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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 -
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 -
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 -
Journal of the American Heart... Dec 2017The cardiovascular complications of cancer therapeutics are the focus of the burgeoning field of cardio-oncology. A common challenge in this field is the impact of... (Review)
Review
BACKGROUND
The cardiovascular complications of cancer therapeutics are the focus of the burgeoning field of cardio-oncology. A common challenge in this field is the impact of cancer drugs on cardiac repolarization (ie, QT prolongation) and the potential risk for the life-threatening arrhythmia torsades de pointes. Although QT prolongation is not a perfect marker of arrhythmia risk, this has become a primary safety metric among oncologists. Cardiologists caring for patients receiving cancer treatment should become familiar with the drugs associated with QT prolongation, its incidence, and appropriate management strategies to provide meaningful consultation in this complex clinical scenario.
METHODS AND RESULTS
In this article, we performed a systematic review (using Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines) of commonly used cancer drugs to determine the incidence of QT prolongation and clinically relevant arrhythmias. We calculated summary estimates of the incidence of all and clinically relevant QT prolongation as well as arrhythmias and sudden cardiac death. We then describe strategies to prevent, identify, and manage QT prolongation in patients receiving cancer therapy. We identified a total of 173 relevant publications. The weighted incidence of any corrected QT (QTc) prolongation in our systematic review in patients treated with conventional therapies (eg, anthracyclines) ranged from 0% to 22%, although QTc >500 ms, arrhythmias, or sudden cardiac death was extremely rare. The risk of QTc prolongation with targeted therapies (eg, small molecular tyrosine kinase inhibitors) ranged between 0% and 22.7% with severe prolongation (QTc >500 ms) reported in 0% to 5.2% of the patients. Arrhythmias and sudden cardiac death were rare.
CONCLUSIONS
Our systematic review demonstrates that there is variability in the incidence of QTc prolongation of various cancer drugs; however, the clinical consequence, as defined by arrhythmias or sudden cardiac death, remains rare.
Topics: Antineoplastic Agents; Death, Sudden, Cardiac; Electrocardiography; Global Health; Humans; Incidence; Long QT Syndrome; Neoplasms
PubMed: 29217664
DOI: 10.1161/JAHA.117.007724 -
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 -
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 -
Value in Health : the Journal of the... Jul 2015Recent improvements in the identification of the genetic basis of long QT syndrome (LQTS) have led to significant changes in the diagnosis and management of this... (Review)
Review
BACKGROUND
Recent improvements in the identification of the genetic basis of long QT syndrome (LQTS) have led to significant changes in the diagnosis and management of this life-threatening condition. Genetic and electrocardiogram (ECG) tests are the most relevant examples among testing strategies for LQTS, yet their cost-effectiveness remains controversial.
OBJECTIVE
The aim of this work was to review the available evidence on the cost-effectiveness of genetic and ECG testing strategies for the diagnosis of LQTS.
METHODS
We performed a systematic review of the literature on the cost-effectiveness of genetic and ECG screening strategies for the early detection of LQTS using MEDLINE, EMBASE, and CRD databases between 2000 and 2013. A weighted version of Drummond checklist was instrumental in further assessing the quality of the included studies.
RESULTS
We identified four eligible articles. Among them, genetic testing in the early detection of LQTS was cost-effective compared with no testing in symptomatic cases and not cost-effective when compared with watchful waiting in asymptomatic first-degree relatives of patients with established LQTS although it reached cost-effectiveness in higher risk subgroups, whereas ECG testing in neonates was highly cost-effective when compared with any screening strategy.
CONCLUSIONS
LQTS profiling and patients' stratification have the potential to improve the disease management. Because of the limited current knowledge in this field, the present review recommends to perform further cost-effectiveness evaluations of the genetic and ECG screening alternatives, especially within European health care systems, which are still not available in the literature on genetic testing.
Topics: Age Factors; Comparative Effectiveness Research; Cost-Benefit Analysis; Electrocardiography; Genetic Predisposition to Disease; Genetic Testing; Health Care Costs; Heart Rate; Humans; Infant, Newborn; Long QT Syndrome; Models, Economic; Phenotype; Predictive Value of Tests; Young Adult
PubMed: 26297099
DOI: 10.1016/j.jval.2015.03.1788 -
The European Respiratory Journal Nov 2017
Topics: Antitubercular Agents; Diarylquinolines; Electrocardiography; Humans; Long QT Syndrome; Tuberculosis, Multidrug-Resistant
PubMed: 29146605
DOI: 10.1183/13993003.01462-2017