title: Prolongation of isovolumetric relaxation time as assessed by Doppler echocardiography predicts doxorubicin-induced systolic dysfunction in humans.
abstract: A reasonably sensitive and specific noninvasive test for doxorubicin cardiotoxicity is needed. In addition, few data exist on the short- and long-term effects of doxorubicin on diastolic filling. To determine if pulsed Doppler indexes of diastolic filling could predict doxorubicin-induced systolic dysfunction, 26 patients (mean age 48 +/- 12 years) were prospectively studied before receiving chemotherapy (control) and 3 weeks after obtaining cumulative doses of doxorubicin. In nine patients developing doxorubicin-induced systolic dysfunction (that is, a decrease in ejection fraction by greater than or equal to 10 ejection fraction units to less than 55%), the isovolumetric relaxation time was prolonged (from 66 +/- 18 to 84 +/- 24 ms, p less than 0.05) after a cumulative doxorubicin dose of 100 to 120 mg/m2. This prolongation preceded a significant decrease in ejection fraction. Other Doppler indexes of filling were impaired after doxorubicin therapy but occurred simultaneously with the decrease in ejection fraction. A greater than 37% increase in isovolumetric relaxation time was 78% (7 of 9) sensitive and 88% (15 of 17) specific for predicting the ultimate development of doxorubicin-induced systolic dysfunction. In 15 patients studied 1 h after the first treatment, doxorubicin enhanced Doppler indexes of filling and shortened isovolumetric relaxation time. In 22 patients, indexes of filling remained impaired and isovolumetric relaxation time was prolonged 3 months after the last doxorubicin dose. In conclusion, doxorubicin-induced systolic dysfunction is reliably predicted by prolongation of Doppler-derived isovolumetric relaxation time. Early after administration, doxorubicin enhances filling and isovolumetric relaxation time. The adverse effects of doxorubicin on both variables persist at least 3 months after cessation of treatment.
authors.affiliation: Division of Cardiology, University of Louisville, Kentucky 40202.
authors.forename: M F
authors.initials: MF
authors.lastname: Stoddard
authors.forename: J
authors.initials: J
authors.lastname: Seeger
authors.forename: N E
authors.initials: NE
authors.lastname: Liddell
authors.forename: T J
authors.initials: TJ
authors.lastname: Hadley
authors.forename: D M
authors.initials: DM
authors.lastname: Sullivan
authors.forename: J
authors.initials: J
authors.lastname: Kupersmith
mesh_terms: D000328:Adult; D000368:Aged; D003971:Diastole / Q000187:drug effects*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D015150:Echocardiography, Doppler; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D011237:Predictive Value of Tests; D013318:Stroke Volume / Q000187:drug effects*; D013599:Systole / Q000187:drug effects*; D013997:Time Factors
chemical_list: D004317:Doxorubicin