Background: The QT interval shortens in response to sympathetic stimulation. Head-up tilt-table (HUT) testing is a straightforward way to achieve brisk sympathetic stimulation. There is not enough information about th...Background: The QT interval shortens in response to sympathetic stimulation. Head-up tilt-table (HUT) testing is a straightforward way to achieve brisk sympathetic stimulation. There is not enough information about the response of the QT interval to HUT, particularly, in patients with orthostatic hypotension (OH). Objective: Analyse the response of the RR, QT and QTc intervals in patients with OH and reflex syncope (NM) during HUT and find differences between groups. Methods: We reviewed the electrocardiograms and compare the RR and QT/QTc intervals during 1) baseline;2) HUT plus hyperventilation;3) positive test. Results: We studied 137 patients, 62 control group (no syncope and negative HUT). On average, the RR HUT interval was shorter than the resting RR by −171 ± 110.4 ms in controls;−228.6 ± 119.4 ms (NM) and −194 ± (OH) (P Conclusion: Significant differences between the reflex group and the OH during a positive test, the QTc decreased in the NM group, but in the OH population increased. This observation has not been described. We hypothesize that QTc prolongation could reflect autonomic nervous system downregulation and could explain to a degree, the increased mortality in this group.展开更多
Background Haloperidol is the most frequently prescribed antipsycbotic for delirium symptoms. The risk of QTc prolongation often raises concerns, although the effect of haloperidol on QTc interval has not yet been inv...Background Haloperidol is the most frequently prescribed antipsycbotic for delirium symptoms. The risk of QTc prolongation often raises concerns, although the effect of haloperidol on QTc interval has not yet been investigated in a randomised placebo-controlled fixed-dose study. Methods A subanalysis of a randomised double-blind placebo-controlled study was conducted to evaluate the effect of prophylactic haloperidol 1 mg or placebo 1 mg orally twice-daily （maximum of 14 doses） on QTc interval in patients aged 70 years and over. Bedside, 12-lead ECGs were recorded before, during and after the one-week intervention period. Automatic QTc measurements were ob- tained in addition to manual measurements of QT and RR intervals, blinded for treatment status. Manual measurements were corrected （QTc） using Bazett （QTc-B）, Framingham （QTc-Fa）, Fridericia （QTc-Fi） and Hodges （QTc-H） methods. Mixed model analyses were used to test for differences in longitudinal course of QTc between patients receiving haloperidol and placebo. Results ECG recordings of 72 patients （haloperidol n = 38） were analysed, 45.8% male. Median （range） haloperidol serum concentration on day 4 was 0.71 （0.32-1.82） μg/L （n = 23）. Longitudinal course of mean QTc did not significantly differ between treatment arms for any of the automatic or manually derived QTc values. Conclusions Low dose oral haloperidol did not result in QTc prolongation in older acutely hospitalised patients. Results may not be generalizable to patients with existing ECG abnormalities such as atrial fibrillation.展开更多
BACKGROUND Despite the controversies about the effectiveness of the current drug regimens for coronavirus disease 2019(COVID-19),these drugs are still the only options available.Moreover,the safety of these drugs is y...BACKGROUND Despite the controversies about the effectiveness of the current drug regimens for coronavirus disease 2019(COVID-19),these drugs are still the only options available.Moreover,the safety of these drugs is yet to be confirmed.A serious concern is the occurrence of various cardiac arrhythmias,particularly QT prolongation.AIM To summarize the incidence and estimate the risk of QT interval prolongation in patients scheduling for conventional treatment(hydroxychloroquine alone or in combination with azithromycin)for COVID-19.METHODS We comprehensively searched Medline,Web of Knowledge,Google Scholar,Scopus,and Cochrane Central Register of Controlled Trials databases until October 31,2020 for all eligible studies under the considered keywords COVID19,arrhythmia,QT interval,therapy,azithromycin,and hydroxychloroquine until.The study protocols were established in compliance with PRISMA-P guidelines(Preferred Reporting Items for Systematic Review and Meta-Analysis–Protocols),and a nine-star Newcastle-Ottawa Scale scoring system was used to assess the methodological quality of all eligible studies.Outcome measures were corrected QT(QTc)prolongation,cardiac arrhythmias,or sudden cardiac death.RESULTS Fifteen studies enrolling 8298 patients with targeted COVID-19 therapeutic regimes were included.The eligible studies found a significant increase in the mean QTc interval following treatment with the described medications compared to baseline QTc with weighted standard differences in means of 0.766.The pooled prevalence rate of QTc prolongation was estimated to be 9.2%(95%confidence interval:4.5%to 18.1%).CONCLUSION Hydroxychloroquine±azithromycin regimen can significantly increase the risk of developing QTc prolongation.展开更多
Background:The mechanism by which ibrutinib,a Bruton's tyrosine kinase inhibitor,can elevate the risk of arrhythmias is not fully elucidated.In this study,we explored how inhibition of off‐target kinases can cont...Background:The mechanism by which ibrutinib,a Bruton's tyrosine kinase inhibitor,can elevate the risk of arrhythmias is not fully elucidated.In this study,we explored how inhibition of off‐target kinases can contribute to this phenomenon.Methods:We performed a Mendelian randomization analysis to examine the causal associations between genetically proxied inhibition of six putative ibrutinib drug targets(ErbB2/HER2,CSK,JAK3,TEC,BLK,and PLCG2)and the atrial fibrillation(AF)risk,proarrhythmic ECG indices,and cardiometabolic traits and diseases.Inverse‐variance weighted random‐effects models and Wald ratio were used to examine the associations between genetically proxied inhibition of these drug targets and the risk of outcomes.Colocalization analyses were employed to examine the robustness of the causally significant findings.ELISAs were used to measure ErbB2 levels in intracardiac plasma samples.Results:Genetically proxied ErbB2 inhibition was associated with an increased AF risk,higher P wave terminal force,and prolonged QTc interval.Patients with AF had significantly higher intracardiac ErbB2 levels compared with patients with paroxysmal supraventricular tachycardia.CSK inhibition prolonged the QRS duration,decreased the QTc interval,and was potentially linked to conduction blocks.PLCG2 inhibition led to decreased P wave terminal force,shorter QTc interval,and increased risk of left bundle branch block.BLK inhibition shortened the QTc interval and was also associated with atrioventricular block.Conclusion:The off‐target effects and downstream targets of ibrutinib,including CSK,PLCG2,ERBB2,TEC,and BLK,may lead to cardiac electrical homeostasis imbalances and lethal cardiovascular diseases.Using drugs that inhibit these targets should be given extra caution.展开更多
文摘Background: The QT interval shortens in response to sympathetic stimulation. Head-up tilt-table (HUT) testing is a straightforward way to achieve brisk sympathetic stimulation. There is not enough information about the response of the QT interval to HUT, particularly, in patients with orthostatic hypotension (OH). Objective: Analyse the response of the RR, QT and QTc intervals in patients with OH and reflex syncope (NM) during HUT and find differences between groups. Methods: We reviewed the electrocardiograms and compare the RR and QT/QTc intervals during 1) baseline;2) HUT plus hyperventilation;3) positive test. Results: We studied 137 patients, 62 control group (no syncope and negative HUT). On average, the RR HUT interval was shorter than the resting RR by −171 ± 110.4 ms in controls;−228.6 ± 119.4 ms (NM) and −194 ± (OH) (P Conclusion: Significant differences between the reflex group and the OH during a positive test, the QTc decreased in the NM group, but in the OH population increased. This observation has not been described. We hypothesize that QTc prolongation could reflect autonomic nervous system downregulation and could explain to a degree, the increased mortality in this group.
文摘Background Haloperidol is the most frequently prescribed antipsycbotic for delirium symptoms. The risk of QTc prolongation often raises concerns, although the effect of haloperidol on QTc interval has not yet been investigated in a randomised placebo-controlled fixed-dose study. Methods A subanalysis of a randomised double-blind placebo-controlled study was conducted to evaluate the effect of prophylactic haloperidol 1 mg or placebo 1 mg orally twice-daily （maximum of 14 doses） on QTc interval in patients aged 70 years and over. Bedside, 12-lead ECGs were recorded before, during and after the one-week intervention period. Automatic QTc measurements were ob- tained in addition to manual measurements of QT and RR intervals, blinded for treatment status. Manual measurements were corrected （QTc） using Bazett （QTc-B）, Framingham （QTc-Fa）, Fridericia （QTc-Fi） and Hodges （QTc-H） methods. Mixed model analyses were used to test for differences in longitudinal course of QTc between patients receiving haloperidol and placebo. Results ECG recordings of 72 patients （haloperidol n = 38） were analysed, 45.8% male. Median （range） haloperidol serum concentration on day 4 was 0.71 （0.32-1.82） μg/L （n = 23）. Longitudinal course of mean QTc did not significantly differ between treatment arms for any of the automatic or manually derived QTc values. Conclusions Low dose oral haloperidol did not result in QTc prolongation in older acutely hospitalised patients. Results may not be generalizable to patients with existing ECG abnormalities such as atrial fibrillation.
文摘BACKGROUND Despite the controversies about the effectiveness of the current drug regimens for coronavirus disease 2019(COVID-19),these drugs are still the only options available.Moreover,the safety of these drugs is yet to be confirmed.A serious concern is the occurrence of various cardiac arrhythmias,particularly QT prolongation.AIM To summarize the incidence and estimate the risk of QT interval prolongation in patients scheduling for conventional treatment(hydroxychloroquine alone or in combination with azithromycin)for COVID-19.METHODS We comprehensively searched Medline,Web of Knowledge,Google Scholar,Scopus,and Cochrane Central Register of Controlled Trials databases until October 31,2020 for all eligible studies under the considered keywords COVID19,arrhythmia,QT interval,therapy,azithromycin,and hydroxychloroquine until.The study protocols were established in compliance with PRISMA-P guidelines(Preferred Reporting Items for Systematic Review and Meta-Analysis–Protocols),and a nine-star Newcastle-Ottawa Scale scoring system was used to assess the methodological quality of all eligible studies.Outcome measures were corrected QT(QTc)prolongation,cardiac arrhythmias,or sudden cardiac death.RESULTS Fifteen studies enrolling 8298 patients with targeted COVID-19 therapeutic regimes were included.The eligible studies found a significant increase in the mean QTc interval following treatment with the described medications compared to baseline QTc with weighted standard differences in means of 0.766.The pooled prevalence rate of QTc prolongation was estimated to be 9.2%(95%confidence interval:4.5%to 18.1%).CONCLUSION Hydroxychloroquine±azithromycin regimen can significantly increase the risk of developing QTc prolongation.
基金funded by the National Natural Science Foundation of China(Grant Nos.81930105 and 82370312).
文摘Background:The mechanism by which ibrutinib,a Bruton's tyrosine kinase inhibitor,can elevate the risk of arrhythmias is not fully elucidated.In this study,we explored how inhibition of off‐target kinases can contribute to this phenomenon.Methods:We performed a Mendelian randomization analysis to examine the causal associations between genetically proxied inhibition of six putative ibrutinib drug targets(ErbB2/HER2,CSK,JAK3,TEC,BLK,and PLCG2)and the atrial fibrillation(AF)risk,proarrhythmic ECG indices,and cardiometabolic traits and diseases.Inverse‐variance weighted random‐effects models and Wald ratio were used to examine the associations between genetically proxied inhibition of these drug targets and the risk of outcomes.Colocalization analyses were employed to examine the robustness of the causally significant findings.ELISAs were used to measure ErbB2 levels in intracardiac plasma samples.Results:Genetically proxied ErbB2 inhibition was associated with an increased AF risk,higher P wave terminal force,and prolonged QTc interval.Patients with AF had significantly higher intracardiac ErbB2 levels compared with patients with paroxysmal supraventricular tachycardia.CSK inhibition prolonged the QRS duration,decreased the QTc interval,and was potentially linked to conduction blocks.PLCG2 inhibition led to decreased P wave terminal force,shorter QTc interval,and increased risk of left bundle branch block.BLK inhibition shortened the QTc interval and was also associated with atrioventricular block.Conclusion:The off‐target effects and downstream targets of ibrutinib,including CSK,PLCG2,ERBB2,TEC,and BLK,may lead to cardiac electrical homeostasis imbalances and lethal cardiovascular diseases.Using drugs that inhibit these targets should be given extra caution.
