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Early Detection of Subclinical Anthracycline Cardiotoxicity on the Basis of QT Dispersion

Yohko Uchikoba, Ryuji Fukazawa, Takashi Ohkubo, Miho Maeda and Shunichi Ogawa

Department of Pediatrics, Graduate School of Medicine, Nippon Medical School

Background: We examined whether dobutamine-stress QT dispersion (QTd) and heart-rate corrected QT dispersion (QTcd) are useful for detecting subclinical anthracycline cardiotoxicity.
Methods: The subjects were10 control subjects and 37 patients divided into 4 groups according to cumulative anthracycline dose: non-anthracycline group (group N), 7 patients; low anthracycline cumulative dose group (group L), 8 patients (<200 mg/m²); medium anthracycline cumulative dose group (group M), 16 patients (200 to <400 mg/m²); and high cumulative group (group H), 6 patients (≥400 mg/m²). Standard 12-lead electrocardiograms were recorded. QTd and QTcd were measured and calculated at rest and after administration of dobutamine at 5 or 30 μg/kg/min. We also estimated cardiac function and cardiac reserve function at rest and after administration of dobutamine at a dose of 5 or 30 μg/kg/min.
Results: At rest, QTd and QTcd were significantly greater in groups M and H. After administration of dobutamine at 30 μg/kg/min, QTd and QTcd were significantly greater in groups L, M, and H. There was good correlation between QTd and the cumulative anthracycline dose; the correlation formula was y=0.051x + 42.2 (r=0.81, p<0.001). The cumulative anthracycline dose of 152.9 mg/m², calculated from the correlation formula, was the cut-off for detection of electrophysiological cardiac abnormalities. Cardiac performance data at rest and dobutamine stress by echocardiography and pulsed Doppler echocardiography are less sensitive for detecting cardiac abnormalities than are QTd and QTcd.
Conclusions: Dobutamine-stress QTd and QTcd are useful for detecting anthracycline cardiotoxicity and subclinical cardiac abnormality at low cumulative anthracycline doses. We must be aware of the possibility of subclinical myocardial abnormalities in patients with a cumulative anthracycline dose of ≥150 mg/m².

J Nippon Med Sch 2010; 77: 234-243

Keywords
anthracycline cardiotoxicity, QT dispersion, heart-rate corrected QT dispersion, dobutamine, malignancy

Correspondence to
Shunichi Ogawa, MD, Department of Pediatrics, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
boston@nms.ac.jp

Received, January 8, 2010
Accepted, May 29, 2010