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1.
JACC Clin Electrophysiol ; 7(1): 16-25, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33478708

RESUMO

OBJECTIVES: This study aimed to characterize corrected QT (QTc) prolongation in a cohort of hospitalized patients with coronavirus disease-2019 (COVID-19) who were treated with hydroxychloroquine and azithromycin (HCQ/AZM). BACKGROUND: HCQ/AZM is being widely used to treat COVID-19 despite the known risk of QT interval prolongation and the unknown risk of arrhythmogenesis in this population. METHODS: A retrospective cohort of COVID-19 hospitalized patients treated with HCQ/AZM was reviewed. The QTc interval was calculated before drug administration and for the first 5 days following initiation. The primary endpoint was the magnitude of QTc prolongation, and factors associated with QTc prolongation. Secondary endpoints were incidences of sustained ventricular tachycardia or ventricular fibrillation and all-cause mortality. RESULTS: Among 415 patients who received concomitant HCQ/AZM, the mean QTc increased from 443 ± 25 ms to a maximum of 473 ± 40 ms (87 [21%] patients had a QTc ≥500 ms). Factors associated with QTc prolongation ≥500 ms were age (p < 0.001), body mass index <30 kg/m2 (p = 0.005), heart failure (p < 0.001), elevated creatinine (p = 0.005), and peak troponin (p < 0.001). The change in QTc was not associated with death over the short period of the study in a population in which mortality was already high (hazard ratio: 0.998; p = 0.607). No primary high-grade ventricular arrhythmias were observed. CONCLUSIONS: An increase in QTc was seen in hospitalized patients with COVID-19 treated with HCQ/AZM. Several clinical factors were associated with greater QTc prolongation. Changes in QTc were not associated with increased risk of death.


Assuntos
Antibacterianos/efeitos adversos , Azitromicina/efeitos adversos , Inibidores Enzimáticos/efeitos adversos , Hidroxicloroquina/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Comorbidade , Creatinina/sangue , Quimioterapia Combinada , Eletrocardiografia , Feminino , Insuficiência Cardíaca/epidemiologia , Hospitalização , Humanos , Síndrome do QT Longo/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Modelos de Riscos Proporcionais , Fatores de Risco , Troponina I/sangue
2.
Eur J Pharmacol ; 893: 173813, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33345848

RESUMO

Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an enormous challenge to the medical system, especially the lack of safe and effective COVID-19 treatment methods, forcing people to look for drugs that may have therapeutic effects as soon as possible. Some old drugs have shown clinical benefits after a few small clinical trials that attracted great attention. Clinically, however, many drugs, including those currently used in COVID-19, such as chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir, may cause cardiotoxicity by acting on cardiac potassium channels, especially hERG channel through their off-target effects. The blocking of the hERG channel prolongs QT intervals on electrocardiograms; thus, it might induce severe ventricular arrhythmias and even sudden cardiac death. Therefore, while focusing on the efficacy of COVID-19 drugs, the fact that they block hERG channels to cause arrhythmias cannot be ignored. To develop safer and more effective drugs, it is necessary to understand the interactions between drugs and the hERG channel and the molecular mechanism behind this high affinity. In this review, we focus on the biochemical and molecular mechanistic aspects of drug-related blockade of the hERG channel to provide insights into QT prolongation caused by off-label use of related drugs in COVID-19, and hope to weigh the risks and benefits when using these drugs.


Assuntos
Azitromicina/efeitos adversos , Azitromicina/uso terapêutico , /tratamento farmacológico , Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Canal de Potássio ERG1/efeitos dos fármacos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Síndrome do QT Longo/induzido quimicamente , Lopinavir/efeitos adversos , Lopinavir/uso terapêutico , Ritonavir/efeitos adversos , Ritonavir/uso terapêutico , Combinação de Medicamentos , Humanos , Síndrome do QT Longo/epidemiologia , Uso Off-Label
3.
Kardiologiia ; 60(7): 11-14, 2020 Aug 11.
Artigo em Russo | MEDLINE | ID: mdl-33155935

RESUMO

Since the first case recorded in the end of 2019, the virus SARS-CоV-2 and the related lung disease COVID-19 have spread over the world and became a threat for public health. The drugs used for treatment of this disease (azithromycin and hydroxychloroquine) can prolong the QT interval on the electrocardiogram to increase the risk of pirouette tachycardia and sudden cardiac death. This article presents a review of potential risks related with the drug treatment of COVID-19 and provides recommendations for management of patients during the pandemic.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Síndrome do QT Longo , Pandemias , Pneumonia Viral , Humanos , Síndrome do QT Longo/epidemiologia
4.
Medicine (Baltimore) ; 99(42): e22740, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080735

RESUMO

Prolonged heart rate-corrected QT (QTc) interval is an independent risk factor for sudden cardiac death, which is the hallmark of Timothy syndrome (TS). There are little data on children with syndactyly and QTc prolongation.To evaluate the characteristics and long-term outcomes in children with syndactyly, and to attempt to identify TS in patients with syndactyly and QTc prolongation.This is a retrospective case-control study of children with syndactyly who visited Beijing Jishuitan Hospital between July 2003 and February 2013. The patients with prolonged QTc intervals are matched 1:4 with patients without prolongation. Genetic testing of the CACNA1C gene is routinely performed in patients with QTc prolongation.The mean age at admission is 3.4 ±â€Š2.3 years. Compared with the normal QTc group, those with QTc prolongation showed higher frequencies of congenital heart disease (11.8% vs 1.5%, P = .042), mental retardation and facial dysmorphia (11.8% vs 0, P = .004), and T wave alternans (23.5% vs 4.4%, P = .01). In the multivariable analysis, only T wave alternans (OR = 10.61, 95%CI: 1.39-81.16, P = .023) is independently associated with QTc prolongation in patients with syndactyly. One child with QTc prolongation had a mutation in the CACNA1C gene. No patients with prolonged QTs interval met the threshold for TS.Children with syndactyly and prolonged QTc interval had more multisystem diseases and electrocardiography abnormalities. T wave alternans is independently associated with QTc prolongation in patients with syndactyly.


Assuntos
Síndrome do QT Longo/epidemiologia , Sindactilia/epidemiologia , Canais de Cálcio Tipo L/genética , Estudos de Casos e Controles , Pré-Escolar , China/epidemiologia , Anormalidades Craniofaciais/epidemiologia , Eletrocardiografia , Feminino , Cardiopatias Congênitas/epidemiologia , Humanos , Deficiência Intelectual/epidemiologia , Masculino , Análise Multivariada , Mutação , Estudos Retrospectivos
5.
JAMA Cardiol ; 5(9): 1036-1041, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32936252

RESUMO

Importance: Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)-associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias. Objective: To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin. Design, Setting, and Participants: This was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020. Main Outcomes and Measures: Change in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events. Results: Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds; P < .001). Those receiving concomitant azithromycin had a greater median (interquartile range) change in QT interval (23 [10-40] milliseconds) compared with those receiving hydroxychloroquine alone (5.5 [-15.5 to 34.25] milliseconds; P = .03). Seven patients (19%) who received hydroxychloroquine monotherapy developed prolonged QTc of 500 milliseconds or more, and 3 patients (8%) had a change in QTc of 60 milliseconds or more. Of those who received concomitant azithromycin, 11 of 53 (21%) had prolonged QTc of 500 milliseconds or more and 7 of 53 (13 %) had a change in QTc of 60 milliseconds or more. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics (adjusted odds ratio, 3.38 [95% CI, 1.03-11.08]) or had a baseline QTc of 450 milliseconds or more (adjusted odds ratio, 7.11 [95% CI, 1.75-28.87]). Ten patients had hydroxychloroquine discontinued early because of potential adverse drug events, including intractable nausea, hypoglycemia, and 1 case of torsades de pointes. Conclusions and Relevance: In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.


Assuntos
Azitromicina/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Síndrome do QT Longo/epidemiologia , Pneumonia Viral/tratamento farmacológico , Idoso , Antibacterianos/uso terapêutico , Antimaláricos/uso terapêutico , Estudos de Coortes , Quimioterapia Combinada , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Medição de Risco
8.
J Interv Card Electrophysiol ; 59(2): 337-345, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32654098

RESUMO

PURPOSE: Hydroxychloroquine, chloroquine, and azithromycin have been used for treatment of COVID-19, but may cause QT prolongation. Minority populations are disproportionately impacted by COVID-19. This study evaluates the risk of QT prolongation and subsequent outcomes after administration of these medications in largely underrepresented minority COVID-19 patients. METHODS: We conducted an observational study on hospitalized COVID-19 patients in the Montefiore Health System (Bronx, NY). We examined electrocardiograms (ECG) pre/post-medication initiation to evaluate QTc, HR, QRS duration, and presence of other arrhythmias. RESULTS: One hundred five patients (mean age 67 years; 44.8% F) were analyzed. The median time from the first dose of any treatment to post-medication ECG was 2 days (IQR: 1-3). QTc in men increased from baseline (440 vs 455 ms, p < 0.001), as well as in women (438 vs 463 ms, p < 0.001). The proportion of patients with QT prolongation increased significantly (14.3% vs 34.3%, p < 0.001) even when adjusted for electrolyte abnormalities. The number of patients whose QTc > 500 ms was significantly increased after treatment (16.2% vs. 4.8%, p < 0.01). Patients with either QTc > 500 ms or an increase of 60 ms had a higher frequency of death (47.6% vs. 22.6%, p = 0.02) with an odds ratio of 3.1 (95% CI: 1.1-8.7). Adjusting for race/ethnicity yielded no significant associations. CONCLUSIONS: Hydroxychloroquine, chloroquine, and/or azithromycin were associated with QTc prolongation but did not result in fatal arrhythmias. Our findings suggest that any harm is unlikely to outweigh potential benefits of treatment. Careful risk-benefit analyses for individual patients should guide the use of these medications. Randomized control trials are necessary to evaluate their efficacies.


Assuntos
Antimaláricos/efeitos adversos , Azitromicina/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Eletrocardiografia/métodos , Síndrome do QT Longo/induzido quimicamente , Pneumonia Viral/tratamento farmacológico , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Antimaláricos/administração & dosagem , Azitromicina/administração & dosagem , Cloroquina/administração & dosagem , Cloroquina/efeitos adversos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Incidência , Síndrome do QT Longo/diagnóstico por imagem , Síndrome do QT Longo/tratamento farmacológico , Síndrome do QT Longo/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Pandemias/estatística & dados numéricos , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Medição de Risco , Distribuição por Sexo , População Urbana
9.
Heart Rhythm ; 17(11): 1930-1935, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32610165

RESUMO

BACKGROUND: Hydroxychloroquine (HCQ) has been promoted as a potential treatment of coronavirus disease 2019 (COVID-19), but there are safety concerns. OBJECTIVE: The purpose of this study was to determine the effects of HCQ treatment on QT interval. METHODS: We retrospectively studied the electrocardiograms of 819 patients treated with HCQ for rheumatologic diseases from 2000 to 2020. The primary outcome was corrected QT (QTc) interval, by Bazett formula, during HCQ therapy. RESULTS: Mean patient age was 64.0 ± 10.9 years, and 734 patients (90%) were men. Median dosage of HCQ was 400 mg daily, and median (25th-75th percentile) duration of HCQ therapy was 1006 (471-2075) days. Mean on-treatment QTc was 430.9 ± 31.8 ms. In total, 55 patients (7%) had QTc 470-500 ms, and 12 (1.5%) had QTc >500 ms. Chronic kidney disease (CKD), history of atrial fibrillation (AF), and heart failure were independent risk factors for prolonged QTc. In a subset of 591 patients who also had a pretreatment electrocardiogram, mean QTc increased from 424.4 ± 29.7 ms to 432.0 ± 32.3 ms (P <.0001) during HCQ treatment. Of these patients, 23 (3.9%) had either prolongation of QTc >15% or on-treatment QTc >500 ms. Over median 5.97 (3.33-10.11) years of follow-up, 269 patients (33%) died. QTc >470 ms during HCQ treatment was associated with a greater mortality risk (hazard ratio 1.78; 95% confidence interval 1.16-2.71; P = .008) in univariable but not in multivariable analysis. CONCLUSION: HCQ is associated with QT prolongation in a significant fraction of patients. The risk of QT prolongation is higher among patients with CKD, AF, and heart failure, who may benefit from greater scrutiny.


Assuntos
Eletrocardiografia , Hidroxicloroquina , Síndrome do QT Longo , Doenças Reumáticas/tratamento farmacológico , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Fibrilação Atrial/epidemiologia , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Eletrocardiografia/métodos , Eletrocardiografia/estatística & dados numéricos , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/epidemiologia , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Avaliação de Processos e Resultados em Cuidados de Saúde , Pandemias , Pneumonia Viral/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Doenças Reumáticas/mortalidade , Risco Ajustado , Fatores de Risco
11.
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
12.
BMC Psychiatry ; 20(1): 277, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493330

RESUMO

BACKGROUND: QT interval prolongation is a growing concern worldwide, posing psychiatric patients to life-threatening fatal arrhythmias i.e., torsade de pointes. This study aimed to identify the prevalence of QT interval prolongation, its associated risk factors and prescribing patterns of QT prolonging drugs among psychiatric patients. METHOD: A prospective observational study was conducted that included psychiatric patients from a tertiary care hospital and a psychiatry clinic in Peshawar, Khyber Pakhtunkhwa, Pakistan. Electrocardiogram was recorded of those patients who were using psychotropic medications for ≥7 days, aged 18 years or more, and of either gender, male or female. The Fredericia correction formula was used for measuring QTc values (corrected QT). Chi-square test was applied to estimate differences between patients with or without prolonged QTc interval whereas, logistic regression analysis was performed to identify various predictors of QT interval prolongation. RESULTS: Out of 405 patients, the QTc interval was prolonged in 23 (5.7%) patients including 1 (0.2%) patient with highly abnormal prolonged QTc interval (> 500 ms). QT drugs (91.6%), female sex (38.7%) and hypertension (10.6%) were the most common QT prolonging risk factors. Prolonged QTc interval was significantly higher among male patients (p = 0.007). CONCLUSION: In the present study, QT interval prolongation was observed in a considerable number of psychiatric patients. While, the high prevalence of QT prolonging risk factors among these patients warrants the increased risk of fatal arrhythmias. Therefore, risk assessment and electrocardiographic monitoring, and prescription of safer alternatives are highly recommended.


Assuntos
Síndrome do QT Longo/epidemiologia , Transtornos Mentais/epidemiologia , Adulto , Eletrocardiografia , Feminino , Humanos , Masculino , Paquistão/epidemiologia , Prevalência , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
15.
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
16.
Therapie ; 75(4): 371-379, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32418730

RESUMO

INTRODUCTION: COVID-19 is an unprecedented challenge for physicians and scientists. Several publicized drugs are being used with not much evidence of their efficacy such as hydroxychloroquine, azithromycin or lopinavir-ritonavir. Yet, the cardiac safety of these drugs in COVID-19 deserves scrutiny as they are known to foster cardiac adverse ADRs, notably QTc interval prolongation on the electrocardiogram and its arrhythmogenic consequences. METHODS: Since March 27th, 2020, the French Pharmacovigilance Network directed all cardiac adverse drug reactions associated with "off-label" use of hydroxychloroquine, azithromycin and lopinavir-ritonavir in COVID-19 to the Nice Regional Center of Pharmacovigilance. Each Regional Center of Pharmacovigilance first assessed causality of drugs. We performed a specific analysis of these cardiac adverse drug reactions amidst an array of risk factors, reassessed the electrocardiograms and estimated their incidence in coronavirus disease 2019. RESULTS: In one month, 120 reports of cardiac adverse drug reactions have been notified, 103 of which associated with hydroxychloroquine alone (86%), or associated with azithromycin (60%). Their estimated incidence is 0.77% to 1.54% of all patients, notwithstanding strong underreporting. Lopinavir-ritonavir came third with 17 reports (14%) and chloroquine fourth with 3 reports (2.5%). There were 8 sudden, unexplained or aborted deaths (7%), 8 ventricular arrhythmias (7%), 90 reports of prolonged QTc (75%) most of them "serious" (64%), 48 of which proved ≥ 500ms, 20 reports of severe conduction disorders (17%) and 5 reports of other cardiac causes (4%). Six reports derived from automedication. DISCUSSION AND CONCLUSION: "Off-label" use of treatments in COVID-19 increases the risk of cardiac ADRs, some of them avoidable. Even if these drugs are perceived as familiar, they are used in patients with added risk factors caused by infection. Precautions should be taken to mitigate the risk, even if they will be proven efficacious.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Cardiopatias/induzido quimicamente , Uso Off-Label , Farmacovigilância , Pneumonia Viral/tratamento farmacológico , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Idoso , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Cloroquina/administração & dosagem , Cloroquina/efeitos adversos , Combinação de Medicamentos , Eletrocardiografia , Feminino , França/epidemiologia , Cardiopatias/epidemiologia , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/epidemiologia , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pandemias , Fatores de Risco , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos
17.
Drugs Aging ; 37(5): 359-372, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32056163

RESUMO

BACKGROUND AND PURPOSE: Chronic kidney disease (CKD) is associated with adverse drug events due to medication errors and the risks of polypharmacy. The aim of this study was to investigate whether multiple pharmacodynamic interactions are a significant problem in CKD patients to improve medication safety. METHODS: The discharge medication of 200 elderly patients with stage 3, 4 and 5/5D CKD was analysed in a retrospective observational study with respect to kidney-related medication errors and multiple pharmacodynamic interactions. The clinical relevance of the most common and hazardous multiple interactions was assessed by evaluating adverse events at the primary or the subsequent hospital stay. RESULTS: Findings showed that 29.5% of the study cohort were at risk of QTc-interval prolongation in association with their medication combinations and half of them exhibited QTc-interval prolongation. The QTc interval was extended among all patients receiving a combination of two or more drugs with 'known' risk of Torsades de pointes. Amiodarone, citalopram and ciprofloxacin turned out to be the most hazardous drugs in this context. Eight percent of the patient population received a regimen of 4-6 potassium-enhancing drugs during their hospital stay, which was not de-escalated in 75.0% in the ambulatory setting. Despite close monitoring in the clinical setting, 37.5% of these patients developed hyperkalaemic episodes during their primary stay and 66.7% during rehospitalization. Of the study cohort, 8.5% received a combination of three drugs with antithrombotic or antiplatelet effects. Of these, 64.7% developed haemorrhagic events with two of them proving fatal. CONCLUSION: Multiple pharmacodynamic interactions related to QTc prolongation, hyperkalaemia and haemorrhage are frequently associated with a negative outcome in older adults with CKD and often require recurrent medical treatment or rehospitalization.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Erros de Medicação/efeitos adversos , Polimedicação , Insuficiência Renal Crônica/tratamento farmacológico , Idoso , Interações Medicamentosas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/epidemiologia , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/epidemiologia , Masculino , Estudos Retrospectivos , Risco
18.
Am J Obstet Gynecol ; 222(3): 263.e1-263.e11, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31520628

RESUMO

BACKGROUND: Most fetal deaths are unexplained. Long QT syndrome is a genetic disorder of cardiac ion channels. Affected individuals, including fetuses, are predisposed to sudden death. We sought to determine the risk of fetal death in familial long QT syndrome, in which the mother or father carries the long QT syndrome genotype. In addition, we assessed whether risk differed if the long QT syndrome genotype was inherited from the mother or father. OBJECTIVE: This was a retrospective review of pregnancies in families with the 3 most common heterozygous pathogenic long QT syndrome genotypes in KCNQ1 (LQT1), KCNH2 (LQT2), or SCN5A (LQT3), which occur in approximately 1 in 2000 individuals. The purpose of our study was to compare pregnancy and birth outcomes in familial long QT syndrome with the normal population and between maternal and paternal carriers of the long QT syndrome genotype. We hypothesized that fetal death before (miscarriage) and after (stillbirths) 20 weeks gestation would be increased in familial long QT syndrome compared with the normal population and that the parent of origin would not affect birth outcomes. STUDY DESIGN: Our study was a multicenter observational case series of 148 pregnancies from 103 families (80 mothers, 23 fathers) with familial long QT syndrome (60 with LQT1, 29 with LQT2, 14 with LQT3) who were recruited from 11 international centers with expertise in hereditary heart rhythm diseases, pediatric and/or adult electrophysiology, and high-risk pregnancies. Clinical databases from these sites were reviewed for long QT syndrome that occurred in men or women of childbearing age (18-40 years). Pregnancy outcomes (livebirth, stillbirth, and miscarriage), birthweights, and gestational age at delivery were compared among long QT syndrome genotypes and between maternal vs paternal long QT syndrome-affected status with the use of logistic regression analysis. RESULTS: Most offspring (80%; 118/148) were liveborn at term; 66% of offspring (73/110) had long QT syndrome. Newborn infants of mothers with long QT syndrome were delivered earlier and, when the data were controlled for gestational age, weighed less than newborn infants of long QT syndrome fathers. Fetal arrhythmias were observed rarely, but stillbirths (fetal death at >20 weeks gestation) were 8 times more frequent in long QT syndrome (4% vs approximately 0.5%); miscarriages (fetal death at ≤20 weeks gestation) were 2 times that of the general population (16% vs 8%). The likelihood of fetal death was significantly greater with maternal vs paternal long QT syndrome (24.4% vs 3.4%; P=.036). Only 10% of all fetal deaths underwent postmortem long QT syndrome testing; 2 of 3 cases were positive for the family long QT syndrome genotype. CONCLUSION: This is the first report to demonstrate that mothers with long QT syndrome are at increased risk of fetal death and to uncover a previously unreported cause of stillbirth. Our results suggest that maternal effects of long QT syndrome channelopathy may cause placental or myometrial dysfunction that confers increased susceptibility to fetal death and growth restriction in newborn survivors, regardless of long QT syndrome status.


Assuntos
Aborto Espontâneo/epidemiologia , Síndrome do QT Longo/epidemiologia , Mães , Natimorto/epidemiologia , Antagonistas Adrenérgicos beta/uso terapêutico , Arritmias Cardíacas/epidemiologia , Peso ao Nascer , Cesárea/estatística & dados numéricos , Pai , Feminino , Doenças Fetais/epidemiologia , Retardo do Crescimento Fetal/epidemiologia , Idade Gestacional , Heterozigoto , Humanos , Síndrome do QT Longo/tratamento farmacológico , Síndrome do QT Longo/genética , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , Risco
19.
J Pediatr Hematol Oncol ; 42(2): e121-e124, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-30830033

RESUMO

Studies have been conducted on adults prescribed with methadone to determine the necessary frequency of QTc monitoring but no consensus has been reached and no similar research has been conducted in the pediatric population. The objective of this retrospective study was to determine the occurrence rate of QTc interval prolongation associated with methadone use in a pediatric oncologic population. In total, 18% of patients developed QTc interval prolongation. These patients had longer baseline QTc intervals and were on more QTc interval-prolonging medications. Our data suggest that these variables may be able to risk stratify patients who require more frequent monitoring.


Assuntos
Analgésicos Opioides/efeitos adversos , Dor do Câncer/tratamento farmacológico , Síndrome do QT Longo/epidemiologia , Metadona/efeitos adversos , Neoplasias/complicações , Adolescente , Adulto , Dor do Câncer/etiologia , Dor do Câncer/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/patologia , Masculino , New York/epidemiologia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
20.
Ren Fail ; 42(1): 54-65, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31878817

RESUMO

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in chronic kidney disease (CKD) patients. QT interval prolongation is a congenital or acquired condition that is associated with an increased risk of torsade de pointes (TdP), sudden cardiac death (SCD), and all-cause mortality in the general population. The prevalence of acquired long QT syndrome (aLQTS) is high, and various acquired conditions contribute to the prolonged QT interval in patients with CKD. More notably, the prolonged QT interval in CKD is an independent risk factor for SCD and all-cause mortality. In this review, we focus on the epidemiological characteristics, risk factors, underlying mechanisms and treatments of aLQTS in CKD, promoting the management of aLQTS in CKD patients.


Assuntos
Morte Súbita Cardíaca/epidemiologia , Síndrome do QT Longo/epidemiologia , Insuficiência Renal Crônica/complicações , Antiarrítmicos/uso terapêutico , Estimulação Cardíaca Artificial/métodos , Morte Súbita Cardíaca/etiologia , Eletrocardiografia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Frequência Cardíaca/efeitos dos fármacos , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/etiologia , Síndrome do QT Longo/terapia , Prevalência , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/terapia , Literatura de Revisão como Assunto , Fatores de Risco
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