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Current Problems in Cardiology Sep 2022Humans and mammals have sex-specific differences in cardiac electrophysiology, linked to the action of sex hormones in the cardiac muscle. These hormones can upregulate... (Review)
Review
Humans and mammals have sex-specific differences in cardiac electrophysiology, linked to the action of sex hormones in the cardiac muscle. These hormones can upregulate or downregulate the expression of ionic channels modulating the cardiac cycle through genomic and non-genomic interactions. Systematic search in PubMed, Medline and EMBASE including keywords pertaining to testosterone and QT interval. Included experimental studies and observation studies and case reports presenting the results of testosterone administration, excess or deficiency in humans and animals. Testosterone has been shown to shorten the action potential duration, by enhancing the expression of K channels and downregulating I increasing the repolarization reserve of the cardiac muscle. This effect has been observed in both genders and animals. Testosterone deficient states can promote arrhythmogenesis. The evidence in this paper may be used to guide clinical considerations, such as increased clinical surveillance of patients in testosterone deficient states using ECG.
Topics: Animals; Arrhythmias, Cardiac; Electrocardiography; Female; Gonadal Steroid Hormones; Humans; Ion Channels; Long QT Syndrome; Male; Mammals; Testosterone
PubMed: 34103195
DOI: 10.1016/j.cpcardiol.2021.100882 -
Pharmacoepidemiology and Drug Safety Jun 2021Hydroxychloroquine, chloroquine, azithromycin, and lopinavir/ritonavir are drugs that were used for the treatment of coronavirus disease 2019 (COVID-19) during the early... (Meta-Analysis)
Meta-Analysis
PURPOSE
Hydroxychloroquine, chloroquine, azithromycin, and lopinavir/ritonavir are drugs that were used for the treatment of coronavirus disease 2019 (COVID-19) during the early pandemic period. It is well-known that these agents can prolong the QTc interval and potentially induce Torsades de Pointes (TdP). We aim to assess the prevalence and risk of QTc prolongation and arrhythmic events in COVID-19 patients treated with these drugs.
METHODS
We searched electronic databases from inception to September 30, 2020 for studies reporting peak QTc ≥500 ms, peak QTc change ≥60 ms, peak QTc interval, peak change of QTc interval, ventricular arrhythmias, TdP, sudden cardiac death, or atrioventricular block (AVB). All meta-analyses were conducted using a random-effects model.
RESULTS
Forty-seven studies (three case series, 35 cohorts, and nine randomized controlled trials [RCTs]) involving 13 087 patients were included. The pooled prevalence of peak QTc ≥500 ms was 9% (95% confidence interval [95%CI], 3%-18%) and 8% (95%CI, 3%-14%) in patients who received hydroxychloroquine/chloroquine alone or in combination with azithromycin, respectively. Likewise, the use of hydroxychloroquine (risk ratio [RR], 2.68; 95%CI, 1.56-4.60) and hydroxychloroquine + azithromycin (RR, 3.28; 95%CI, 1.16-9.30) was associated with an increased risk of QTc prolongation compared to no treatment. Ventricular arrhythmias, TdP, sudden cardiac death, and AVB were reported in <1% of patients across treatment groups. The only two studies that reported individual data of lopinavir/ritonavir found no cases of QTc prolongation.
CONCLUSIONS
COVID-19 patients treated with hydroxychloroquine/chloroquine with or without azithromycin had a relatively high prevalence and risk of QTc prolongation. However, the prevalence of arrhythmic events was very low, probably due to underreporting. The limited information about lopinavir/ritonavir showed that it does not prolong the QTc interval.
Topics: Azithromycin; COVID-19; Chloroquine; Humans; Hydroxychloroquine; Long QT Syndrome; Lopinavir; Observational Studies as Topic; Ritonavir; COVID-19 Drug Treatment
PubMed: 33772933
DOI: 10.1002/pds.5234 -
How to Estimate QT Interval in Patients With Left or Right Bundle Branch Block: A Systematic Review.Journal of Clinical PsychopharmacologyProlonged QT interval related to psychopharmacological treatment is a risk factor for potentially life-threatening arrhythmias. Electrocardiographic measurements are...
PURPOSE/BACKGROUND
Prolonged QT interval related to psychopharmacological treatment is a risk factor for potentially life-threatening arrhythmias. Electrocardiographic measurements are recommended in patients with cardiovascular risk factors before initiating treatment with potentially QT-prolonging medications, such as certain antidepressants or antipsychotics. In patients with left bundle branch block (LBBB) or right bundle branch block (RBBB), conventional QT-estimation methods will lead to overestimation of the QT interval, as the conduction defect, reflected by the QRS duration, will increase the QT interval without representing longer repolarization as in drug-induced QT prolongation.
METHODS/PROCEDURES
We conducted a systematic review of methods to estimate QT interval in the presence of LBBB or RBBB. We searched electronic databases Embase and Medline (last search, August 12, 2020).
FINDINGS/RESULTS
We found 8 different methods, including linear correction formulae with and without correction for heart rate, or simpler formula correcting QRS duration with empirically derived modifiers. Only 3 of 8 methods were applicable in the presence of RBBB, whereas all 8 methods could be applied in the presence of LBBB.
IMPLICATIONS/CONCLUSIONS
The QT interval is overestimated in patients with LBBB or RBBB, when using conventional measurements. Several alternative correction formulae exist, which can be applied using standard measurements from ordinary electrocardiographic readings. However, it is currently unknown whether or not the QT prolongation observed in the presence of bundle branch block significantly increases the risk of arrhythmias, as these formulae have not been tested against patient-specific clinical outcomes.
Topics: Bundle-Branch Block; Electrocardiography; Heart Disease Risk Factors; Heart Rate; Humans; Long QT Syndrome; Risk Factors
PubMed: 33657070
DOI: 10.1097/JCP.0000000000001373 -
American Journal of Therapeutics
Effects of Hydroxychloroquine With or Without Azithromycin on QT Interval in COVID-19: A Systematic Review. Electrophysiology Collaborative Consortium for Meta-analysis-Electram Investigators.
Topics: Humans; Azithromycin; COVID-19 Drug Treatment; Electrocardiography; Electrophysiology; Hydroxychloroquine; Drug Therapy, Combination; Long QT Syndrome
PubMed: 33416244
DOI: 10.1097/MJT.0000000000001238 -
Psychopharmacology Feb 2021Management of anxiety, delirium, and agitation cannot be neglected in coronavirus disease (COVID-19). Antipsychotics are usually used for the pharmacological management...
RATIONALE
Management of anxiety, delirium, and agitation cannot be neglected in coronavirus disease (COVID-19). Antipsychotics are usually used for the pharmacological management of delirium, and confusion and behavioral disturbances. The concurrent use of treatments for COVID-19 and antipsychotics should consider eventual drug-drug interactions OBJECTIVE: To systematically review evidence-based available on drug-drug interactions between COVID-19 treatments and antipsychotics.
EVIDENCE REVIEW
Three databases were consulted: Lexicomp® Drug Interactions, Micromedex® Solutions Drugs Interactions, and Liverpool© Drug Interaction Group for COVID-19 therapies. To acquire more information on QT prolongation and Torsade de Pointes (TdP), the CredibleMeds® QTDrugs List was searched. The authors made a recommendation agreed to by consensus. Additionally, a systematic review of drug-drug interactions between antipsychotics and COVID-19 treatment was conducted.
RESULTS
The main interactions between COVID-19 drugs and antipsychotics are the risk of QT-prolongation and TdP, and cytochromes P450 interactions. Remdesivir, baricinitib, and anakinra can be used concomitantly with antipsychotics without risk of drug-drug interaction (except for hematological risk with clozapine and baricinitib). Favipiravir only needs caution with chlorpromazine and quetiapine. Tocilizumab is rather safe to use in combination with antipsychotics. The most demanding COVID-19 treatments for coadministration with antipsychotics are chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir because of the risk of QT prolongation and TdP and cytochromes interactions. The systematic review provides highly probable drug interaction between lopinavir/ritonavir plus quetiapine and ritonavir/indinavir plus risperidone.
CONCLUSIONS
Clinicians prescribing antipsychotics should be aware of the likely risk of drug-drug interaction with COVID-19 medication and may benefit from taking into account present recommendations of use to preserve patient safety.
Topics: Antipsychotic Agents; Antiviral Agents; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Long QT Syndrome; SARS-CoV-2; Torsades de Pointes; COVID-19 Drug Treatment
PubMed: 33410987
DOI: 10.1007/s00213-020-05716-4 -
World Journal of Clinical Cases Nov 2020Since the beginning of the pandemic, coronavirus disease-2019 (COVID-19) in children has shown milder cases and a better prognosis than adults. Although the respiratory...
BACKGROUND
Since the beginning of the pandemic, coronavirus disease-2019 (COVID-19) in children has shown milder cases and a better prognosis than adults. Although the respiratory tract is the primary target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cardiovascular involvement is emerging as one of the most significant and life-threatening complications of SARS-CoV-2 infection in adults.
AIM
To summarize the current knowledge about the potential cardiovascular involvement in pediatric COVID-19 in order to give a perspective on how to take care of them during the current pandemic emergency.
METHODS
Multiple searches in MEDLINE, PubMed were performed using the search terms "COVID-19" or "SARS-CoV-2" were used in combination with "myocardial injury" or "arrhythmia" or "cardiovascular involvement" or "heart disease" or "congenital heart disease" or "pulmonary hypertension" or "long QT" or "cardiomyopathies" or "channelopathies" or "Multisystem inflammatory system" or "PMIS" or "MIS-C" or "Pediatric multisystem inflammatory syndrome" or "myocarditis" or "thromboembolism to identify articles published in English language from January 1st, 2020 until July 31st, 2020. The websites of World Health Organization, Centers for Disease control and Prevention, and the Johns Hopkins Coronavirus Resource Center were reviewed to provide up to date numbers and infection control recommendations. Reference lists from the articles were reviewed to identify additional pertinent articles. Retrieved manuscripts concerning the subject were reviewed by the authors, and the data were extracted using a standardized collection tool. Data were subsequently analyzed with descriptive statistics. For Pediatric multisystemic inflammatory syndrome temporally associated with COVID-19 (PMIS), multiple meta-analyses were conducted to summarize the pooled mean proportion of different cardiovascular variables in this population in pseudo-cohorts of observed patients.
RESULTS
A total of 193 articles were included. Most publications used in this review were single case reports, small case series, and observational small-sized studies or literature reviews. The meta-analysis of 16 studies with size > 10 patients and with complete data about cardiovascular involvement in children with PMIS showed that PMIS affects mostly previously healthy school-aged children and adolescents presenting with Kawasaki disease-like features and multiple organ failure with a focus on the heart, accounting for most cases of pediatric COVID-19 mortality. They frequently presented cardiogenic shock (53%), ECG alterations (27%), myocardial dysfunction (52%), and coronary artery dilation (15%). Most cases required PICU admission (75%) and inotropic support (57%), with the rare need for extracorporeal membrane oxygenation (4%). Almost all of these children wholly recovered in a few days, although rare deaths have been reported (2%). Out of PMIS cases we identified 10 articles reporting sporadic cases of myocarditis, pulmonary hypertension and cardiac arrythmias in previously healthy children. We also found another 10 studies reporting patients with pre-existing heart diseases. Most cases consisted in children with severe COVID-19 infection with full recovery after intensive care support, but cases of death were also identified. The management of different cardiac conditions are provided based on current guidelines and expert panel recommendations.
CONCLUSION
There is still scarce data about the role of cardiovascular involvement in COVID-19 in children. Based on our review, children (previously healthy or with pre-existing heart disease) with acute COVID-19 requiring hospital admission should undergo a cardiac workup and close cardiovascular monitoring to identify and treat timely life-threatening cardiac complications.
PubMed: 33269260
DOI: 10.12998/wjcc.v8.i21.5250 -
The Journal of International Advanced... Dec 2020Establish outcomes following cochlear implantation (CI) in patients with Jervell and Lange-Nielsen Syndrome (JLNS). Methods Systematic review and narrative synthesis....
Establish outcomes following cochlear implantation (CI) in patients with Jervell and Lange-Nielsen Syndrome (JLNS). Methods Systematic review and narrative synthesis. Databases searched on Medline, Pubmed, Embase, Web of Science, Cochrane Collection and ClinicalTrials.gov. No limits placed on language or year of publication. Review conducted in accordance with the PRISMA statement. Searches identified 63 abstracts and 19 full texts. Of these, 9 studies met inclusion criteria reporting outcomes in 66 patients with at least 72 implants. Hearing outcomes were generally good. Mortality secondary to cardiac complications within the follow up period occurred in at least five cases (7.6%), though three of these were thought to be unrelated to surgery. Potentially dangerous arrhythmias without associated morbidity were also noted in at least five patients. The methodological quality of included studies was modest, predominantly consisting of case reports and non-controlled case series with small numbers of patients. All studies were OCEBM grade IV. One study contributed 41/66 patients (62%). Hearing outcomes following CI in JLNS are generally good with the majority of patients experiencing useful hearing improvement. Significant peri-operative cardiac risks exist and should be discussed with the patient and family during pre-operative counselling and prompt thorough investigation, pre-operative optimisation and peri-operative monitoring.
Topics: Cochlear Implantation; Hearing; Humans; Jervell-Lange Nielsen Syndrome; Prospective Studies; Retrospective Studies
PubMed: 33136028
DOI: 10.5152/iao.2020.9025 -
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 -
General Hospital Psychiatry 2020Though not approved by the United States Food and Drug Administration, intravenous haloperidol (IVH) is widely used off-label to manage agitation and psychosis in... (Review)
Review
INTRODUCTION
Though not approved by the United States Food and Drug Administration, intravenous haloperidol (IVH) is widely used off-label to manage agitation and psychosis in patients with delirium in the hospital setting. Over the years, concerns have emerged regarding side effects of IVH, particularly its potential to cause QT prolongation, torsades de pointes (TdP), extrapyramidal symptoms and catatonia.
METHODS
We conducted a systematic review of literature of published literature related to side effects of IVH in PubMed in accordance with PRISMA guidelines.
RESULTS
77 of 196 identified manuscripts met inclusion criteria, including 34 clinical trials and 34 case reports or series.
DISCUSSION
Extrapyramidal symptoms, catatonia and neuroleptic malignant syndrome appears to be relatively rare with IVH. In most prospective studies, IVH did not cause greater QT prolongation than placebo, and rates of TdP with IVH appear to be low. There is not clear evidence to suggest that IVH carries greater risk for QT prolongation or TdP than other antipsychotics.
CONCLUSIONS
Based on the available literature, we provide modified evidence-based monitoring recommendations for clinicians prescribing IVH in hospital settings. Specifically, we recommend electrocardiogram monitoring only when using doses >5 mg of IVH and telemetry only for high-risk patients receiving cumulative doses of at least 100 mg or with accurately corrected QTc >500 ms.
Topics: Antipsychotic Agents; Electrocardiography; Haloperidol; Humans; Long QT Syndrome; Prospective Studies; Torsades de Pointes
PubMed: 32979582
DOI: 10.1016/j.genhosppsych.2020.08.008 -
Journal of Clinical Medicine Aug 2020Long-QT syndrome (LQTS) is primarily an electrical disorder characterized by a prolonged myocardial action potential. The delay in cardiac repolarization leads to...
BACKGROUND
Long-QT syndrome (LQTS) is primarily an electrical disorder characterized by a prolonged myocardial action potential. The delay in cardiac repolarization leads to electromechanical (EM) abnormalities, which adds a diagnostic value for LQTS. Prolonged left ventricular (LV) contraction was identified as a potential risk for arrhythmia. The aim of this meta-analysis was to assess the best predictor of all EM parameters for cardiac events (CEs) in LQTS patients.
METHODS
We systematically searched all electronic databases up to March 2020, to select studies that assessed the relationship between echocardiographic indices-contraction duration (CD), mechanical dispersion (MD), QRS onset to peak systolic strain (QAoC), and the EM window (EMW); and electrical indices- corrected QT interval (QT, QT dispersion, RR interval in relation to CEs in LQTS. This meta-analysis included a total of 1041 patients and 373 controls recruited from 12 studies.
RESULTS
The meta-analysis showed that LQTS patients had electrical and mechanical abnormalities as compared to controls-QT, WMD 72.8; QT dispersion, WMD 31.7; RR interval, WMD 91.5; CD, WMD 49.2; MD, WMD 15.9; QAoC, WMD 27.8; and EMW, WMD -62.4. These mechanical abnormalities were more profound in symptomatic compared to asymptomatic patients in whom disturbances were already manifest, compared to controls. A CD ≥430 ms had a summary sensitivity (SS) of 71%, specificity of 84%, and diagnostic odds ratio (DOR) >19.5 in predicting CEs. EMW and QT had a lower accuracy.
CONCLUSIONS
LQTS is associated with pronounced EM abnormalities, particularly prolonged LV myocardial CD, which is profound in symptomatic patients. These findings highlight the significant role of EM indices like CD in managing LQTS patients.
PubMed: 32878246
DOI: 10.3390/jcm9092820