[Acute heart failure and early development of left ventricular dysfunction in patients with ST segment elevation acute myocardial infarction managed with primary percutaneous coronary intervention]. / Akutní srdecní selhání a casný rozvoj dysfunkce levé komory a patientu s akutním infarktem myokardu s elevacemi ST lécených primární perkutánní koronární intervencí.

BACKGROUND: Acute heart failure during ST elevation myocardial infarction (STEMI) makes worse prognosis. The aim of the work was to find independent factors with relationship to acute heart failure (AHF) and the early development of left ventricular dysfunction within the prospective followed patients with STEMI. METHODS: A total of 593 patients with STEMI treated by primary PCI (164 patients with AHF) were the study population. The activity of BNP and NT-ProBNP were measured at hospital admission and 24 h after MI onset. Left ventricular angiography was done before PCI; echocardiography was undertaken between the third and fifth day after MI. RESULTS: The patients with AHF had higher level of glycaemia, creatinine, uric acid, HDL-cholesterol, leukocytosis and natriuretic peptid. The total hospital mortality was 3.7%. 0.2% within the patients without AHF, 3.2%, 14.3%, resp. 63.6% within the patients with mild AHF, with pulmonary oedema, resp. with cardiogenic shock. The patients with AHF had lower ejection fraction (45.4 +/- 11.9% vs 53.0 +/- 10.3%). According to the multiple logistic regression we found higher glycaemia, age, heart rate, anterior wall MI, lower aortic pulse pressure and collaterals of infarct related artery as factors with independent relationship to AHF. Higher glycaemia, age, heart rate, anterior wall MI and lower aortic pulse pressure were found as independent factors with relationship to left ventricular dysfunction. According to ROC analysis possible cut off corresponding with AHF we suggested 29.5 mm Hg for LVEDP, 28.5 for dP/dt/P, 9.5 mmol/l for glycaemia, 50 mm Hg for aortic pulse pressure. CONCLUSIONS: Our results found the development of AHF in one third of patients with STEMI. AHF increases the risk of in-hospital mortality and the risk depends upon severity of failure. As the independent factors with relationship to development of AHF or left ventricular dysfunction we detected higher glycaemia, heart rate, anterior wall MI, age. Lower risk had patients with higher aortic pulse pressure.

[The influence of rehabilitation on peak oxygen consumption in patients after myocardial infarction treated with beta-blockers]. / Vliv rehabilitate na vrcholovou spotrebu kyslíku u nemocných po infarktu myokardu lécentch betablokátory.

UNLABELLED: THE PURPOSE OF THE STUDY was to verify whether rehabilitation programs improve both stress tolerance and peak oxygen consumption (pVO2) plus the consumption of oxygen at the level of anaerobe threshold (AT) in patients after myocardial infarction treated with beta-blockers. Our objective was to find out the differences in changes in the above indicators in elderly patients. THE SET of consisted of 2 groups of patients aged over 65 (56 +/- 6.1) a > or = 65 let (69 +/- 4.7). The first group contained 96 and the second group 31 patients, respectively. Prior and after the rehabilitation program, stress echocardiography (SE) and symptom-limited spiroergometric test were performed in the patients. RESULTS: A statistically significant improvement in stress tolerance and in the oxygen consumptions indicators was recorded in the group of younger patients (< 65 years of age), both at the peak and at the anaerobe threshold levels (p < 0.001). Patients aged 65 or older recorded a statistically significant improvement in stress tolerance (p < 0.01) on the one hand, but only minor, statistically insignificant improvement in pVO2 and AT oxygen consumption on the other. CONCLUSION: A two-month rehabilitation program improves both stress tolerance and the peak oxygen consumption in patients after myocardial infarction treated with beta-blockers. The improvement is statistically insignificant in elderly patients. The above finding supports our opinion that elderly patients need long-term controlled training which should be performed at regular intervals and with the necessary intensity.

[Chronic fatigue syndrome in cancer patients. Diagnostic and treatment options]. / Unavový syndrom u onkologického pacienta: moznosti diagnostiky a lécby.

Fatigue is the most frequent symptom accompanying a cancer disease and its treatment according to the visual analogue scale. Fatigue is reported by as many as 100% of patients in the course of cancer treatment and still by 40 to 70% of patients one year after the treatment has finished. This symptom has become known under the designation of "cancer-related fatigue" in the English language literature on the subject. The knowledge of the causes and mechanisms of fatigue is relatively limited. Based on practical guidelines, an algorithm has been used to detect, evaluate and influence by treatment the syndrome of fatigue caused by a cancer disease. Research in the field has been focused on both pharmacological and non-pharmacological approach. The highest efficiency in the treatment of fatigue syndrome has been recorded for the treatment of anaemia with erythropoietin, while aerobic exercise programmes have proven to be most efficient among the behavioural measures. In spite of a dramatically growing interest in the above problem in the past decade, a number of issues continue unresolved with respect to chronic fatigue syndrome related to a cancer disease or to its treatment. Based on their own experience and on the relevant literature, the authors deal with issues of chronic fatigue syndrome and the options for its diagnosing and treatment in patients undergoing cancer treatment.

[Comparison of plasmatic levels of B-natriuretic peptide with echocardiographic indicators of left ventricle function after doxorubicin therapy]. / Srovnání plazmatických hladin B-natriuretického peptidu s echokardiografickými ukazateli funkce levé komory srdecní po lécbe doxorubicinem.

THE STUDY OBJECTIVE: The aim of the study was to find out the relationship between plasmatic levels of brain natriuretic peptide (BNP) and echocardiographic indicators of left ventricle (LV) function in patients who were in a long-term remission after the therapy of hematological malignity and examined in order to diagnose the late cardiotoxicity of doxorubicin. METHODS AND PATIENT SAMPLE: We enrolled 55 patients (31 men/24 women) aged 43 +/- 16 (median 41; 21-79) who were treated for historically diagnosed malignant lymphoma. At the time of examination, all patients were in a long-term remission and, at the same time, they completed their initial therapy 6.2 +/- 1.5 (median 5; 5-10) years ago. Patients were examined via resting echocardiography before and after the therapy and during the follow-up examination. We determined the left ventricle ejection fraction (LV EF), parameters of diastolic function and the Doppler parameters of systolic and diastolic function (MPI-Tei index). During the follow-up examination, we measured plasmatic levels of BNP (standard levels were between 0 and 29 pmol/1). RESULTS: Follow-up examination showed that EF of five patients (9 %) decreased below 50% and three patients had symptoms of heart failure. Although EF of another eleven patients (20%) was in the physiological range, it decreased by more than 10% as compared with their pre-treatment EF values. Seventeen patients (30 %) showed higher MPI > 0.55 and twenty patients (36%) demonstrated diastolic dysfunction (impaired relaxation). BNP > 29 pmol/l was observed only in patients with EF < 50% and heart failure symptoms. BNP values significantly correlated only with endsystolic (r = 0.82; p < 0.0001) and enddiastolic (r = 0.72; p < 0.0001) volume of LV. On the other hand, BNP of 11.4 pmol/l showed negative predictive value for the following parameters: 80% for decrease of EF by more than 10%; 72% for detection of MPI > 0.55; and 70% for detection of relaxation disorder, i.e. the diagnostics of subclinical cardiotoxicity. CONCLUSIONS: The present study highlights the practical importance of measuring BNP levels when diagnosing the late changes of LV functions after doxorubicin chemotherapy. Standard cut-off BNP (29 pmol/1) used in diagnostics of heart failures identifies patients with pathological EF and heart failure symptoms. Cut-off BNP of 11.4 pmol/l has sufficient negative predictive value to exclude subclinical damage to the myocardium.

[Late cardiotoxicity in patients with malignant lymphoma treated with doxorubicin chemotherapy]. / Pozdní kardiotoxicita u nemocných lécených pro maligní lymfomy chemoterapií s doxorubicinem.

AIM OF THE STUDY: Chronic cardiotoxicity of doxorubicin occurs at least one year after the chemotherapy is finished. As such, it is a serious late complication in patients with malignant lymphomas. The aim of the study was to identify the incidence of late clinical and subclinical doxorubicin cardiotoxicity and cardiopulmonary performance of patients being in remission for five and more years from the initial therapy. GROUP OF PATIENTS: We worked with 96 patients (47 men and 49 women) aged 43 +/- 15 (median 41, 23-79) years. Average period of monitoring was 6.2 +/- 1.5 (median 6.5-10) years. On the basis of therapy protocol, the patients were administered a maximum doxorubicin cumulative dose (CD DOX) of 377 +/- 147 (median 300, 50-880) mg/m2. Additional treatment after initial conventional therapy was performed in 32 patients (33%) due to high risk, progression or relapse of tumour. EXAMINATION METHODS: Patients were examined by resting echocardiography before and after initial therapy, and during follow-up examination after 5 years. Also, dynamic stress echocardiography and spiroergometry were performed during follow-up examination. Left ventricle ejection fraction (LVEF) decrease below 50 %, progressive decrease of LVEF > 10 % as compared with initial value, and decreased peak oxygen intake pVO2 < 20 ml/kg/min were considered as pathological. We also evaluated systolic function and index of myocardial performance (Tei-index). RESULTS: Clinical cardiotoxicity was observed in 4 % of patients, subclinical in 31% of patients. Diastolic dysfunction was found in 38 % of patients; pathological values of Tei-index were noted in 31% of patients. Value of stress increment of LVEF was 13 +/- 4 % (median 12; 5-25). Decreased pVO2 was observed in 15 % of patients. Cardiovascular disease and age > 60 years represent a higher risk of left ventricular dysfunction. Additional treatment after initial therapy represents a higher risk only if diastolic dysfunction is found (OR = 2.37, p < 0.05). Multi-dimensional regression analysis proved the relationship between pathological EF, CD DOX > or = 300 mg/m2, age > 60 years and cardiovascular disease (for CD DOX p < 0.05; age p < 0.01; concomitant cardiovascular disease p < 0.01, with r = 0.57 and p < 0.02 values for the overall model). CONCLUSIONS: The above-mentioned findings should positively influence the approach of oncologists and haematologists to long-term cardiological monitoring (at least with the help of resting echocardiography) in adult patients treated with antracyclines during initial chemotherapy.

Evaluation of acute and early cardiotoxicity in survivors of Hodgkin's disease treated with ABVD or BEACOPP regimens.

The study was conducted to compare the presence of cardiotoxicity after the treatment of Hodgkin's disease with the standard ABVD or BEACOPP protocol. We examined 29 patients treated by means of the ABVD regimen and 34 treated with the BEACOPP regimen. Using rest echocardiography we assessed the left ventricular function before and after the therapy. One year after the completion of therapy, a control examination was performed with a battery of tests; the rest and dynamic stress echocardiography and cardiopulmonary tests were carried out to assess cardiopulmonary performance. A similar significant deterioration of ejection fraction and diastolic function was apparent after the treatment in both sub-groups with a further progression at the one-year control. Only one patient from the BEACOPP sub-group showed a pathological drop of EF <50%. The most affected parameters of left ventricular function (LV) were Doppler indices. We found a significant relationship of the parameters of LV function compared with age, the cumulative dose of doxorubicin and the cumulative dose of radiotherapy. Multivariate analysis demonstrated that diastolic dysfunction correlated with advanced age and the cumulative dose of doxorubicin, and decreased cardiopulmonary performance with advanced age, radiotherapy, and female gender. Both parameters were significantly influenced by the presence of hypertension. The used regimens demonstrated similar subclinical cardiotoxicity, thus the most aggressive regimen, BEACOPP, is not accompanied by a higher rate of cardiac impairment. The clinical value of such subclinical cardiotoxicity will be estimated in a further prospective follow-up.

[Effect of high-dose chemotherapy with subsequent transplantation of blood-forming cells on left ventricle function in patients with malignant lymphomas treated with doxorubicin in primary chemotherapy]. / Vliv vysokodávkované chemoterapie s následnou transplantací krvetvorných bunek na funkci levé komory srdecní u nemocných s maligními lymfomy lécenými doxorubicinem v primární chemoterapii.

PURPOSE OF STUDY: The authors examined whether high-dose chemotherapy with hematogenic tissue transplantation might negatively affect function of left ventricle (LV) in oncology patients with malignant lymphomas initially treated with conventional chemotherapy consisting of doxorubicin (DOX) in contrast to patients treated without the transplantation in medium-term follow up. PATIENTS AND METHODOLOGY: The follow up group included 77 patients (39 women/38 men) at the age of 36 +/- 15 (median 30, 16-67 years). All 77 patients were treated with initial chemotherapy with DOX, 22 out of that group later received high-dose chemotherapy with hematogenic tissue transplantation (HTT). 16 (73 %) patients of this subgroup underwent autologous transplantation and 5 (23 %) allogeneic transplantation. One female patient (4 %) underwent both autologous and allogeneic transplantation. The follow up period after completion of initial chemotherapy was 5-10 years (median 6 years). The patients were examined with rest echocardiography before start, after chemotherapy, and during follow-up examination. Spiroergometric test (SET) was only performed at the follow-up examination. RESULTS: Both subgroups showed significant decrease of ejection fraction (EF) after chemotherapy, with further decrease in the control examination period, without mutual difference. While the HTT (HTT+) group showed no EF drop below 50 %, in the non-HTT (HTT-) group EF dropped in two (4 %) patients after chemotherapy and in four (8%) patients at the control examination. Progressing decrease of EF > 10 % was reported with 25 % of the HTT- patients (p < 0.05), but with just 13 % of the HTT+ patients (non-significant). The diastolic insufficiency (DF) was present identically in both groups with 36 % of the patients, which represents a statistically significant increase in comparison to the pre-chemotherapy condition. SET did not show any differences in burden toleration and circulation indicators between the two groups. The drop of pVO2 < 20 ml/kg/min occurred with 22 patients of both groups. Linear regression data analysis revealed existence of a significant relationship between EF change, some diastolic function indicators, pVO2 and cumulative dose of DOX (p < 0.05). The current age significantly and negatively correlated with pVO2 (p < 0.001) and DF indicators (p < 0.001). The follow up period inversely correlates with the changes of EF (p < 0.05) and pVO2 (p < 0.05), not correlating with diastolic function indicators. Multi-variant analysis did not confirm any higher risk of administration of high-dose chemotherapy with HTT for significant drop of EF or its drop down to the pathological zone below 50 % (OR = 0.46; non-significant), for discovery of reduced cardio-pulmonary performance (pVO2 < 20 ml/kg/min) (OR = 0.35; non-significant) or for development of diastolic dysfunction (OR = 1.0; non-significant). CONCLUSIONS: Treatment with high-dose chemotherapy with HTT application within medium-term follow up does not result in any significant systolic or diastolic malfunction of myocardium and deterioration of cardiopulmonary performance in comparison to patients not undergoing this therapy. Treatment with cardiotoxic doxorubicin administered in the context of basic conventional chemotherapy is most likely to be responsible for occurrence of the pathological effects across the followed up group. Length of monitoring is a significant factor correlating with changed ejection fraction. This finding justifies the need for long-term prospective monitoring of ejection fraction of the left ventricle in adult patients treated with cardiotoxic chemotherapy.

Cardiac function and cardiopulmonary performance in patients after treatment for non-Hodgkin's lymphoma.

Authors conducted a one-year prospective study to determine whether CHOP regimen (cyclophosphamide, doxorubicin, vincristin, and prednisone), used in the treatment of aggressive non-Hodgkin s lymphoma, is associated with the presence of an early impairment of cardiac function. Forty seven patients were prospectively examined (27 male and 20 female) aged 49+/-14 years who were treated with CHOP regimen. Rest echocardiography was performed at baseline and one-year control. Cardiopulmonary exercise test was carried out at one-year control examination. The ejection fraction (EF), parameters of diastolic function, myocardial performance index (MPI), and pVO2 were used as parameters of cardiopulmonary performance. The cumulative dose (CD) of doxorubicin was 277+/-56 (300 mg/m(2)) was given. The baseline EF 64+/-5% (64%) decreased to 58+/-7% (57%) at the one-year control (p<0.0001). 23% of patients exhibited a drop in EF >10% during the follow-up. 43% revealed a pathologically increased value of MPI >0.55, and 47% impaired diastolic function compared to the baseline values, respectively. 21% of patients exhibited a decrease of pVO(2) < 20 ml/kg/min, and 17% pVO(2) < 80% of the reference value, respectively. None of the patients developed signs of heart failure. The Doppler parameters of both diastolic and global LV function were the most affected measures and significantly influenced the cardiopulmonary performance. Multivariate analysis showed that CD > or =300 mg/m(2) (OR=8.08; p<0.05) and the presence of risk factors (OR=9.48; p<0.008) are the best predictors of cardiotoxicity. The results show that subclinical cardiac impairment was frequent in patients receiving the CHOP regimen with safe cumulative doses of doxorubicin. The value of described changes for the development of heart failure has to be assessed during the prospective follow-up.

Echocardiographic evaluation of early and chronic cardiotoxicity in adult patients treated for Hodgkin's disease with ABVD regimen.

The prospective study was conducted to determine whether standard regimen ABVD used in the treatment of Hodgkin's disease is accompanied by the presence of early and chronic myocardial impairment. The study comprised 52 patients (30 male and 22 female) aged 34+/-15 years (range 18-71; median 30) with Hodgkin's disease and the control group with 40 healthy volunteers (21 male and 19 female) aged 40+/-8 years (range 20-70; median 38). The maximal administered cumulative dose (CD) of doxorubicin was 297+/-50 mg/m2 (range 150-450; median 300). Radiotherapy of the mediastinum was delivered to 27 (52%) patients with a mean dose 41+/-4 Gy (range 30-46; median 42). Echocardiography was performed at baseline and before each course of chemotherapy. The control examination was done at one month after the treatment and after one year. The stress echocardiography was performed at one-year control. Significant change of ejection fraction (EF) during the treatment was observed only in 10 (18%) patients (7 male/3 female) aged 29+/-13 years (range 18-56; median 22). The mean toxic CD of doxorubicin was 170+/-33 mg/m2 (range 100-200; median 175) and the mean time of the onset EF decline was 13.3+/-3 weeks (range 8-16; median 14). These changes were asymptomatic, and all patients completed the treatment successfully. Four patients (8%) demonstrated significant asymptomatic decline of EF after the chemotherapy. When compared the value of EF after one-year examination, a stable significant decline of EF in the sub-group with early toxicity was found. Despite a difference in the rest EF, the exercise increment of EF did not reveal any significant difference among tested groups and the contractile reserve of the left ventricle in patients was not impaired. The present data shows that the treatment of Hodgkin's disease with the standard ABVD regimen is accompanied with mild early and chronic asymptomatic changes of the left ventricular function. These changes were not reversible during one-year follow-up.

The evaluation of left ventricular function in childhood cancer survivors by pharmacological stress echocardiography.

Late cardiotoxicity after anthracycline chemotherapy for childhood cancer is well recognized sequelae. Many long-term survivors may have subclinical cardiac dysfunction undetectable at a baseline evaluation. Various tests have been utilized for the diagnosis of left ventricular impairment. Recently, low-dose dobutamine stress echocardiography has been proposed as a more sensitive screening test. We have applied low-dose dobutamine stress echocardiography (5-10 microg/kg/min) in 36 asymptomatic survivors (20 male/16 female aged 14.6+/-4.7 years) treated with a cumulative dose of 226+/-106 mg/m2 of doxorubicin. The median follow-up was 5 years. Control group consisted of 20 sex and age matched volunteers (12 male/8 female aged 12.6+/-4.9 years). We found significant differences in mean velocity of circumferential fibre shortening, myocardial performance index (Tei index), left ventricular posterior wall thickening and endsystolic wall stress at a baseline. The stress response was significantly blunted only in a patient group in the following parameters: endsystolic wall stress, isovolumic relaxation time and myocardial performance index. The threshold response was abnormal (0-5% improvement of a variable only) in 45% of subjects from a control group in one or two parameters. On the contrary, 63% of subjects from a patient group responded pathologically (the worsening of a variable) in one or more parameters. We have not found a good correlation between risk factors of late cardiotoxicity and stress changes of left ventricular function parameters. Low-dose dobutamine stress echocardiography is safe and feasible diagnostic tool in children and adolescents. Dobutamine significantly increases the differences in cardiac variables between healthy population and asymptomatic survivors for childhood cancer. In comparison to the controls, most asymptomatic patients revealed subclinical myocardial damage at test. The predictive value for the development of clinical symptoms and cardiac complications need to be assessed in a large prospective study.

[Dynamic stress echocardiography in asymptomatic patients treated for malignant diseases in childhood]. / Dynamická zátezová echokardiografie u asymptomatických pacientu lécených v detství pro maligní onemocnení.

INTRODUCTION: The authors used echocardiography at rest and dynamic stress echocardiography to assess left ventricular function in asymptomatic patients treated during childhood or adolescence by chemotherapy containing anthracyclines. MATERIAL AND METHODS: 137 patients were examined (81 men, 56 women) aged 16.6 +/- 4.8 years (median 17 years) where at the age of 9.1 +/- 4.8 years (median 9 years) malignant disease was detected and treatment with a cumulative dose of anthracyclines 242 +/- 110 mg/m2 (median 240 mg/m2) was administered. The control group was formed by 30 subjects (14 men, 16 women) aged 19.5 +/- 5.2 years (median 20 years). The echocardiographic examination was made at rest and immediately after a dynamic stress on an ergometer with a load of 25 W/2 mins. RESULTS: In 8% patients (n = 11) a reduction of the fractional shortening (FS) LV < 30% was found. The values of the ejection fraction (EF), the median shortening of the circumferential fibre and endosystolic wall stress, excursion and thickening of the posterior wall of the LV were significantly worse as compared with the group with fractional shortening > or = 30% and the control group. The maximum drop of EF was to 40% and of FS to 20%. The values of the index of the global LV function (according to Teie) were as compared with the control group worse in both sub-groups of patients. No differences were found in the exercise tolerance between groups. Values of the ejection fraction at rest and after a exercise were in the sub-group with FS < 30% significantly lower as compared with the others. The values of the stress increment of EF were elevated in all sub-groups. In none of the subjects the load caused a decline of the EF. CONCLUSIONS: Chemotherapy with anthracyclines leads to a late disorder of several indicators of left ventricular function. Asymptomatic patients with a drop of the EF value to 40% or FS to 20% preserve their load tolerance and contraction reserve of the left ventricle. The finding of a preserved contraction reserve and good exercise tolerance implies a more favourable prognosis of the patient. Echocardiography at rest should be made repeatedly after treatment, in case of a pathological finding a loading test must be indicated to evaluate the contraction reserve and its possible development.

[Disorders of the cardiovascular system during treatment of oncologic diseases]. / Poskození kardiovaskulárního aparátu pri lécbe onkologických onemocnení.

The author presents a review of cardiovascular complications of anti-tumourous treatment. Cardiovascular toxicity is an interdisciplinary problem which can lead to serious complications of oncological treatment and considerably reduce its benefit for the patient. Cytostatics can produce a number of undesirable side-effects such as arrhythmias, angina pectoris, acute myocardial infarction, sudden death, cardiac failure. The most serious cardiotoxicity is probably chronic cardiac failure after anthracycline treatment. Interest in the diagnosis, monitoring and treatment of cardiotoxicity was aroused by new findings of cardiac complications after some cytostatics, high dosage chemotherapy and transplantation of haematopoietic cells.

[Diagnostic possibilities of late cardiotoxic sequelae of chemotherapy with anthracyclines]. / Diagnostické moznosti pozdních následku kardiotoxické chemoterapie antracykliny.

Anthracyclines areamong the most frequently used cytostatics in the treatment of haematological malignities and some solid tumours in childhood and adult age. They affect cellular proliferation in several ways. One of them is the formation of semiquinone radicals which form with oxygen toxic peroxides which damage the myocyte and lead to cardiotoxicity. Cardiotoxicity of anthracyclines has become a clinical problem as it restricts the administered dose of the cytostatic and has become particularly urgent after discovery of the late toxicity which appears some years after termination of anti-tumourous treatment. Damage of the left ventricle is usually characterized by partial reversible contractile dysfunction (early damage) or progressing contractile dysfunction (late damage). The diagnosis of cardiotoxicity is important during the period of treatment but in particular after completed chemotherapy. The application of diagnostic methods before and in the course of chemotherapy is indicated when large doses of anthracyclines will be administered or when in the patient risk factors cumulate or if he developed signs of cardiotoxicity. The use of diagnostic methods after termination of treatment is valuable for early detection of late cardiotoxicity for timing of further diagnostic methods currently used in cardiology. In the routine diagnosis the authors prefer follow up of the left ventricle by assessment of the ejection fraction by echocardiography or by radionuclide examination. In paediatrics we follow up indicators of systolic left ventricular function in relation to changes of the after load. The authors present also a review of other diagnostic methods and procedures which may prove useful in the diagnosis of cardiotoxicity of anthracyclines.

Methylenetetrahydrofolate reductase polymorphism, type II diabetes mellitus, coronary artery disease, and essential hypertension in the Czech population.

Increased plasma concentrations of homocysteine have been found in patients with coronary artery disease (CAD) and essential hypertension (EH) and in patients with diabetic complications. The 677C/T methylenetetrahydrofolate reductase (MTHFR) gene polymorphism is related to the MTHFR enzyme activity and to the plasma homocysteine concentration. This study was designed to investigate an association of this polymorphism with CAD, EH, and type II diabetes mellitus in the Czech population. The MTHFR genotypes were assessed by the polymerase chain reaction-based methodology in a sample of 1199 unrelated Caucasian subjects with CAD, EH, type II diabetes, or a combination of these diseases, and in healthy subjects. Allele frequencies of the MTHFR polymorphism differed considerably between women with and without type II diabetes mellitus (P = 0.00069), with a higher frequency of the C allele in the diabetic women. In addition, the MTHFR T allele frequency was significantly higher in normotensive subjects with CAD compared with normotensive subjects without this disease (P = 0.020). Both associations were confirmed by multiple logistic regressions. In conclusion, while the C allele of the 677C/T MTHFR polymorphism is associated with type II diabetes mellitus in women, the T allele is associated with CAD only in normotensive subjects of Czech origin.

The C766T low-density lipoprotein receptor related protein polymorphism and coronary artery disease, plasma lipoproteins, and longevity in the Czech population.

Low-density lipoprotein receptor related protein (LRP) is a multifunctional endocytic receptor involved in various biological processes including the regulation of the coagulation-fibrinolysis balance, the lipoprotein metabolism, and cellular migration, all of which relate to the development of atherosclerosis. Polymorphisms affecting the function or expression of LRP may thus influence the individual risk of atherosclerosis development. This study investigated the association between the C766T LRP polymorphism, coronary artery disease (CAD), and plasma lipoprotein levels in a large sample of Caucasian subjects of Czech nationality. In addition, the 4G/5G promoter polymorphism of the gene coding for plasminogen activator inhibitor 1 (PAI-1), the known ligand of LRP with strong antifibrinolytic potential, was ascertained to investigate its possible association with CAD. Both polymorphisms were studied using polymerase chain reaction analysis in 654 patients with angiographically confirmed CAD and in 525 controls. No statistically significant differences in allele frequencies of the polymorphisms studied were detected between patients and controls, even when men, women, hypertonic, and type II diabetic subjects were compared separately. However, the frequency of the T allele of the LRP polymorphism was significantly higher in patients than controls when only subjects with the 5G/5G PAI-1 genotype were analyzed. In addition, the T LRP allele frequency was significantly lower in subjects aged 60 years or over than in those who were younger in both groups. No significant association was observed between the LRP or PAI-1 polymorphisms and plasma lipoprotein levels in the CAD patients. Our results demonstrate that the T allele of the C766T LRP polymorphism is negatively related to longevity, and that it increases the risk of CAD development in subjects with the 5G/5G PAI-1 genotype.

[Cardiotoxicity of antineoplastic therapy]. / Kardiotoxicita protinádorové lécby.

Cardiotoxicity is a serious complication of anti-tumorous treatment. Cytostatics can cause a number of undesirable side-effects such as arrhythmias, angina pectoris, acute myocardial infarction, sudden death, cardiac failure. The probably most serious cardiotoxicity is chronic cardiac failure after treatment with anthracyclines. Interest in the diagnosis, monitoring and treatment of cardiotoxicity revealed new findings of cardiac complications after various cytostatics, high-dosage chemotherapy and transplantation of haematopoietic cells. Prospective paediatric studies provided evidence of the serious character of late cardiotoxicity of anthracyclines. The authors review the most frequent cardiac complications of anti-tumorous treatment. They emphasize in particular the toxicity of anthracyclines and its possible prevention.