Faculty Bibliography

OBJECTIVES/OBJECTIVE:This study sought to determine the relationship between long QT syndrome (LQTS) subtype (LTQ1, LTQ2, LTQ3) and postnatal cardiac events (CEs). BACKGROUND:LQTS presenting with 2:1 atrioventricular block or torsades de pointes in the fetus and/or neonate has been associated with risk for major CEs, but overall outcomes and predictors remain unknown. METHODS:A retrospective study involving 25 international centers evaluated the course of fetuses/newborns diagnosed with congenital LQTS and either 2:1 atrioventricular block or torsades de pointes. The primary outcomes were age at first CE after dismissal from the newborn hospitalization and death and/or cardiac transplantation during follow-up. CE was defined as aborted cardiac arrest, appropriate shock from implantable cardioverter-defibrillator, or sudden cardiac death. RESULTS:A total of 84 fetuses and/or neonates were identified with LQTS (12 as LQT1, 35 as LQT2, 37 as LQT3). Median gestational age at delivery was 37 weeks (interquartile range: 35 to 39 weeks) and age at hospital discharge was 3 weeks (interquartile range: 2 to 5 weeks). Fetal demise occurred in 2 and pre-discharge death in 1. Over a median of 5.2 years, there were 1 LQT1, 3 LQT2, and 23 LQT3 CEs (13 aborted cardiac arrests, 5 sudden cardiac deaths, and 9 appropriate shocks). One patient with LQT1 and 11 patients with LQT3 died or received cardiac transplant during follow-up. The only multivariate predictor of post-discharge CEs was LQT3 status (LQT3 vs. LQT2: hazard ratio: 8.4; 95% confidence interval: 2.6 to 38.9; p < 0.001), and LQT3, relative to LQT2, genotype predicted death and/or cardiac transplant (p < 0.001). CONCLUSIONS:In this large multicenter study, fetuses and/or neonates with LQT3 but not those with LQT1 or LQT2 presenting with severe arrhythmias were at high risk of not only frequent, but lethal CEs.

Implantable loop recorders (ILRs) can be a valuable tool in monitoring patients with inherited arrhythmia. This paper reports on a family with long QT syndrome (type 2 [LQT2]) in which a pseudopolymorphic wide complex tachycardia detected by ILR was ultimately diagnosed as a supraventricular aberrant rhythm, facilitated by noncompliance with beta-blocker therapy. (Level of Difficulty: Intermediate.).

Background: Long QT syndrome (LQTS) may present in the fetus or neonate with signature rhythms of torsades de pointes (TdP) or AV block (AVB).
Objective(s): To describe management and outcomes of a signature perinatal LQTS presentation.
Method(s): This is an ongoing retrospective study currently involving 11 centers. Patients were included for in utero or neonatal (<30 days) TdP/AVB. In utero TdP was diagnosed by fMCG or echocardiographic suspicion of TdP followed by postnatal LQTS confirmation. Cardiac events were appropriate ICD discharge, aborted cardiac arrest, or death/transplant.
Result(s): Forty eligible patients were included (14 male; 20 diagnosed in utero, 1 fetal demise). All live births underwent genotyping (15 SCN5A, 8 KCNH2, 5 KCNQ1, 5 CACNA1C, 1 CALM3, 1 KCNE2, 4 negative). Median GA at delivery was 37 weeks (IQR 35, 39) and first postnatal QTc was 625 ms (561, 688). Pre-discharge management was antiarrhythmic drugs in 36, sympathectomy in 7 (6 L, 0 R, 1 bilateral), and cardiac device implantation in 22 (PM 14, ICD 8). Considering all patients, median age at first post-discharge cardiac event was 38 months with further management consisting of sympathectomy (8 L, 1 R) or device implantation (8 PM, 9 ICD). Seizures occurred in 8 patients and significant developmental delay in 10. Nine patients died (6 SCD, 1 status epilepticus, 1 brain death, 1 respiratory failure), and 2 underwent heart transplantation. LQTS genotype strongly correlated with time to first post-discharge event (Figure).
Conclusion(s): Signature LQTS presentation portends high risk for neurologic and cardiac events, especially with SCN5A/CACNA1C genotypes. Such data should be useful to inform future therapeutic strategies. [Figure presented]
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BACKGROUND:Atrial standstill is an arrhythmogenic condition characterized by the absence of spontaneous electrical and mechanical atrial activity or in response to stimulation. There are few reported familial cases which have been associated with SCN5A mutations co-segregating with GJA5 or RYR2 however isolated SCN5A mutations are rare. OBJECTIVE:The purpose of this study was to determine the clinical and biophysical consequence of a novel SCN5A mutation identified in a family with progressive atrial standstill and sudden death. METHODS:The family of a sporadic case of congenital atrial standstill underwent genetic screening. Human Embryonic Kidney 293 cells were transfected with wild-type (WT) or mutant SCN5A cDNAs. Biophysical properties were studied using whole-cell using patch clamp methods. RESULTS:A novel homozygous SCN5A mutation, p.V1340L was identified in the proband and her sister. The proband had complete atrial standstill whereas the sister had partial atrial standstill. Heterozygous mutations were identified in the mother, father and brother. All three had normal sinus rhythm and were asymptomatic. The mutant Nav1.5(V1340L) reduced Nav1.5 current density as well as showed a depolarizing shift in the voltage-dependent steady-state activation (WT: -35.3±1.62 mV; V1340L: -22.4±2.59 mV; P = 0.001). CONCLUSIONS:A homozygous loss-of-function SCN5A mutation likely results in atrial standstill and sudden death due to suppression of initiation of action potential.

In patients with partial anomalous pulmonary venous return of the right superior pulmonary veins to the superior vena cava, surgical repair generally consists of either intraatrial baffle with or without caval enlargement, or superior caval transection and cavoatrial anastomosis to the right atrial appendage. We discuss here a novel technique of superior caval enlargement without need for patch material or reimplantation.