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Mayo Clinic Proceedings. Innovations,... Feb 2021To systematically review the literature and to estimate the risk of chloroquine (CQ) and hydroxychloroquine (HCQ) cardiac toxicity in patients with coronavirus disease...
OBJECTIVE
To systematically review the literature and to estimate the risk of chloroquine (CQ) and hydroxychloroquine (HCQ) cardiac toxicity in patients with coronavirus disease 2019 (COVID-19).
METHODS
We searched multiple data sources including PubMed/MEDLINE, Ovid Embase, Ovid EBM Reviews, Scopus, and Web of Science and medrxiv.org from November 2019 through May 27, 2020. We included studies that enrolled patients with COVID-19 treated with CQ or HCQ, with or without azithromycin, and reported on cardiac toxic effects. We performed a meta-analysis using the arcsine transformation of the different incidences.
RESULTS
A total of 19 studies with a total of 5652 patients were included. The pooled incidence of torsades de pointes arrhythmia, ventricular tachycardia, or cardiac arrest was 3 per 1000 (95% CI, 0-21; =96%) in 18 studies with 3725 patients. Among 13 studies of 4334 patients, the pooled incidence of discontinuation of CQ or HCQ due to prolonged QTc or arrhythmias was 5% (95% CI, 1-11; =98%). The pooled incidence of change in QTc from baseline of 60 milliseconds or more or QTc of 500 milliseconds or more was 9% (95% CI, 3-17; =97%). Mean or median age, coronary artery disease, hypertension, diabetes, concomitant QT-prolonging medications, intensive care unit admission, and severity of illness in the study populations explained between-studies heterogeneity.
CONCLUSION
Treatment of patients with COVID-19 with CQ or HCQ is associated with an important risk of drug-induced QT prolongation and relatively higher incidence of torsades de pointes, ventricular tachycardia, or cardiac arrest. Therefore, these agents should not be used routinely in the management of COVID-19 disease. Patients with COVID-19 who are treated with antimalarials for other indications should be adequately monitored.
PubMed: 33163895
DOI: 10.1016/j.mayocpiqo.2020.10.005 -
PLoS Medicine Mar 2020Electrocardiographic QT interval prolongation is the most widely used risk marker for ventricular arrhythmia potential and thus an important component of drug... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Electrocardiographic QT interval prolongation is the most widely used risk marker for ventricular arrhythmia potential and thus an important component of drug cardiotoxicity assessments. Several antimalarial medicines are associated with QT interval prolongation. However, interpretation of electrocardiographic changes is confounded by the coincidence of peak antimalarial drug concentrations with recovery from malaria. We therefore reviewed all available data to characterise the effects of malaria disease and demographic factors on the QT interval in order to improve assessment of electrocardiographic changes in the treatment and prevention of malaria.
METHODS AND FINDINGS
We conducted a systematic review and meta-analysis of individual patient data. We searched clinical bibliographic databases (last on August 21, 2017) for studies of the quinoline and structurally related antimalarials for malaria-related indications in human participants in which electrocardiograms were systematically recorded. Unpublished studies were identified by the World Health Organization (WHO) Evidence Review Group (ERG) on the Cardiotoxicity of Antimalarials. Risk of bias was assessed using the Pharmacoepidemiological Research on Outcomes of Therapeutics by a European Consortium (PROTECT) checklist for adverse drug events. Bayesian hierarchical multivariable regression with generalised additive models was used to investigate the effects of malaria and demographic factors on the pretreatment QT interval. The meta-analysis included 10,452 individuals (9,778 malaria patients, including 343 with severe disease, and 674 healthy participants) from 43 studies. 7,170 (68.6%) had fever (body temperature ≥ 37.5°C), and none developed ventricular arrhythmia after antimalarial treatment. Compared to healthy participants, patients with uncomplicated falciparum malaria had shorter QT intervals (-61.77 milliseconds; 95% credible interval [CI]: -80.71 to -42.83) and increased sensitivity of the QT interval to heart rate changes. These effects were greater in severe malaria (-110.89 milliseconds; 95% CI: -140.38 to -81.25). Body temperature was associated independently with clinically significant QT shortening of 2.80 milliseconds (95% CI: -3.17 to -2.42) per 1°C increase. Study limitations include that it was not possible to assess the effect of other factors that may affect the QT interval but are not consistently collected in malaria clinical trials.
CONCLUSIONS
Adjustment for malaria and fever-recovery-related QT lengthening is necessary to avoid misattributing malaria-disease-related QT changes to antimalarial drug effects. This would improve risk assessments of antimalarial-related cardiotoxicity in clinical research and practice. Similar adjustments may be indicated for other febrile illnesses for which QT-interval-prolonging medications are important therapeutic options.
Topics: Action Potentials; Adolescent; Adult; Aged; Aged, 80 and over; Antimalarials; Arrhythmias, Cardiac; Body Temperature Regulation; Cardiotoxicity; Child; Child, Preschool; Electrocardiography; Female; Heart Conduction System; Heart Rate; Humans; Infant; Malaria; Male; Middle Aged; Predictive Value of Tests; Risk Assessment; Risk Factors; Severity of Illness Index; Treatment Outcome; Young Adult
PubMed: 32134952
DOI: 10.1371/journal.pmed.1003040 -
Journal of Arrhythmia Feb 2020Brugada syndrome (BrS) is an inherited arrhythmic disease associated with an increased risk of major arrhythmic events (MAE). Previous studies reported that a wide QRS...
BACKGROUND
Brugada syndrome (BrS) is an inherited arrhythmic disease associated with an increased risk of major arrhythmic events (MAE). Previous studies reported that a wide QRS complex may be useful as a predictor of MAE in BrS patients. We aimed to assess the correlation of wide QRS complex with MAE by a systematic review and meta-analysis.
METHODS
We comprehensively searched the databases of MEDLINE and EMBASE from inception to June 2019. Included studies were cohort and case control studies that reported QRS duration and the relationship between wide QRS complex (>120 milliseconds) and MAE (sudden cardiac death, sudden cardiac arrest, ventricular fibrillation, sustained ventricular tachycardia, or appropriate shock). Data from each study were combined using the random-effects model.
RESULTS
Twenty-two studies from 2007 to 2018 were included in this meta-analysis involving 4,814 BrS patients. The mean age was 46.1 ± 12.8 years. The patients were predominately men (77.6%). Wide QRS duration was an independent predictor of MAE (pooled risk ratio 1.55, 95% confidence interval: 1.04-2.30, = .30, = 38.4%). QRS duration was wider in BrS who had history of MAE (weight mean difference = 8.12 milliseconds, 95% confidence interval: 5.75-10.51 milliseconds).
CONCLUSIONS
Our study demonstrated that QRS duration is wider in BrS who had history of MAE, and a wide QRS complex is associated with 1.55 times higher risk of MAE in BrS populations. Wide QRS complex can be considered for risk stratification in prediction of MAE in patients with BrS, especially when considering implantable cardioverter-defibrillator placement in asymptomatic patients.
PubMed: 32071633
DOI: 10.1002/joa3.12290 -
BMC Cardiovascular Disorders Dec 2019A number of published literature has reported that, physiologically, heart rate variability (HRV) in patients with postural orthostatic tachycardia syndrome (POTS) to be... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A number of published literature has reported that, physiologically, heart rate variability (HRV) in patients with postural orthostatic tachycardia syndrome (POTS) to be greatly confounded by age, sex, race, physical fitness, and circadian rhythm. The purpose of this study was to compare between POTS patients versus healthy participants, in terms of heart rate (HR) and HRV after Head-Up tilt test (HUTT), by systematic review and meta-analysis of available published literature.
METHODS
MEDLINE (using PubMed interphase), EMBASE and SCOPUS were systematically searched for observational studies comparing POTS patients versus healthy patients, in terms of HR and HRV. HRV was grouped into Time and frequency domain outcome measurements. The time domain was measured as mean RR- interval and mean the square root of the mean of squares of successive R-R waves (rMSSD) in milliseconds. The frequency domain was measured as mean values of Low frequency power (LF), High frequency power (HF), LF/HF-ratio, LF-normalized units (LF(n.u)) and HF-normalized units (HF(n.u)). Demographic data, comorbidities, and mean values of HR, RR- interval, rMSSD, LF, HF, LF/HF-ratio, LF-(n.u) and H.F-n.u were extracted from each group and compared, by their mean differences as an overall outcome measure. Computer software, RevMan 5.3 was utilized, at a 95% significance level.
RESULTS
Twenty (20) eligible studies were found to report 717 POTS and 641 healthy participants. POTS group had a higher mean HR (p < 0.05), lower mean RR-Interval (p < 0.05), lower rMSSD (p < 0.05) than healthy participants. Furthermore, POTS group had lower mean HF(p > 0.05), lower mean LF(p > 0.05), and lower mean HF(n.u) (p > 0.05), higher LF/HF-Ratio (p > 0.05) and higher LF(n.u) (p > 0.05) as compared to healthy participants.
CONCLUSION
POTS patients have a higher HR than healthy patients after HUTT and lower HRV in terms of time domain measure but not in terms of frequency domain measure. HR and time domain analyses of HRV are more reliable than frequency domain analysis in differentiating POTS patients from the healthy participants. We call upon sensitivity and specificity studies.
Topics: Adolescent; Adult; Case-Control Studies; Child; Female; Heart Rate; Humans; Male; Middle Aged; Observational Studies as Topic; Postural Orthostatic Tachycardia Syndrome; Posture; Tilt-Table Test; Time Factors; Young Adult
PubMed: 31888497
DOI: 10.1186/s12872-019-01298-y -
NeuroImage Apr 2019Magnetoencephalography (MEG) is a non-invasive neuroimaging technique that provides whole-head measures of neural activity with millisecond temporal resolution. Over the...
Magnetoencephalography (MEG) is a non-invasive neuroimaging technique that provides whole-head measures of neural activity with millisecond temporal resolution. Over the last three decades, MEG has been used for assessing brain activity, most commonly in adults. MEG has been used less often to examine neural function during early development, in large part due to the fact that infant whole-head MEG systems have only recently been developed. In this review, an overview of infant MEG studies is provided, focusing on the period from birth to three years. The advantages of MEG for measuring neural activity in infants are highlighted (See Box 1), including the ability to assess activity in brain (source) space rather than sensor space, thus allowing direct assessment of neural generator activity. Recent advances in MEG hardware and source analysis are also discussed. As the review indicates, efforts in this area demonstrate that MEG is a promising technology for studying the infant brain. As a noninvasive technology, with emerging hardware providing the necessary sensitivity, an expected deliverable is the capability for longitudinal infant MEG studies evaluating the developmental trajectory (maturation) of neural activity. It is expected that departures from neuro-typical trajectories will offer early detection and prognosis insights in infants and toddlers at-risk for neurodevelopmental disorders, thus paving the way for early targeted interventions.
Topics: Brain; Evoked Potentials; Functional Neuroimaging; Humans; Infant; Magnetoencephalography
PubMed: 30685329
DOI: 10.1016/j.neuroimage.2019.01.059 -
PloS One 2018Cardiac autonomic neuropathy in type 2 dibetes mellitus (T2DM) patients is frequent and associated with high cardiovascular mortality. Heart rate variability (HRV) is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cardiac autonomic neuropathy in type 2 dibetes mellitus (T2DM) patients is frequent and associated with high cardiovascular mortality. Heart rate variability (HRV) is the gold standard to measure cardiac autonomic neuropathy. We aimed to conduct a systematic review and meta-analysis to evaluate the impact of T2DM on HRV parameters.
METHODS
The PubMed, Cochrane Library, Embase and Science Direct databases were searched on 1st October 2017 using the keywords "diabetes" AND ("heart rate variability" OR "HRV"). Included articles had to report HRV parameters in T2DM patients and healthy controls measured during 24 hours with a Holter-electrocardiogram. Measurements of HRV retieved were: RR-intervals (or Normal to Normal intervals-NN), standard deviation of RR intervals (SDNN), percetange of adjacent NN intervals differing by more than 50 milliseconds (pNN50), square root of the mean squared difference of successive RR intervals (RMSSD), total power, Low Frequency (LF), High Frequency (HF) and LF/HF ratio, as per Task Force recommendations.
RESULTS
We included twenty-five case-control studies with 2,932 patients: 1,356 with T2DM and 1,576 healthy controls. T2DM patients had significantly (P<0.01) lower RR-intervals (effect size = -0.61; 95%CI -1.21 to -0.01), lower SDNN (-0.65; -0.83 to -0.47), lower RMSSD (-0.92; -1.37 to -0.47), lower pNN50 (-0.46; -0.84 to -0.09), lower total power (-1.52; -2.13 to -0.91), lower LF (-1.08; -1.46 to -0.69]), and lower HF (-0.79; -1.09 to -0.50). LF/HF did not differ between groups. Levels of blood glucose and HbA1c were associated with several HRV parameters, as well as Time from diagnosis of T2DM.
CONCLUSIONS
T2DM was associated with an overall decrease in the HRV of T2DM patients. Both sympathetic and parasympathetic activity were decreased, which can be explained by the deleterious effects of altered glucose metabolism on HRV, leading to cardiac autonomic neuropathy.
Topics: Adult; Aged; Body Mass Index; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Heart Rate; Humans; Male; Middle Aged; Regression Analysis; Risk Factors
PubMed: 29608603
DOI: 10.1371/journal.pone.0195166 -
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