Neuroendocrine changes during the evolution of doxorubicin-induced left ventricular dysfunction in adult lymphoma patients

Abstract

Doxorubicin-induced cardiotoxicity was used as a model to prospectively investigate neuroendocrine changes during the development of left ventricular dysfunction. Radionuclide ventriculography, frequency domain analysis of heart rate variability (HRV), and plasma noradrenaline and natriuretic peptide measurements were performed in 27 adult lymphoma patients at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg/m(2). The left ventricular ejection fraction (LVEF) decreased from 58.1+/-1.4% to 50.3+/-1.1% (P<0.001) and 49.3+/-1.7% (P<0.001) after cumulative doxorubicin doses of 400 and 500 mg/m(2) respectively. With a doxorubicin dose of up to 400 mg/m(2) there was an increase in sympathetic tone, characterized by a decrease in the normalized high-frequency (HF(nu)) power (P=0.011), and increases in the normalized low-frequency (LF(nu)) power (P=0.011), the LF/HF ratio (P=0.021) and the plasma noradrenaline concentration (P=0.034). The decrease in LVEF was correlated with the changes in LF(nu) and HF(nu) power (r=0.540, P=0.012) and LF/HF ratio (r=-0.452, P=0.04). However, after the cumulative doxorubicin dose of 500 mg/m(2) the changes in HRV components and plasma noradrenaline levels returned towards baseline. This was accompanied by increased concentrations of plasma atrial natriuretic peptide (P=0.004) and brain natriuretic peptide (P=0.021). Our findings suggest that doxorubicin-induced left ventricular dysfunction is associated with an early change in sympathovagal balance towards sympathetic predominance. Along with further progression of left ventricular dysfunction, there is an attenuation of sympathetic tone, which may be attributable to sympatho-adrenal inhibition by increased secretion of natriuretic peptides.

Cardiorespiratory Fitness in Breast Cancer Patients: A Call for Normative Values

“…These oxygen free radicals are thought to play a central role in the evolution of the cardiotoxic effects of anthracyclines . Moreover, several lines of evidence suggest that cytotoxic damage caused by anthracyclines leads to compensatory alterations in autonomic tone, which may have important implications for heart rate reserve and CRF . Radiotherapy used to treat breast cancer can cause cardiac perfusion defects that are associated with abnormalities in regional wall motion .…”

Clinical Correlation between Brain Natriutetic Peptide and Anthracyclin-induced Cardiac Toxicity

“…The avascularizatin rate of the left ventricle applying echocardiogram is an important means to observe and monitor heart failure, and it is good for the diagnosis of heart failure that has been developed already, however, it is not useful for the prediction of early cardiotoxicity. Not only plasma BNP concentration could be measured rapidly and readily, even in cases with normal avascularization rate, if the concentration were elevated, the increase of ventricular load could be suspected, and thus it could be applied as a factor that could predict early cardiotoxicity (14)(15)(16)(17)(18)(19). In our study, among 86 patients, more than 60% were malignant lymphoma patients, and they received the combination chemotherapy of cyclophosphamide, vincristine, and prednisolon including anthracyclin.…”

“…Brain natriuretic peptide (BNP) is a type of cardiac neurohormone secreted by the ventricles due to the increase of ventricular volume and pressure, elevation of serum concentration of BNP has been known to be significantly correlated to the left ventricular end diastolic pressure as well as pulmonary capillary wedge pressure in heart failure patients (14). Pertinent to this, since serum concentration of BNP reflects left ventricular dysfunction, it has been applied to the diagnosis as well as treatment of heart failure patients and to predict prognosis (16,17). Anthracyclin has been also known to induce the degeneration of ventricular muscles and thus to show congestive heart failure features (5).…”

Heart rate responses induced by acoustic tempo and its interaction with basal heart rate

“…The lnLF to lnHF component ratio (lnLF/lnHF ratio) was evaluated by dividing the lnLF component by the lnHF component. The lnLF/lnHF ratio of the HRV is an index of sympathetic nerve activity4546.…”