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Acta Clinica Croatica Dec 2021Congenital long QT syndrome (LQTS) is a disorder of myocardial repolarization defined by a prolonged QT interval on electrocardiogram (ECG) that can cause ventricular... (Review)
Review
Congenital long QT syndrome (LQTS) is a disorder of myocardial repolarization defined by a prolonged QT interval on electrocardiogram (ECG) that can cause ventricular arrhythmias and lead to sudden cardiac death. LQTS was first described in 1957 and since then its genetic etiology has been researched in many studies, but it is still not fully understood. Depending on the type of monogenic mutation, LQTS is currently divided into 17 subtypes, with LQT1, LQT2, and LQT3 being the most common forms. Based on the results of a prospective study, it is suggested that the real prevalence of congenital LQTS is around 1:2000. Clinical manifestations of congenital LQTS include LQTS-attributable syncope, aborted cardiac arrest, and sudden cardiac death. Many patients with congenital LQTS will remain asymptomatic for life. The initial diagnostic evaluation of congenital LQTS includes obtaining detailed personal and multi-generation family history, physical examination, series of 12-lead ECG recordings, and calculation of the LQTS diagnostic score, called Schwartz score. Patients are also advised to undertake 24-hour ambulatory monitoring, treadmill/cycle stress testing, and LQTS genetic testing for definitive confirmation of the diagnosis. Currently available treatment options include lifestyle modifications, medication therapy with emphasis on beta-blockers, device therapy and surgical therapy, with beta-blockers being the first-line treatment option, both in symptomatic and asymptomatic patients.
Topics: Arrhythmias, Cardiac; Death, Sudden, Cardiac; Electrocardiography; Genotype; Humans; Long QT Syndrome; Prospective Studies
PubMed: 35734489
DOI: 10.20471/acc.2021.60.04.22 -
General Hospital Psychiatry 2020Though not approved by the United States Food and Drug Administration, intravenous haloperidol (IVH) is widely used off-label to manage agitation and psychosis in... (Review)
Review
INTRODUCTION
Though not approved by the United States Food and Drug Administration, intravenous haloperidol (IVH) is widely used off-label to manage agitation and psychosis in patients with delirium in the hospital setting. Over the years, concerns have emerged regarding side effects of IVH, particularly its potential to cause QT prolongation, torsades de pointes (TdP), extrapyramidal symptoms and catatonia.
METHODS
We conducted a systematic review of literature of published literature related to side effects of IVH in PubMed in accordance with PRISMA guidelines.
RESULTS
77 of 196 identified manuscripts met inclusion criteria, including 34 clinical trials and 34 case reports or series.
DISCUSSION
Extrapyramidal symptoms, catatonia and neuroleptic malignant syndrome appears to be relatively rare with IVH. In most prospective studies, IVH did not cause greater QT prolongation than placebo, and rates of TdP with IVH appear to be low. There is not clear evidence to suggest that IVH carries greater risk for QT prolongation or TdP than other antipsychotics.
CONCLUSIONS
Based on the available literature, we provide modified evidence-based monitoring recommendations for clinicians prescribing IVH in hospital settings. Specifically, we recommend electrocardiogram monitoring only when using doses >5 mg of IVH and telemetry only for high-risk patients receiving cumulative doses of at least 100 mg or with accurately corrected QTc >500 ms.
Topics: Antipsychotic Agents; Electrocardiography; Haloperidol; Humans; Long QT Syndrome; Prospective Studies; Torsades de Pointes
PubMed: 32979582
DOI: 10.1016/j.genhosppsych.2020.08.008 -
Circulation Feb 2020Long QT syndrome (LQTS) is the first described and most common inherited arrhythmia. Over the last 25 years, multiple genes have been reported to cause this condition...
BACKGROUND
Long QT syndrome (LQTS) is the first described and most common inherited arrhythmia. Over the last 25 years, multiple genes have been reported to cause this condition and are routinely tested in patients. Because of dramatic changes in our understanding of human genetic variation, reappraisal of reported genetic causes for LQTS is required.
METHODS
Utilizing an evidence-based framework, 3 gene curation teams blinded to each other's work scored the level of evidence for 17 genes reported to cause LQTS. A Clinical Domain Channelopathy Working Group provided a final classification of these genes for causation of LQTS after assessment of the evidence scored by the independent curation teams.
RESULTS
Of 17 genes reported as being causative for LQTS, 9 () were classified as having limited or disputed evidence as LQTS-causative genes. Only 3 genes () were curated as definitive genes for typical LQTS. Another 4 genes () were found to have strong or definitive evidence for causality in LQTS with atypical features, including neonatal atrioventricular block. The remaining gene () had moderate level evidence for causing LQTS.
CONCLUSIONS
More than half of the genes reported as causing LQTS have limited or disputed evidence to support their disease causation. Genetic variants in these genes should not be used for clinical decision-making, unless accompanied by new and sufficient genetic evidence. The findings of insufficient evidence to support gene-disease associations may extend to other disciplines of medicine and warrants a contemporary evidence-based evaluation for previously reported disease-causing genes to ensure their appropriate use in precision medicine.
Topics: Atrioventricular Block; Evidence-Based Medicine; Female; Genetic Diseases, Inborn; Genetic Predisposition to Disease; Humans; Long QT Syndrome; Male; Multicenter Studies as Topic
PubMed: 31983240
DOI: 10.1161/CIRCULATIONAHA.119.043132 -
Heart Rhythm Apr 2023Fetal long QT syndrome (LQTS) may present with sinus bradycardia, functional 2:1 atrioventricular block (AVB), and ventricular arrhythmias (ventricular tachycardia... (Meta-Analysis)
Meta-Analysis Review
Fetal long QT syndrome (LQTS) may present with sinus bradycardia, functional 2:1 atrioventricular block (AVB), and ventricular arrhythmias (ventricular tachycardia [VT]/torsades de pointes [TdP]) and lead to fetal or postnatal death. We performed a systematic review and individual participant data meta-analysis of 83 studies reporting outcomes of 265 fetuses for which suspected LQTS was confirmed postnatally and determined risk of adverse perinatal and postnatal outcomes using logistic and stepwise logistic regression. A longer fetal QTc was more predictive of death than any other antenatal factor (receiver operating characteristic [ROC] area under the curve [AUC] 0.85; 95% confidence interval [CI] 0.66-1.00). Risk of death was significantly increased with fetal QTc >600 ms. Neither fetal heart rate nor heart rate z-score predicted death (ROC AUC 0.51; 95% CI 0.31-0.71; and ROC AUC 0.59; 95% CI 0.37-0.80, respectively). The combination of antenatal VT/TdP or functional 2:1 AVB and lack of family history of LQTS was also highly predictive of death (ROC AUC 0.82; 95% CI 0.76-0.88). Our data provide clinical screening tools to enable prediction and intervention for fetuses with LQTS at risk of death.
Topics: Humans; Pregnancy; Female; Electrocardiography; Long QT Syndrome; Torsades de Pointes; Heart Rate, Fetal; Atrioventricular Block; Fetus; DNA-Binding Proteins
PubMed: 36566891
DOI: 10.1016/j.hrthm.2022.12.026 -
Frontiers in Genetics 2019Short QT syndrome (SQTS) is a rare syndrome and affects different types of genes. However, data on differences of clinical profile and outcome of different SQTS types...
BACKGROUND
Short QT syndrome (SQTS) is a rare syndrome and affects different types of genes. However, data on differences of clinical profile and outcome of different SQTS types are sparse.
METHODS
We conducted a pooled analysis of 110 SQTS patients. Patients have been diagnosed between 2000 and 2017 at our institution (n = 12) and revealed using a literature review (n = 98). 29 studies were identified by analysing systematic data bases (PubMed, Web of Science, Cochrane Libary, Cinahl).
RESULTS
67 patients with genotype positive SQTS origin and 43 patients with genotype negative origin were found. A significant difference is documented between the sex with a higher predominance of male in genotype negative SQTS patients and predominance of females in genotype positive SQTS patients (male 52% versus 84%, female 45% versus 14%; p = 0.0016). No relevant difference of their median age (genotype positive 27 ± 19 versus genotype negative 29 ± 15; p = 0.48) was found. Asymptomatic patients and patients reporting symptoms such as syncope, sudden cardiac death, atrial flutter and ventricular fibrillation documented in both groups were similar except atrial fibrillation (genotype positive 19% versus genotype negative 0%; p = 0.0055). The QTc interval was not significantly different in both groups (genotype positive 315 ± 32 versus genotype negative 320 ± 19; p = 0.30). The treatments (medical treatment and ICD implantation) in both groups were comparable. Electrophysiology studies were not significantly higher documented in patients with genotype positive and negative origin (24% versus 9%; p = 0.075). Events at follow up such as VT, VF, and SCD were not higher presented in patients with genotype positive (13% versus 9%) (p = 0.25). 54% of genotype positive SQTS patients showed SQTS 1 followed by STQS 2 (21%) and SQTS 3 (10%).
CONCLUSIONS
The long-term risk of a malignant arrhythmic event is not higher in patients with genotype positive. However, patients with genotype positive present themselves more often with AF with a female predominance. Also, other events at follow up such as syncope, atrial flutter and palpitation were not significantly higher (9% versus 0%; p = 0.079).
PubMed: 32010184
DOI: 10.3389/fgene.2019.01312 -
Current Problems in Cardiology Sep 2022Humans and mammals have sex-specific differences in cardiac electrophysiology, linked to the action of sex hormones in the cardiac muscle. These hormones can upregulate... (Review)
Review
Humans and mammals have sex-specific differences in cardiac electrophysiology, linked to the action of sex hormones in the cardiac muscle. These hormones can upregulate or downregulate the expression of ionic channels modulating the cardiac cycle through genomic and non-genomic interactions. Systematic search in PubMed, Medline and EMBASE including keywords pertaining to testosterone and QT interval. Included experimental studies and observation studies and case reports presenting the results of testosterone administration, excess or deficiency in humans and animals. Testosterone has been shown to shorten the action potential duration, by enhancing the expression of K channels and downregulating I increasing the repolarization reserve of the cardiac muscle. This effect has been observed in both genders and animals. Testosterone deficient states can promote arrhythmogenesis. The evidence in this paper may be used to guide clinical considerations, such as increased clinical surveillance of patients in testosterone deficient states using ECG.
Topics: Animals; Arrhythmias, Cardiac; Electrocardiography; Female; Gonadal Steroid Hormones; Humans; Ion Channels; Long QT Syndrome; Male; Mammals; Testosterone
PubMed: 34103195
DOI: 10.1016/j.cpcardiol.2021.100882 -
Annals of Noninvasive Electrocardiology... Jan 2023QTc prolongation is key in diagnosing long QT syndrome (LQTS), however 25%-50% with congenital LQTS (cLQTS) demonstrate a normal resting QTc. T wave morphology (TWM) can... (Review)
Review
INTRODUCTION
QTc prolongation is key in diagnosing long QT syndrome (LQTS), however 25%-50% with congenital LQTS (cLQTS) demonstrate a normal resting QTc. T wave morphology (TWM) can distinguish cLQTS subtypes but its role in acquired LQTS (aLQTS) is unclear.
METHODS
Electronic databases were searched using the terms "LQTS," "long QT syndrome," "QTc prolongation," "prolonged QT," and "T wave," "T wave morphology," "T wave pattern," "T wave biomarkers." Whole text articles assessing TWM, independent of QTc, were included.
RESULTS
Seventeen studies met criteria. TWM measurements included T-wave amplitude, duration, magnitude, Tpeak-Tend, QTpeak, left and right slope, center of gravity (COG), sigmoidal and polynomial classifiers, repolarizing integral, morphology combination score (MCS) and principal component analysis (PCA); and vectorcardiographic biomarkers. cLQTS were distinguished from controls by sigmoidal and polynomial classifiers, MCS, QTpeak, Tpeak-Tend, left slope; and COG x axis. MCS detected aLQTS more significantly than QTc. Flatness, asymmetry and notching, J-Tpeak; and Tpeak-Tend correlated with QTc in aLQTS. Multichannel block in aLQTS was identified by early repolarization (ERD ) and late repolarization (LRD ), with ERD reflecting hERG-specific blockade. Cardiac events were predicted in cLQTS by T wave flatness, notching, and inversion in leads II and V , left slope in lead V ; and COG last 25% in lead I. T wave right slope in lead I and T-roundness achieved this in aLQTS.
CONCLUSION
Numerous TWM biomarkers which supplement QTc assessment were identified. Their diagnostic capabilities include differentiation of genotypes, identification of concealed LQTS, differentiating aLQTS from cLQTS; and determining multichannel versus hERG channel blockade.
Topics: Humans; Electrocardiography; Long QT Syndrome; Genotype; Biomarkers
PubMed: 36345173
DOI: 10.1111/anec.13015 -
Journal of the American Heart... Jul 2022Background Diagnosis is particularly challenging in concealed or asymptomatic long QT syndrome (LQTS). Provocative testing, unmasking the characterization of LQTS, is a... (Meta-Analysis)
Meta-Analysis Review
Background Diagnosis is particularly challenging in concealed or asymptomatic long QT syndrome (LQTS). Provocative testing, unmasking the characterization of LQTS, is a promising alternative method for the diagnosis of LQTS, but without uniform standards. Methods and Results A comprehensive search was conducted in PubMed, Embase, and the Cochrane Library through October 14, 2021. The fixed effects model was used to assess the effect of the provocative testing on QTc interval. A total of 22 studies with 1137 patients with LQTS were included. At baseline, QTc interval was 40 ms longer in patients with LQTS than in controls (mean difference [MD], 40.54 [95% CI, 37.43-43.65]; <0.001). Compared with the control group, patients with LQTS had 28 ms longer ΔQTc upon standing (MD, 28.82 [95% CI, 23.05-34.58]; <0.001), nearly 30 ms longer both at peak exercise (MD, 27.31 [95% CI, 21.51-33.11]; <0.001) and recovery 4 to 5 minutes (MD, 29.85 [95% CI, 24.36-35.35]; <0.001). With epinephrine infusion, QTc interval was prolonged both in controls and patients with QTS, most obviously in LQT1 (MD, 68.26 [95% CI, 58.91-77.60]; <0.001) and LQT2 (MD, 60.17 [95% CI, 50.18-70.16]; <0.001). Subgroup analysis showed QTc interval response to abrupt stand testing and exercise testing varied between LQT1, LQT2, and LQT3, named Type Ⅰ, Type Ⅱ, and Type Ⅲ. Conclusions QTc trend Type Ⅰ and Type Ⅲ during abrupt stand testing and exercise testing can be used to propose a prospective evaluation of LQT1 and LQT3, respectively. Type Ⅱ QTc trend combined epinephrine infusion testing could distinguish LQT2 from control. A preliminary diagnostic workflow was proposed but deserves further evaluation.
Topics: Electrocardiography; Epinephrine; Exercise Test; Genotype; Humans; Long QT Syndrome
PubMed: 35861842
DOI: 10.1161/JAHA.122.025246 -
Cureus Sep 2021Long QT syndrome (LQTS) is one of the most common inherited cardiac channelopathies with a prevalence of 1:2000. The condition can be congenital or acquired with 15... (Review)
Review
Long QT syndrome (LQTS) is one of the most common inherited cardiac channelopathies with a prevalence of 1:2000. The condition can be congenital or acquired with 15 recognized genotypes; the most common subtypes are LQTS 1, 2, and 3 making up to 85%-90% of the cases. LQTS is characterized by delayed ventricular cardiomyocyte repolarization manifesting on the surface electrocardiogram (EKG) by a prolonged corrected QT (QTc) interval. The mainstay of treatment for this condition involves in part or combination medical therapy via β-blockers as first-line (or other anti-arrhythmic), left cardiac sympathectomy, or implantable cardiac defibrillator placement. Given the high rate of adverse cardiac events (ACE) or sudden cardiac death (SCD) in this population of patients with this disease, this review seeks to highlight the genotype-specific treatment consensus in β-blocker therapy of the most common subtypes. A database search of PubMed, PMC, and Medline was conducted to ascertain the most recent data in the last five years on the management of LQTS types 1-3 and the role of β-blockers in reducing ACE in these types. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adhered to in the study selection, and selected studies focused on humans, written in the English Language, and within the last five years of LQTS subtypes 1, 2, and 3. Eleven relevant studies were selected after considering inclusion criteria, exclusion criteria, and quality appraisal within the last five years, focusing on β-blocker selection directed based on the subtypes of LQTS. Two meta-analyses, one cohort study, and eight reviews provided significant data that non-selective β-blockers unequivocally are of benefit in these LQTS types. Summary of findings suggested nadolol followed by propranolol yields the best results in LQTS 1, while nadolol would yield the best effect in LQTS 2 and 3.
PubMed: 34646680
DOI: 10.7759/cureus.17632 -
European Journal of Clinical... May 2022Many drugs are associated with the risk of QT prolongation and torsades de pointes (TdP), and different risk assessment tools (RATs) are developed to help clinicians to... (Review)
Review
PURPOSE
Many drugs are associated with the risk of QT prolongation and torsades de pointes (TdP), and different risk assessment tools (RATs) are developed to help clinicians to manage related risk. The aim of this systematic review was to summarize the evidence of different RATs for QT prolonging pharmacotherapy.
METHODS
A systematic review was conducted using PubMed and Scopus databases. Studies concerning risk assessment tools for QT prolonging pharmacotherapy, including older adults, were included. Screening and selection of the studies, data extraction, and risk of bias assessment were undertaken.
RESULTS
A total of 21 studies were included, involving different risk assessment tools. Most commonly used tools were risk scores (n = 9), computerized physician order entry systems (n = 3), and clinical decision support systems (n = 6). The tools were developed mainly for physicians and pharmacists. Risk scores included a high number of risk factors, both pharmacological and non-pharmacological, for QT prolongation and TdP. The inclusion of patients' risk factors in computerized physician order entry and clinical decision support systems varied.
CONCLUSION
Most of the risk assessment tools for QT prolonging pharmacotherapy give a comprehensive overview of patient-specific risks of QT prolongation and TdP and reduce modifiable risk factors and actual events. The risk assessment tools could be better adapted to different health information systems to help in clinical decision-making. Further studies on clinical validation of risk assessment tools with randomized controlled trials are needed.
Topics: Aged; DNA-Binding Proteins; Electrocardiography; Humans; Long QT Syndrome; Risk Assessment; Risk Factors; Torsades de Pointes
PubMed: 35156131
DOI: 10.1007/s00228-022-03285-3