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ECG with severely prolonged QT interval and initiation of fast polymorphic ventricular tachycardia degenerating into ventricular fibrillation.
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Key Clinical Message
Low‐dose QT‐prolonging drugs may have detrimental effects on women with Turner's syndrome. Preventive measures would be to use potential QT‐prolonging drugs with precaution and ensure that both before and during treatment, ECGs are evaluated and drug treatment stopped if the QT interval increases.
Context in source publication
Context 1
... cessfully cardioverted. After the procedure, however, the ECG showed considerable changes, including significant QT prolongation (600 msec: Fig. 2) and negative T-waves. As a consequence, she was kept under continu- ous ECG monitoring. Approximately 17 h after the amio- darone infusion, she developed cardiac arrest with ventricular fibrillation (Fig. 3). She was successfully resus- citated by immediate cardioversion and received no addi- tional amiodarone treatment. The ECG normalized after <2 ...
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Introduction
Recent years have seen a shift in perspective on Turner syndrome, as it is no longer considered a significant disability due to therapeutic advances. The delay of diagnosis and the underdiagnosis are common in Turner syndrome, especially because of the great phenotypic variability and lack of firm diagnostic criteria.
Aim
Our first ai...
Increased prenatal diagnoses of sex chromosome aneuploidies (SCAs) amid limited knowledge of their prognoses heighten the need to understand how families contend with the implications of an SCA. To explore the experiences of parents and individuals who received a genetic diagnosis of an SCA (excluding Turner syndrome), we conducted semistructured q...
Citations
... A prolonged QT interval can be overlooked in women with TS because of their increased resting heart rate, and correction with either the Bazett or better Hodge formula is necessary (345). The major concern about QT prolongation has been the use of QT-prolonging drugs that in extreme cases may cause fatal torsade de pointes arrythmia (349). However, a recent follow-up study including 112 patients followed for 10 years did not find any cases with ventricular arrhythmia or sudden cardiac death even though 74% were treated with at least one drug that potentially could increase the QT interval (350). ...
Turner syndrome is a condition in females missing the second sex chromosome (45,X) or parts thereof. It is considered a rare genetic condition and is associated with a wide range of clinical stigmata, such as short stature, ovarian dysgenesis, delayed puberty and infertility, congenital malformations, endocrine disorders, including a range of autoimmune conditions and type 2 diabetes and neurocognitive deficits. Morbidity and mortality is clearly increased compared with the general population and the average age at diagnosis is quite delayed. During recent years it has become clear that a multidisciplinary approach is necessary towards the patient with Turner syndrome. A number of clinical advances has been implemented, and these are reviewed. Our understanding of the genomic architecture of Turner syndrome is advancing rapidly, and these latest developments are reviewed and discussed. Several candidate genes, genomic pathways and mechanisms, including an altered transcriptome and epigenome are also presented.
... The condition also appears to be associated with a heightened risk of supraventricular arrythmias including AF (Cho et al., 2020;Choi et al., 2021;Nielsen et al., 2017;Sozen et al., 2008) and stroke (Silberbach et al., 2018). In terms of effect size, a recent study within a young Korean population reported a three-fold elevation in new AF diagnoses within the TS group across a 6.8yr follow-up period compared to a matched control sample (adjusted hazard ratio = 2.75); no strong age-related effects were noted (Cho et al., 2020). ...
Atrial fibrillation (AF) is a cardiac condition characterised by an irregular heartbeat, atrial pathology and an elevated downstream risk of thrombosis and heart failure, as well as neurological sequelae including stroke and dementia. The prevalence and presentation of, risk factors for, and therapeutic responses to, AF differ by sex, and this sex bias may be partially explained in terms of genetics. Here, we consider four sex-linked genetic mechanisms that may influence sex-biased phenotypes related to AF and provide examples of each: X-linked gene dosage, X-linked genomic imprinting, sex-biased autosomal gene expression, and male-limited Y-linked gene expression. We highlight novel candidate risk genes and pathways that warrant further investigation in clinical and preclinical studies. Understanding the biological basis of sex differences in AF should allow better prediction of disease risk, identification of novel risk/protective factors, and the development of more effective sex-tailored interventions.
... TS is a classic situation with low progesterone and estradiol levels and a high FSH level, which could therefore play a role in QTc duration. Nielsen et al. illustrated the case of a 58-year-old woman with TS absent of long QT gene mutations, who developed significant QT prolongation (465 to 600 ms) 12 h after a single dose of 300 mg of intravenous amiodarone for AF [57]. Seventeen hours later, she had a cardiac arrest with VF treated by immediate cardioversion without additional amiodarone treatment with normalization of her ECG within a few days. ...
Significant variations from the normal QT interval range of 350 to 450 milliseconds (ms) in men and 360 to 460 ms in women increase the risk for ventricular arrhythmias. This difference in the QT interval between men and women has led to the understanding of the influence of sex hormones on the role of gender-specific channelopathies and development of ventricular arrhythmias. The QT interval, which represents the duration of ventricular repolarization of the heart, can be affected by androgen levels, resulting in a sex-specific predilection for acquired and inherited channelopathies such as acquired long QT syndrome in women and Brugada syndrome and early repolarization syndrome in men. Manipulation of the homeostasis of these sex hormones as either hormonal therapy for certain cancers, recreational therapy or family planning and in transgender treatment has also been shown to affect QT interval duration and increase the risk for ventricular arrhythmias. In this review, we highlight the effects of endogenous and exogenous sex hormones in the physiological and pathological states on QTc variation and predisposition to gender-specific pro-arrhythmias.
... The mechanism behind QTc prolongation in TS is unknown, although there are theories suggesting that it is due to the loss of a sex chromosome or associated with (administration) of sex hormones. (10,11) In the general population, a prolonged QTc interval is associated with cardiac arrhythmia, torsades de pointes, a form of ventricular tachycardia, and even death. (12) Whether the reported QTc prolongation in patients with TS contributes to a higher mortality rate in this population is not clear. ...
Context
Turner syndrome (TS) is a genetic condition and reported to be associated with a prolonged rate-corrected QT interval (QTc).
Objectives
To evaluate the prevalence of QTc prolongation in patients with TS, to compare their QTc intervals with healthy controls, and to investigate whether QTc prolongation is associated with a monosomy 45,X karyotype.
Methods
Girls (n=101) and women (n=251) with TS visiting our expertise center from 2004-2018 were included in this cross-sectional study. QT intervals of 12-leaded electrocardiograms were measured manually, using Bazett’s and Hodges’ formulas to correct for heart rate. A QTc interval of >450 ms for girls and >460 ms for women was considered prolonged. QTc intervals of patients with TS were compared to the QTc intervals of healthy girls and women from the same age-groups derived from the literature.
Results
In total, 5% of the population with TS had a prolonged QTc interval using Bazett’s formula and 0% using Hodges’ formula. Mean QTc intervals of these patients were not prolonged compared to the QTc interval of healthy individuals from the literature. Girls showed shorter mean QTc intervals compared to women. We found no association between monosomy 45,X and prolongation of the QTc interval.
Conclusions
This study shows that the QTc interval in girls and women with TS is not prolonged compared to the general population derived from the literature, using both Bazett’s and Hodges’ formulas. Furthermore, girls show shorter QTc intervals compared to women, and a monosomy 45,X karyotype is not associated with QTc prolongation.
... Deaths without any obvious cardiac cause also occur with increased frequency in Turner syndrome, and cardiac arrhythmias related to a prolonged QT interval have been implicated in some cases (Nielsen, Nielsen, Trolle, Gravholt, & Andersen, 2017). The corrected QT interval is prolonged in 33% of children and 20% of adults with Turner syndrome, who may harbor an increased burden of rare gene variants associated with Long QT syndrome Trolle et al., 2013). ...
Turner syndrome is recognized now as a syndrome familiar not only to pediatricians and pediatric specialists, medical geneticists, adult endocrinologists, and cardiologists, but also increasingly to primary care providers, internal medicine specialists, obstetricians, and reproductive medicine specialists. In addition, the care of women with Turner syndrome may involve social services, and various educational and neuropsychologic therapies. This article focuses on the recognition and management of Turner syndrome from adolescents in transition, through adulthood, and into another transition as older women. It can be viewed as an interpretation of recent international guidelines, complementary to those recommendations, and in some instances, an update. An attempt was made to provide an international perspective. Finally, the women and families who live with Turner syndrome and who inspired several sections, are themselves part of the broad readership that may benefit from this review.
... Careful assessment of the QTc interval before the initiation of such agents and electrocardiographic surveillance at least in those with preexisting QTc prolongation should be considered, as illustrated in a recent case report. 80 Decisions should be made on a case-by-case basis, balancing the benefits of these drugs against their potential risks. Because the arrhythmia torsades de pointes is the cause of sudden cardiac death in those with prolonged QTc in the setting of long-QT syndrome, postmortem assessment of women with TS who die suddenly would indicate that prolonged QTc may be the cause by excluding more common causes such AoD, stroke, myocardial infarction, or coronary malformations. ...
Girls and women with Turner syndrome face a lifelong
struggle with both congenital heart disease and acquired cardiovascular
conditions. Bicuspid aortic valve is common, and many have left-sided
heart obstructive disease of varying severity, from hypoplastic leftsided
heart syndrome to minimal aortic stenosis or coarctation of the
aorta. Significant enlargement of the thoracic aorta may progress to
catastrophic aortic dissection and rupture. It is becoming increasingly
apparent that a variety of other cardiovascular conditions, including
early-onset hypertension, ischemic heart disease, and stroke, are the
major factors reducing the life span of those with Turner syndrome. The
presentations and management of cardiovascular conditions in Turner
syndrome differ significantly from the general population. Therefore, an
international working group reviewed the available evidence regarding
the diagnosis and treatment of cardiovascular diseases in Turner
syndrome. It is recognized that the suggestions for clinical practice
stated here are only the beginning of a process that must also involve
the establishment of quality indicators, structures and processes for
implementation, and outcome studies.
... The mechanism behind QTprolongation is unresolved but an increased number of patients with polymorphisms in the QT-genes have been found among TS women with prolonged QT-intervals (Trolle et al., 2013). The clinical significance of prolonged QT-intervals is unresolved, but there may be a risk in treating women with TS with QT-prolonging drugs (Nielsen et al., 2017). ...
... The clinical relevance of these potential abnormalities may be twofold: (1) right-axis deviation in an individual with TS is correlated with the presence of partially abnormal pulmonary venous return (310) and should trigger further diagnostics in those cases that are not already known and (2) QTc prolongation is associated with an increased risk for arrhythmias or even sudden cardiac death in the general population. Yet, it should be emphasized that there is no published evidence so far for sudden cardiac death related to QTc prolongation in women with TS, although case-based QTc prolongation due to a dose of amiodarone followed by cardiac arrest has been seen (311). Additional uncertainties include the threshold to define QT prolongation, and calculation method to define QTc interval in TS -in view of the increased intrinsic heart rate in many individuals with TS, Hodge's formula may be preferred over Bazett's formula, because it takes the higher heart rate into account (312). ...
Turner syndrome affects 25–50 per 100,000 females and can involve multiple organs through all stages of life,
necessitating multidisciplinary approach to care. Previous guidelines have highlighted this, but numerous important
advances have been noted recently. These advances cover all specialty fields involved in the care of girls and women with
TS. This paper is based on an international effort that started with exploratory meetings in 2014 in both Europe and the
USA, and culminated with a Consensus Meeting held in Cincinnati, Ohio, USA in July 2016. Prior to this meeting, five
groups each addressed important areas in TS care: 1) diagnostic and genetic issues, 2) growth and development during
childhood and adolescence, 3) congenital and acquired cardiovascular disease, 4) transition and adult care, and 5) other
comorbidities and neurocognitive issues. These groups produced proposals for the present guidelines. Additionally, four
pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and
Evaluation) evaluation with a separate systematic review of the literature. These four questions related to the efficacy
and most optimal treatment of short stature, infertility, hypertension, and hormonal replacement therapy. The guidelines
project was initiated by the European Society for Endocrinology and the Pediatric Endocrine Society, in collaboration with
The European Society for Pediatric Endocrinology, The Endocrine Society, European Society of Human Reproduction and
Embryology, The American Heart Association, The Society for Endocrinology, and the European Society of Cardiology.
The guideline has been formally endorsed by the European Society for Endocrinology, the Pediatric Endocrine Society,
the European Society for Pediatric Endocrinology, the European Society of Human Reproduction and Embryology and the Endocrine Society. Advocacy groups appointed representatives who participated in
pre-meeting discussions and in the consensus meeting.
... The clinical relevance of these potential abnormalities may be twofold: (1) right-axis deviation in an individual with TS is correlated with the presence of partially abnormal pulmonary venous return (310) and should trigger further diagnostics in those cases that are not already known and (2) QTc prolongation is associated with an increased risk for arrhythmias or even sudden cardiac death in the general population. Yet, it should be emphasized that there is no published evidence so far for sudden cardiac death related to QTc prolongation in women with TS, although case-based QTc prolongation due to a dose of amiodarone followed by cardiac arrest has been seen (311). Additional uncertainties include the threshold to define QT prolongation, and calculation method to define QTc interval in TS -in view of the increased intrinsic heart rate in many individuals with TS, Hodge's formula may be preferred over Bazett's formula, because it takes the higher heart rate into account (312). ...
Turner syndrome (TS) is a chromosomal disorder that affects 25–50 per 100,000 live born females. Patients with TS face a heavy burden of cardiovascular disease (congenital and acquired) with an increased risk of mortality and morbidity compared to the general population. Cardiovascular diseases are a major cause of death in females with TS. Approximately 50% of TS patients have a congenital heart abnormality, with a high incidence of bicuspid aortic valve (BAV), coarctation of the aorta (CoA) and generalised arteriopathy. Frequently, females with TS have systemic hypertension, which is also a risk factor for progressive cardiac dysfunction and aortopathy. This paper aims to provide an overview of the cardiovascular assessment, management and follow up strategies in this high-risk population of TS patients.
