Impact of Medical Castration on Malignant Arrhythmias in Patients With Prostate Cancer

Abstract

Background Medical castration, gonadotropin-releasing hormone agonists, and antiandrogens have been widely applied as a treatment for prostate cancer. Sex steroid hormones influence cardiac ion channels. However, few studies have examined the proarrhythmic properties of medical castration. Methods and Results This study included 149 patients who underwent medical castration using gonadotropin-releasing hormones with/without antiandrogen for prostate cancer. The changes in the ECG findings during the therapy and associations of the electrocardiographic findings with malignant arrhythmias were studied. The QT and corrected QT (QTc) intervals prolonged during the therapy compared with baseline (QT, 394±32 to 406±39 ms [P<0.001]; QTc, 416±27 to 439±31 ms [P<0.001]). The QTc interval was prolonged in 119 (79.9%) patients during the therapy compared with baseline. In 2 (1.3%) patients who had no structural heart disease, torsade de pointes (TdP) and ventricular fibrillation (VF) occurred ≥6 months after starting the therapy. In patients with TdP/VF, the increase in the QTc interval from the pretreatment value was >80 ms. However, in patients without TdP/VF, the prevalence of an increase in the QTc interval from the pretreatment value of >50 ms was 11%, and an increase in the QTc interval from the pretreatment value >80 ms was found in only 4 (3%) patients. Conclusions Medical castration prolongs the QT/QTc intervals in most patients with prostate cancer, and it could cause TdP/VFs even in patients with no risk of QT prolongation before the therapy. An increase in the QTc interval from the pretreatment value >50 ms might become a predictor of TdP/VF. Much attention should be paid to the QTc interval throughout all periods of medical castration to prevent malignant arrhythmias.

Keywords: QT prolongation; medical castration; prostate cancer; torsade de pointes; ventricular fibrillation.

Figure 1. The QT and corrected QT (QTc) intervals during medical castration therapy.

A, The QT and QTc intervals before and during the medical castration therapy. B, Increase in the QT (ΔQT) interval and increase in the QTc (ΔQTc) interval from the pretreatment value in patients who developed malignant arrhythmias during the medical castration therapy and those who did not. The QT and QTc intervals and those changes during medical castration therapy.

Figure 2. Representative ECG recordings obtained in a patient who developed torsade de pointes and ventricular fibrillation during medical castration therapy.

A, Twelve‐lead ECGs before and 22 months after the medical castration. B, Tracings of the bedside continuous single‐lead ECG monitoring. Torsade de pointes and ventricular fibrillation spontaneously occurred 22 months after the medical castration. HR indicates heart rate; and QTc, corrected QT.