[Assessment of cardiotoxicity of high dose cyclophosphamide with electrocardiographic, echocardiographic, and troponin I monitoring in patients with breast tumors].

BACKGROUND

High-dose cyclophosphamide is the nucleus for virtually all high-dose chemotherapy protocols. Non-hematologic dose-limiting toxicity is represented by acute cardiomyopathy, even fatal in a minority of patients. The pathophysiology of such a cardiotoxicity is still poorly understood. Postmortem studies revealed hemorrhagic myocardial cell death, endothelial damage, and interstitial edema. Recently troponins, in particular troponin I, have been found to represent uniquely sensitive and specific markers of myocyte membrane integrity, thus to increase in response to myocardial cell damage in different clinical settings.

METHODS

We performed a multiparametric monitoring in 16 consecutive breast cancer patients undergoing cyclophosphamide, by means of serial ECGs, cardiac enzymes determinations (creatine phosphokinase, MB mass and troponin I) through 0 to 72 hours, and echocardiography at baseline and after 48 hours.

RESULTS

Neither overt cardiac failure nor enzyme elevation were recorded. Serial ECGs revealed a reduction in QRS voltage and/or ST segment abnormalities in 6 cases. Echocardiography showed an increase in left ventricular diastolic and/or systolic diameters and volumes in 4 cases but without any decrease in fractional shortening and ejection fraction under normal values: in 2 of them abnormalities of diastolic function (E/A mitral Doppler ratio, isovolumic relaxation time and deceleration time) were also recorded.

CONCLUSIONS

Our protocol of cyclophosphamide administration did not cause cardiac toxicity by myocardial cell damage, as analyzed by troponin I levels, thus suggesting that myocyte membrane injury is not the first mechanism of it. ECG (i.e. QRS voltages) and echo-Doppler (i.e. E/A ratio) monitoring lead to hypothesize that endothelial injury and interstitial edema with subsequent reduction in left ventricular diastolic compliance may be the first signs of cardiac dysfunction in this clinical setting.