Recurrent syncope associated with a distinct ECG pattern consisting of short QT interval, early repolarization and atrioventricular block

Abstract

A 17-year-old apparently healthy individual with recurrent syncopal episodes during walking was referred to our institution for further evaluation. Baseline ECG showed sinus rhythm with prominent J-waves and ST-segment elevation and a short QT interval of 320 ms (Fig. 1). The corrected QT (QTc) interval was 283, 295 and 288 m using the Bazett’s, the Fredericia’s and the Framingham’s formula, respectively. There was no family history of sudden cardiac death. Transthoracic echocardiography revealed a structurally normal heart. Exercise treadmill test failed to induce any arrhythmic or ischemic events, while the early repolarization features (J-waves and ST-segment elevation) were normalized. A drug-free tilt table test was negative for neurocardiogenic syncope. Holter monitoring revealed several asymptomatic episodes of abrupt advanced AV block during day and night, with a maximum pause of 4.2 s (Fig. 2). No episodes of atrial or ventricular arrhythmic events were recorded. Late potentials (RMS-40, LAS-40) as detected and calculated by signal-averaged ECG were positive. Sodium channel blocking test with procainamide (10 mg/kg) failed to induce the diagnostic type 1 ECG pattern of Brugada syndrome (BS) in the right precordial leads. Quinidine administration (900 mg) normalized the absolute QT and QTc values to 380 and 425 m, respectively. Electrophysiological study (EPS) demonstrated normal AH (110 ms) and HV (49 ms) intervals. Right ventricular programmed stimulation at three basic cycle lengths (600, 500 and 430 m) with up to three extra stimuli failed to induce any ventricular arrhythmias. The atrial and ventricular refractory periods were 190 and 200 ms, respectively. No atrial arrhythmias were induced and no episodes of AV block were documented during EPS. A dual-chamber cardioverter defibrillator (ICD) was implanted. The patient was asymptomatic after a 12-month follow-up period. Genomic DNA was prepared from peripheral blood lymphocytes using standard methods. The entire open reading frame of the KCNQ1, KCNH2 and SCN5A genes was analyzed. The following non-coding genetic variants were identified: KCNQ1 (1638 G [ A S546S), KCNH2 (G3152 ? 22 G [ A) and SCN5A (5457 C [ T D1819D, 3183 G [ A E1061E). The KCNJ2, CACNA1C and CACNB2 genes were not screened for mutations.