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Evaluation of the QT interval in patients with drug-induced QT prolongation and torsades de pointes.Journal of Cardiovascular... Oct 2020Data on the optimal location of the electrocardiogram (ECG) leads for the diagnosis of drug-induced long QT syndrome (diLQTS) with torsades de pointes (TdP) are lacking.
BACKGROUND
Data on the optimal location of the electrocardiogram (ECG) leads for the diagnosis of drug-induced long QT syndrome (diLQTS) with torsades de pointes (TdP) are lacking.
METHODS
We systematically reviewed the literature for the ECGs of patients with diLQTS and subsequent TdP. We assessed T wave morphology in each lead and measured the longest QT interval in the limb and chest leads in a standardized fashion.
RESULTS
Of 84 patients, 61.9% were female and the mean age was 58.8 years. QTc was significantly longer in chest versus limb leads (mean (SD) 671 (102) vs. 655 (97) ms, p = .02). Using only limb leads for QT interpretation, 18 (21.4%) ECGs were noninterpretable: 10 (11.9%) due to too flat T waves, 7 (8.3%) due to frequent, early PVCs and 1 (1.2%) due to too low ECG recording quality. In the chest leads, ECGs were noninterpretable in nine (10.7%) patients: six (7.1%) due to frequent, early PVCs, one (1.2%) due to insufficient ECG quality, two (2.4%) due to missing chest leads but none due to too flat T waves. The most common T wave morphologies in the limb leads were flat (51.0%), broad (14.3%), and late peaking (12.6%) T waves. Corresponding chest lead morphologies were inverted (35.5%), flat (19.6%), and biphasic (15.2%) T waves.
CONCLUSIONS
Our results indicate that QT evaluation by limb leads only underestimates the incidence of diLQTS experiencing TdP and favors the screening using both limb and chest lead ECG.
Topics: Electrocardiography; Female; Humans; Long QT Syndrome; Middle Aged; Pharmaceutical Preparations; Torsades de Pointes; Ventricular Premature Complexes
PubMed: 32700358
DOI: 10.1111/jce.14687 -
European Journal of Clinical... Dec 2020To evaluate the toxicity of azithromycin in neonates, infants, and children. (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the toxicity of azithromycin in neonates, infants, and children.
METHODS
A systematic review was performed for relevant studies using Medline (Ovid), PubMed, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, and International Pharmaceutical Abstracts. We calculated the pooled incidence of adverse drug reactions (ADRs) associated with azithromycin based on prospective studies (RCTs and prospective cohort studies) and analyzed the risk difference (RD) of ADRs between azithromycin and placebo or other antibiotics using meta-analysis of RCTs.
RESULTS
We included 133 studies with 4243 ADRs reported in 197,675 neonates, infants, and children who received azithromycin. The safety of azithromycin as MDA in pediatrics was poorly monitored. The main ADRs were diarrhea and vomiting. In prospective non-MDA studies, the most common toxicity was gastrointestinal ADRs (938/1967; 47.7%). The most serious toxicities were cardiac (prolonged QT or irregular heart beat) and idiopathic hypertrophic pyloric stenosis (IHPS). Compared with placebo, azithromycin did not show increased risk ADRs based on RCTs (risk difference - 0.17 to 0.07). The incidence of QT prolonged was higher in the medium-dosage group (10-30 mg/kg/day) than that of low-dosage group (≤ 10 mg/kg/day) (82.0% vs 1.2%).
CONCLUSION
The safety of azithromycin as MDA needs further evaluation. The most common ADRs are diarrhea and vomiting. The risk of the most serious uncommon ADRs (cardiac-prolonged QT and IHPS) is unknown.
Topics: Age of Onset; Anti-Bacterial Agents; Azithromycin; Child; Diarrhea; Humans; Incidence; Long QT Syndrome; Placebos; Prospective Studies; Pyloric Stenosis, Hypertrophic; Randomized Controlled Trials as Topic; Risk Assessment; Vomiting
PubMed: 32681202
DOI: 10.1007/s00228-020-02956-3 -
Heart Rhythm Sep 2020Chloroquine and hydroxychloroquine are now being widely used for treatment of COVID-19. Both medications prolong the QT interval and accordingly may put patients at...
Chloroquine and hydroxychloroquine are now being widely used for treatment of COVID-19. Both medications prolong the QT interval and accordingly may put patients at increased risk for torsades de pointes and sudden death. Published guidance documents vary in their recommendations for monitoring and managing these potential adverse effects. Accordingly, we set out to conduct a systematic review of the arrhythmogenic effect of short courses of chloroquine or hydroxychloroquine. We searched on MEDLINE and Embase, as well as in the gray literature up to April 17, 2020, for the risk of QT prolongation, torsades, ventricular arrhythmia, and sudden death with short-term chloroquine and hydroxychloroquine usage. This search resulted in 390 unique records, of which 41 were ultimately selected for qualitative synthesis and which included data on 1515 COVID-19 patients. Approximately 10% of COVID-19 patients treated with these drugs developed QT prolongation. We found evidence of ventricular arrhythmia in 2 COVID-19 patients from a group of 28 treated with high-dose chloroquine. Limitations of these results are unclear follow-up and possible publication/reporting bias, but there is compelling evidence that chloroquine and hydroxychloroquine induce significant QT-interval prolongation and potentially increase the risk of arrhythmia. Daily electrocardiographic monitoring and other risk mitigation strategies should be considered in order to prevent possible harms from what is currently an unproven therapy.
Topics: Antimalarials; Betacoronavirus; COVID-19; Coronavirus Infections; Death, Sudden; Humans; Hydroxychloroquine; Long QT Syndrome; Pandemics; Pneumonia, Viral; SARS-CoV-2; Torsades de Pointes; COVID-19 Drug Treatment
PubMed: 32438018
DOI: 10.1016/j.hrthm.2020.05.008 -
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 -
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 -
Journal of the American Heart... Jan 2020Background Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death. SUDEP shares many features with sudden cardiac death and sudden...
Background Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death. SUDEP shares many features with sudden cardiac death and sudden unexplained death in the young and may have a similar genetic contribution. We aim to systematically review the literature on the genetics of SUDEP. Methods and Results PubMed, MEDLINE Epub Ahead of Print, Ovid Medline In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Scopus were searched through April 4, 2017. English language human studies analyzing SUDEP for known sudden death, ion channel and arrhythmia-related pathogenic variants, novel variant discovery, and copy number variant analyses were included. Aggregate descriptive statistics were generated; data were insufficient for meta-analysis. A total of 8 studies with 161 unique individuals were included; mean was age 29.0 (±SD 14.2) years; 61% males; ECG data were reported in 7.5% of cases; 50.7% were found prone and 58% of deaths were nocturnal. Cause included all types of epilepsy. Antemortem diagnosis of Dravet syndrome and autism (with duplication of chromosome 15) was associated with 11% and 9% of cases. The most frequently detected known pathogenic variants at postmortem were in Na and K ion channel subunits, as were novel potentially pathogenic variants (11%). Overall, the majority of variants were of unknown significance. Analysis of copy number variant was insignificant. Conclusions SUDEP case adjudication and evaluation remains limited largely because of crucial missing data such as ECGs. The most frequent pathogenic/likely pathogenic variants identified by molecular autopsy are in ion channel or arrhythmia-related genes, with an ≈11% discovery rate. Comprehensive postmortem examination should include examination of the heart and brain by specialized pathologists and blood storage.
Topics: Adolescent; Adult; Arrhythmias, Cardiac; Child; Child, Preschool; Death, Sudden, Cardiac; Epilepsy; Female; Genetic Predisposition to Disease; Genetic Variation; Humans; Infant; Male; Middle Aged; Phenotype; Potassium Channels; Risk Assessment; Risk Factors; Sodium Channels; Sudden Unexpected Death in Epilepsy; Young Adult
PubMed: 31865891
DOI: 10.1161/JAHA.119.012264 -
Journal of Cardiovascular... Jan 2020
Topics: Action Potentials; Cardiac Pacing, Artificial; Death, Sudden, Cardiac; Electrocardiography; Heart Conduction System; Heart Rate; Humans; Long QT Syndrome; Pacemaker, Artificial; Tachycardia, Ventricular; Treatment Outcome; Ventricular Premature Complexes
PubMed: 31808227
DOI: 10.1111/jce.14305 -
Congenital Heart Disease Nov 2019Left cardiac sympathetic denervation (LCSD) has been proposed as useful therapy for long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Left cardiac sympathetic denervation (LCSD) has been proposed as useful therapy for long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT), in addition to anti-arrhythmic agents and implantable cardioverter defibrillators. This study aimed to assess the current evidence for LCSD and compare the open vs the video-assisted thoracoscopic surgery (VATS) approaches.
METHODS
MEDLINE, Embase and Cochrane library databases were searched up to December 2018 for studies reporting the long-term outcomes of LCSD in LQTS, CPVT patients. The incidence of cardiac events (CEs) before and after surgery, the change in QTc interval, and surgical complications were pooled to estimate the efficacy of LCSD. Meta-regression was used to estimate the effects of surgical approach (open vs VATS) on outcomes following LCSD.
RESULTS
Twenty-seven papers met our inclusion criteria (647 patients). VATS was used in 408 patients (63.1%), open surgery in 239 (36.9%). Mean follow-up was 32.3 ± 32.5 months. Postsurgery, 398/585 patients (68.0%) were free of CEs and QTc decreased from 522 ± 61.6 ms to 494 ± 52.3 ms. Meta-regression showed no differences between the two approaches in the incidence of CEs and surgical complications. VATS was associated with a smaller reduction in QTc (β-coefficient -20.04, 95% CI -36.82 to -3.27, P = .019).
CONCLUSIONS
LCSD was associated with a reduction in the incidence of CEs in LQTS, CPVT patients and in the duration of QTc. Open surgery was associated with a greater reduction in QTc. Due to the limitations that hindered our study, a randomized trial is warranted to fully establish LCSD safety and efficacy.
Topics: Adolescent; Adult; Anti-Arrhythmia Agents; Child; Child, Preschool; Defibrillators, Implantable; Electric Countershock; Female; Heart; Heart Rate; Humans; Long QT Syndrome; Male; Postoperative Complications; Risk Factors; Sympathectomy; Tachycardia, Ventricular; Thoracic Surgery, Video-Assisted; Treatment Outcome; Young Adult
PubMed: 31621201
DOI: 10.1111/chd.12855 -
Antiviral Therapy 2019The purpose of this review is to critically analyse data regarding the prevalence and risk factors for developing a prolonged QTc interval and subsequent sudden cardiac... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The purpose of this review is to critically analyse data regarding the prevalence and risk factors for developing a prolonged QTc interval and subsequent sudden cardiac death (SCD) in persons living with HIV (PLWH).
METHODS
A systematic literature search using PubMed and Google Scholar databases was performed using the following search terms: 'HIV and prolonged QTc' and 'managing HIV-patients with prolonged QTc'. References within articles of interest were also evaluated.
RESULTS/DISCUSSION
PLWH are at an increased risk of having a prolonged QTc interval. Some risk factors for this include the virus itself, concomitant medications, comorbid conditions, addictions and electrolyte disturbances. PLWH who have an increased HIV RNA viral load or decreased CD4 T-cell count are at further risk for progressing to sudden cardiac death (SCD). Many medications commonly prescribed in the PLWH population, such as antiretrovirals and antimicrobials used in opportunistic infection prophylaxis, have also been shown to promote QTc prolongation through inhibition of human ether-a-go-go potassium channels or through drug metabolism inhibition of other QTc prolonging drugs.
CONCLUSIONS
Due to the high number of risk factors associated with QTc prolongation, clinicians should incorporate baseline and routine ECG monitoring for PLWH to potentially lower the increased risk of SCD in PLWH.
Topics: Anti-Infective Agents; Anti-Retroviral Agents; CD4 Lymphocyte Count; Death, Sudden, Cardiac; Disease Management; Female; HIV Infections; Humans; Long QT Syndrome; Male; Prevalence; Risk Assessment; Risk Factors; Viral Load
PubMed: 31570667
DOI: 10.3851/IMP3335 -
International Heart Journal Sep 2019Contemporary studies have identified rs10494366 in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene as a new genetic marker in modulating the QT interval and... (Meta-Analysis)
Meta-Analysis
Contemporary studies have identified rs10494366 in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene as a new genetic marker in modulating the QT interval and sudden cardiac death (SCD) in general populations. However, the conclusions were not coincident. Therefore, we conducted for the first time a system evaluation of the relativity of rs10494366, the QT interval, and sudden death by meta-analysis. In our study, the meta-analysis displayed the GG genotype of rs10494366 correlated with the QT interval in women with no heterogeneity, and in diabetes mellitus (DM) patients with minor heterogeneity. In the Caucasian population, the correlation of rs10494366 and sudden death was significant. The heterogeneity referred to the relevance between rs10494366 and sudden death in the Asian population. In conclusion, the minor allele of rs10494366 may have an impact on the QT interval in women or DM patients and may have a potential role in sudden death in the Caucasian population.
Topics: Adaptor Proteins, Signal Transducing; Alleles; Asian People; China; Death, Sudden, Cardiac; Electrocardiography; Female; Genetic Predisposition to Disease; Genotype; Humans; Long QT Syndrome; Male; Polymorphism, Single Nucleotide; Survival Analysis
PubMed: 31447468
DOI: 10.1536/ihj.19-024