Long QT Syndrome and Pregnancy

University of Rochester, Rochester, New York, United States
Journal of the American College of Cardiology (Impact Factor: 16.5). 03/2007; 49(10):1092-8. DOI: 10.1016/j.jacc.2006.09.054
Source: PubMed


This study was designed to investigate the clinical course of women with long QT syndrome (LQTS) throughout their potential childbearing years.
Only limited data exist regarding the risks associated with pregnancy in women with LQTS.
The risk of experiencing an adverse cardiac event, including syncope, aborted cardiac arrest, and sudden death, during and after pregnancy was analyzed for women who had their first birth from 1980 to 2003 (n = 391). Time-dependent Kaplan-Meier and Cox proportional hazard methods were used to evaluate the risk of cardiac events during different peripartum periods.
Compared with a time period before a woman's first conception, the pregnancy time was associated with a reduced risk of cardiac events (hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.10 to 0.76, p = 0.01), whereas the 9-month postpartum time had an increased risk (HR 2.7, 95% CI 1.8 to 4.3, p < 0.001). After the 9-month postpartum period, the risk was similar to the period before the first conception (HR 0.91, 95% CI 0.55 to 1.5, p = 0.70). Genotype analysis (n = 153) showed that women with the LQT2 genotype were more likely to experience a cardiac event than women with the LQT1 or LQT3 genotype. The cardiac event risk during the high-risk postpartum period was reduced among women using beta-blocker therapy (HR 0.34, 95% CI 0.14 to 0.84, p = 0.02).
Women with LQTS have a reduced risk for cardiac events during pregnancy, but an increased risk during the 9-month postpartum period, especially among women with the LQT2 genotype. Beta-blockers were associated with a reduction in cardiac events during the high-risk postpartum time period.

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Available from: Silvia G Priori, Jan 03, 2014
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    • "In general, lethality of cardiac events seems to be predominant in LQTS3 patients than in LQTS1 and LQTS2 patients (91). Women with LQTS have a reduced risk for cardiac events during pregnancy, but the risk quite increases during the 9-month postpartum period, specially in the women with mutation in the KCNH2 gene (92). "
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    ABSTRACT: Primary cardiac arrhythmias are often caused by defects, predominantly in the genes responsible for generation of cardiac electrical potential, i.e., cardiac rhythm generation. Due to the variability in underlying genetic defects, type, and location of the mutations and putative modifiers, clinical phenotypes could be moderate to severe, even absent in many individuals. Clinical presentation and severity could be quite variable, syncope, or sudden cardiac death could also be the first and the only manifestation in a patient who had previously no symptoms at all. Despite usual familial occurrence of such cardiac arrhythmias, disease causal genetic defects could also be de novo in significant number of patients. Long QT syndrome (LQTS) is the most eloquently investigated primary cardiac rhythm disorder. A genetic defect can be identified in ∼70% of definitive LQTS patients, followed by Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) and Brugada syndrome (BrS), where a genetic defect is found in <40% cases. In addition to these widely investigated hereditary arrhythmia syndromes, there remain many other relatively less common arrhythmia syndromes, where researchers also have unraveled the genetic etiology, e.g., short QT syndrome (SQTS), sick sinus syndrome (SSS), cardiac conduction defect (CCD), idiopathic ventricular fibrillation (IVF), early repolarization syndrome (ERS). There exist also various other ill-defined primary cardiac rhythm disorders with strong genetic and familial predisposition. In the present review we will focus on the genetic basis of LQTS and its clinical management. We will also discuss the presently available genetic insight in this context from Saudi Arabia.
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    • "It is not yet known why the postpartum period and the perimenopausal period are associated with increased arrhythmogenicity only in LQT2 (and not for example in LQT1). However, β-blockers reduce the risk for cardiac events during these high-risk periods (Seth et al. 2007; Buber et al. 2011). "
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    • "The combination of these effects helps control cardiac repolarization preventing excessive prolongation of the action potential duration which is associated with a risk of the ventricular arrhythmia torsades de pointes. These cellular findings correlate nicely with clinical studies showing a protective effect of the female hormone progesterone on LQTS-associated arrhythmias (Nakagawa et al., 2006; Rodriguez et al., 2001; Seth et al., 2007). These progesterone-mediated effects are consistent with the findings of different levels of nitrosylation of the L-type Ca 2+ channels (see Murphy work) "
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