Early Detection of Doxorubicin Cardiomyopathy Using Two-Dimensional Strain Echocardiography

Doxorubicin is one of the most effective chemotherapeutic agents; however, it causes dose-dependent cardiomyopathy that may lead to heart failure. Conventional measures of ventricular function, such as fractional shortening, are insensitive in detecting early doxorubicin cardiomyopathy. We tested whether novel two-dimensional radial strain echocardiography (2DSE) can detect early doxorubicin injury following chronic administration in a rat model. 14 male Sprague Dawley rats (240 to 260 g) received doxorubicin 2.5 mg/k i.v. per wk for 10 (n = 4) or 12 wk (n = 10); 17 controls received saline (10 wk, n = 7 and 12 wk, n = 10). Serial 2DSE from 0 to 12 wk was done at the mid left ventricle using Vivid 7 echo (General Electric, Waukesha, WI, USA). With Q analysis software, radial strain was obtained. From the two-dimensional (2D) image, anatomical M-mode through the anterior/inferior walls was used to measure fractional shortening. Fibrosis (Masson's trichrome) and caspase-3 activity were measured from excised hearts. Radial strain was lower in the doxorubicin group (12 wk: 26.7 ± 3 versus 38.3 ± 2.6%, p = 0.006), with significant difference by 8 wk whereas fractional shortening was lower with doxorubicin only after 12 wk (30.2 ± 1.7 versus 37.6 ± 1.4%, p = 0.02). Doxorubicin group had lower cardiac mass (0.85 ± 0.09 versus 1.14 ± 0.04 g, p = 0.001), higher caspase-3 activity (1.95 ± 0.2 fold increase over control, p < 0.0001) and fibrosis (3.9 ± 0.7 versus 0.7 ± 0.1%, p = 0.005). Radial strain was related directly to cardiac mass (r = 0.61, p = 0.0007) and inversely to caspase-3 activity (r = −0.5, p = 0.005). 2-dimensional radial strain echocardiography is useful in the early detection of doxorubicin cardiac injury and the reduction in radial strain is associated with histologic markers of doxorubicin cardiomyopathy. (E-mail: rmigrino@mcw.edu)