[Pathogenesis, prevention and detection of cardiotoxicity of anthracycline cytostatic agents]

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.

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.

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.

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.

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.)