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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 -
International Journal of Clinical... Feb 2017Background QTc-interval prolongation has been associated with serious adverse events, such as Torsade de Pointes and sudden cardiac death. In the prevention of... (Meta-Analysis)
Meta-Analysis Review
Background QTc-interval prolongation has been associated with serious adverse events, such as Torsade de Pointes and sudden cardiac death. In the prevention of QTc-prolongation, special attention should go to high-risk patients. Aim of the review The aim of this review is to summarize and assess the evidence for different risk factors for QTc-prolongation (demographic factors, comorbidities, electrolytes, QTc-prolonging medication). Methods Potential studies were retrieved based on a systematic search of articles published until June 2015 in the databases Medline and Embase. Both terms about QTc-prolongation/Torsade de Pointes and risk factors were added in the search strategy. The following inclusion criteria were applied: randomized controlled trials and observational studies; inclusion of ≥500 patients from a general population (not limited to specific disease states); assessment of association between QTc-interval and risk factors. For the articles that met the inclusion criteria, the following data were extracted: study design, setting and study population, number of patients and cases of QTc-prolongation, method of electrocardiogram-monitoring, QTc-correction formula, definition of QTc-prolongation, statistical methods and results. Quality assessment was performed using the GRADE approach (for randomized controlled trials) and the STROBE-recommendations (for observational studies). Based on the number of significant results and the level of significance, a quotation of the evidence was allocated. Results Ten observational studies could be included, with a total of 89,532 patients [prospective cohort design: N = 6; multiple regression analyses: N = 5; median STROBE score = 17/22 (range 15-18)]. Very strong evidence was found for hypokalemia, use of diuretics, antiarrhythmic drugs and QTc-prolonging drugs of list 1 of CredibleMeds. Little or no evidence was found for hyperlipidemia, the use of digoxin or statins, neurological disorders, diabetes, renal failure, depression, alcohol abuse, heart rate, pulmonary disorders, hormone replacement therapy, hypomagnesemia, history of a prolonged QTc-interval/Torsade de Pointes, familial history of cardiovascular disease, and the use of only QTc-prolonging drugs of list 2 or 3 of CredibleMeds. Conclusion This systematic review gives a clear overview of the available evidence for a broad range of risk factors for QTc-prolongation.
Topics: Age Factors; Anti-Arrhythmia Agents; Brugada Syndrome; Cardiac Conduction System Disease; Diuretics; Electrocardiography; Humans; Long QT Syndrome; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Smoking
PubMed: 28012118
DOI: 10.1007/s11096-016-0414-2 -
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 -
Heart, Lung & Circulation Mar 2019Multiple case studies have suggested that video-assisted thoracoscopic sympathectomy (VATS) reduces the occurrence and frequency of symptoms in long QT syndrome (LQTS)...
BACKGROUND
Multiple case studies have suggested that video-assisted thoracoscopic sympathectomy (VATS) reduces the occurrence and frequency of symptoms in long QT syndrome (LQTS) [1,2,3]. To date there has not been a literature review to report on the short-term and long-term outcomes of this procedure. Our primary aims are to review the literature findings on the clinical outcomes of VATS sympathectomy for long QT and present a local centre case report on the outcomes of T2-T5 sympathectomy.
METHODS
Relevant articles were identified by a systematic search of PubMed, Cochrane and Scopus databases, from November 1985 to October 2015. A total of 520 patients from 21 publications were included for analysis and discussion in three main areas: presenting symptoms and indication for surgery, perioperative complications, and patient quality of life following surgery. Our case study reviews a 49-year-old female with recently diagnosed long QT syndrome and intolerance to beta blocker therapy successfully managed with T2-T5 thoracic sympathectomy.
RESULTS
The most common presenting indication for operative management of long QT syndrome was syncope (208/520 patients) and tachyarrhythmia (207/520 patients). T1-T5 left sympathectomy was performed in 15/21 published reports (332/520 patients) with partial stellate removal or in its entirety. Follow-up of patients ranged from 1 month to 11 years. Four patients died in the postoperative period, from fatal arrhythmias. The most common postoperative findings were no symptoms (64/520 patients); tachyarrhythmia (55/520 patients), syncope (45/520 patients), and Horner's syndrome (13/520 patients with 27 patients reporting associated symptoms). Thirteen cases reported on the QTc changes post sympathectomy and 9/13 cases involving 220/520 patients showed marked QTc reduction following surgery. Mean preoperative QTc was 558ms and median 559ms. Mean postoperative QTc was 476ms and median 466ms. Our patient showed a marked reduction in QTc following surgery, with no evidence of arrhythmias and reduced beta blocker dependence.
CONCLUSIONS
Surgical management of LQTS has historically involved a left cervicothoracic stellectomy removing stellate ganglia and typically part of the left thoracic sympathetic chain resulting in reduction in symptoms but increasing the risk of Horner's syndrome and intermittent temperature changes [4,5]. Surgical resection of the thoracic ganglia alone for management of LQTS is scarce in the literature. Short-term follow-up in our case study following a T2-T5 sympathectomy revealed reduction in symptoms, no requirement for beta blocker therapy and reduced QTc interval. Further follow-up using greater patient numbers will further support T2-T5 sympathectomy as an option for surgical management of LQTS.
Topics: Electrocardiography; Heart Conduction System; Humans; Long QT Syndrome; Stellate Ganglion; Sympathectomy; Thoracic Surgery, Video-Assisted
PubMed: 29525134
DOI: 10.1016/j.hlc.2018.02.005 -
Journal of Clinical Medicine Research May 2018Drug induced long QT syndrome is quite common in daily clinical practice but its impact is unknown.
BACKGROUND
Drug induced long QT syndrome is quite common in daily clinical practice but its impact is unknown.
METHODS
PubMed and EMBASE databases (until May 2, 2017) were searched to identify studies reporting drug induced long QT syndrome and followed the PRISMA guidelines. The main outcomes measured in these studies were QTc prolongation, ventricular arrhythmias, torsade de pointes (TdP) and death.
RESULTS
Out of 176 non-duplicate reports, 36 studies satisfied inclusion criteria and provided data on patients exposed to drugs that can potentially cause long QT. Totally, 14,756 patients were exposed and 930 patients (6.3%) were found to have QTc prolongation. The number of males was 6,400 and females were 5,723 patients. The mean age of the patients was 43.8 ± 9.36 years. Ventricular arrhythmias were found in 379 patients (2.6%), 26 patients were found to have premature atrial contractions (PACs) and premature ventricular contractions (PVCs). TdP was found in 49 patients (0.33 %), sudden cardiac death (SCD) was found in five patients and 586 patients were found to have all-cause mortality.
CONCLUSIONS
Around 6% of patients have risk of QT prolongation when exposed but only 0.3% developed TdP and 2.6% developed ventricular arrhythmias. Risk of developing arrhythmias is higher with concomitant use of multiple QT prolonging drugs.
PubMed: 29581800
DOI: 10.14740/jocmr3338w -
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 2018QT/RR hysteresis (QT-hys) is an index of the time accommodation of ventricular repolarization to heart rate changes. This report comprehensively reviews studies... (Review)
Review
BACKGROUND
QT/RR hysteresis (QT-hys) is an index of the time accommodation of ventricular repolarization to heart rate changes. This report comprehensively reviews studies addressing QT-hys as a biomarker of medical conditions.
METHODS
This is a secondary analysis of data from a recent systematic review pertaining to methods of assessment of QT-hys. Articles included in the former review were filtered in order to select original articles investigating the association of QT-hys with medical conditions in humans.
RESULTS
Nineteen articles fulfilled our inclusion criteria. Given the heterogeneity of the methods and investigated conditions, no pooled analysis of data could be implemented. QT-hys was mostly studied as a risk marker of severe arrhythmias, as a predictor of the long QT syndrome (LQTS) phenotypes and genotypes and as a marker of exercise-induced ischemia. An increased QT-hys appears to be implicated in arrhythmogenesis, although the evidence in this regard relies on few human studies. An augmented QT-hys was reported in the LQTS, predominantly in the LQT2 genotype, but conflicting results were obtained between studies using different methods of assessment. In addition, QT-hys appears to be a useful marker of stress-induced myocardial ischemia in patients suspected of coronary artery disease.
CONCLUSIONS
QT-hys evaluation has potential clinical utility in at least some clinical conditions. Further studies of the clinical validity of QT-hys assessment are warranted, particularly condition specific studies based on QT-hys evaluation methods that provide separate estimates of QT-hys and QT/RR dependency.
Topics: Arrhythmias, Cardiac; Electrocardiography; Heart Rate; Humans; Long QT Syndrome
PubMed: 29083088
DOI: 10.1111/anec.12514