Activation recovery interval as an electrocardiographic repolarization index to detect doxorubicin-induced cardiotoxicity

Abstract

BackgroundIt has been reported that early detection and treatment of cancer therapy- related cardiac dysfunction (CTRCD) improves its prognosis. The detailed relationships between electrocardiographic repolarization indices and decreased left ventricular function in CTRCD have not been elucidated. We closely assessed such relationships in patients with doxorubicin (DOX)-induced CTRCD. MethodsThis retrospective, single-center, cohort study included 471 consecutive patients with malignant lymphoma who received chemotherapy including DOX. Of them, 17 patients with CTRCD and 68 patients without CTRCD who underwent 12‑lead electrocardiogram and an echocardiogram before and after chemotherapy were eventually analyzed. The fluctuations of the following electrocardiographic repolarization indices were evaluated in lead V5: QT, JT, T peak to T end interval (Tp-e), and activation recovery interval (ARI). These indices were corrected by heart rate with the Fridericia formula. ResultsThe median period from the end of chemotherapy to the diagnosis of the CTRCD group was 346 days (IQR 170–1283 days). After chemotherapy, the QT interval was significantly prolonged in both with and without CTRCD groups compared with that before chemotherapy (pre QTc vs. post QTc in CTRCD group, 386 ± 27 ms vs. 411 ± 37 ms, p = 0.03, pre QTc vs. post QTc in non-CTRCD group, 388 ± 24 ms vs. 395 ± 25 ms, p = 0.04, respectively). ARIc after chemotherapy was characteristically observed only in the CTRCD group (pre ARIc vs. post ARIc in CTRCD group, 258 ± 53 ms vs. 211 ± 28 ms, p = 0.03, pre ARIc vs. post ARIc in non-CTRCD group, 221 ± 19 ms vs. 225 ± 23 ms, NS, respectively) and had negative correlations with left ventricular ejection fraction (r = −0.56, p < 0.001). Using the receiver-operating characteristic curve, the relationship between ARIc and CTRCD morbidity was examined. The optimal cut-off point of ARIc prolongation between before and after chemotherapy was 18 ms (sensitivity 75 %, specificity 79 %, area under the curve 0.76). ConclusionsARIc prolongation may be useful in the early detection of developing late-onset chronic DOX-induced CTRCD and lead to early treatment for cardiac protection.