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Pacing and Clinical Electrophysiology :... Mar 2018Corrected QT interval (QTc) on the electrocardiogram is a marker of ventricular repolarization. Recent studies have examined its value in predicting the occurrence of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Corrected QT interval (QTc) on the electrocardiogram is a marker of ventricular repolarization. Recent studies have examined its value in predicting the occurrence of atrial fibrillation (AF).
METHODS AND RESULTS
We conducted a meta-analysis to determine whether alterations in QTc interval are associated with an increased risk of incident AF. The PUBMED and EMBASE databases were searched for all studies that evaluated the incident AF associated with prolonged QTc interval published before December 2016. Sensitivity and subgroup analysis were subsequently performed. A total of six studies including eight data sets for prolonged QTc interval were eligible. Subjects with prolonged QTc interval as a categorical variable had a significantly higher risk of AF during follow-up (hazard ratio [HR]: 1.16; 95% confidence interval [CI], 1.09-1.24, I = 90%) based on Bazett formula. In continuous variable analysis, we found a statistically significant risk for AF (HR, 1.17; 95% CI, 1.09-1.25; I = 0) every 10-ms prolongation in QTc. AF type, QTc cut-off value, geographical location, follow-up duration, and study population may be the possible reasons for the significant heterogeneity among the studies.
CONCLUSIONS
Prolonged QTc interval is associated with an increased risk of AF. And the potential mechanisms underlying this cause-and-effect relationship need further investigation.
Topics: Atrial Fibrillation; Electrocardiography; Humans; Long QT Syndrome; Predictive Value of Tests; Risk Factors
PubMed: 29380395
DOI: 10.1111/pace.13292 -
European Journal of Clinical... Feb 2021The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide resulting in significant morbidity and mortality. Arrhythmias are prevalent...
BACKGROUND
The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide resulting in significant morbidity and mortality. Arrhythmias are prevalent and reportedly, the second most common complication. Several mechanistic pathways are proposed to explain the pro-arrhythmic effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A number of treatment approaches have been trialled, each with its inherent unique challenges. This rapid systematic review aimed to examine the current incidence and available treatment of arrhythmias in COVID-19, as well as barriers to implementation.
METHODS
Our search of scientific databases identified relevant published studies from 1 January 2000 until 1 June 2020. We also searched Google Scholar for grey literature. We identified 1729 publications of which 1704 were excluded.
RESULTS
The incidence and nature of arrhythmias in the setting of COVID-19 were poorly documented across studies. The cumulative incidence of arrhythmia across studies of hospitalised patients was 6.9%. Drug-induced long QT syndrome secondary to antimalarial and antimicrobial therapy was a significant contributor to arrhythmia formation, with an incidence of 14.15%. Torsades de pointes (TdP) and sudden cardiac death (SCD) were reported. Treatment strategies aim to minimise this through risk stratification and regular monitoring of corrected QT interval (QTc).
CONCLUSION
Patients with SARS-CoV-2 are at an increased risk of arrhythmias. Drug therapy is pro-arrhythmogenic and may result in TdP and SCD in these patients. Risk assessment and regular QTc monitoring are imperative for safety during the treatment course. Further studies are needed to guide future decision-making.
Topics: Anti-Arrhythmia Agents; Anti-Bacterial Agents; Antimalarials; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Azithromycin; Bradycardia; COVID-19; Cardiac Pacing, Artificial; Death, Sudden, Cardiac; Electric Countershock; Hospitalization; Humans; Hydroxychloroquine; Incidence; Long QT Syndrome; SARS-CoV-2; Tachycardia, Ventricular; Torsades de Pointes; Ventricular Fibrillation; COVID-19 Drug Treatment
PubMed: 33043453
DOI: 10.1111/eci.13428 -
Medicine Aug 2021Lopinavir, ritonavir, atazanavir, and saquinavir had been reportedly used or suggested for coronavirus disease 2019 (COVID-19) treatment. They may cause...
BACKGROUND
Lopinavir, ritonavir, atazanavir, and saquinavir had been reportedly used or suggested for coronavirus disease 2019 (COVID-19) treatment. They may cause electrocardiography changes. We aim to evaluate risk of PR prolongation, QRS widening, and QT prolongation from lopinavir, ritonavir, atazanavir, and saquinavir.
METHODS
In accordance with preferred reporting items for systematic reviews and meta-analyses guidelines, our search was conducted in PubMed Central, PubMed, EBSCOhost, and ProQuest from inception to June 25, 2020. Titles and abstracts were reviewed for relevance. Cochrane Risk of Bias Tool 2.0 and Downs and Black criteria was used to evaluate quality of studies.
RESULTS
We retrieved 9 articles. Most randomized controlled trials have low risk of biases while all quasi-experimental studies have a positive rating. Four studies reporting PR prolongation however only 2 studies with PR interval >200 ms. One of which, reported its association after treatment with ritonavir-boosted saquinavir treatment while another, during treatment with ritonavir-boosted atazanavir. No study reported QRS widening >120 ms with treatment. Four studies reporting QT prolongation, with only one study reaching QT interval >450 ms after ritonavir-boosted saquinavir treatment on healthy patients. There is only one study on COVID-19 patients reporting QT prolongation in 1 out of 95 patients after ritonavir-boosted lopinavir treatment.
CONCLUSION
Limited evidence suggests that lopinavir, ritonavir, atazanavir, and saquinavir could cause PR prolongation, QRS widening, and QT prolongation. Further trials with closer monitoring and assessment of electrocardiography are needed to ascertain usage safety of antivirals in COVID-19 era.
Topics: Adult; Atazanavir Sulfate; Cytochrome P-450 CYP3A Inhibitors; Drug Therapy, Combination; Electrocardiography; Humans; Long QT Syndrome; Lopinavir; Ritonavir; Saquinavir
PubMed: 34397829
DOI: 10.1097/MD.0000000000026787 -
Journal of Human Lactation : Official... Feb 2015Breastfeeding is the optimal method for feeding a newborn. However, some mothers may have difficulties lactating. Domperidone is widely used as a galactagogue but to the... (Review)
Review
Breastfeeding is the optimal method for feeding a newborn. However, some mothers may have difficulties lactating. Domperidone is widely used as a galactagogue but to the best of our knowledge has not been approved by any health authority. The objective of this review was to assess the benefit-risk ratio of domperidone for stimulating lactation. The benefit-risk ratio of domperidone as a galactagogue was assessed following a literature search of the PubMed database up to July 2013. Four studies were selected to assess domperidone efficacy and demonstrated an increased milk production. The limited data (60 mother-baby pairs) and the moderate methodological quality of 1 study remain insufficient to conclude on domperidone efficacy. Regarding the safety of domperidone, 7 studies were selected that exposed 113 infants to domperidone through breastfeeding. No adverse effects were observed in 85 infants, and no information was provided for the remaining 28. The limited data available remain in favor of a safe domperidone profile in infants and mothers. However, in large studies focused on gastrointestinal disorders, domperidone is responsible for drug-induced long QT syndrome and sudden cardiac death. The use of domperidone as a galactagogue is worrisome as drug-induced long QT syndrome occurred mostly in women. In these circumstances, an improvement of breastfeeding practices seems to be more effective and safer than the use of an off-label domperidone treatment.
Topics: Breast Feeding; Domperidone; Female; Galactogogues; Humans; Infant, Newborn; Milk, Human; Risk Assessment
PubMed: 25475074
DOI: 10.1177/0890334414561265 -
Journal of the American Academy of... Jan 2015To evaluate the effect of antipsychotics on the corrected QT (QTc) interval in youth. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the effect of antipsychotics on the corrected QT (QTc) interval in youth.
METHOD
We searched PubMed (http://www.ncbi.nlm.nih.gov/pubmed) for randomized or open clinical trials of antipsychotics in youth <18 years with QTc data, meta-analyzing the results. Meta-regression analyses evaluated the effect of age, sex, dose, and study duration on QTc. Incidences of study-defined QTc prolongation (>440-470 milliseconds), QTc >500 milliseconds, and QTc change >60 milliseconds were also evaluated.
RESULTS
A total of 55 studies were meta-analyzed, evaluating 108 treatment arms covering 9 antipsychotics and including 5,423 patients with QTc data (mean age = 12.8 ± 3.6 years, female = 32.1%). Treatments included aripiprazole: studies = 14; n = 814; haloperidol: studies = 1; n = 15; molindone: studies = 3; n = 125; olanzapine: studies = 5; n = 212; paliperidone: studies = 3; n = 177; pimozide: studies = 1; n = 25; quetiapine: studies = 5; n = 336; risperidone: studies = 23; n = 2,234; ziprasidone: studies = 10, n = 523; and placebo: studies = 19, n = 962. Within group, from baseline to endpoint, aripiprazole significantly decreased the QTc interval (-1.44 milliseconds, CI = -2.63 to -0.26, p = .017), whereas risperidone (+1.68, CI = +0.67 to +2.70, p = .001) and especially ziprasidone (+8.74, CI = +5.19 to +12.30, p < .001) significantly increased QTc. Compared to pooled placebo arms, aripiprazole decreased QTc (p = .007), whereas ziprasidone increased QTc (p < .001). Compared to placebo, none of the investigated antipsychotics caused a significant increase in the incidence of the 3 studied QTc prolongation measures, but there was significant reporting bias.
CONCLUSION
Based on these data, the risk of pathological QTc prolongation seems low during treatment with the 9 studied antipsychotics in otherwise healthy youth. Nevertheless, because individual risk factors interact with medication-related QTc effects, both medication and patient factors need to be considered when choosing antipsychotic treatment.
Topics: Adolescent; Antipsychotic Agents; Child; Clinical Trials as Topic; Electrocardiography; Humans; Long QT Syndrome
PubMed: 25524787
DOI: 10.1016/j.jaac.2014.10.002 -
Drug Safety Oct 2022Electrocardiogram (ECG) monitoring is an important tool to detect and mitigate the risk of potentially fatal drug-induced QT prolongation and remains fundamental in... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Electrocardiogram (ECG) monitoring is an important tool to detect and mitigate the risk of potentially fatal drug-induced QT prolongation and remains fundamental in supporting the quality use of high-risk QT interval prolonging medicines.
OBJECTIVE
The aim of this systematic review was to determine the prevalence of baseline and/or follow-up ECG use in adult patients taking high-risk QT interval prolonging medicines in clinical practice.
METHODS
CINAHL, Cochrane Library, Embase, PubMed, EThOS, OpenGrey and Proquest were searched for studies in adults that reported ECG use at baseline and/or at follow-up in relation to the initiation of a high-risk QT interval prolonging medicine in any clinical setting; either hospital or non-hospital. Two reviewers independently assessed the methodological quality of included studies. Proportional meta-analysis was conducted with all studies reporting baseline ECG use, before medicine initiation, and follow-up ECG use, within 30 days of medicine initiation.
RESULTS
There was variability in baseline ECG use according to the practice setting. The prevalence of baseline ECG use for high-risk QT interval prolonging medicines was moderate to high in the hospital setting at 75.1% (95% CI 64.3-84.5); however, the prevalence of baseline ECG use was low in the non-hospital setting at 33.7% (95% CI 25.8-42.2). The prevalence of follow-up ECG use was low to moderate in the hospital setting at 39.2% (95% CI 28.2-50.8) and could not be determined for the non-hospital setting.
CONCLUSIONS
The use of ECG monitoring for high-risk QT interval prolonging medicines is strongly influenced by the clinical practice setting. Baseline ECG use occurs more in the hospital setting in comparison to the non-hospital setting. There is lower use of follow-up ECG in comparison to baseline ECG.
Topics: Adult; Electrocardiography; Humans; Long QT Syndrome; Prevalence; Risk Factors
PubMed: 35947343
DOI: 10.1007/s40264-022-01215-x -
Heart Rhythm Nov 2022Electronic gaming has recently been reported as a precipitant of life-threatening cardiac arrhythmia in susceptible individuals.
BACKGROUND
Electronic gaming has recently been reported as a precipitant of life-threatening cardiac arrhythmia in susceptible individuals.
OBJECTIVE
The purpose of this study was to describe the population at risk, the nature of cardiac events, and the type of game linked to cardiac arrhythmia associated with electronic gaming.
METHODS
A multisite international case series of suspected or proven cardiac arrhythmia during electronic gaming in children and a systematic review of the literature were performed.
RESULTS
Twenty-two patients (18 in the case series and 4 via systematic review; aged 7-16 years; 19 males [86%]) were identified as having experienced suspected or proven ventricular arrhythmia during electronic gaming; 6 (27%) had experienced cardiac arrest, and 4 (18%) died suddenly. A proarrhythmic cardiac diagnosis was known in 7 (31%) patients before their gaming event and was established afterward in 12 (54%). Ten patients (45%) had catecholaminergic polymorphic ventricular tachycardia, 4 (18%) had long QT syndrome, 2 (9%) were post-congenital cardiac surgery, 2 (9%) had "idiopathic" ventricular fibrillation, and 1 (after Kawasaki disease) had coronary ischemia. In 3 patients (14%), including 2 who died, the diagnosis remains unknown. In 13 (59%) patients for whom the electronic game details were known, 8 (62%) were war games.
CONCLUSION
Electronic gaming can precipitate lethal cardiac arrhythmias in susceptible children. The incidence appears to be low, but syncope in this setting should be investigated thoroughly. In children with proarrhythmic cardiac conditions, electronic war games in particular are a potent arrhythmic trigger.
Topics: Male; Child; Humans; Arrhythmias, Cardiac; Heart; Tachycardia, Ventricular; Death, Sudden; Video Games; Death, Sudden, Cardiac
PubMed: 37850595
DOI: 10.1016/j.hrthm.2022.08.003 -
British Medical Bulletin Sep 2018Sudden cardiac death (SCD) of young athletes during competition or training is a tragic event. The long QT syndrome (LQTS) is an arrythmogenic disorder characterized by...
INTRODUCTION
Sudden cardiac death (SCD) of young athletes during competition or training is a tragic event. The long QT syndrome (LQTS) is an arrythmogenic disorder characterized by prolonged ventricular repolarization leading to torsade de pointes evident at electrocardiogram (ECG). Implantable cardioverter defibrillator is an option to revert ventricular fibrillation to sinus rhythm, although the implantation may result in denial of sports participations to the athlete. The authors reviewed the current literature on LQTS in young athletes, to clarify the role of different screening technologies to prevent SCD.
SOURCES OF DATA
A systematic review of the literature was performed applying the PRISMA guidelines according to the PRISMA checklist and algorithm. A comprehensive search of PubMed, Medline, CINAHL, Cochrane, Embase and Google Scholar databases using various combinations of the keywords: 'QT', 'syndrome', 'screening', 'young', 'athletes', 'genetic', 'electrocardiogram', 'echocardiography' and 'prevention' were used.
AREAS OF AGREEMENT
Young athletes with LQTS are at greater risk of SCD.
AREAS OF CONTROVERSY
Different detection screening technologies, including ECG monitoring and genetic testing, are recommended, even though their role is not fully understood.
GROWING POINTS
ECG and genetic testing screening programmes could reduce the incidence of SCD, and they may positively impact on the health and safety of young athletes during sport.
AREAS TIMELY FOR DEVELOPING RESEARCH
Further studies should analyze other modalities of screening to allow early detection of cardiovascular conditions to prevent SCD in young athletes.
Topics: Athletes; Death, Sudden, Cardiac; Electrocardiography; Genetic Predisposition to Disease; Genetic Testing; Humans; Long QT Syndrome; Mass Screening
PubMed: 29931253
DOI: 10.1093/bmb/ldy017 -
PLoS Medicine Sep 2021Amodiaquine is a 4-aminoquinoline antimalarial similar to chloroquine that is used extensively for the treatment and prevention of malaria. Data on the cardiovascular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Amodiaquine is a 4-aminoquinoline antimalarial similar to chloroquine that is used extensively for the treatment and prevention of malaria. Data on the cardiovascular effects of amodiaquine are scarce, although transient effects on cardiac electrophysiology (electrocardiographic QT interval prolongation and sinus bradycardia) have been observed. We conducted an individual patient data meta-analysis to characterise the cardiovascular effects of amodiaquine and thereby support development of risk minimisation measures to improve the safety of this important antimalarial.
METHODS AND FINDINGS
Studies of amodiaquine for the treatment or prevention of malaria were identified from a systematic review. Heart rates and QT intervals with study-specific heart rate correction (QTcS) were compared within studies and individual patient data pooled for multivariable linear mixed effects regression. The meta-analysis included 2,681 patients from 4 randomised controlled trials evaluating artemisinin-based combination therapies (ACTs) containing amodiaquine (n = 725), lumefantrine (n = 499), piperaquine (n = 716), and pyronaridine (n = 566), as well as monotherapy with chloroquine (n = 175) for uncomplicated malaria. Amodiaquine prolonged QTcS (mean = 16.9 ms, 95% CI: 15.0 to 18.8) less than chloroquine (21.9 ms, 18.3 to 25.6, p = 0.0069) and piperaquine (19.2 ms, 15.8 to 20.5, p = 0.0495), but more than lumefantrine (5.6 ms, 2.9 to 8.2, p < 0.001) and pyronaridine (-1.2 ms, -3.6 to +1.3, p < 0.001). In individuals aged ≥12 years, amodiaquine reduced heart rate (mean reduction = 15.2 beats per minute [bpm], 95% CI: 13.4 to 17.0) more than piperaquine (10.5 bpm, 7.7 to 13.3, p = 0.0013), lumefantrine (9.3 bpm, 6.4 to 12.2, p < 0.001), pyronaridine (6.6 bpm, 4.0 to 9.3, p < 0.001), and chloroquine (5.9 bpm, 3.2 to 8.5, p < 0.001) and was associated with a higher risk of potentially symptomatic sinus bradycardia (≤50 bpm) than lumefantrine (risk difference: 14.8%, 95% CI: 5.4 to 24.3, p = 0.0021) and chloroquine (risk difference: 8.0%, 95% CI: 4.0 to 12.0, p < 0.001). The effect of amodiaquine on the heart rate of children aged <12 years compared with other antimalarials was not clinically significant. Study limitations include the unavailability of individual patient-level adverse event data for most included participants, but no serious complications were documented.
CONCLUSIONS
While caution is advised in the use of amodiaquine in patients aged ≥12 years with concomitant use of heart rate-reducing medications, serious cardiac conduction disorders, or risk factors for torsade de pointes, there have been no serious cardiovascular events reported after amodiaquine in widespread use over 7 decades. Amodiaquine and structurally related antimalarials in the World Health Organization (WHO)-recommended dose regimens alone or in ACTs are safe for the treatment and prevention of malaria.
Topics: Adolescent; Adult; Amodiaquine; Antimalarials; Bradycardia; Cardiotoxicity; Child; Child, Preschool; Female; Heart Conduction System; Heart Rate; Humans; Infant; Long QT Syndrome; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Young Adult
PubMed: 34492005
DOI: 10.1371/journal.pmed.1003766 -
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