P465Refractory ventricular tachycardia progressing to dilated cardiomyopathy: an unusual evolution of the andersen-tawil syndrome

Abstract

An asymptomatic 7-year-old girl was referred to our outpatient clinic due to an irregular pulse detected during a routine consultation. The patient had no previous personal or family history of heart disease or sudden death. Physical examination was unremarkable except for some dysmorphic features, namely low-set ears, prominent forehead, small hands and syndactyly of the toes. The electrocardiogram (ECG) and Holter showed numerous, polymorphic premature ventricular contractions (PVC), ventricular bigeminy, short runs of non-sustained polymorphic ventricular tachycardia (NSVT) and bidirectional VT. QTc interval seemed quite normal but an enlarged U-wave was distinctive, associated with prolonged QUc interval. No serum electrolyte abnormalities were found and the transthoracic echocardiography confirmed a structurally and functionally normal heart. An exercise stress test was performed, showing an adequate functional capacity. No increase of the NSVT burden with effort was noted. As the patient's father had periodic paralysis and considering her arrhythmia and dysmorphic features, the diagnosis of Andersen-Tawil syndrome (ATS) was suspected. The molecular genetic analysis demonstrated a mutation in the KCNJ2 gene. Drug therapy with oral propranolol was initially started but did not suppress the short runs of polymorphic PVC and NSTV on ECG and Holter recordings. Other drugs were tried (namely flecainide in isolation and on top of beta-blocker, as well as calcium antagonists), without effectively controlling the arrhythmic burden. An electrophysiological study was performed and mapping of the ventricular ectopy revealed that ectopic beats originated from different parts of left Purkinje network, more frequently from the left inferior septum. Atrial and ventricular stimulation inhibited the arrhythmia but radiofrequency catheter ablation was unsuccessful. During follow-up, despite maintaining frequent and complex PVC and runs of polymorphic NSVT, the patient remained remarkably asymptomatic without any evidence of tachycardia-induced cardiomyopathy. Four years later since the first clinical assessment, she started complaining from fatigue and the transthoracic echocardiogram revealed severely depressed biventricular function. All the treatments initially pursued to suppress the ventricular ectopy were unsuccessful (including optimized dose of beta-blocker, amiodarone and quinidine). Since the lack of response to the different attempted approaches, maintaining end-staged heart failure in the presence of a severe dilated cardiomyopathy, she was successfully submitted to heart transplant.