Effect of phenylephrine provocation on dispersion of repolarization in congenital long QT syndrome

Introduction: Syncope and sudden death are associated with sympathetic stimulation in LQT1 while LQT2 patients are more susceptible to arrhythmias during nonexertional states. Abnormal spatial (QTd)- and transmural (TDR)-dispersion of repolarization may indicate increased arrhythmogenicity. This study compares the effect of phenylephrine on QTd and TDR in genotyped LQTS to control (C). Methods and Results: Seventeen LQT1, 12 LQT2, and 18 age- and sex-matched normal controls received 2 mcg/kg of phenylephrine intravenously. At baseline and peak phenylephrine effect, BP, QT, RR, Bazett's QTc, precordial QTd (QTmax-QTmin), and T-peak to T-end (Tp-e) intervals were determined blinded to the patient's clinical and genotype status. Baseline QT intervals and QTc were significantly longer in LQT1 and LQT2 compared to C. Baseline QTd and Tp-e were greater in LQT2 than either LQT1 or C: QTd = 79 ± 29 ms (LQT2), 53 ± 26 (LQT1), and 45 ± 15 (C) and Tp-e = 120 ± 30 ms (LQT2), 99 ± 20 (LQT1), and 90 ± 11 (C). Overall, phenylephrine exerted no significant effect on either QTd or Tp-e except with subgroup analysis of symptomatic LQTS where LQT1 and LQT2 patients had a divergent response with TDR. Conclusions: Phenylephrine-induced bradycardia decreased TDR in symptomatic LQT1 but increased TDR in symptomatic LQT2. The observed effects of phenylephrine are consistent with the protective effect of beta-blocker in LQT1 and the increased arrhythmogenicity noted during nonexertional states in LQT2.