrovascular accidents) and cases when the hypertension disease combines with another disease (e.g. diabetic nephropathy). The primary objective of the non-intervention multicentre prospective observational open clinical assessment NCT-CZ 14/04/LOZ was to verify on a large sample of patients the safety of Lozap and Lozap H in current clinical practice. MATERIAL AND METHOD: The six-month clinical study enrolled patients with recently diagnosed hypertension and/or poorly controlled hypertension [blood pressure > or = 140/90 mm Hg: 4432 patients (96%); blood pressure: < or = 139/89 mm Hg 84 patients (2%); value unspecified: 83 patients (2%)]. A standard form was used for data acquisition. A total of 4,599 patients was enrolled (of which 2,386 women, i.e. 51.9%) with mean age 61 +/- 12 years (18-95 years; median 60 years) with additional risk factors (cardiovascular diseases in 48%, diabetes mellitus in 33%, lipid metabolism disorder in 42%, obesity in 45% and smoking in 26% of cases, respectively). 2,631 patients (57%) had previously diagnosed hypertension. The average blood pressure (BP) at enrolment in the study was 159/95mm Hg (median 160/95 mm Hg), and the average heart rate was 76 strokes/min (median 76). RESULTS: The most frequently used dose was 50 mg of losartan (Lozap or Lozap H)--in 4,006 patients (87%) at enrolment in the study and in 3,982 patients (87%) at the end of the study. Adverse effects related to the treatment during the study were reported in a total of 9 patients (0.2%). The therapy was assessed as well tolerated in 96% of patients (4,409), as fairly tolerated in 3% of patients (131) and as poorly tolerated in 0.1% of patients (4). Systolic and diastolic blood pressure decreased by 23mm Hg and 14mm Hg respectively to a mean value of 136/81 mm Hg (median 135/80mm Hg) (P < 0.001 for both systolic and diastolic BP). Improvement in patient status was recorded in 93% of cases (4,254 patients) and no change was recorded in 6% of cases (294 patients). CONCLUSION: Losartan in the form of Lozap or Lozap is a safe and effective treatment of patients with hypertensive disease. It is effective and safe beginning with the dose of 50 mg and its combination with a diuretic represents a good and safe therapy in patients with insufficient BP response to a 50 mg dose of losartan alone. In case of poor blood pressure response the dose has to be titrated to 100 mg.

[Dual antiplatelet treatment]. / Duální protidesticková lécba.

Atherothrombosis is the most frequent cause ofcerebrovascular and cardiovascular incidents. In spite of indisputable progress in treatment the residual risk remains high. Further means are needed to improve the prognosis for patients. Just as in the treatment of hypertension or dyslipidemia we are presently going down the route of combined medication, which affects the thrombosis process at different stages and thus increases the final effect. The article summaries the current possibilities for dual antiplatelet treatment and its indications.

[Huge sinus of Valsalva aneurysm in patient with cystic medial necrosis of the aorta]. / Obrovské aneuryzma Valsalvova sinu u pacientky s cystickou medionekrózou aorty.

In this case we present a patient with unruptured non-coronary sinus of Valsalva aneurysm associated with diverse clinical findings, caused by acquired degenerative changes of the aortic wall. A previously healthy 36-year-old female was admitted to the neurological clinic of our hospital having suffered from an episode of unconsciousness prior to admission, with accompanying seizures. For the preceding two months she had also been suffering from dyspnoea and palpitation. Neurological examination, computed tomography of the head and electroencephalography were with normal findings. Thereafter, due to paroxysm of supraventricular tachycardia she was referred to cardiology clinic. On routine physical examination a diastolic murmur was detected and the patient was referred for transthoracic echocardiography. This examination revealed a large, unruptured noncoronary sinus of Valsalva aneurysm, which was thereafter confirmed by transoesophageal echocardiography a angiography. The patient was indicated for surgical correction with aortic valve and aortic root replacement by Bentall procedure. Histological examination of the part of resected aneurysm found cystic medial degeneration of the aortic wall, also called cystic medial necrosis.

Protracted infection of pacemaker leads with development of large vegetations: three years follow up. Case report.

A case history of a patient with permanent pacemaker reports inaccurate diagnosis of inflammation at the site of operation wound and a protracted infection of pacemaker leads. Inadequate therapy led to protracted inflammation with the leads fixed in the superior vena cava and the development of large vegetations in the right heart. Finally, the condition was resolved by surgical explantation and long-term antibiotic therapy. This case history describes infectious complications related to the implantation of a permanent pacemaker and the role of echocardiography in diagnosis of vegetations and points out the surgical treatment as a method of choice.

[Echocardiographic quantification of changes in left ventricular kinetics in patients during hospitalization for a first myocardial infarct and treated with direct angioplasty]. / Echokardiografická kvantifikace zmen kinetiky levé komory v prubehu hospitalizace u pacientu s prvním infarktem myokardu osetreným prímou angioplastikou.

UNLABELLED: The authors quantified the changes of left ventricular kinetics during hospitalization after a first transmural myocardial infarction treated by direct percutaneous coronary angioplasty. For accurate quantification a group as close as possible to experimental conditions was selected. 64 patients (43 men), mean age 67.3 years (44-86) were investigated. The echocardiographic examination was made within 24 hours after admission and on discharge (9.8 days). A 16-segment of the left ventricle was used, the kinetics were evaluated by 4-grade score. The ejection fraction was calculated by Simpson's method from 4 cycles, the wall motion score index was calculated by the standard procedure. During the follow up period significant improvement of left ventricular kinetics occurred. The ejection fraction improved from the original 46 +/- 11% (median 41.5) to 51 +/- 11% (median 50.0) (p < 0.005), the wall motion score index from 1.6 +/- 0.3 (median 1.65) improved to 1.5 +/- 0.3 (median 1.60) (p < 0.005). Improvement of the investigated parameters correlated with the clinical course, 87% of the patients being free of any complications. CONCLUSION: Successful direct angioplasty leads in patients with a first myocardial infarction to improvement of the ejection fraction and wall motion score index already during the first 10 days.

Echocardiographic evaluation of acute cardiotoxicity in the treatment of Hodgkin disease according to the German Hodgkin's Lymphoma Study Group.

Echocardiography is a sensitive method for detecting wall motion abnormalities, as well as for monitoring cardiotoxicity during treatment with anthracyclines. Using echocardiography, this study investigated possible acute cardiotoxicty associated with primary treatment of Hodgkin's disease according to German Hodgkin's Lymphoma Study Group (GHSG) clinical trial protocols for adults. A group of 88 patients (48 men) was registered in the prospective, randomized clinical trial involving the treatment of Hodgkin's disease using third and fourth generation GHSG protocols. These patients were monitored by echocardiography. The average age was 34 years (range, 18-65; median, 32). The average anthracycline dose was 174 mg/m2 (median 200 mg/m2), and the average mediastinum irradiation dose was 21 Gy (median 30 Gy). Left ventricle end-systolic diameter (ESD) and left ventricle end-diastolic diameter (EDD), as well as fractional shortening (FS) and ejection fraction (EF) (M-mode calculation) were evaluated, as was the presence of pericardial effusion and wall motion abnormalities. The examinations were conducted before and at the end of therapy (up to 2 months). Results show that all evaluated parameters changed from one follow-up examination to the other, but these changes did not reach statistical significance. ESD increased from 30 +/- 4 to 31 +/- 4 mm. EDD increased from 49 +/- 4 to 49 +/- 5 mm. Ejection fraction changed from 69 +/- 7 to 66 +/- 7% and fractional shortening was unchanged (from 38 +/- 7 to 38 +/- 7%). In seven patients (8%), we observed new wall motion abnormalities characterized by hypokinesis without decrease of left ventricular function. Significant changes in the amount of pericardial effusion were not observed. In four patients (5%), there was progression of Hodgkin's disease. In conclusion, treatment according to third and fourth generation clinical trial protocols of the GHSG leads only to minimal wall motion changes, without concomitant reduction of left ventricular function, thus not meeting the criteria, acute cardiotoxicity.

Tumour necrosis factor-alpha soluble receptors type I are related to symptoms and left ventricular function in hypertrophic cardiomyopathy.

BACKGROUND: High circulating levels of tumour necrosis factor-alpha (TNF-alpha) and its soluble receptors (sTNFRI, sTNFRII) are involved in the pathogenesis of congestive heart failure due to left ventricular (LV) systolic dysfunction. However, their role in hypertrophic cardiomyopathy (HCM) has not been elucidated. OBJECTIVES: To determine the circulating serum levels of sTNFRI in a wide spectrum of patients with HCM, and to study in detail their relationship with symptom severity and various echocardiographic disease characteristics. PATIENTS AND METHODS: sTNFRI serum levels were measured in 66 patients with HCM and 30 age-matched healthy subjects using enzyme linked immunosorbent assay for serum levels of soluble TNF-a receptor type I at rest and at 1, 3 (sTNFRI-3e) and 6 h after dobutamine stress echocardiography (DSE). RESULTS: sTNFRI-r levels were significantly higher in patients with HCM than in control subjects (2.8+/-0.8 compared with 1.4+/-0.5 ng/mL, P<0.002). In patients with HCM, there was a significant difference in sTNFRI-r levels between mildly (New York Heart Association [NYHA] functional class I and II) and severely (NYHA functional class III and IV) symptomatic patients (1.4+/-0.9 compared with 4.8+/-1.0 ng/mL, p<0.001). Higher sTNFRI-r and sTNFRI-3e levels were found in patients with an LV restrictive filling pattern during DSE compared with sustained abnormal relaxation (p<0.052, p<0.004, respectively), and in patients with reduced compared with normal increments in LV fractional shortening during DSE (p<0.02, p<0.003, respectively). CONCLUSIONS: Significant differences in sTNFRI serum levels between patients with HCM and healthy subjects were shown. In patients with HCM, sTNFRI levels were higher in severely symptomatic patients, and in patients with reduced LV systolic and diastolic reserve during DSE. These data suggest that TNF may be involved in the pathogenesis of HCM.

[Acute type B aortic dissection treated with endovascular implantation of a stent-graft]. / Akutní disekce aorty typu B lécená endovaskulární implantací stentgraftu.

Type B of the Stanford classification of dissection of the aorta is found in one third of patients with dissection of the aorta. The diagnosis of this disease is not simple. The clinical condition of these patients arouses frequently suspicion of other diseases, some diagnostic methods have a low sensitivity, other are frequently unavailable. Treatment of dissection type B may be either conservative or surgical, whereby better short-term and long-term results are recorded according to older reports by conservative methods. During recent years a new therapeutic method in type B dissection of the aorta is endovascular implantation of a stentgraft at the site of the false entry into the lumen. So far there does not exist any long-term investigation of patients with dissection of the aorta type B after stentgraft implantation. According to contemporary knowledge this new method could be used in patients with dissection of the aorta type B and reverse the hitherto adverse course of the disease. Our description of a case draws attention to the difficult diagnosis of this serious disease--dissection of the aorta--and demonstrates at the same time this new therapeutic method.

[Emergency myocardial revascularization during a developing myocardial infarct]. / Urgentní revaskularizace myokardu pri rozvíjejícím se infarktu myokardu.

In 1996-1998 in our Cardiocentre urgent revascularizations were made in 28 patients with developing acute myocardial infarction (AIM) with manifestations of different grades of acute circulatory failure up to developed cardiogenic shock and cardiac arrest. In all patients complete revascularization with a mean number of 2.9 bypasses per patient was made, in one patient at the same time a rupture of the interventricular septum was closed and in two patients an insufficient mitral valve was replaced. From the whole group two patients died during the early postoperative period, two were revised on account of postoperative haemorrhage and two had signs of low cardiac output. Twenty-two patients had a postoperative course without complications. Urgent surgical revascularization in patients developing AIM and circulatory deterioration is the method of primary and definite treatment when primary PTCA is not suitable.

[T-lymphocyte subpopulations in chronic active hepatitis]. / Subpopulace lymfocytu T u chronické aktivní hepatitidy.

In 33 patients with chronic active hepatitis quantitative changes were found in the ratio of different sub-populations of T lymphocytes in the peripheral blood stream which were either associated with treatment or with the presence of HbsAg in serum. A reduction of CD 3 positive lymphocytes was found in patients not treated by immunosuppression. In HbsAg positive patients an increase of CD 4 positive lymphocytes was found, as compared with HBsAg negative patients. Signs of activity of the hepatic process correlated with the presence of sign CD 8.

[A low-energy protein diet--its effect on lipid and protein metabolism]. / Nízkoenergetická bílkovinná dieta--vliv na metabolismus lipidu a bílkovin.

The Czechoslovak low-energy protein diet contains 1559 kj per day, incl. 33.0 g protein, 50 g carbohydrate, 4.0 g fat, 6.0 g fibre and recommended vitamin and mineral allowances. The diet was administered to 75 subjects with a mean age of 39.88 +/- 1.21 years and a body weight of 112.57 +/- 2.89 kg, and a body weight index (BMI) of 39.44 +/- 0.94, for 28 days. During treatment the body weight declined by 9.67 +/- 0.41 kg and the BMI by 3.74 +/- 0.20. At the same time there was a significant decline of the total cholesterol (p less than 0.001), LDL cholesterol (p less than 0.001), HDL cholesterol (p less than 0.01) and triacylglycerols (p less than 0.05). In 20 subjects with hyperlipidaemia similar changes of the total cholesterol and LDL cholesterol were recorded, while the decrease of HDL cholesterol (p less than 0.001) and triacylglycerols (p less than 0.001) was more marked. The nitrogen balance became during the fourth week on the diet positive (+0.64 g), there was a transitory decline of the total protein concentration. The serum amino acid concentration did not change significantly with the exception of isoleucine, the level of which increased. The serum immunoglobulin concentration did not change significantly. It may be concluded that the low-energy protein diet has a favourable impact on the lipid metabolism, without a marked negative effect on the protein metabolism.

[Treatment with autovaccines and the immunologic profile of patients]. / Lécba autovakcínami a imunologický profil nemocných.

In a group of 33 patients with chronic inflammations of the upper airways and deglutition pathways the effect of treatment with autovaccines in the form of nasal drops was investigated. In 77.7% a therapeutic success was recorded still after an interval of 1-3 years following termination of treatment. In the entire group parameters of humoral and cellular immunity were tested. In none of the patients severe forms of immunodeficiency were found. In 16 patients an immunological check-up was made after termination of autovaccine treatment. Although differences were revealed in the immunological picture, none of them attained the level of statistical significance. The action of autovaccines could be explained by the non-specific action of bacterins. Common immunological examinations methods are so far unable to define all cooperative relations between different immunocompetent cells and systems.