title: Early detection of doxorubicin cardiomyopathy using two-dimensional strain echocardiography.
abstract: 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.
authors.affiliation: Cardiovascular Division, Medical College of Wisconsin, Milwaukee, WI 53226, USA. rmigrino@mcw.edu
authors.forename: Raymond Q
authors.initials: RQ
authors.lastname: Migrino
authors.forename: Deepika
authors.initials: D
authors.lastname: Aggarwal
authors.forename: Eugene
authors.initials: E
authors.lastname: Konorev
authors.forename: Tejas
authors.initials: T
authors.lastname: Brahmbhatt
authors.forename: Megan
authors.initials: M
authors.lastname: Bright
authors.forename: Balaraman
authors.initials: B
authors.lastname: Kalyanaraman
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D004317:Doxorubicin / Q000009:adverse effects*; D025401:Echocardiography, Stress / Q000379:methods*; D005355:Fibrosis; D006331:Heart Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging* / Q000473:pathology; D006333:Heart Failure / Q000139:chemically induced / Q000000981:diagnostic imaging; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008297:Male; D023421:Models, Animal; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced / Q000000981:diagnostic imaging
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin