Evolution of Electrocardiographic Repolarization Parameters During Antiandrogen Therapy in Patients with Prostate Cancer and Hypogonadism

Andrei Cristian Dan Gheorghe,Ana Ciobanu,Ioan Tiberiu Nanea,George Daniel Radavoi,Viorel Jinga,Gabriela Silvia Gheorghe,Andreea Simona Hodorogea

doi:10.1007/s12012-020-09566-6

Abstract

We assessed the effects of antiandrogen therapy on ECG parameters of ventricular repolarization related to arrhythmic risk in 35 patients aged 70.3 ± 7 years with advanced prostate cancer treated with degarelix associated with enzalutamide (group A, 26 patients) or degarelix monotherapy (group B, 9 patients). We analyzed Fridericia corrected Q-T interval (QTc), Q-T dispersion (QTd), J-Tpeak interval (JTp), mean and maximum Tpeak-Tend interval (Tpe) and Tpe/QT ratio, Tpeak-Tend dispersion (Tped), index of cardio-electrophysiological balance (iCEB) from ECG tracings, and occurrence of ventricular premature beats (VPB) recorded by Holter ECG, before initiation of medication (M0) and after 6 months of treatment (M1). The groups had similar demographics except for a higher prevalence of prior myocardial infarction in group B (p = 0.01). All patients had low serum testosterone at M1. Baseline QTc, QTd, maxTpe/QT, meanTpe, maxTpe, Tped values were higher in B compared to A. They had a significant prolongation at M1 only in A. 20 patients in A and 6 in B had a 10% prolongation or decrease of iCEB (p = 0.66). In 5 patients, VPB severity increased from non-complex to complex: 3 in A and 2 in B (p = 0.31), but no sustained ventricular arrhythmia was registered. In conclusion, after 6 months of treatment, patients with hypogonadism on degarelix associated with enzalutamide had significant prolongation of QTc, QTd, maxTpe, meanTpe/QT, maxTpe/QT, Tped compared to patients on degarelix alone. The proportion of patients with 10% iCEB variation was similar between groups. There was no record of severe arrhythmias during the first 6 months of treatment.

Highlights

Chemotherapy, targeted therapy, and monoclonal antibodies therapy used in oncological and autoimmune systemic diseases have many cardiovascular deleterious effects according to the cardio-oncology guidelines of the European Society of Cardiology [1], but there are concerns regarding the Handling Editor: Martin Štěrba.1 3 Vol:.(1234567890)Cardiovascular Toxicology (2020) 20:390–400Several electrocardiographic indices are recommended for the assessment of cardiac repolarization and arrhythmic risk stratification: corrected Q-T interval (QTc), QT interval dispersion (QTd), Tpeak—Tend interval (Tpe), Tpeak— Tend/QT ratio (Tpe/QT), Tpeak—Tend interval dispersion (Tped), J-Tpeak interval (JTp)
Prolongation of QTc is associated with prolongation of action potential duration at cellular level, which is involved in a higher risk of occurrence of early afterdepolarization, and triggers activity responsible for arrhythmia [7]
The concomitant prolongation of JTp and QTc intervals is associated with an increased risk of cardiac arrhythmias [7]

Summary

Introduction

Several electrocardiographic indices are recommended for the assessment of cardiac repolarization and arrhythmic risk stratification: corrected Q-T interval (QTc), QT interval dispersion (QTd), Tpeak—Tend interval (Tpe), Tpeak— Tend/QT ratio (Tpe/QT), Tpeak—Tend interval dispersion (Tped), J-Tpeak interval (JTp). The prolongation of QTc of more than 60 ms increases the risk of cardiac arrhythmia [1]. Tpe/QT is constant and seems more useful in predicting arrhythmic risk [7]. Additional repolarization indices, such as JTp and Tpe/JTp, do not appear to be superior to the aforementioned tests [7]. The concomitant prolongation of JTp and QTc intervals is associated with an increased risk of cardiac arrhythmias [7]. The prolongation or decrease of iCEB more than 10% from the baseline values seems sensitive to the cardiac repolarization changes induced by drugs [7, 9]

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