Serum cardiac troponin I levels and ECG/Echo monitoring in breast cancer patients undergoing high-dose (7 g/m(2)) cyclophosphamide

High-dose cyclophosphamide (HD-CTX) is largely employed in high-dose chemot herapy (HD-CHT) protocols. HD-CTX close-limiting toxicity expresses itself as cardiac toxicity which is fatal in a minority of patients. The pathophys iology of IID-CTX-associated cardiotoxicity is still poorly understood. Aut opsy studies in patients who died from acute IID-CTX-induced cardiac toxici ty revealed hemorrhagic myocardial cell death and interstitial edema. Recen tly troponins, in particular troponin I (cTnI), have been found to represen t a uniquely sensitive and specific marker of myocyte membrane integrity an d therefore to increase in response to minimal myocardial cell damage in di fferent settings, including doxorubicin-induced cardiotoxicity. We performe d a multiparametric cardiologic monitoring in 16 consecutive breast cancer patients undergoing HD-CTX by means of serial ECG registrations and cardiac enzymes (CPK, CPK-MB and cTuI) determinations plus echocardiography in ord er to clarify acute cardiac events following IID-CTX administration. Neithe r overt cardiac toxicity nor cardiac enzymes elevation were recorded. Seria l ECGs revealed in six cases little and reversible reduction of QRS voltage and/or ST abnormalities. Echo monitoring showed in four cases mild and tra nsient increase of LV diastolic/systolic diameter/volume without decrease o f FS% or EF% below normal values: in two of them abnormalities of diastolic function (E/A mitral doppler ratio) were also recorded. We conclude that o ur protocol of HD-CTX administration does not cause myocardial cell damage as analyzed by serum cTnI levels, thus suggesting that myocyte membrane inj ury may not be the first direct mechanism of IID-CTX cardiotoxicity. ECG (i e QRS voltages) and Echo (ie E/A ratio) monitoring leads us to hypothesize that slight interstitial edema with reduction of LV diastolic compliance ma y be initial signs of cardiac dysfunction in this clinical setting.