▪ Long QT2 (KCNH2): LQT2 patients may be at risk for life-threatening arrhythmias during sudden noises and startle LQT2 is particularly known to be lifethreatening in females of childbearing age as compared with male counterparts of the same generational age Postpartum LQT2 women are also a high-risk cohort ▪ Long QT3 (SCN5A): LQT3 events occur during times of relative bradycardia and thus may manifest during sleep Patients with SCN5A mutations have a Na+ channel gain-of-function mutation In some LQT3 patients with phenotypic prolonged QT intervals, shortening of the QT intervals with lidocaine or mexiletine has established a paradigm shift from β-blockers alone to consideration of a Na+ blocker in conjunction with a β-blocker ▪ Neonatal LQTS: Symptomatic LQTS in the first year of life is of significant concern, and this is a high-risk patient population Reports of extreme bradycardia as well as 2 : 1 functional AV block have raised QT awareness Although early mortality rates for neonates with LQTS and 2 : 1 AV block was as high as 50% to 60%,131,132 recent publications have shown a more optimistic outcome with use of βblockers, occasional mexiletine, and pacing.133 Important in this retrospective review was the observation that 75% of patients have improvement in their conduction (2 : 1 to 1 : 1) over the first year of life Treatmentof Long QT Syndrome Traditionally, the management options with LQTS were primarily determined by a combination of factors, including the baseline QT interval and clinical symptoms Untreated patients with symptomatic LQTS or significant QT prolongation are at a risk of developing syncope and sudden cardiac death Given that effective treatments are available, there is little excuse not to recommend treatment for symptomatic LQTS patients and asymptomatic patients who are genotype/phenotype positive The treatment of asymptomatic patients and those with borderline QT prolongation (460 to 470 ms) is more controversial Treatment can be divided antiadrenergic therapies (β-blockers and left cardiac sympathetic denervation [LCSD]), ICDs, and gene-specific therapies such as mexiletine In addition, avoidance of excessive stimulant intake, heat exhaustion, electrolyte perturbations, and medications known to prolong the QT interval should be avoided β-Blockers In a landmark paper on LQTS, β-blockers and left stellate ganglionectomy reduced the incidence of life-threatening cardiac events from 53% to 9% in untreated patients and those not receiving antiadrenergic-specific therapies.134 In a follow-up study 15 years later, of 869 patients on β-blockers, Moss showed a reduction in the cardiac event rate in probands and of family members over a 5-year time frame β-blockers remain the mainstay therapy for LQTS Propranolol and nadolol are the two most commonly used β-blockers are clearly effective in LQT1, where the perturbation of the IKs channel makes the patients sensitive to catecholamines Vincent showed that in a large series of LQTI patients followed for over a decade, β-blockers reduced life-threatening cardiac events by 97%.135 The study also highlighted the importance of noncompliance as a major concern, especially in adolescents However, not all β-blockers are equally effective In a study by Chockalingham of 382 LQT1 and LQT2 patients, propranolol provided significantly better QTc shortening in patients with a baseline prolonged QT interval compared with metoprolol and nadolol.136 Nadolol and propranolol were equally effective in symptomatic LQTS, whereas patients on metoprolol had significant breakthrough events; therefore it was strongly recommended that metoprolol should be avoided Part of the antiarrhythmic benefit of propranolol and nadolol over metoprolol may have less to do with the true β-blocking adrenergic properties and more to do with the sodium-channel blocking properties One of the more frequently discussed LQTS conundrums is the role and efficacy of β-blockers in LQT3 LQT3 patients tend to have events during bradycardia The misconception that β-blockers were problematic in LQT3 patients likely related to the inclusion of very high risk infants (600 ms) and a belief that bradycardia would be further exacerbated by β-blockers and thus worsen the clinical phenotype Wilde et al., in a recent large multicenter study of 403 LQT3 patients, found that βblockers were associated with an 83% reduction in cardiac events in females.137 There were fewer events in the male patients; thus conclusive risk reduction could not be proved However, it did not appear that β-blockers were proarrhythmic Left Cardiac Sympathetic Denervation In high-risk patients in whom β-blockers are either not effective in preventing syncope or arrhythmias, are not tolerated, or in the case of patients who are noncompliant, there should be a strong consideration for LCSD.138 LCSD should be considered and discussed before consideration of an implantable cardioverter-defibrillator (ICD) Implantable Cardioverter/Defibrillator In the case of LQTS patients who have experienced a documented cardiac arrest, the present consensus is to implant an ICD138 regardless of patient therapy and compliance This will likely evolve in the untreated LQT1 patient without profound QTc prolongation, and a trial of β-blockers may be considered before ICD implantation The decision to place an ICD in a LQTS patients without a prior cardiac arrest is more controversial It is important to remember that children are active and at risk for injury to the ICD, either through somatic growth or repetitive movement Whereas ICDs can be lifesaving, the risk of inappropriate ICD shocks remains high.139,140 Although some inappropriate