Monitoring of the very early changes of left ventricular diastolic function in patients with acute leukemia treated with anthracyclines.

AIM: To analyze the very early changes of diastolic LV function during and after chemotherapy (CT) in patients with newly diagnosed acute leukemia. METHODS: 26 patients with acute leukemia have been studied. The cardiac echo evaluation was performed at the baseline (before CT), after the first CT (mean cumulative anthracyclines dose 136.3-/+28.3 mg m(-2)), after the last CT (mean cumulative anthracyclines dose 464.3-/+117.5 mg m(-2)) and circa 6 months after the completion of CT. RESULTS: We found a significant decrease in LVEF (65.3-/+4.5' vs 60.2-/+5.7', p<0.01), the fractional shortening of the LV (34.8-/+3.7', vs 29.5-/+5.0', p<0.01), but the mitral flow rapid filling velocity (E-wave) was not changed (0.74-/+0.18 ms(-1), vs 0.67-/+0.17 ms(-1), p ns), and atrial filling velocity (A-wave) increased (0.66-/+0.15 ms(-1) vs 0.78-/+0.18 ms(-1), p<0.01). E/A ratio significantly decreased (1.18-/+0.35 vs 0.89-/+0.27, p<0.01). IVRT increased (71.5-/+11.6 ms vs 84.0-/+11.6 ms, p<0.01). DT E-wave velocity increased (162.3-/+25.8 ms vs 206.7-/+25.5 ms, p<0.01). After the first CT, the signs of LV diastolic dysfunction were detected in 5 (19.2') patients. 6 months after the last CT, two of these patients (7.7') developed LV systolic dysfunction with the clinical symptoms of heart failure. Six months after the last CT, 12 (46.2') patients developed the signs of LV diastolic dysfunction. CONCLUSION: Chemotherapy can induce early changes of diastolic left ventricular function. We consider using Doppler echocardiography as the election tool not only for baseline cardiologic screening but also for the monitoring of the earliest subclinical signs of cardiotoxicity.

The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia.

Cardiotoxicity is a serious and relatively frequent complication of anti-tumorous treatment. Anthracyclines represent the greatest risk. Biochemical markers of structural and functional myocardial damage have been gaining ground in cardiotoxicity monitoring. The aim of the study was to monitor cardiotoxicity of induction chemotherapy in acute myeloid leukemia (AML) patients and to assess the potential for use of biochemical markers in early diagnostics of cardiotoxicity. Fifteen consecutive adult patients with a newly diagnosed AML were studied. All patients received induction chemotherapy containing Idarubicin (IDA) 3 x 12 mg/m2 and intermediate doses of Cytarabine (8 x 1.5 g/m2). Serial measurements of plasma N-terminal pro brain natriuretic peptide (NT-proBNP) values were performed at the baseline, the day following each IDA infusion, after 14 days and after circa 1 month, i.e. before the next chemotherapy. Cardio-specific markers (cTnT, CK-MB mass) were measured at the baseline and after the last IDA infusion. The mean baseline value of NT-proBNP in newly diagnosed AML patients was 129.7+/-59.6 pg/ml. The mean NT-proBNP value increased after the first IDA infusion to 307.3+/-171.4 pg/ml (p=0.02). In most of the patients, the second and the third IDA infusions were not associated with a further increase in the NT-proBNP value and levels after 2 and 4 weeks were not significantly different from the baseline. However, in one of the patients the NT-proBNP values were increasing after each IDA infusion (after the last one 786.2 pg/ml) and within 14 days he developed congestive heart failure due to left ventricular diastolic dysfunction as assessed by echocardiography. At that time, the NT-proBNP value was 1,184.0 pg/ml; after diuretics it decreased significantly. In all patients, plasma cTnT and CK-MB mass concentrations were within the reference interval at the baseline and after the induction chemotherapy. Our results suggest that induction chemotherapy in AML (IDA 36 mg/m2 and intermediate doses of Cytarabine): 1. does not cause detectable damage of the myocyte structure, 2. is in all patients associated with acute neurohumoral activation (transient elevation of NT-proBNP) indicating acute subclinical cardiotoxicity, 3. may lead to congestive heart failure and NT-proBNP seems to be a promising early marker and predictor of this complication.

[Late ventricular potentials--relation to the results of programmed ventricular stimulation, the incidence of ventricular ectopic arrhythmias and left ventricular function]. / Pozdní komorové potenciály--vztah k výsledku programované stimulace srdecních komor, k výskytu komorových ektopických arytmií a k funkci levé komory.

The authors evaluated the incidence of late ventricular potentials (LVP) in 84 patients (63 men and 21 women) with programmed stimulation of the ventricles. At the same time they described the relationship of the mentioned potentials to the finding of ventricular ectopic arrhythmias during ECG monitoring and left ventricular function (ultrasonographic examination). Non-invasive recording of late ventricular potentials is due to the assessed sensitivity, i.e. 73%, and specificity i.e. 67% (in relation to the results of programmed ventricular stimulation) a useful method for evaluation of the arrhythmogenic substrate of the heart muscle. The authors detected LVP in 35% of 37 subjects without arrhythmias, in 58% of 31 subjects with premature ventricular contractions class 3 to 5 according to Lown and in 60% of 15 subjects with relapsing ventricular tachycardias. LVP are more frequent in patients with impaired left ventricular function. They were recorded during the ejection fraction of the left ventricle beneath 50% in 69% of 16 subjects and in the left ventricular ejection fraction above 50% in 44% of 68 subjects.

[Programmed ventricular stimulation in the evaluation of the clinical significance of premature ventricular contractions]. / Prínos programované stimulace komor k posouzení klinické významnosti komorových predcasných stahu.

The authors subjected 34 patients (27 men and 7 women) to invasive electrophysiological examination. All patients had early ventricular contractions class 3-5 according to Lown which were recorded during ECG monitoring in bed or by Holter's system. A pathological excitability of the ventricular myocardium was found during programmed stimulation in 29% of the subjects. The excitability of the heart muscle was substantially enhanced by the incidence of ischaemic heart disease and reduced left ventricular function. The decreased frequency and severity of early ventricular contractions during bicycle ergometry, the absence of palpitations and syncopes increases the probability of normal excitability of the ventricular myocardium.

[Arrhythmic syncope and invasive electrophysiologic heart function tests]. / Arytmické synkopy a invazivní srdecní elektrofyziologické vysetrení.

The authors submitted to electrophysiological examination a total of 100 patients (66 men and 34 women) with brief disorders of consciousness where they ruled out extracardiac causes of unconsciousness, impaired blood flow through the heart and the syndrome of s-a node dysfunction. Forty-three subjects had severe arrhythmias during ECG monitoring in bed or by Holter's system (20 subjects paroxysms of ventricular tachycardia, 14 subjects ventricular extrasystoles according to Lown class 3-5, six subjects had transient high-grade a-v blocks, three subjects had symptomatic paroxysms of supraventricular tachycardia). In 57 patients ECG monitoring did not reveal ectopic arrhythmias and high-grade a-v blocks. Invasive examination confirmed or diagnosed arrhythmic syncopes in 49% of the entire group of 100 patients. It assessed the arrhythmic cause of syncopes in 33% of 57 subjects without severe arrhythmias and in 70% of 43 subjects with severe arrhythmias detected during ECG monitoring.

Changes in pulmonary and systemic haemodynamics after the administration of various vasodilators in patients with pulmonary hypertension.

The authors investigated the influence of some vasodilatory drugs on pulmonary and systemic haemodynamic parameters in 69 patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (with the exception of two patients with diffuse pulmonary fibrosis and one patient with recurrent pulmonary thromboembolism). The investigated vasodilatory drugs were as follows: Dihydralazine Spofa--8 patients, Corinfar--10 patients, Ketanserin--13 patients, Nit-Ret 7 patients, Nitroglycerin Spofa--10 patients, Nitro-Mack--11 patients, Iso-Mack retard--10 patients. The haemodynamic parameters were measured before and at various time intervals after the administration of the vasodilatory agent (Dihydralazine 50 mg perorally--30th and 60th minute, Corinfar--20 mg sublingually--60th minute, and in 7 patients following a 6 months period of 30-60 mg Corinfar daily dose, Ketanserin--10 mg intravenously--10th, 20th and 40th minute, Nit-Ret--2.5 mg perorally--30th and 60th minute, Nitroglycerin Spofa--0.5 mg sublingually--10th and 30th minute, Nitro-Mack--1 mg intravenously--immediately following the end of a slow i. v. infusion for 20 minutes, Iso-Mack retard--20 mg perorally, 60th minute). The blood gases were measured at the same time intervals, too. The results in various groups were as follows: Dihydralazine administration was not followed by any significant change in PAP, CO, PVR, while a significant decrease in AOP and SVR was ascertained. A significant decrease of PaCO2 and no change in PaO2 were measured. Following Corinfar administration, no change in PAP, CO or PVR and a significant decrease of PaCO2 and no change in PaO2 were measured. Following Corinfar administration, no change in PAP, CO or PVR and a significant decrease in AOP were determined. No significant changes in blood gases were measured. Following a 6 month Corinfar treatment period in 7 subjects, no significant changes in pulmonary haemodynamics or blood gases values were found. No clinical benefit of this drug could be estimated. Ketanserin administration was not followed by any changes in pulmonary haemodynamics, whereas a significant decrease in AOP and SVR were found. The administration of Nit-Ret was followed by a significant decrease of CO, whereas no changes in PAP, AOP or PVR and SVR were found. No significant changes in the blood gas tenses values were measured. The administration of Nitroglycerin Spofa was followed by a significant decrease in RAP, PAP, AOP, RVEDP as well as in CO. No significant changes in blood gases were observed. The application of 1 mg Nitro-Mack intravenously was followed by a significant decrease in RAP, PAP, AOP and CO.(ABSTRACT TRUNCATED AT 400 WORDS)

[Long-term study of disorders of heart rhythm in patients with chronic diseases of the respiratory system]. / Dlouhodobé sledování poruch srdecního rytmu u nemocných s chronickými chorobami dýchacího ústrojí.

The authors investigated the incidence of arrhythmias by the method of continuous recording of ECG tracings according to Holter in 16 patients with chronic respiratory diseases three times in the course of two years. The incidence of arrhythmias was very frequent, more serious disorders (class 3 or a higher class according to Lown's classification) were very rare. The authors provided evidence of a great variability in the incidence of arrhythmias in the same patients during different periods of investigation. They did not reveal a relationship between the incidence of arrhythmias and the degree of functional affection of the lungs, the severity of hypoxaemia and the drop of the maximum aerobic capacity of the lungs. They did not find a relationship between the incidence of arrhythmias and the pressure in the pulmonary artery, or the size of the right or left ventricle or the thickness of their wall. The authors do not consider the finding of arrhythmias in patients with chronic lung disease an unequivocally serious finding, as reported sometimes in the literature.