Prolongation of isovolumetric relaxation time as assessed by Doppler echocardiography predicts doxorubicin-induced systolic dysfunction in humans

Division of Cardiology, University of Louisville, Kentucky 40202.

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.

This article has been cited by other articles:

				F Paul, J Dorr, J Wurfel, H-P Vogel, and F Zipp Early mitoxantrone-induced cardiotoxicity in secondary progressive multiple sclerosis J. Neurol. Neurosurg. Psychiatry, February 1, 2007; 78(2): 198 - 200. [Full Text] [PDF]

				T. G. Neilan, D. S. Jassal, T. M. Perez-Sanz, M. J. Raher, A. D. Pradhan, E. S. Buys, F. Ichinose, D. B. Bayne, E. F. Halpern, A. E. Weyman, et al. Tissue Doppler imaging predicts left ventricular dysfunction and mortality in a murine model of cardiac injury Eur. Heart J., August 1, 2006; 27(15): 1868 - 1875. [Abstract] [Full Text] [PDF]

				S. Tassan-Mangina, D. Codorean, M. Metivier, B. Costa, C. Himberlin, C. Jouannaud, A. M. Blaise, J. Elaerts, and P. Nazeyrollas Tissue Doppler imaging and conventional echocardiography after anthracycline treatment in adults: Early and late alterations of left ventricular function during a prospective study Eur J Echocardiogr, March 1, 2006; 7(2): 141 - 146. [Abstract] [Full Text] [PDF]

				S. Kilickap, I. Barista, E. Akgul, K. Aytemir, S. Aksoyek, S. Aksoy, I. Celik, S. Kes, and G. Tekuzman cTnT can be a useful marker for early detection of anthracycline cardiotoxicity Ann. Onc., May 1, 2005; 16(5): 798 - 804. [Abstract] [Full Text] [PDF]

				D. Tallarico, V. Rizzo, F. di Maio, F. Petretto, G. Bianco, G. Placanica, M. Marziali, V. Paravati, N. Gueli, F. Meloni, et al. Myocardial Cytoprotection by Trimetazidine Against Anthracycline-Induced Cardiotoxicity in Anticancer Chemotherapy Angiology, March 1, 2003; 54(2): 219 - 227. [Abstract] [PDF]

				M.T. Meinardi, D.J. van Veldhuisen, J.A. Gietema, W.V. Dolsma, F. Boomsma, M.P. van den Berg, C. Volkers, J. Haaksma, E.G.E. de Vries, D.Th. Sleijfer, et al. Prospective Evaluation of Early Cardiac Damage Induced by Epirubicin-Containing Adjuvant Chemotherapy and Locoregional Radiotherapy in Breast Cancer Patients J. Clin. Oncol., May 15, 2001; 19(10): 2746 - 2753. [Abstract] [Full Text] [PDF]

				G Tjeerdsma, M T Meinardi, W T A van der Graaf, M P van den Berg, N H Mulder, H J G M Crijns, E G E de Vries, and D J van Veldhuisen Early detection of anthracycline induced cardiotoxicity in asymptomatic patients with normal left ventricular systolic function: autonomic versus echocardiographic variables Heart, April 1, 1999; 81(4): 419 - 423. [Abstract] [Full Text]

				M. D. Cheitlin, J. S. Alpert, W. F. Armstrong, G. P. Aurigemma, G. A. Beller, F. Z. Bierman, T. W. Davidson, J. L. Davis, P. S. Douglas, L. D. Gillam, et al. ACC/AHA Guidelines for the Clinical Application of Echocardiography : A Report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee on Clinical Application of Echocardiography) Developed in Collaboration With the American Society of Echocardiography Circulation, March 18, 1997; 95(6): 1686 - 1744. [Full Text]