Assessment of left ventricular diastolic function during trastuzumab treatment in patients with HER2-positive breast cancer

Kazunori Honda, Kyosuke Takeshita, Kenta Murotani, Ayako Mitsuma, Hironori Hayashi, Nobuyuki Tsunoda, Toyone Kikumori, Toyoaki Murohara, Yuichi Ando

The ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (e', E/e' ratio) as estimated by tissue Doppler imaging is a noninvasive surrogate for the left ventricular diastolic function. Because diastolic dysfunction usually precedes systolic dysfunction in cardiovascular diseases, we investigated whether monitoring the E/e' ratio can help to predict the risk of trastuzumab-induced cardiotoxicity. E/e' ratio on tissue Doppler imaging was retrospectively reviewed to assess its value for early detection of the left ventricular ejection fraction (LVEF) decline in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who received trastuzumab with or without cytotoxic chemotherapy. Echocardiography was performed at baseline and every 3 months after treatment began. Among 129 patients, LVEF declined in 25 (19 %) during trastuzumab treatment; the decline was grade 2 in 23 patients and grade 3 in 2. Elevation of the E/e' ratio to more than 15 was detected in 17 patients (13 %), 7 of whom (5.4 % of total) concurrently had LVEF decline. A weak negative correlation was observed between E/e' elevation and the worst LVEF decline (P = 0.0077), which was confirmed by multiple regression analysis (P = 0.023). E/e' ratio at baseline or 3 months after beginning trastuzumab treatment was not significantly associated with the subsequent LVEF decline. Monitoring of the left ventricular diastolic function on the basis of the E/e' ratio at baseline or 3 months after is unlikely to predict LVEF decline in patients who receive trastuzumab. However, there is a potential chronological relation between E/e' elevation and LVEF decline, implying that the degree of E/e' elevation could have a role as a surrogate marker for predicting the LVEF decline characteristic of trastuzumab-induced cardiotoxicity.