Should theophylline be added to the J wave syndrome therapeutic armamentarium?

Abstract

The substrate for both early repolarization syndrome (ERS) and Brugada syndrome (BrS), the so-called J wave syndromes, has been shown to develop as a consequence of genetic variants causing a loss of function of inward currents such as sodium (I Na ) and calcium (I Ca ) channel currents or a gain of function in outward currents such as the transient outward current (I to ). The result is an outward shift of the balance of currents active during the early phases of the epicardial action potential in the right ventricular outflow tract (RVOT) in the case of BrS and in the inferior left ventricle in the case of ERS. 1,2 The principal goal of therapy in both cases is therefore to effect an inward shift in the balance of currents. This can be accomplished either by boosting inward calcium channel current using -adrenergic agent or phosphodiesterase III inhibitors or by reducing outward currents, particularly I to , using agents such as quinidine. 3 Agents that augment the L-type calcium channel current, including adrenergic agents like isoproterenol, denopamine, or orciprenaline, have proved useful. 4-9 Isoproterenol, at times in combination with quinidine, has been utilized successfully to control ventricular fibrillation (VF) storms and normalizing ST elevation particularly in children. 7,10-26 Administration of isoproterenol is a Class IIa recommendation for BrS patients presenting with electrical storms. 27 Phosphodiesterase III inhibitors such as cilostazol 6,7,28 normalize ST segment elevation in BrS as well as ERS by augmenting ICa as well as by reducing I to secondary to an increase in cyclic adenosine monophosphate (cAMP) and heart rate. 29,30 Milrinone is another phosphodiesterase III inhibitor recently identified in an experimental model of BrS as a more potent alternative to cilostazol in suppressing ST elevation and arrhythmogenesis. 31,32 No clinical reports are available as yet for milrinone. In this issue of PACE, 33 Perrin et al. describe successful use of another phosphodiesterase inhibitor, theophylline, to suppress electrical storms associated with early repolarization. The case involves a 12-year-old boy with recurrent nocturnal seizures found to be caused by polymorphic ventricular tachycardia with the characteristic mode of onset of idiopathic VF. 34 Hydroquinidine (900 mg/day) caused complete disappearance of the ER pattern, but did not prevent the development of recurrent episodes of life-threatening ventricular tachycardia (VT)/VF, necessitating the implantation of an implantable cardioverter defibrillator (ICD). In succeeding months, the patient received frequent appropriate ICD shocks for nocturnal polymorphic ventricular tachycardia. Despite three ablation procedure to eliminate premature ventricular contractions, switch of quinidine to disopyramide and nocturnal pacing at 95 beats/min, electrical storms continued, triggered by Conflict of interest: None. hypervagotonia during sleep. Theophylline was initiated at 500 mg twice daily in conjunction with hydroquinidine (300 mg/day), leadin...