Early detection of anthracycline induced cardiotoxicity in asymptomatic patients with normal left ventricular systolic function: autonomic versus echocardiographic variables

Abstract

Objective-To investigate left ventricular dysfunction in patients who had been treated with anthracycline based chemotherapy. Methods-Autonomic function was compared with left ventricular diastolic function in 20 asymptomatic women with normal systolic function (left ventricular ejection fraction (LVEF) > 0.50) treated for breast cancer with high dose anthracycline based chemotherapy, and 20 age matched healthy controls. Left ventricular diastolic function was assessed echocardiographically by measuring the early peak flow velocity to atrial peak flow velocity ratio, isovolumic relaxation time, and deceleration time. Heart rate variability analysis was assessed for time domain and frequency domain parameters. Results-The mean (SD) age of the patients was 45 (7) years and the mean LVEF was 0.59 (0.06). The time interval after the end of chemotherapy was 29 (27) months. One or more diastolic variables were abnormal in 50% of the patients. Heart rate variability was abnormal in 85% of patients. Mean values of both time domain and frequency domain parameters were decreased (p < 0.05), in particular the parasympathetic indices. Conclusions-Autonomic impairment occurs in a large proportion of asymptomatic patients with normal systolic left ventricular function after high dose anthracycline based chemotherapy. In particular, heart rate variability analysis may be a sensitive tool to identify the first signs of cardiotoxicity in these patients.

Early Detection of Doxorubicin Cardiomyopathy Using Two-Dimensional Strain Echocardiography

“…However, it has been demonstrated that left ventricular ejection fraction and fractional shortening are insensitive to detection of doxorubicin cardiomyopathy (McKillop, Bristow 1983, Tjeerdsma, Meinardi 1999. Other measures were found useful in earlier detection of doxorubicin cardiomyopathy such as indices of diastolic dysfunction (Marchandise, Schroeder 1989, Stoddard, Seeger 1992, but considerable individual variability limits practical applicability in the clinical setting (Bu'Lock, Mott 1999) 2-dimensional strain echocardiography is a rapid, easy and objective way of measuring myocardial function.…”

“…The development of cardiomyopathy impacts further chemotherapy and has implications in the medium and long term prognoses of patients. Current practice relies on evaluation of left ventricular systolic function using ejection fraction or fractional shortening by echocardiography or nuclear ventriculography to detect development of cardiomyopathy, but these are insensitive and unreliable markers of early doxorubicin injury (McKillop, Bristow 1983, Tjeerdsma, Meinardi 1999). An easy, rapid, sensitive and reliable method of earlier detection of doxorubicin injury has potential clinical impact in the assessment and therapeutic decision-making in these patients.…”

Trastuzumab‐associated cardiotoxicity

“…21 Although unproved, tachycardia also may be a sensitive tool with which to identify the first signs of trastuzumab-associated cardiotoxicity. However, although the signs and symptoms of anthracycline-induced and trastuzumab-associated cardiotoxicity may be similar, 22 closer examination reveals important differences, including dose-relatedness and the degree of reversibility.…”

Impairment of heart rate variability control during arsenic trioxide treatment for acute promyelocytic leukemia

“…Impairment of HRV, which was related to the abnormality in autonomic regulation, has also been reported in patients treated with chemotherapies including anthracyclines, vinca alkaloids and paclitaxel. 5 We monitored 24-h ambulatory electrocardiograms (ECGs) during and after As 2 O 3 treatment in six patients with APL, and tried to clarify the mechanism of cardiac toxicity.…”

“…Impairment of HRV has been reported during and after the chemotherapy for patients with cancer. 5 HF and LF components have been considered as the most important indices of HRV. 4 The vagal activity is a major contributor of HF component, and both sympathetic and vagal effects relate to LF component.…”