Long QT syndrome and pregnancy

University of Rochester, Rochester, New York, United States
Journal of the American College of Cardiology (Impact Factor: 15.34). 03/2007; 49(10):1092-8. DOI: 10.1016/j.jacc.2006.09.054
Source: PubMed

ABSTRACT 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.


Available from: Silvia G Priori, Jan 03, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Long QT syndrome is the most commonly recognised cause of sudden cardiac death in children. With a prevalence of 1 in 2000, family screening is identifying large numbers of hitherto asymptomatic gene carriers in the community, about a third of whom have a normal QT interval. The mainstay of treatment is long term uninterrupted beta blocker therapy, a treatment with many potential side effects. This article reviews the evidence and suggests a cohort who may, after assessment in a specialised cardiac-genetic clinic, be spared this treatment because of very low baseline risk. These are asymptomatic boys and prepubertal girls with a heart rate corrected QT interval persistently less than 470 ms who do not indulge in high risk activities (especially swimming) and do not have a missense mutation in the c-loop region of the KCNQ1 (long QT 1) gene.
    Archives of Disease in Childhood 09/2014; 100(3). DOI:10.1136/archdischild-2014-306864 · 2.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Long QT syndrome is a genetic disorder associated with life threatening ventricular arrhythmias and sudden death. This inherited arrhythmic disorder exhibits genetic heterogeneity, incomplete penetrance, and variable expressivity. During the past two decades there have been major advancements in understanding the genotype-phenotype correlations in LQTS. This genotype-phenotype relationship can lead to improved management of LQTS. However, development of genotype-specific or mutation-specific management strategies is very challenging. This review describes the pathophysiology of LQTS, genotype-phenotype correlations, and focuses on the management of LQTS. In general, the treatment of LQTS consists of lifestyle modifications, medical therapy with beta-blockers, device and surgical therapy. We further summarize current data on the efficacy of pharmacological treatment options for the three most prevalent LQTS variants including beta-blockers in LQT1, LQT2 and LQT3, sodium channel blockers and ranolazine for LQT3, potassium supplementation and spironolactone for LQT2, and possibly sex hormone-based therapy for LQT2.
    Paediatric Drugs 10/2014; 16(6). DOI:10.1007/s40272-014-0090-4 · 1.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: We recently showed that progesterone treatment abolished arrhythmias and sudden cardiac death in a transgenic rabbit model of long QT syndrome type 2 (LQT2). Moreover, levels of cardiac sarcoplasmic reticulum Ca(2)(+) -ATPase2a (SERCA2a) were upregulated in LQT2 heart extracts. We hypothesized that progesterone treatment upregulated SERCA2a expression, thereby reducing Ca(2+)-dependent arrhythmias in LQT2 rabbits. We therefore investigated the effect of progesterone on SERCA2a regulation in isolated cardiomyocytes. Materials & methods: Cardiomyocytes from neonate rabbits (3-5 days old) were isolated, cultured, and treated with progesterone and other pharmacological agents. Immunoblotting was performed on total cell lysates and SR-enriched membrane fractions for protein abundance, and mRNA transcripts were quantified using real-time PCR. The effect of progesterone on baseline Ca(2+) transients and Ca(2+) clearance was determined using digital imaging. Results: Progesterone treatment increased the total pool of SERCA2a protein by slowing its degradation. Using various pharmacological inhibitors of degradation pathways, we showed that progesterone-associated degradation of SERCA2a involves ubiquitination, and progesterone significantly decreases the levels of ubiquitin-tagged SERCA2a polypeptides. Our digital imaging data revealed that progesterone significantly shortened the decay and duration of Ca(2+) transients. Conclusion: Progesterone treatment increases protein levels and activity of SERCA2a. Progesterone stabilizes SERCA2a, in part, by decreasing the ubiquitination level of SERCA2a polypeptides.
    AJP Cell Physiology 09/2014; 307(11). DOI:10.1152/ajpcell.00127.2014 · 3.67 Impact Factor