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2.
Circ Arrhythm Electrophysiol ; 13(8): e008627, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32654514

RESUMO

BACKGROUND: During acute infections, the risk of malignant ventricular arrhythmias is increased, partly because of a higher propensity to develop QTc prolongation. Although it is generally believed that QTc changes almost exclusively result from concomitant treatment with QT-prolonging antimicrobials, direct effects of inflammatory cytokines on ventricular repolarization are increasingly recognized. We hypothesized that systemic inflammation per se can significantly prolong QTc during acute infections, via cytokine-mediated changes in K+ channel expression. METHODS: We evaluated (1) the frequency of QTc prolongation and its association with inflammatory markers, in patients with different types of acute infections, during active disease and remission; (2) the prevalence of acute infections in a cohort of consecutive patients with Torsades de Pointes; (3) the relationship between K+ channel mRNA levels in ventricles and peripheral blood mononuclear cells and their changes in patients with acute infection over time. RESULTS: In patients with acute infections, regardless of concomitant QT-prolonging antimicrobial treatments, QTc was significantly prolonged but rapidly normalized in parallel to CRP (C-reactive protein) and cytokine level reduction. Consistently in the Torsades de Pointes cohort, concomitant acute infections were highly prevalent (30%), despite only a minority (25%) of these cases were treated with QT-prolonging antimicrobials. KCNJ2 K+ channel expression in peripheral blood mononuclear cell, which strongly correlated to that in ventricles, inversely associated to CRP and IL (interleukin)-1 changes in acute infection patients. CONCLUSIONS: During acute infections, systemic inflammation rapidly induces cytokine-mediated ventricular electrical remodeling and significant QTc prolongation, regardless concomitant antimicrobial therapy. Although transient, these changes may significantly increase the risk of life-threatening ventricular arrhythmia in these patients. It is timely and warranted to transpose these findings to the current coronavirus disease 2019 (COVID-19) pandemic, in which both increased amounts of circulating cytokines and cardiac arrhythmias are demonstrated along with a frequent concomitant treatment with several QT-prolonging drugs. Graphic Abstract: A graphic abstract is available for this article.


Assuntos
Doenças Transmissíveis/metabolismo , Citocinas/metabolismo , Parada Cardíaca/metabolismo , Frequência Cardíaca , Ventrículos do Coração/metabolismo , Inflamação/metabolismo , Leucócitos Mononucleares/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Torsades de Pointes/metabolismo , Potenciais de Ação , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos/efeitos adversos , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/fisiopatologia , Feminino , Parada Cardíaca/epidemiologia , Parada Cardíaca/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Humanos , Inflamação/epidemiologia , Inflamação/fisiopatologia , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Canais de Potássio Corretores do Fluxo de Internalização/genética , Prevalência , Fatores de Risco , Transdução de Sinais , Fatores de Tempo , Torsades de Pointes/epidemiologia , Torsades de Pointes/fisiopatologia , Adulto Jovem
3.
J Interv Card Electrophysiol ; 59(2): 329-336, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32494896

RESUMO

BACKGROUND: Cardiovascular and arrhythmic events have been reported in hospitalized COVID-19 patients. However, arrhythmia manifestations and treatment strategies used in these patients have not been well-described. We sought to better understand the cardiac arrhythmic manifestations and treatment strategies in hospitalized COVID-19 patients through a worldwide cross-sectional survey. METHODS: The Heart Rhythm Society (HRS) sent an online survey (via SurveyMonkey) to electrophysiology (EP) professionals (physicians, scientists, and allied professionals) across the globe. The survey was active from March 27 to April 13, 2020. RESULTS: A total of 1197 respondents completed the survey with 50% of respondents from outside the USA, representing 76 countries and 6 continents. Of respondents, 905 (76%) reported having COVID-19-positive patients in their hospital. Atrial fibrillation was the most commonly reported tachyarrhythmia whereas severe sinus bradycardia and complete heart block were the most common bradyarrhythmias. Ventricular tachycardia/ventricular fibrillation arrest and pulseless electrical activity were reported by 4.8% and 5.6% of respondents, respectively. There were 140 of 631 (22.2%) respondents who reported using anticoagulation therapy in all COVID-19-positive patients who did not otherwise have an indication. One hundred fifty-five of 498 (31%) reported regular use of hydroxychloroquine/chloroquine (HCQ) + azithromycin (AZM); concomitant use of AZM was more common in the USA. Sixty of 489 respondents (12.3%) reported having to discontinue therapy with HCQ + AZM due to significant QTc prolongation and 20 (4.1%) reported cases of Torsade de Pointes in patients on HCQ/chloroquine and AZM. Amiodarone was the most common antiarrhythmic drug used for ventricular arrhythmia management. CONCLUSIONS: In this global survey of > 1100 EP professionals regarding hospitalized COVID-19 patients, a variety of arrhythmic manifestations were observed, ranging from benign to potentially life-threatening. Observed adverse events related to use of HCQ + AZM included prolonged QTc requiring drug discontinuation as well as Torsade de Pointes. Large prospective studies to better define arrhythmic manifestations as well as the safety of treatment strategies in COVID-19 patients are warranted.


Assuntos
Antiarrítmicos/administração & dosagem , Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/epidemiologia , Infecções por Coronavirus/epidemiologia , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Inquéritos e Questionários , Arritmias Cardíacas/tratamento farmacológico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Estudos Transversais , Eletrocardiografia/métodos , Feminino , Humanos , Incidência , Síndrome do QT Longo/diagnóstico por imagem , Síndrome do QT Longo/tratamento farmacológico , Síndrome do QT Longo/epidemiologia , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Prognóstico , Índice de Gravidade de Doença , Taxa de Sobrevida , Torsades de Pointes/diagnóstico por imagem , Torsades de Pointes/tratamento farmacológico , Torsades de Pointes/epidemiologia , Resultado do Tratamento
4.
Eur Heart J Acute Cardiovasc Care ; 9(3): 215-221, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32372695

RESUMO

More than 2,000,000 individuals worldwide have had coronavirus 2019 disease infection (COVID-19), yet there is no effective medical therapy. Multiple off-label and investigational drugs, such as chloroquine and hydroxychloroquine, have gained broad interest due to positive pre-clinical data and are currently used for treatment of COVID-19. However, some of these medications have potential cardiac adverse effects. This is important because up to one-third of patients with COVID-19 have cardiac injury, which can further increase the risk of cardiomyopathy and arrhythmias. Adverse effects of chloroquine and hydroxychloroquine on cardiac function and conduction are broad and can be fatal. Both drugs have an anti-arrhythmic property and are proarrhythmic. The American Heart Association has listed chloroquine and hydroxychloroquine as agents which can cause direct myocardial toxicity. Similarly, other investigational drugs such as favipiravir and lopinavir/ritonavir can prolong QT interval and cause Torsade de Pointes. Many antibiotics commonly used for the treatment of patients with COVID-19, for instance azithromycin, can also prolong QT interval. This review summarizes evidenced-based data regarding potential cardiac adverse effects due to off-label and investigational drugs including chloroquine and hydroxychloroquine, antiviral therapy, monoclonal antibodies, as well as common antibiotics used for the treatment of COVID-19. The article focuses on practical points and offers a point-of-care protocol for providers who are taking care of patients with COVID-19 in an inpatient and outpatient setting. The proposed protocol is taking into consideration that resources during the pandemic are limited.


Assuntos
Antimaláricos/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Cloroquina/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Hidroxicloroquina/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Antibacterianos/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Antimaláricos/farmacocinética , Antimaláricos/toxicidade , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/complicações , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/complicações , Cardiotoxicidade/epidemiologia , Cloroquina/farmacocinética , Cloroquina/toxicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Inibidores do Citocromo P-450 CYP3A/efeitos adversos , Humanos , Hidroxicloroquina/farmacocinética , Hidroxicloroquina/toxicidade , Uso Off-Label/estatística & dados numéricos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/epidemiologia
5.
Heart Rhythm ; 17(9): 1425-1433, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32407884

RESUMO

Background: There is no known effective therapy for patients with coronavirus disease 2019 (COVID-19). Initial reports suggesting the potential benefit of hydroxychloroquine/azithromycin (HY/AZ) have resulted in massive adoption of this combination worldwide. However, while the true efficacy of this regimen is unknown, initial reports have raised concerns about the potential risk of QT interval prolongation and induction of torsade de pointes (TdP). Objective: The purpose of this study was to assess the change in corrected QT (QTc) interval and arrhythmic events in patients with COVID-19 treated with HY/AZ. Methods: This is a retrospective study of 251 patients from 2 centers who were diagnosed with COVID-19 and treated with HY/AZ. We reviewed electrocardiographic tracings from baseline and until 3 days after the completion of therapy to determine the progression of QTc interval and the incidence of arrhythmia and mortality. Results: The QTc interval prolonged in parallel with increasing drug exposure and incompletely shortened after its completion. Extreme new QTc interval prolongation to >500 ms, a known marker of high risk of TdP, had developed in 23% of patients. One patient developed polymorphic ventricular tachycardia suspected as TdP, requiring emergent cardioversion. Seven patients required premature termination of therapy. The baseline QTc interval of patients exhibiting extreme QTc interval prolongation was normal. Conclusion: The combination of HY/AZ significantly prolongs the QTc interval in patients with COVID-19. This prolongation may be responsible for life-threatening arrhythmia in the form of TdP. This risk mandates careful consideration of HY/AZ therapy in light of its unproven efficacy. Strict QTc interval monitoring should be performed if the regimen is given.


Assuntos
Azitromicina/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Síndrome do QT Longo/epidemiologia , Pneumonia Viral/tratamento farmacológico , Torsades de Pointes/epidemiologia , Idoso , Antibacterianos/uso terapêutico , Antimaláricos/uso terapêutico , Infecções por Coronavirus/complicações , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos
7.
Circulation ; 140(13): 1070-1080, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31378084

RESUMO

BACKGROUND: Male hypogonadism, arising from a range of etiologies including androgen-deprivation therapies (ADTs), has been reported as a risk factor for acquired long-QT syndrome (aLQTS) and torsades de pointes (TdP). A full description of the clinical features of aLQTS associated with ADT and of underlying mechanisms is lacking. METHODS: We searched the international pharmacovigilance database VigiBase for men (n=6 560 565 individual case safety reports) presenting with aLQTS, TdP, or sudden death associated with ADT. In cardiomyocytes derived from induced pluripotent stem cells from men, we studied electrophysiological effects of ADT and dihydrotestosterone. RESULTS: Among subjects receiving ADT in VigiBase, we identified 184 cases of aLQTS (n=168) and/or TdP (n=68; 11% fatal), and 99 with sudden death. Of the 10 ADT drugs examined, 7 had a disproportional association (reporting odds ratio=1.4-4.7; P<0.05) with aLQTS, TdP, or sudden death. The minimum and median times to sudden death were 0.25 and 92 days, respectively. The androgen receptor antagonist enzalutamide was associated with more deaths (5430/31 896 [17%]; P<0.0001) than other ADT used for prostate cancer (4208/52 089 [8.1%]). In induced pluripotent stem cells, acute and chronic enzalutamide (25 µM) significantly prolonged action potential durations (action potential duration at 90% when paced at 0.5 Hz; 429.7±27.1 (control) versus 982.4±33.2 (acute, P<0.001) and 1062.3±28.9 ms (chronic; P<0.001), and generated afterdepolarizations and/or triggered activity in drug-treated cells (11/20 acutely and 8/15 chronically). Enzalutamide acutely and chronically inhibited delayed rectifier potassium current, and chronically enhanced late sodium current. Dihydrotestosterone (30 nM) reversed enzalutamide electrophysiological effects on induced pluripotent stem cells. CONCLUSIONS: QT prolongation and TdP are a risk in men receiving enzalutamide and other ADTs. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03193138.


Assuntos
Androgênios/metabolismo , Antineoplásicos/efeitos adversos , Hipogonadismo/epidemiologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Síndrome do QT Longo/epidemiologia , Miócitos Cardíacos/fisiologia , Feniltioidantoína/análogos & derivados , Torsades de Pointes/epidemiologia , Antineoplásicos/uso terapêutico , Diferenciação Celular , Células Cultivadas , Bases de Dados Factuais , Humanos , Hipogonadismo/tratamento farmacológico , Cooperação Internacional , Síndrome do QT Longo/tratamento farmacológico , Masculino , Farmacovigilância , Feniltioidantoína/efeitos adversos , Feniltioidantoína/uso terapêutico , Risco , Torsades de Pointes/tratamento farmacológico , Pesquisa Médica Translacional
8.
Int J Med Sci ; 16(7): 1018-1022, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31341415

RESUMO

Introduction: Macrolides, linezolid, imipenem-cilastatin, fluoroquinolones, penicillin combinations, and ceftriaxone are known to be associated with Torsades de pointes/QT prolongation (TdP/QTP). Other antibiotics may also lead to TdP/QTP, but no study has systemically compared TdP/QTP associations for many available antibiotics. Objectives: The objective of this study was to evaluate the association between TdP/QTP and many available antibiotics using the FDA Adverse Event Report System (FAERS). Methods: FAERS reports from January 1, 2015 to December 31, 2017 were analyzed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify TdP/QTP cases. We calculated the Reporting Odds Ratios (RORs) and corresponding 95% confidence intervals (95%CI) for the association between antibiotics and TdP/QTP. An association was considered to be statistically significant when the lower limit of the 95%CI was greater than 1.0. Results: A total of 2,042,801 reports (including 3,960 TdP/QTP reports) were considered, after inclusion criteria were applied. Macrolides had the greatest proportion of TdP/QTP reports. Of the 4,092 reports associated with macrolides, 108 reports (2.6%) were associated with TdP/QTP. Significant TdP/QTP RORs (95%CI) for the antibiotics were (in descending order): macrolides 14.32 (11.80-17.38), linezolid 12.41 (8.52-18.08), amikacin 11.80 (5.57-24.97), imipenem-cilastatin 6.61 (3.13-13.94), fluoroquinolones 5.68 (4.78-6.76), penicillin combinations 3.42 (2.35-4.96), and ceftriaxone 2.55 (1.41-4.62). Conclusion: This study confirms prior evidence for TdP/QTP associations with macrolides, linezolid, imipenem-cilastatin, fluoroquinolones, penicillin combinations, and ceftriaxone. This study also identifies a new association between amikacin and TdP/QTP.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Antibacterianos/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Torsades de Pointes/induzido quimicamente , Adulto , Feminino , Humanos , Síndrome do QT Longo/epidemiologia , Masculino , Pessoa de Meia-Idade , Farmacovigilância , Torsades de Pointes/epidemiologia , Estados Unidos , United States Food and Drug Administration/estatística & dados numéricos
9.
Therapie ; 74(6): 599-609, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31053339

RESUMO

Quite a number of antipsychotic and antidepressant drugs are known to cause significant QT-prolongation. Psychiatric patients constitute a population at notable risk of drug-induced QT-prolongation. The aims were to explore frequency of use of QTc-interval prolonging agents and QT-prolonging drug-drug interactions, and prevalence of risk factors for QTc-interval prolongation in patients reporting to psychiatry out-patient department (OPD) in a tertiary care hospital in India. This prospective cross-sectional study was carried out in the psychiatry OPD at All India Institute of Medical Sciences (AIIMS), Rishikesh, Uttarakhand, India from October 1, 2017 to September 30, 2018 using the relevant prescriptions (i.e., the OPD case record forms and treatment sheets). For each patient, the entire medication list was analyzed for the possibility of interactions, with particular attention on the high-risk QT prolonging ones. Arizona Center for Education and Research on Therapeutics (AZCERT) QT drug lists were used to classify TdP risks of psychotropic and other medications. One thousand three hundred twenty-six (1326) patients attending the psychiatry OPD during the study period were scrutinized. Seven hundred fifty-one 751 patients (56.6%) were males whereas 575 (43.4%) were females in our study. Of the 1326 patients, 636 patients (47.9%) were identified as receiving interacting medications with the ability to induce torsades de pointe (TdP). Nine hundred seventeen (917) interacting medication pairs with torsadogenic risk were encountered. The most frequently interacting medications were from antipsychotic (794), antidepressant (519), antimicrobial (84), proton pump inhibitor (80), anticonvulsant (66), and anti-nausea (25) therapeutic categories. As per AZCERT classification (CredibleMeds TdP risk-stratification lists), 597 (36.8%), 443 (27.3%) and 432 (26.7%) of the interacting medications were associated with known, possible, and conditional risk of TdP, respectively. Concurrent prescriptions of QT-prolonging drugs is frequent in psychiatry OPD setting. Appropriate precautions should be instituted to obviate undesirable outcomes arising out of these interactions. This highlights the pressing need for clear protocols & strategies for implementation to motivate careproviders with clarity in the context of drug use guidelines for rational and safe prescribing in psychiatry.


Assuntos
Interações Medicamentosas , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/epidemiologia , Transtornos Mentais/tratamento farmacológico , Psicotrópicos/efeitos adversos , Adulto , Assistência Ambulatorial/estatística & dados numéricos , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Masculino , Transtornos Mentais/epidemiologia , Prevalência , Estudos Prospectivos , Psicotrópicos/uso terapêutico , Fatores de Risco , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/epidemiologia , Adulto Jovem
10.
J Oncol Pharm Pract ; 25(1): 198-204, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29298624

RESUMO

Since the introduction of regulatory drug approval guidance on the evaluation of QT interval prolongation, an increasing number of drug monographs has included cautions on the risk of QT prolongation. For example, QT prolongation is mentioned in the Canadian product monographs of 29 drugs commonly seen in oncology practice. This presents two major challenges. First, most guidelines and risk predictive tools for QT prolongation have been developed for hospitalized patients in acute care settings. In contrast, most QT-prolonging oncology drugs are used in medically stable patients in the ambulatory setting. Second, many oncology drugs are unique for their indications and non-QT prolonging alternative agents are often not available. In this review, we will outline an empiric initial approach to ambulatory cancer patients who are treated with oncology drugs which may prolong QT interval. This includes the predictive value of QT prolongation on torsades de pointes, the risk factors of the patients and the drugs, and the limitations of existing guidance in this area.


Assuntos
Assistência Ambulatorial/métodos , Antineoplásicos/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Neoplasias/tratamento farmacológico , Eletrocardiografia/métodos , Humanos , Síndrome do QT Longo/epidemiologia , Síndrome do QT Longo/fisiopatologia , Neoplasias/epidemiologia , Neoplasias/fisiopatologia , Fatores de Risco , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/epidemiologia , Torsades de Pointes/fisiopatologia
11.
J Clin Psychopharmacol ; 39(1): 72-77, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30531476

RESUMO

OBJECTIVE: The aim of our study was to assess the impact of psychiatric medications and concomitant risk factors on the prevalence of QTc prolongation and torsades de pointes (TdP) in hospitalized subjects. We examined the association between individual risk scores and QTc prolongation and proposed an evidence-based protocol for electrocardiogram monitoring on psychotropic medications. METHOD: Electrocardiograms (ECGs) of subjects hospitalized over a 1-year period were analyzed for QTc prolongation, associated risk factors, and use of medications. Analysis was performed using logistic regression to identify independent predictors of QTc prolongation, and the Pearson χ test was used for risk score assessment. RESULTS: A total of 1249 ECGs of 517 subjects were included in this study. Eighty-seven subjects had QTcB intervals greater than 470 milliseconds for females and greater than 450 milliseconds for males. Twelve (2.3%) subjects had QTcB of 500 milliseconds or greater, or greater than 60 milliseconds of change from baseline. Of these subjects, only 1 case of QTc interval change was related to routine use of psychiatric medications. There were no incidents of TdP. Age, diabetes, hypokalemia, overdose, diphenhydramine, and haloperidol were significant independent predictors of QTc prolongation. Risk scores were significantly correlated with QTc prolongation (P = 0.001). CONCLUSION: Our retrospective review study found that the occurrence of TdP and QTc prolongation was low in this subject population. QT abnormalities were associated with known risk factors, and risk scores correlated well with QTc prolongation. Providers can use the protocol proposed in this study, which incorporates risk scores and the CredibleMeds classification system to determine the need for ECG monitoring and to guide treatment.


Assuntos
Síndrome do QT Longo/epidemiologia , Psicotrópicos/efeitos adversos , Medição de Risco/métodos , Torsades de Pointes/epidemiologia , Adulto , Idoso , Estudos Transversais , Eletrocardiografia , Feminino , Georgia/epidemiologia , Humanos , Pacientes Internados/estatística & dados numéricos , Síndrome do QT Longo/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Torsades de Pointes/induzido quimicamente , Adulto Jovem
12.
Psychiatry Res ; 270: 341-347, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30292087

RESUMO

Severe mental disorders have been reported to be associated with an increased cardiovascular risk. To measure the potential risk excess as compared, not with the baseline cardiovascular risk for the general population, but with the cardiovascular risk associated with drug iatrogenia. 197 reported cases of cardiovascular adverse reaction to antipsychotic drugs as compared to the reported cases of this type of adverse reactions to drugs other than antipsychotics entered in the Spanish Pharmacovigilance System database (FEDRA) (1995-2018) in an observational case/non-case study. Risk estimates of association were reporting odds ratio (ROR), and, chi-square test (χ2). Overall disproportionality for the whole drug class was found [ROR 2.3 (95% CI 2.0-2.7)], χ2 = 127.07]. When the two types of antipsychotics (typical and atypical) were analysed separately, we also found statistically significant disproportionality, and this disproportionality is similar between both groups, with disproportionality measures around 2.30, with the confidence intervals not including the 1. The disproportionality observed suggests a risk excess that might be greater than expected, which holds particularly true for torsade de pointes, sudden death and cardiac arrhythmias in patients treated with any of the two types of antipsychotics. There was no significant risk for ischaemic heart disease.


Assuntos
Antipsicóticos/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Transtornos Mentais/tratamento farmacológico , Adolescente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/epidemiologia , Aleitamento Materno , Estudos de Casos e Controles , Criança , Pré-Escolar , Bases de Dados Factuais , Morte Súbita/epidemiologia , Exposição Dietética , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Razão de Chances , Farmacovigilância , Fatores de Risco , Espanha/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Torsades de Pointes/epidemiologia , Adulto Jovem
13.
Eur J Clin Pharmacol ; 74(12): 1645-1651, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30112668

RESUMO

INTRODUCTION: Several drug classes (antiarrhythmics, antimicrobials, antidepressants, phenothiazines, opiates, prokinetics of digestive tract, etc.) have been related to ventricular hyperkinetic arrhythmias such as torsade de pointes (TdP). TdPs are usually heralded by an abnormal prolongation of heart rate-corrected QT interval on the electrocardiogram, so-called drug-induced long heart rate-corrected QT (diLQTc). We do not know to what extent the drug-induced QTc prolongation is able to predict malignant arrhythmias. Thus, we have retrospectively examined the clinical history of patients with diLQTc. METHODS: The case record, concerning the period January 2008-December 2017, was collected from two hospitals. diLQTc was defined as drug-induced heart rate-corrected QT of ≥ 450 ms or ≥ 470 ms, respectively in male or female patients. The primary purpose was to verify whether in diLQTc patients the length of this electrocardiographic segment was associated with the risk of symptoms or events (TdP, ventricular fibrillation). RESULTS: Seventy-three validated cases of diLQTc were gathered. Among them, the QTc duration was not able to predict the occurrence of symptoms or events (odds ratio, 0.998; 95% CI, 0.984 to 1.013; p = 0.8821). Likewise, a diQTc lasting longer than 500 ms compared to diQTc comprised between 450 and 500 ms was not associated with an increased risk of arrhythmic events. CONCLUSIONS: In our diLQTc patients, QTc duration did not predict occurrence of symptoms, or arrhythmic events. Thus, other determinants should be postulated to clarify why sometimes diQTc prolongation propitiates ventricular malignant arrhythmias whereas in other cases this arrhythmogenic effect is lacking.


Assuntos
Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Eletrocardiografia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/epidemiologia , Fibrilação Ventricular/induzido quimicamente , Fibrilação Ventricular/epidemiologia
14.
Pharmacoepidemiol Drug Saf ; 27(12): 1316-1324, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30106193

RESUMO

PURPOSE: Our aim was to describe trends in the prescription of domperidone for insufficient lactation in England, the characteristics of women prescribed it postpartum, and the impact of a 2014 European Medicines Agency (EMA) recommendation to restrict its use due to a potential increased risk of sudden cardiac death associated with its use. METHODS: We conducted a population-based cohort study with interrupted time series analysis using data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics. We identified women with live births from 2002 to 2015, excluding those with nonlactation indications for domperidone (n = 247 349). We evaluated trends in the prescription rate of domperidone in the 6 months postpartum and differences in this rate before and after the EMA recommendation. RESULTS: Domperidone was prescribed among 1438 deliveries at a rate of 1.24 per 100 person-years. This rate increased from 0.56 to 2.1 per 100 person-years between 2002-2004 and 2011-2013 (rate ratio: 3.8; 95% confidence interval [CI], 3.2-4.6). Prescribing decreased in level by 0.35 (95% CI, -0.86 to 0.16) per 100 person-years immediately following the recommendation with little change in trend (0.003; 95% CI, -0.059 to 0.065 per 100 person-years). Following the recommendation, prescription of doses >30 mg and coprescription of drugs with a risk of torsade de pointes decreased. No arrhythmic events were observed among domperidone users. CONCLUSIONS: Although we observed an important increase in prescribing during the study period, domperidone remains infrequently prescribed postpartum in England. While overall prescribing changed little, some prescribing practices became more restricted following the EMA's recommendation.


Assuntos
Domperidona/administração & dosagem , Antagonistas de Dopamina/administração & dosagem , Revisão de Uso de Medicamentos , Lactação/efeitos dos fármacos , Adulto , Estudos de Coortes , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/prevenção & controle , Domperidona/efeitos adversos , Antagonistas de Dopamina/efeitos adversos , Relação Dose-Resposta a Droga , Prescrições de Medicamentos/normas , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Inglaterra/epidemiologia , União Europeia/organização & administração , Feminino , Órgãos Governamentais/normas , Humanos , Análise de Séries Temporais Interrompida , Guias de Prática Clínica como Assunto , Fatores de Risco , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/epidemiologia , Torsades de Pointes/prevenção & controle , Adulto Jovem
15.
Postgrad Med ; 130(8): 660-665, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30145917

RESUMO

OBJECTIVES: Patients admitted in coronary care units are susceptible to QT interval prolongation due to numerous risk factors. The purpose of this study was to identify the prevalence of risk factors for QT interval prolongation; QT prolonging medications; drug-drug interactions; their predictors; and torsades de pointes risks of drugs. METHODS: After obtaining approval, this cross-sectional study was carried out during one-year period in coronary care units of two major tertiary care hospitals of Khyber Pakhtunkhwa, Pakistan. The Arizona Center for Education and Research on Therapeutics QT drugs lists and Micromedex DrugReax® were used to identify the QT prolonging medications and QT prolonging drug-drug interactions. RESULTS: Total 649 patients were included in this study. The most frequent QT prolonging risk factors included use of ≥ 1 QT prolonging drugs (74.9%) and myocardial infarction (61.3%). Total 181 patients were presented with 361 QT prolonging drug-drug interactions. There was significant association of the occurrence of QT prolonging drug-drug interactions with female gender (p = 0.01), 9-10 prescribed medications (p = 0.001), and > 10 prescribed medications (p < 0.001). CONCLUSIONS: The majority of patients presented with multiple risk factors for QT prolongation in coronary care units which may precipitate lethal outcomes.


Assuntos
Unidades de Cuidados Coronarianos/estatística & dados numéricos , Interações Medicamentosas , Torsades de Pointes/induzido quimicamente , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Comorbidade , Estudos Transversais , Diabetes Mellitus/epidemiologia , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão , Polimedicação , Prevalência , Fatores de Risco , Fatores Sexuais , Centros de Atenção Terciária/estatística & dados numéricos , Torsades de Pointes/epidemiologia
16.
Heart Rhythm ; 15(4): 478-484, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29605013

RESUMO

BACKGROUND: Compared with men, women have longer corrected QT (QTc) intervals, lower clearance of dofetilide, and higher rates of drug-induced torsades de pointes, but the dofetilide dosing algorithm is the same for men and women. OBJECTIVE: The purpose of this study was to evaluate the tolerability of the 500 µg twice daily dose of dofetilide for men and women. METHODS: Men and women admitted to Duke University Medical Center (January 1, 2006, to October 19, 2012) for the initiation of dofetilide 500 µg twice daily were matched 1:1 on age and estimated creatinine clearance. Electrocardiograms throughout dosing were analyzed, and rates of dofetilide discontinuations and dose reductions were compared in unadjusted and adjusted analyses. RESULTS: For 220 matched men and women, the median age was 62.5 years (interquartile range 55-69 years) and the median eCrCl was 98.1 mL/min (interquartile range 77.6-126.2 mL/min). Women were less likely than men to have hypertension and interventricular conduction delay but were otherwise similar. During dofetilide initiation, women were more likely than men to have their dofetilide dose discontinued or reduced (55% vs 32%; P < .001). In most women (82%) and men (69%), the reason for dose adjustment was significant QTc prolongation. In the adjusted analysis, female sex was associated with higher rates of dofetilide dose discontinuations or reductions (odds ratio 3.01; 95% confidence interval 1.58-5.71; P < .01). CONCLUSION: More than half of women who initiated on 500 µg twice daily of dofetilide required medication discontinuations or dose reductions, mostly because of QTc prolongation. Additional studies are needed to evaluate the optimal dosing algorithm of dofetilide in women.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Tolerância a Medicamentos , Eletrocardiografia/efeitos dos fármacos , Fenetilaminas/efeitos adversos , Sulfonamidas/efeitos adversos , Torsades de Pointes/induzido quimicamente , Idoso , Antiarrítmicos/administração & dosagem , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/fisiopatologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Fenetilaminas/administração & dosagem , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Sulfonamidas/administração & dosagem , Torsades de Pointes/epidemiologia , Torsades de Pointes/fisiopatologia
17.
Am J Cardiol ; 121(2): 182-187, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29174490

RESUMO

Patients with long QT syndrome (LQTS) are at a high risk of cardiac events. Many patients with LQTS are treated with antidepressant drugs (ADs). We investigated the LQTS genotype-specific risk of recurrent cardiac arrhythmic events (CAEs) associated with AD therapy. The study included 59 LQT1 and 72 LQT2 patients from the Rochester-based LQTS Registry with corrected QT (QTc) prolongation and a history of AD therapy. Using multivariate Anderson-Gill models, we estimated the LQTS genotype-specific risk of recurrent CAEs (ventricular tachyarrhythmias, aborted cardiac arrest, or sudden cardiac death) associated with time-dependent ADs. Specifically, we examined the risk associated with all ADs, selective serotonin reuptake inhibitor (SSRI), and ADs classified on the CredibleMeds list (www.CredibleMeds.org) as "Conditional" or "Known risk of Torsades de pointes (TdP)." After adjusting for baseline QTc duration, sex, and time-dependent beta-blocker usage, there was an increased risk of recurrent CAEs associated with ADs in LQT1 patients (hazard ratio = 3.67, 95% confidence interval 1.98-6.82, p < 0.001) but not in LQT2 patients (hazard ratio = 0.89, 95% confidence interval 0.49-1.64, p = 0.716; LQT1 vs LQT2 interaction, p < 0.001). Similarly, LQT1 patients who were on SSRIs or ADs with "Known risk of TdP" had a higher risk of recurrent CAEs than those patients off all ADs, whereas there was no association in LQT2 patients. ADs with "Conditional risk of TdP" were not associated with the risk of recurrent CAEs in any of the groups. In conclusion, the risk of recurrent CAEs associated with time-dependent ADs is higher in LQT1 patients but not in LQT2 patients. Results suggest a LQTS genotype-specific effect of ADs on the risk of arrhythmic events.


Assuntos
Antidepressivos/uso terapêutico , Arritmias Cardíacas/epidemiologia , Morte Súbita Cardíaca/epidemiologia , Síndrome do QT Longo/epidemiologia , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Eletrocardiografia , Feminino , Genótipo , Parada Cardíaca/epidemiologia , Humanos , Síndrome do QT Longo/genética , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Taquicardia Ventricular/epidemiologia , Torsades de Pointes/epidemiologia , Fibrilação Ventricular/epidemiologia
18.
Indian Heart J ; 69(6): 707-713, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29174246

RESUMO

AIM: To define the incidence, presentation, and outcomes of drug-induced Torsades de Pointes (TdP) with intravenous (IV) amiodarone. METHODS: From January 2014 to August 2016 a total of 268 patients received IV amiodarone, 142 for ventricular tachycardia, 104 for atrial flutter/fibrillation, and 22 for incessant atrial tachycardia. A uniform dosing of amiodarone to yield 1gm/day was used in all patients. RESULTS: Four of the 268 patients (M:F 1:3) with mean age of 51.25+9.17years developed pause dependent TdP degenerating to VF, after a mean dose of 690+176.63mg, infused over 12+5.88h. The QTc that was 505+9.02ms at the time of TdP normalized to 433.75+6.13ms 48-72h after stopping amiodarone. There was no immediate or late mortality, and patients are well at 5-10 months of follow-up. None of the patients tested positive for LQTS genes. CONCLUSION: The incidence of drug-induced TdP with IV amiodarone is about 1.5%. Risk factors include female sex, left ventricular dysfunction, electrolyte abnormalities, baseline prolonged QTc, concomitant beta-blocker, and digoxin therapy. Amiodarone induced TdP has favorable prognosis if recognized and treated promptly, and these patients should not receive amiodarone by any route in future.


Assuntos
Amiodarona/efeitos adversos , Torsades de Pointes/epidemiologia , Amiodarona/administração & dosagem , Antiarrítmicos/administração & dosagem , Antiarrítmicos/efeitos adversos , Eletrocardiografia , Feminino , Humanos , Incidência , Índia/epidemiologia , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/fisiopatologia
19.
Int J Clin Pharm ; 39(6): 1256-1264, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28895028

RESUMO

Background QT prolongation and associated arrhythmias, torsades de pointes (TdP), are considerable negative outcomes of many antipsychotic and antidepressant agents frequently used by psychiatric patients. Objective To identify the prevalence, levels, and predictors of QT prolonging drug-drug interactions (QT-DDIs), and AZCERT (Arizona Center for Education and Research on Therapeutics) classification of drugs involved in QT-DDIs. Setting Psychiatry wards of three major tertiary care hospitals of Khyber-Pakhtunkhwa, Pakistan. Method This was a multicenter cross-sectional study. Micromedex DrugReax was used for identification of QT-DDIs. TdP risks were identified by the AZCERT classification. Multivariate logistic regression analysis was performed to identify predictors of QT-DDIs. Main outcome measure Prevalence of QT-DDIs (overall, age-wise and gender-wise) and their levels of severity and documentation; AZCERT classes of drugs involved in QT-DDIs; and odds ratios for predictors of QT-DDIs. Results Of 600 patients, 58.5% were female. Median age was 25 years (IQR = 20-35). Overall 51.7% patients had QT-DDIs. Of total 698 identified QT-DDIs, most were of major-severity (98.4%) and fair-documentation (93.7%). According to the AZCERT classification, 36.4% of the interacting drugs were included in list-1 (known risk of TdP), 26.9% in list-2 (possible risk of TdP) and 27.5% in list-3 (conditional risk of TdP). Drugs commonly involved in QT-DDI were olanzapine (n = 146), haloperidol (138), escitalopram (122), risperidone (91), zuclopenthixol (87), quetiapine (n80) and fluoxetine (74). In multivariate logistic regression analysis, QT-DDIs were significantly associated with 6-7 prescribed medications (p = 0.04) and >7 medications (p = 0.03). Similarly, there was significant association of occurrence of QT-DDIs with 2-3 QT drugs (p < 0.001) and >3 QT drugs (p < 0.001). Conclusion A considerable number of patients are exposed to QT-DDIs in psychiatry. There is a need to implement protocol for monitoring the outcomes of QT-DDIs.


Assuntos
Antidepressivos/efeitos adversos , Antipsicóticos/efeitos adversos , Interações Medicamentosas , Síndrome do QT Longo/epidemiologia , Unidade Hospitalar de Psiquiatria/estatística & dados numéricos , Torsades de Pointes/epidemiologia , Adulto , Antidepressivos/classificação , Antipsicóticos/classificação , Estudos Transversais , Humanos , Masculino , Paquistão/epidemiologia , Prevalência , Centros de Atenção Terciária , Adulto Jovem
20.
Int J Cardiol ; 243: 511-515, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28576628

RESUMO

BACKGROUND: Multiple risk factors play a role in the development of QTc-prolongation and Torsade de Pointes (TdP). Cases of TdP are underreported and data on the incidence of TdP is scarce. The aim of this study was to investigate the incidence of TdP in a Belgian university hospital and describe the characteristics of TdP-cases using a risk score. METHODS: All cases from 2011 till 2013 coded with the ICD-9 code 427.1 in the University Hospitals of Leuven were selected. The medical files were reviewed and demographical, medical, medication and electrocardiographic data were collected. We focused on TdP-cases that were probably caused by the acquired long QT-syndrome. The RISQ-PATH score was used to quantify the risk in these cases (≥10 points as high risk for QTc-prolongation/TdP). RESULTS: Over three years, 41 TdP-cases were identified of which 19 cases were secondary to the acquired long QT-syndrome (52.6% females, mean age of 74±12years). This corresponds with an incidence of 0.16‰/year in a hospital population. Most of the patients (N=17) were treated with at least one QTc-prolonging drug (most frequently amiodarone, sotalol and furosemide) of whom 12 patients with ≥1 QTc-prolonging drug of list 1 of CredibleMeds. Fifteen patients had an electrocardiogram in a 24-hours interval before the TdP with a prolonged QTc-interval (≥450/470ms). All the patients had a RISQ-PATH score≥10. CONCLUSIONS: Although the incidence of 0.16‰/year might seem low, this means that approximately 173 possibly lethal TdP-cases can be expected in Belgian hospitals each year. All TdP-cases were associated with a high RISQ-PATH score.


Assuntos
Vigilância da População , Centros de Atenção Terciária , Torsades de Pointes/diagnóstico , Torsades de Pointes/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Bélgica/epidemiologia , Eletrocardiografia/tendências , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária/tendências , Torsades de Pointes/fisiopatologia
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