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Publications and source records attributed to L Elbl.
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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.
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.
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.
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.
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.
To evaluate whether polymorphisms in genes whose products are involved in lipid metabolism and fibrinolysis alter the risk of coronary artery disease (CAD), allele frequencies of four genetic polymorphisms were ascertained by PCR-based methods in 175 Czech male patients with coronary artery disease and in 222 Czech men with no symptoms of CAD. The following polymorphisms were studied: apolipoprotein B (apo B) signal peptide insertion/deletion polymorphism, 5' apolipoprotein(a) [apo(a)] TTTTA repeat polymorphism, apolipoprotein E (apo E) varepsilon2, varepsilon3, varepsilon4 polymorphism, and plasminogen activator inhibitor-1 (PAI-1) 4G/5G promoter polymorphism. Apo B and apo(a) allele frequencies differed significantly between the CAD and the control groups (P<0.01 each), with higher frequencies of apo B deletion and apo(a) shorter repeat alleles in the CAD group. We did not observe any differences in allele frequencies of either PAI-1 or apo E polymorphisms but the genotype frequencies of apo E were slightly different between the two groups (P<0.05). In addition, we observed a gene-gene interaction between the PAI-1 and apo(a) polymorphisms with respect to the risk of CAD. None of the polymorphisms studied were associated with the severity of CAD or a history of myocardial infarction. Our findings support the idea that several polymorphisms in apolipoprotein genes may by themselves and/or in interaction with other polymorphisms contribute to risk factors for CAD in men.
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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.
The objective of the work was to evaluate the suitability and safety of resistance training in patients after myocardial infarction (IM), in older patients and to assess the suitable time for including resistance exercise into the rehabilitation programme. The group comprises a total of 74 patients after IM aged 27-76 years (57 +/- 9). The group included 65 men and 9 women. The authors divided the whole group into two sub-groups by age. The first group is formed by patients under 65 years and the second one by those aged > 65 years. The authors included resistance training from the third week of the rehabilitation programme. During the resistance exercise none of the patients suffered from impaired rhythm or stenocardia. The total muscular strength during the initial tests was in the first group (< 65 years) 105 +/- 26 kg and 93 +/- 26 kg in the group of older patients. At the end of the rehabilitation programme in both groups a statistically significant increase of the total strength was recorded. In the first group it was 120 +/- 20 kg and in the older patients 108 +/- 23 kg, i.e. an increase by 14 and 16%. The mean value of the ejection fraction (EF) was at the onset of rehabilitation 58 +/- 7% and did not differ substantially in the two groups. The mean EF value at the end of rehabilitation was 59 +/- 9% in the first group and 58 +/- 10% in the second group (n.s.). The body weight expressed as the body mass index was initially significantly lower in the older patients (25.5 +/- 2.6 kg/m2 vs. 27.4 +/- 3.3 kg/m2, p < 0.01). During the rehabilitation programme in both groups a slight but statistically significant decline of body weight was recorded. In the first group (< 65 years) to 27.0 +/- 3.2 kg/m2 and in the group of older patients to 25.2 +/- 2.4 kg/m2 (p < 0.01). It can be concluded that the application of resistance exercise as a supplement of classical aerobic training is a suitable, beneficial and safe extension of the regabilitation programme. The use of resistance exercise is suitable even in older patients, it is well tolerated and is not associated with cardiovascular complications. Resistance exercise can be applied already after two weeks of the aerobic programme.
The authors evaluated using clinical and echocardiographic examination the effect of chemotherapy involving bolus administration of doxorubicin on the heart muscle in 90 patients with non-Hodgkin lymphoma and with Hodgkin lymphoma. In 18% of patients they found an asymptomatic decrease of the left ventricular ejection fraction during chemotherapy, chronic cardiotoxicity was recorded in 5% patients, in 2% of the patients one year after termination of chemotherapy a clinically latent myocardial infarction was found. The diastolic function was impaired (impaired relaxation) in 44% patients after terminated chemotherapy and in 50% after one year. Echocardiographic examination provided evidence that the impaired systolic and diastolic function persists even after one year following termination of chemotherapy. High-dose chemotherapy with administration of peripheral stem cells did not lead to marked deterioration of left ventricular function as compared with patients who did not undergo this treatment. The main clinical complications--death, cardiotoxicity, relapse of the malignant disease, cardiovascular complications--were present in the course of a 18.5-month follow up after establishment of the diagnosis in 32% of the patients.
The authors investigated by echocardiography changes of left ventricular function in 79 patients with non-Hodgkin lymphoma or Hodgkin's disease who were treated by chemotherapy containing doxorubicin. In 22% patients they diagnosed during treatment a significant gradual decline of the left ventricular ejection fraction (change > 10% or a drop of EF below 50%) after a cumulative dose of 185 +/- 52 mg/m2 doxorubicin (median 200 mg/m2). Changes of the ejection fraction were at the expense of an increasing endsystolic left ventricular volume. These changes correlated closely with the increase of endsystolic stress of the left ventricular wall (r = -0.87). After administration of a cumulative doxorubicin dose of 100 mg/m2 a significant deterioration of indicators of diastolic filling of the left ventricle occurred--of the isovolumic relaxation period (IRP) and deceleration time (DT). The contribution of these early changes of diastolic function of the left ventricle for assessment of the risk of development of systolic dysfunction is not unequivocal. Prolongation of IRP > 12% as compared with the baseline value and at the same time above 95 ms had a 50% sensitivity, 50% specificity, a 26% positive prediction value a 74% negative prediction value and 50% diagnostic accuracy, change of DT > 13%, and at the same time prolongation above 200 ms had a 47% sensitivity 55% specificity, a 22% positive prediction value, a 78% negative prediction value and a 53% diagnostic accuracy. The authors found a significant relationship between the assessed changes of left ventricular function and clinical and haemodynamic indicators. Only the patients' age correlated significantly with IRP and DT values. Changes of the left ventricular ejection fraction were not associated with clinical signs of cardiac failure, they did not call for cardiological intervention and did not affect the course of chemotherapy. Contrary to some statements in the literature, the authors did not consider the described functional changes as sufficient to justify interference with chemotherapy. On the other hand, their importance for the development of late sequelae of chemotherapy with anthracyclines in adult patients must be based on long-term prospective follow-up.
Anemia is probably the most widespread syndrome associated with a very wide spectrum of pathological conditions with a different genesis. In malignities and their treatment it is one of the very serious complications the impact of which is manifested in particular in the state of the circulation. Thus anemia can cause deterioration of primary cardiac and cardiovascular complications which develop either as a result of the malignant disease or as a result of its treatment by cardiotoxic drugs. Thus risk conditions with the functional consequence of cardiovascular impairement are potentiated. This can complicate the disease or limit therapeutic possibilities. In the submitted work the authors tried to analyze the importance of anemia from the aspect of cardiovascular pathophysiology and outline results of their own observation supported by data from the literature concerned with this problem. From the observations ensues that in the group of patients studied by the authors who had careful substitution treatment with erythrocyte concentrates there were no serious drops of Hb which could be of fundamental importance from the aspect of cardiovascular damage. For this reason the cardiovascular status can be evaluated only from the aspect of primary toxicity of oncological treatment (if we omit direct damage by the disease) and it is not necessary to consider the consequences of hematological complications which must be taken into account when HB levels are lower than 70 g/l.
Stress echocardiography is nowadays an integral part of the diagnosis of ischaemic heart disease. In the submitted review the authors draw attention to the fact that ischaemic heart disease is no longer the domain of stress echocardiography. In recent years the interest of cardiologists in this method increased also in other cardiac diseases. Based on the appropriate pathophysiological mechanism of cardiac affection stress echocardiography is used to test left ventricular function after a dynamic or pharmacological stress, i.e. increased cardiac activity and cardiac minute volume in a number of heart diseases where we must know the extent of left ventricular affection and the functional reserve of the myocardium. These tests were also introduced to evaluate the impact of valvular disease and function of artificial grafts to evaluate left ventricular function in the transplanted heart. Stress echocardiograph holds its place also in paediatrics.
Recently in various departments interest in dobutamine stress echocardiography is increasing. Originally this examination was meant for the diagnosis of suspected ischaemic heart disease in patients unable to tolerate a physical load. Clinical applications of this test are constantly expanding and comprise a number of risk patients. The purpose of the submitted paper is to discuss the safety of dobutamine stress echocardiography. The authors submit an analysis of 259 examinations of patients with suspected ischaemic heart disease (46%), after acute myocardial infection (42%) and patients with significant left ventricular dysfunction (12%). 231 examinations (89%) were made up to the defined maximum. The test was terminated prematurely in 12 patients on account of arrhythmia, in 10 because the test was positive, in two because of extracardiac effects, in three instances on account of hypotension and in one patient on account of pressure hyperreaction. Arrhythmias were recorded in 26%, discontinuous ventricular tachycardia was recorded only in two patients (0.7) with severe left ventricular dysfunction. Hypotension was found in 13%, pressure hyperreaction in 2%. Palpitations were noted in 15% of the examined patients and extracardiac side-effects in 31%. None of the side-effects called for therapeutic intervention. The authors consider dobutamine stress echocardiography a safe test which is well tolerated by the majority of patients and there is a minimum of side-effects. A higher risk must be foreseen in patients with reduced left ventricular function, hypertrophy of the left ventricle and those with an history of arrhythmias.
The cardiotoxicity of anthracycline antibiotics is a serious complication of anti-tumourous treatment. One of the possible ways how to prevent it or at least restrict it substantially is to use cardioprotective substances. The latter include ICRF-187 bispiperazinedione (dexrazoxan) which is manufactured and supplied by CHIRON Cop. under the name Cardioxane. The authors investigated by echocardiography indicators of systolic and diastolic function of the left ventricle in patients where cumulative doses of 180-240 mg/sq.m of doxorubicin were achieved. In 10 patients to whom Cardioxane was administered no changes of left ventricular function were recorded. In 18 patients treated with boluses of doxorubicin significant deterioration of left ventricular diastolic function developed. The authors provided evidence that relatively small cumulative doses of doxorubicin administered as boluses lead to impaired left ventricular diastolic function. These changes were not recorded in patients who were given the cardioprotective substance ICRF-187 (Cardioxane).
The quick reduction of differentiated myeloma cells by VAD chemotherapy (vincristine, adriamycin, dexamethasone) causes, according to the investigation by Bell et al., the acceleration of the proliferation of myeloma stem cells. In 1990 Bell demonstrated that this proliferation could be stopped by administering 500 mg of cyclophosphamide in 1-week intervals. We therefore modified the classical VAD scheme to the following "C-VAD" scheme:vincristine 0.5 mg/day in continuous infusion on the first to the 4th day, adriamycin 9 mg/m2/day in continual infusion on the 1st to the 4th day, dexamethasone 40 mg p.o. or i.v. always on 4 days starting with the 1st, 10th and 20th days, cyclophosphamide 600 mg i.v. on the 5th, 10th and 20th days). A further cycle follows on the 28th day. In the present paper the effect and the tolerance of this C-VAD scheme is evaluated: In the group of 21 patients with refractory myeloma 9 remissions were achieved, 5 partial remissions, in 6 patients the disease progressed, 1 patient died after the 2nd cycle without the possibility of evaluating the therapeutic response. The mean remission length was 10.2 months. The tolerance of chemotherapy was satisfactory, C-VAD chemotherapy did not cause any serious drop in the number of leucocytes and thrombocytes. Echocardiographically lower adriamycin cardiotoxicity was demonstrated in continual administration in comparison with the bolus administration. The C-VAD scheme is considered to be suitable for comparison with the VAD chemotherapy in a randomized study.