Sertindole and impaired atrioventricular function, in the absence of Q–T prolongation: A case report

Abstract

SERTINDOLE IS AN atypical antipsychotic agent with high-affinity and concomitant moderate-potency blocking effect to the rapid component of the human cardiac delayed rectifier potassium current (IKr),1 encoded by the human Ether-à-go-go-related (hERG) gene. This property underlies the prolongation of the Q–T interval observed during sertindole administration and may cause life-threatening ventricular arrhythmias. We report the case of a 52-year-old male patient who was diagnosed with schizophrenia and was treated with antipsychotic medication from the age of approximately 40 years old, and who was recently started on sertindole. Sertindole was initiated following serious tardive dyskinesia (TD) caused by his previous medication (quetiapine). After 6 weeks of sertindole treatment (16 mg/day), TD remitted and improvement in his psychotic symptoms was observed. The electrocardiograms (ECG) showed normal Q–T intervals (baseline ECG, QTc = 400 msec; heart rate [HR], 70/min; PR, 180 msec; second ECG [2 weeks later following 8 mg/day of sertindole], QTc = 424 msec; HR, 105/min; PR, 180 msec; third ECG [3 weeks later following 16 mg/day of sertindole], QTc = 413 msec; HR, 100/min; PR, 180 msec; and fourth ECG without further changes). Six months following the initiation of sertindole the patient reported five syncopal episodes without clear prodromal symptoms. The patient recalled two sporadic syncopal episodes in his mid 20s. Electroencephalography (EEG) and brain computed tomography were carried out and were within normal limits. Non-interventional cardiological investigation (echocardiography, stress-test, Holter ECG and head-up tilting test) were normal. During the tilting test, blood pressure changed from 135/75 mmHg (baseline) to 130/68 mmHg immediately after tilting, ruling out orthostatic hypotension. Throughout the test, blood pressure and HR range were 15 mmHg and 10 beats per minute, respectively, ruling out vasovagal syncope. Electrophysiological study was negative for sinus node dysfunction and ventricular arrhythmogenesis, but documented an abnormal atrioventricular conduction: (i) H–V interval of 72 (normal values: 35–55 msec); and (ii) Wenckebach point of atrioventricular conduction at an atrial pacing cycle length of 490 msec. Two weeks after the discontinuation of sertindole, H–V was not shortened (70 msec) and based on the current indications for pacemaker implantation and considering the co-morbid psychiatric disease, a pacemaker was implanted and the patient has remained free of symptoms. Since the recurrent syncopal episodes coincided with sertindole administration, sertindole was implicated as a possible triggering factor, unmasking a subclinical defect in the conduction system. This may be attributed to the effect of sertindole on (i) the IKr current and its predominance in the atrioventricular conduction;2 and (ii) the Purkinje fibers.3 Clinicians should be aware of this possible effect of the drug.