[The risk of cardiovascular diseases induced by radiotherapy]. / Riziko vzniku kardiovaskulárnych ochorení v súvislosti s rádioterapiou.

At present the number of cancer survivors is still increasing. However, their long-term quality of life after anticancer treatment can be decreased. Radiotherapy may represent a risk for the future of some oncologic patients. The late cardiovascular effects of radiotherapy to the area of thorax, cranium and to the abdominal area are the actual multidisciplinary problem. The unique problem is mediastinal radiotherapy which may induce the development of the cardiomyopathy, constrictive pericarditis, coronary artery disease, myocardial infarction, valvular defects, arrhythmias and other complications. Exact knowledge of pathophysiological mechanisms of radiation induced cardiovascular damage after radiotherapy as well as using of new diagnostic cardiologic methods might be useful for the detection of subclinical abnormalities and their early treatment already in the asymptomatic patients.

High resolution electrocardiography in healthy dogs: time domain parameters and comparison of the non-stationary (Wigner distribution) versus standard stationary frequency domain analysis methods.

Fractionated heart activation can be detected as late potentials from surface recordings of signal-averaged electrocardiograms (SA ECG) which are considered as a marker of sustained ventricular tachycardia. For animal studies, reference values in time and frequency domain analyses are essentially missing. In the present study, we have established reference values in SA ECG time domain analysis and time-frequency representation of heart activation in healthy dogs. A group of 25 healthy mongrel dogs (body weight 12-15 kg) was investigated. Wigner distribution and our modification of Fast Fourier transform (FFT), gliding window FFT, was applied in SA ECG frequency domain analysis. Reference values in time domain SA ECG were established. Time and voltage criteria were adapted to short duration of heart cycle and fast voltage decrement of the QRS complex in dogs. Wigner distribution and gliding window FFT were applied in order to describe mean heart activation in the frequency domain. Contribution of higher frequencies (30-80 Hz) was detected by both frequency analysis methods in the second third of ventricular activation in healthy animals. Presented results could offer a basis for further experimental arrhythmologic studies.

Signal-averaged electrocardiography in survivors of Hodgkin's disease treated with and without dexrazoxane.

Doxorubicin is one of the most effective anticancer drug, but its usefulness is limited by the risk of developing cardiomyopathy, cardiac dysfunction and ventricular arrhythmias. Dexrazoxane is used to protect against doxorubicin cardiotoxicity. It is uncertain whether the dexrazoxane-mediated cardioprotective effect will be reflected in electrophysiological properties of the heart. The aim of the present study was to evaluate the occurrence of frequency-domain signal-averaged electrocardiographic (SAECG) abnormalities of the QRS complex and the initial ST segment in patients treated with and without dexrazoxane. Thirty children and young adults 2 months - 15 years after completion of doxorubicin-containing therapy for Hodgkin's disease were evaluated with SAECG. Patients from group I (n = 13) received combined therapy with doxorubicin and dexrazoxane (DOX/DZX), patients from group II (n = 17) received doxorubicin without dexrazoxane (DOX). Using fast Fourier transformation within the QRS complex and the initial ST segment, area ratio (AR) values 40-100/0-40 Hz were calculated. Significant differences in these frequency parameters in the QRS complex between DOX/DZX group and DOX group (19.45+/-12.72 vs 46.18+/-43.06; p = 0.03) might indicate protective effect of dexrazoxane on electrophysiological myocardial properties.

Frequency-domain analysis of the QRS complex after treatment of childhood cancer with anthracycline cytostatics.

Long-term cardiac complications, occurring several years after completion of anticancer treatment, may develop from subclinical myocardial damage induced during cardiotoxic therapy. The aim of this study was to evaluate the usefulness of frequency-domain signal-averaged ECG analysis of the QRS complex for assessing the cardiotoxicity of anthracycline cytostatics. Altogether, 172 signal-averaged electrocardiography (SAECG) registrations were performed in 50 repeatedly evaluated oncologic patients. These registrations were performed 0.2-15 years after completion of anthracycline therapy for childhood cancer. The control group consisted of 120 healthy children and young volunteers; in 20 of these controls, SAECGs were performed repeatedly. Using gliding window fast Fourier transformation within the QRS complex, values area ratio (AR) 60-120 Hz/0-120 Hz were calculated in X, Y, and Z lead. Area ratio of patients after anthracycline therapy was significantly higher than those in control group in X lead. Differences in frequency content in the QRS complex between patients and controls might signal an initial stage of anthracycline-induced myocardial damage.

[Frequency analysis of the QRS complex: a new method of detecting development of myocardial damage after anthracycline cytostatics]. / Frekvencná analýza komplexu QRS: nový spôsob detekcie vývoja poskodenia myokardu po antracyklínových cytostatikách.

The aim of the study was to investigate the effect of the new modification of frequency-domain analysis of ECG signal (gliding-window FFT) in long-term monitoring of cardiac status of patients who received a potentially cardiotoxic anthracycline therapy in childhood. Area ratio (60-120/0-120 Hz) peaks within QRS complex were significantly higher in 60 patients compared with 70 healthy children and young adults. Persistent abnormalities in frequency content of ECG signal in oncologic patients might indicate myocardial damage induced by anthracyclines. (Fig. 1, Ref. 17.)

Late effects of anthracycline therapy in childhood on signal-averaged ECG parameters.

The aim of this study was to investigate the long-term effects of anthracycline cytostatics upon the frequency-domain characteristics of the signal-averaged electrocardiogram (SAECG) and to evaluate the differences in the frequency content according to gender. At mean follow-up period of 4 years 188 SAECGs were repeatedly performed in 62 childhood cancer survivors, who were in complete remission 1-14 years following anthracycline therapy (mean dose 256 mg/m2). No patient had an abnormal end-of-therapy echocardiogram. The control group consisted of 100 healthy children and young adults. 23% patients vs 5% controls had abnormal area ratio (AR) values (over the 97th percentil of normal controls). Abnormalities in AR remained persistent in 15% of cancer survivors. Frequency-domain analysis revealed significantly higher AR 40-100/0-40 Hz in patients after anthracycline therapy than in controls. Within the patient group significantly higher AR were observed in females than in males. Permanent altered frequency components in SAECGs from cancer survivors, evident particularly in female patients, might signal an increased electrical instability in these patients.

Signal-averaged ECG in patients after anthracycline therapy for childhood cancer.

Late cardiac complications after anthracycline therapy is an increasingly common problem among survivors of childhood cancer. Routine clinical examination may be normal, but subclinical cardiac abnormalities, which may progress with time, are documented in high percentage of these patients. Microstructural myocardial alterations may result in production of micropotential level signals (late potentials, LP) and altered frequency components of signal-averaged ECGs (SAECG). SAECG abnormalities are valuable in risk stratification of patients with various heart diseases culminating in fatal arrhythmias or heart failure. Forty-five pediatric oncologic patients (mean age 14.4 +/- 4.1 years) were included in the study. SAECG was performed 3 months-12 years (median 5.5 years) following completion of anthracycline therapy. The total cumulative doses of anthracyclines were 90-555 (median 230) mg/m2. The control group consisted of 30 healthy age-matched volunteers. LP were present in six (13.3%) patients after anthracycline therapy at 40 Hz high-pass filter setting. Using frequency-domain analysis within the QRS complex, area ratio 1 (area of 20 to 50 Hz/area of 0 to 20 Hz) and area ratio 2 (area of 40 to 100 Hz/area of 0 to 40 Hz) were calculated. Twenty (44.4%) and fourteen (31.1%) had abnormal values in area ratios 1 and 2, respectively, within the QRS complex. Area ratios 1 and 2 of patients after anthracycline therapy were significantly higher than those in control group (p = 0.0187 and p = 0.0043). Our preliminary results suggest that chemotherapy with anthracyclines, even in low dosage, is associated with increased incidence of SAECG abnormalities. The potential of this simple, noninvasive method to detect subclinical anthracycline-induced myocardial alterations and facilitate prognostic stratification of cancer survivors is promising, however, the clinical value of SAECG remains to be established in a larger and a longer study.

[High-resolution electrocardiography in monitoring myocardial damage after therapy with anthracyclines in children]. / Vysokorozlisovacia elektrokardiografia v programe sledovania poskodenia myokardu po antracyklínovej liecbe u detí.

BACKGROUND: Anthracycline cytostatics, widely used in oncologic practice, may induce discrete myocardial damage occasionally culminating in life-threatening cardiologic complications. The most serious clinical manifestations of anthracycline cardiotoxicity are dilated cardiomyopathy, heart failure and fatal arrhythmias. OBJECTIVES, STARTING POINT AND MAIN PURPOSE: High-resolution electrocardiography (HRECG) is one of the latest cardiologic methods, which can be promising for early identification of patients at risk of anthracycline cardiotoxicity. The aim of this study is the evaluation of the incidence of HRECG abnormalities in a group of paediatric patients treated with anthracyclines and the usefulness of HRECG for stratification of patients at risk of the clinical cardiotoxicity. PATIENTS AND METHODS: A set of 60 oncologic paediatric patients treated with anthracyclines was divided into two groups. The first group was formed by 15 patients undergoing evaluation during their anthracycline therapy (median after the last administration of antracyclines was 3.2 days). Their average age at the time of examination was 14.7 +/- 4.1 years. The total cumulative dose of antracyclines was 40-300 mg/m2 (median 150 mg/m2). The second group was formed by 45 patients who were evaluated after completing anthracycline therapy. The interval of time from the last administration of antracycline in this subgroup of patients was 3 months-12 years (median 5.5 years). Their average age at the time of HRECG examination was 14 +/- 4.1 years. The total cumulative dose of anthracyclines was 90-440 mg/m2 (median 230 mg/m2). Six patients of this group (13.3%) were treated also with mediastinal radiotherapy (18-40 Gy). 43 patients (95.5%) of second group were in complete remission, two other patients yielded a progression of their malignancy. 10 patients (22%) were examined by HRECG 2-5 times in app. two-month intervals. The control group was formed by 30 randomly selected healthy children and adolescents with normal ECG. Average age was 15.1 +/- 5.8 years. Using HRECG the time- and frequency-domain characteristics of the ECG signal were analyzed. The time-domain analysis was performed at 40-250 Hz filter. The frequency-domain analysis was performed by fast Fourier transformation (FFT), a 120 ms segment starting 20 ms before the end of the QRS complex was analyzed. The altered frequency content was expressed as the ratio of frequency areas (area ratio, AR) 20-50 Hz/0-20Hz. The average level of noise was 0.56 microV in the first group, 0.62 microV in the second group of patients and 0.68 microV in the control group. RESULTS: Abnormalities in the time-domain analysis (ventricular late potentials, VLP) were present in 2 (13.3%) of 15 patients during the anthracycline therapy in the first group and in 4 (8.8%) of 45 patients after completing therapy in the second group. No abnormalities in the time-domain analysis were detected in the control group. Using frequency-domain analysis, abnormalities in AR20-50 Hz/0-20 Hz were found in 8 (53.3%) of 15 patients of the first group, and in 11 (24.4%) of 45 patients of the second group. Significant differences were observed in the frequency parameters of the ECG signal in patients of the first group in comparison to the control group (p = 0.0018) and also when comparing the patients of the second group and the control group (p = 0.045). CONCLUSION: The HRECG results in time- and frequency-domain analyses indicate to high incidence of HRECG abnormalities in patients examined both during and after the antracycline therapy in comparison to the control group. The prognostic use of the HRECG abnormalities must be established in a larger and longer study. (Fig. 4, Tab. 2, Ref. 43.)

Signal-averaged ECG in patients with antidepressant therapy.

The signal-averaged electrocardiography (SAECG) identifies patients at risk of ventricular arrhythmias and sudden cardiac death. Since the similarity has been known of the pharmacology of class I antiarrhythmics and tricyclic antidepressants, the potential proarrhythmic effects of antidepressants has become a particular problem. The influence of sodium channel blocking antidepressant drugs on the SAECG time-domain parameters was evaluated, using high-pass filters of 25 Hz and 40 Hz. SAECG was performed in 11 depressed patients with normal cardiac status before and for 4 weeks after antidepressant initiation. At the filter setting of 25 Hz, a significant worsening of all studied SAECG parameters (filtered QRS duration, low-amplitude signal duration, root mean square voltage in the first and in the last 40 ms of the filtered QRS) was found in our patient group. Using a 40 Hz high-pass filter, the results were similar. Antidepressant therapy significantly prolonged filtered QRS duration, significantly reduced root mean square voltages in the first and in the last 40 ms of the filtered QRS and non-significantly prolonged low amplitude signal duration. Amitriptyline and maprotiline induced late potentials (LP) in 2 patients at 40 Hz high pass filter setting. No patient had LP at 25-250 Hz. Our pilot study indicates that sodium channel blocking antidepressant drugs may affect SAECG variables similarly to class I antiarrhythmics. SAECG might be useful in categorizing of antidepressant agents and risk stratification of psychiatric patients.

[Pathogenesis, prevention and detection of cardiotoxicity of anthracycline cytostatic agents]. / Patogenéza, prevencia a detekcia kardiotoxicity antracyklínových cytostatík.

BACKGROUND: Anthracycline antibiotics represent a part of therapeutic schemes in the treatment of a wide spectrum of malignancies. Precisely due to their cytostatic effectiveness they are being applied in spite of the risk of cardiac damage of patients. Anthracycline cardiotoxicity may culminate in potentially irreversible heart failure and fatal arrhythmias. Consequences of cardiotoxicity can complicate and shorten the lives of patients with formerly favourable prognosis of the malignant disease, and even of those that have been cured. OBJECTIVES: The aim of the presented study was to provide a review on current opinions concerning the pathophysiological mechanisms of cardiotoxicity due to anthracycline antibiotics, as well as the possibilities of cardiotoxicity prevention and detection. The procedure of cardiac monitoring of anthracycline effects is performed in order to detect the initial stage of myocardial impairment which is on the level of microstructural alterations. This requirement is mostly fulfilled by the invasive method of endomyocardial biopsy. Also the noninvasive method of high-resolution electrocardiography may reflect anatomic-electrophysiological abnormalities on the level of cardiomyocytes and interstitium. We decided to verify the usefulness of this method in the sense of the ability to detect the risk of the cardiotoxicity origin following anthracycline application. METHODS: We have repeatedly observed 34 hospitalized patients with cancer before or during chemotherapy. On the basis of high-resolution electrocardiography we have analysed the ECG signal in regard to time, frequency and time-frequency relation. RESULTS: In this study we present our initial experience with this method in combination with electrocardiographic and echocardiographic findings. In regard to the fact that the observations were of short term character we interpret our results of high-resolution electrocardiography as being preliminary. We report 4 illustrative cases of patients who independent of the dosage, yielded distinct responses toward the applied potentially cardiotoxic therapy. CONCLUSIONS: We consider the high-resolution electrocardiography in regard to its noninvasive character and low demand of time and finance to represent a perspective method of cardiac monitoring of the negative anthracycline effect. Not only ours but also the first experience in the world confirm this presupposition. By means of this method we have been able to detect initial alterations due to already low cumulative doses of anthracyclines (120 mg/m2 in a patient with ischemic heart disease and 260 mg/m2 in a patient with unimpaired myocardium prior to treatment). Our results also confirm the fact that the problem of cardiotoxicity must be necessarily strictly individualized. (Fig. 19, Ref. 80.)

The antihypertensive treatment and high-resolution electrocardiography.

After six months of antihypertensive treatment the regression of the initially present myocardial hypertrophy was observed: The decrease in blood pressure values is in correlation with the regression of the left ventricular hypertrophy. No correlation with parameters of high-resolution electrocardiography was noted. In one patient, a deterioration of late potentials was observed. It became more pronounced following the treatment. The monitoring of antihypertensive treatment effects by echocardiography and high-resolution electrocardiography may be therefore considered useful, especially in expected regression of the left ventricular hypertrophy. In individual cases of very outstanding regression, there exists the potential possibility of the process, resulting in the risk of arrhythmogenic substrate formation and subsequent generation of dysrhythmias.

Gliding window fast Fourier transform analysis--a new method for discovering the contribution of higher frequencies in signal-averaged ECG.

OBJECTIVE: An attempt to detect the 'parasitic contribution' of high frequencies in the electrocardiogram signal. DESIGN: A new method--gliding window fast Fourier transform analysis (GWFFTA)--was developed. It was applied in healthy subjects and in patients with acute myocardial infarction. SETTING: Faculty of Medicine and University Hospital. PATIENTS: The GWFFTA was used in 29 healthy volunteers and in a group of 30 patients with myocardial infarction, on day 7 to 14 after admission to a coronary unit. INTERVENTION: Noninvasive examination, performed under standard conditions. MAIN RESULTS: GWFFTA provides better reproducible results compared with 'classic' fast Fourier transform analysis. The parasitic contribution of high frequencies within QRS complex and ST segment in patients with acute myocardial infarction is independent of presence or absence of late potentials. Contribution of high frequencies are three times higher in patients with acute myocardial infarction than in healthy probands. CONCLUSIONS: GWFFTA is a reproducible method of detection of high frequencies during whole heart activation. Contribution of high frequencies in patients with acute myocardial infarction reflects the state of the entire myocardium. It is also confirmed by the lack of correlation with the presence or absence of late potentials. Late potentials are more reflective of focal changes.

Does the heart electric activation split upon the infarcted area? An attempt at its detection by high-resolution electrocardiography.

Based on the presumption of the activation front splitting, the authors present their own proposal for the estimation of the myocardial electric activation course and for the detection of micropotentials 'hidden' within QRS complexes by the method of high-resolution electrocardiography. After filtration of QRS complex the values of delta RMS and those of cumulative amplitudes are calculated from the initial and from the terminal parts of QRS complexes. The presence of late potentials is reflected in a slowing down of the termination of activation course. As compared with healthy subjects, a slower rise of activation was observed in patients with myocardial infarction of the anterior wall. The curves of cumulative amplitudes rose very slowly during the first 70 ms of heart ventricle activation, explained according to the hypothesis of authors as being due to splitting of the activation front at the infarction focus. The usefulness of the proposed method was checked in patients with arterial hypertension and left ventricular hypertrophy, and in a group of patients with myocardial infarction. By the construction of cumulative amplitude curves from the onset of filtered QRS complexes, myocardial foci not reflected by 'classic' late potentials can be detected. The partial cumulative amplitudes of the QRS complex are suitable for comparative studies.