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2.
J Stroke Cerebrovasc Dis ; 28(11): 104308, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31416760

RESUMO

Stroke involving some areas of the cerebral hemisphere, such as insula, amygdala, and lateral hypothalamus, may cause changes in autonomic control of cardiac function. A 58-year-old woman presented to the emergency department for acute onset of left facial-brachial-crural hemiparesis and dysarthria. A brain CT scan showed subacute ischemic lesion with hemorrhagic infarction in right insular-rolandic cortex. Over the next few days ECG showed severe bradycardia with elongation of QTc, significative pauses (5 seconds), runs of nonsustained ventricular tachycardia and torsades de pointes. Drug induced and other several possible causes of elongation of QT and bradycardia such as hypokalemia, a history of heart failure, and structural heart disease were ruled out. The case confirms that insular cortex plays a major role in stroke-induced cardiovascular changes.


Assuntos
Córtex Cerebral/irrigação sanguínea , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Síndrome do QT Longo/etiologia , Acidente Vascular Cerebral/complicações , Torsades de Pointes/etiologia , Potenciais de Ação , Bradicardia/etiologia , Bradicardia/fisiopatologia , Estimulação Cardíaca Artificial , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Síndrome do QT Longo/terapia , Pessoa de Meia-Idade , Marca-Passo Artificial , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/fisiopatologia , Torsades de Pointes/diagnóstico , Torsades de Pointes/fisiopatologia , Torsades de Pointes/terapia , Resultado do Tratamento
3.
BMC Infect Dis ; 19(1): 544, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221100

RESUMO

BACKGROUND: Bedaquiline was recently introduced into World Health Organization (WHO)-recommended regimens for treatment of drug resistant tuberculosis. There is limited data on the long-term safety of bedaquiline. Because bedaquiline prolongs the QT interval, there are concerns regarding cardiovascular safety. The Western Cape Province in South Africa has an established pharmacovigilance programme: a targeted spontaneous reporting system which solicits reports of suspected adverse drug reactions (ADRs) in patients with HIV-1 and/or tuberculosis infection. Since 2015, bedaquiline has been included in the treatment regimens recommended for resistant tuberculosis in South Africa. We describe ADRs in patients on bedaquiline-containing tuberculosis treatment that were reported to the Western Cape Pharmacovigilance programme. METHODS: We reviewed reports of suspected ADRs and deaths received between March 2015 and June 2016 involving patients receiving bedaquiline-containing tuberculosis treatment. A multidisciplinary panel assessed causality, and categorised suspected ADRs using World Health Organisation-Uppsala Monitoring Centre system categories. "Confirmed ADRs" included all ADRs categorised as definite, probable or possible. Preventability was assessed using Schumock and Thornton criteria. Where a confirmed ADR occurred in a patient who died, the panel categorised the extent to which the ADR contributed to the patient's death as follows: major contributor, contributor or non-contributor. RESULTS: Thirty-five suspected ADRs were reported in 32 patients, including 13 deaths. There were 30 confirmed ADRs, of which 23 were classified as "possible" and seven as "probable". Bedaquiline was implicated in 22 confirmed ADRs in 22 patients. The most common confirmed ADR in patients receiving bedaquiline was QT prolongation (8 cases, 7 of which were severe). A fatal arrhythmia was suspected in 4 sudden deaths. These 4 patients were all taking bedaquiline together with other QT-prolonging drugs. There were 8 non-bedaquiline-associated ADRs, of which 7 contributed to deaths. CONCLUSIONS: Confirmed ADRs in patients receiving bedaquiline reflect the known safety profile of bedaquiline. Quantifying the incidence and clinical consequences of severe QT-prolongation in patients receiving bedaquiline-containing regimens is a research priority to inform recommendations for patient monitoring in treatment programmes for drug resistant tuberculosis. Pharmacovigilance systems within tuberculosis treatment programmes should be supported and encouraged, to provide ongoing monitoring of treatment-limiting drug toxicity.


Assuntos
Antituberculosos/efeitos adversos , Doenças Cardiovasculares/etiologia , Diarilquinolinas/efeitos adversos , Adulto , Antituberculosos/uso terapêutico , Diarilquinolinas/uso terapêutico , Feminino , Infecções por HIV/complicações , Infecções por HIV/patologia , Humanos , Síndrome do QT Longo/tratamento farmacológico , Síndrome do QT Longo/etiologia , Masculino , África do Sul , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Tuberculose/patologia , Adulto Jovem
5.
Eur J Clin Pharmacol ; 75(8): 1099-1108, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31011758

RESUMO

PURPOSE: To assess the effect of ethnicity, food, and itraconazole (strong CYP3A4 inhibitor) on the pharmacokinetics of ivosidenib after single oral doses in healthy subjects. METHODS: Three phase 1 open-label studies were performed. Study 1: Japanese and Caucasian subjects received single doses of 250, 500, or 1000 mg ivosidenib (NCT03071770). Part 1 of study 2 (a two-period crossover study): subjects received 500 mg ivosidenib after either an overnight fast or a high-fat meal. Subjects received 1000 mg ivosidenib after an overnight fast in the single period of part 2 (NCT02579707). Study 3: in period 1, subjects received 250 mg ivosidenib; then, in period 2, subjects received oral itraconazole (200 mg once daily) on days 1-18, plus 250 mg ivosidenib on day 5 (NCT02831972). RESULTS: Ivosidenib was well tolerated in all three studies. Study 1: pharmacokinetic profiles were generally comparable, although AUC and Cmax were slightly lower in Japanese subjects than in Caucasian subjects, by ~ 30 and 17%, respectively. Study 2: AUC increased by ~ 25% and Cmax by ~ 98%, when ivosidenib was administered with a high-fat meal compared with a fasted state. Study 3: co-administration of itraconazole increased ivosidenib AUC by 169% (90% CI 145-195) but had no effect on ivosidenib Cmax. CONCLUSIONS: No ivosidenib dose adjustment is deemed necessary for Japanese subjects. High-fat meals should be avoided when ivosidenib is taken with food. When co-administered with strong CYP3A4 inhibitors, monitoring for QT interval prolongation (a previously defined adverse event of interest) is recommended and an ivosidenib dose interruption or reduction may be considered. CLINICALTRIALS.GOV : NCT03071770, NCT02579707, and NCT02831972.


Assuntos
Antineoplásicos/farmacocinética , Inibidores do Citocromo P-450 CYP3A/farmacologia , Glicina/análogos & derivados , Itraconazol/farmacologia , Síndrome do QT Longo/epidemiologia , Piridinas/farmacocinética , Administração Oral , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático , Estudos Cross-Over , Relação Dose-Resposta a Droga , Interações Medicamentosas/etnologia , Feminino , Interações Alimento-Droga/etnologia , Glicina/administração & dosagem , Glicina/efeitos adversos , Glicina/farmacocinética , Voluntários Saudáveis , Humanos , Itraconazol/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/etiologia , Masculino , Pessoa de Meia-Idade , Piridinas/administração & dosagem , Piridinas/efeitos adversos
6.
PLoS One ; 14(1): e0209297, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30605455

RESUMO

BACKGROUND: Cardiovascular diseases, including sudden cardiac death (SCD), are the leading cause of death in hemodialysis (HD) patients. A prolonged QT interval on the electrocardiogram (ECG) is a risk factor for SCD in HD patients. This study investigated whether the heart rate-corrected QT (QTc) interval becomes prolonged along with dialysis vintage. METHODS: A total of 102 HD patients were retrospectively studied. Their ECG data were analyzed at 1, 4, and 7 years after HD initiation. The control group comprised 68 age-matched individuals who had normal renal function and two available ECG reports at an interval of more than 4 years. QTc was measured according to the Bazett formula. The association between QTc interval and dialysis vintage was studied. Additionally, clinically relevant variables related to QTc duration at 1 year after HD initiation were assessed. RESULTS: Average QTc interval at 4 and 7 years after HD initiation was significantly longer than that at 1 year after HD initiation (443, 445, and 437 ms) (p<0.05). On the other hand, QTc interval in the control group was 425 ms in the first year and 426 ms after an average of 6 years. They had no significant differences, although they were much shorter than that in HD patients. Multivariate regression analysis of baseline variables revealed that the corrected calcium levels (p = 0.041) and diabetes (p = 0.043) were independently associated with longer QTc interval. CONCLUSIONS: The QTc interval at 1 year after HD initiation was longer than in the control subjects and was prolonged over several years of HD treatment. Providing clinical management with a focus on QTc interval may be helpful for reducing the incidence of SCD in HD patients.


Assuntos
Frequência Cardíaca/fisiologia , Diálise Renal/efeitos adversos , Adulto , Idoso , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Estudos de Casos e Controles , Morte Súbita Cardíaca/etiologia , Eletrocardiografia , Feminino , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Síndrome do QT Longo/etiologia , Síndrome do QT Longo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
7.
QJM ; 112(5): 343-350, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30690642

RESUMO

BACKGROUND: Brugada syndrome (BrS) is a heritable sudden cardiac death (SCD) disease with male predominance. Information on gender difference of BrS remains scarce. AIM: To investigate the gender difference of BrS in Han Chinese. DESIGN: We consecutively enrolled 169 BrS patients (153 males and 16 females) from Han Chinese in Taiwan from 1998 to 2017. METHODS: Clinical characteristics, electrocardiographic parameters and SCN5A mutation status were compared between genders. RESULTS: The percentage of family history of SCD in females was slightly higher (31.3% vs. 15%, P = 0.15). Females exhibited longer QTc (457.8 ± 33.0 vs. 429.5 ± 42.1 ms, P < 0.01). Regarding cumulative event occurrence by age, Mantel-Cox test showed females had earlier age of onset of first cardiac events (SCD or syncope) than males (P = 0.049), which was mainly attributed to syncope (P < 0.01). Males with SCD exhibited longer QRS duration (114.2 ± 26.8 vs. 104.8 ± 15.3 ms, P = 0.02) and QTc (442.5 ± 57.4 vs. 422.9 ± 28.8 ms, P = 0.02). Males with syncope exhibited longer PR interval (181.2 ± 33.7 vs. 165.7 ± 27.1 ms, P = 0.01), whereas females with SCD or syncope had a trend towards slower heart rates (69.1 ± 9.6 vs. 82.2 ± 16.3 bpm, P = 0.10) than female with no or mild symptoms. There was no difference in the percentage of SCN5A mutation between genders. CONCLUSION: Gender difference is present in BrS. Females have longer QTc and suffer from syncope earlier than males. Risk of SCD in males is associated with boarder QRS complex and longer QTc, whereas risk of syncope is associated with longer PR interval in males and slower heart rate in females.


Assuntos
Síndrome de Brugada/genética , Morte Súbita Cardíaca/epidemiologia , Síndrome do QT Longo/epidemiologia , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Fatores Sexuais , Síncope/etiologia , Adulto , Síndrome de Brugada/complicações , Síndrome de Brugada/fisiopatologia , Morte Súbita Cardíaca/etiologia , Eletrocardiografia , Feminino , Humanos , Síndrome do QT Longo/etiologia , Masculino , Pessoa de Meia-Idade , Mutação , Sistema de Registros , Medição de Risco , Distribuição por Sexo , Síncope/epidemiologia , Taiwan/epidemiologia
8.
Heart Lung ; 48(2): 148-154, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30391074

RESUMO

BACKGROUND: The role of QTc-prolongation, in relation to the increased mortality in COPD, is unclear. OBJECTIVES: To estimate the prevalence and prognostic impact, assessed as mortality, of QTc-prolongation in COPD, restrictive spirometric pattern (RSP), and normal lung function (NLF), respectively. METHODS: All individuals (n = 993) with COPD and age- and sex-matched non-obstructive referents were identified from well-defined population-based cohorts examined in Northern Sweden in 2002-04. In 2005, the study-sample was invited to re-examination including ECG; QTc was calculated and mortality data collected until 31st December 2010. RESULTS: The prevalence of QTc-prolongation was higher among people with RSP than among those with NLF and, although similar in NLF and COPD, the prevalence increased by COPD-severity. Among participants with COPD, those with QTc prolongation had higher mortality than those with normal QTc, while no such differences were found among participants with NLF or RSP. CONCLUSION: Among participants with COPD, the prevalence of QTc-prolongation increased by disease-severity and was associated with mortality.


Assuntos
Eletrocardiografia , Síndrome do QT Longo/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Idoso , Comorbidade , Feminino , Humanos , Síndrome do QT Longo/etiologia , Síndrome do QT Longo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fatores de Risco , Espirometria , Taxa de Sobrevida/tendências , Suécia/epidemiologia
9.
Heart ; 105(7): 559-565, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30366934

RESUMO

OBJECTIVE: HIV-infected (HIV+) individuals may be at increased risk for sudden arrhythmic cardiac death. Some studies have reported an association between HIV infection and prolongation of the electrocardiographic QT interval, a measure of ventricular repolarisation, which could potentiate ventricular arrhythmias. We aimed to assess whether HIV+ men have longer QT intervals than HIV-uninfected (HIV-) men and to determine factors associated with QT duration. METHODS: We performed resting 12-lead ECGs in 774 HIV+ and 652 HIV- men in the Multicenter AIDS Cohort Study (MACS). We used multivariable linear and logistic regression analyses to assess associations between HIV serostatus and Framingham corrected QT interval (QTc), after accounting for potential confounders. We also determined associations among QTc interval and HIV-related factors in HIV+ men. In a subgroup of participants, levels of serum markers of inflammation were also assessed. RESULTS: After adjusting for demographics and risk factors, QTc was 4.0 ms longer in HIV+ than HIV- men (p<0.001). Use of antiretroviral therapy (ART), specific ART drug class use and other HIV-specific risk factors were not associated with longer QTc. Among the subgroup with inflammatory biomarker measurements, higher interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and B-cell activating factor levels were independently associated with longer QTc and their inclusion partially attenuated the HIV effect. CONCLUSIONS: HIV+ men had longer QTc, which was associated with higher levels of systemic inflammatory factors. This longer QTc may contribute to the increased risk for sudden arrhythmic cardiac death in some HIV+ individuals.


Assuntos
Antirretrovirais , Fator Ativador de Células B/sangue , Morte Súbita Cardíaca/prevenção & controle , Infecções por HIV , Molécula 1 de Adesão Intercelular/sangue , Interleucina-6/sangue , Síndrome do QT Longo , Adulto , Antirretrovirais/classificação , Antirretrovirais/uso terapêutico , Biomarcadores/sangue , Correlação de Dados , Morte Súbita Cardíaca/etiologia , Eletrocardiografia/métodos , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/terapia , Humanos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/epidemiologia , Síndrome do QT Longo/etiologia , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Testes Sorológicos/métodos , Estados Unidos/epidemiologia
10.
Eur J Intern Med ; 61: 34-39, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30482635

RESUMO

BACKGROUND: Long QT and use of QT-prolonging drugs are common among older patients receiving polytherapies, but real-world evidence on their impact in clinical practice is controversial. We investigated prevalence, variables associated and clinical implications of prolonged corrected QT (QTc) among patients from the Syncope and Dementia study. METHODS: Observational, prospective, multicenter study. Patients≥65 years with dementia and fall suspected for syncope in the previous three months were enrolled. Several clinical variables and the complete list of medications were recorded for each patient. A 12­lead ECG was obtained and corrected QT was calculated by the Bazett's formula. One-year followup for death and recurrent syncope was performed. RESULTS: Prolonged QTc was observed in 25% of the 432 enrolled patients (mean age 83.3), and was significantly associated with male gender (OR 2.09; 95% CI 1.34-3.26) and diuretics use (OR 1.85; 95% CI 1.18-2.90). At one-year 23.3% of patients died and 30.4% reported at least one recurrent event. Variables associated with one-year mortality were: age, male gender, atrial fibrillation (AF), use of calcium channel blockers and prolonged QTc (OR 1.80; 95% CI 1.01-3.20). Among patients with prolonged QTc a significant interaction for mortality was found with AF. Recurrent events were associated with the use of antiplatelets, cholinesterase. inhibitors and antipsychotics, but not with prolonged QTc. CONCLUSIONS: We documented a high prevalence of prolonged QTc, that was associated with male gender and diuretics but not with psychoactive medications. Patients with prolonged QTc had higher one-year mortality, that was four-fold increased in those with concomitant AF.


Assuntos
Demência/fisiopatologia , Diuréticos/efeitos adversos , Síndrome do QT Longo/etiologia , Síndrome do QT Longo/mortalidade , Síncope/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Antipsicóticos , Bloqueadores dos Canais de Cálcio , Eletrocardiografia , Feminino , Humanos , Itália/epidemiologia , Modelos Logísticos , Masculino , Prevalência , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Síncope/diagnóstico
11.
Neurosci Lett ; 700: 70-77, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29758301

RESUMO

Human-ether-a-go-go-related channel (hERG) is a voltage gated potassium channel (Kv11.1) abundantly expressed in heart and brain tissues. In addition to playing an important role in mediation of repolarizing K+ currents (IKr) in Action Potential (AP), hERG is notorious for its propensity to interact with various medications. The drug-induced block of K+ currents across hERG channel are strongly associated with dysrhythmic conditions collectively known as drug-induced long-QT-syndrome. The recent availability of the high-resolution Cryo-EM structures for the hERG channel has provided unique opportunity to resolve structural mechanisms involved into the process of voltage-gating of hERG channels, map various roles played by components of ventricular and neuronal membranes and then to connect it to cellular pathways through which diverse chemical compounds might be affecting function of the channel. Specifically, lipids and lipid derivatives such as polyunsaturated fatty acids (PUFAs), ceramides and steroids have been shown to directly interact with the lipid facing amino acids in various Kv channels including hERG. In this review, possible lipophilic pathways of hERG activators and blockers, together with the existence of fenestration windows and effects of PUFAs, ceramides and steroids are explored throughout different sections. Finally, the interplay between long QT inducing drugs and phospholipidosis is briefly discussed.


Assuntos
Canal de Potássio ERG1/fisiologia , Lipídeos/fisiologia , Ceramidas/metabolismo , Ceramidas/farmacologia , Canal de Potássio ERG1/agonistas , Canal de Potássio ERG1/antagonistas & inibidores , Canal de Potássio ERG1/química , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Insaturados/farmacologia , Humanos , Síndrome do QT Longo/etiologia , Lipídeos de Membrana/fisiologia , Simulação de Acoplamento Molecular , Transdução de Sinais , Esteroides/metabolismo , Esteroides/farmacologia
12.
J Pharm Pract ; 32(1): 48-53, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29092657

RESUMO

BACKGROUND:: Higher rates of corrected QT (QTc) prolongation have been reported in patients with cirrhosis. The impact of liver transplantation and prescription medications on the natural history of QTc prolongation has yet to be well characterized. METHODS:: This was a single-center review of patients receiving (group 1) or listed for (group 2) a liver transplant during 2014. Patients in group 1 were followed prospectively from the date of transplantation to assess rates of QTc normalization posttransplant. In group 2, patients were evaluated from the date of listing up until December 2015 to assess the prevalence of QTc prolongation among liver transplant candidates. RESULTS:: In group 1, 22 (75.9%) patients with QTc intervals >460 milliseconds at the time of transplant established normal baseline QTc intervals following transplantation. The median time to this QTc normalization was 17 days. In group 2, 30 (16.9%) patients had at least 1 documented QTc interval >500 milliseconds with prevalence rates of 42.9%, 19.0%, and 10.2% in patients with natural model of end-stage liver disease scores of >30, 16 to 30, and <16, respectively ( P < .01). Overall, 49.4% of patients in group 1 and 47.5% of patients in group 2 were prescribed QTc prolonging medications. CONCLUSION:: QTc prolongation will resolve following transplantation in the majority of patients and generally occurs within the first several weeks. Among the listed liver transplant candidates, higher rates of clinically significant QTc prolongation may be observed in patients with more severe underlying cirrhosis. QTc prolonging medications are commonly prescribed in this population and warrant monitoring following initiation.


Assuntos
Cirrose Hepática/complicações , Transplante de Fígado , Síndrome do QT Longo/epidemiologia , Medicamentos sob Prescrição/administração & dosagem , Idoso , Estudos de Coortes , Eletrocardiografia , Doença Hepática Terminal/cirurgia , Feminino , Humanos , Cirrose Hepática/fisiopatologia , Síndrome do QT Longo/etiologia , Masculino , Pessoa de Meia-Idade , Medicamentos sob Prescrição/efeitos adversos , Prevalência , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo
13.
Acta Cardiol ; 74(1): 53-58, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29513133

RESUMO

INTRODUCTION: Risk assessment for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) remains complex. The goal of this study was to assess electrocardiogram (ECG)-derived risk factors on SCD in a large HCM population Methods: Retrospective review of adults with HCM evaluated at Mayo Clinic, Rochester, MN from 1 December 2002 to 31 December 2012 was performed. Data inclusive of ECG and 24-hour ambulatory Holter monitor were assessed. SCD events were documented by ventricular fibrillation (VF) noted on implantable cardioverter defibrillator (ICD), or appropriate VT or VF-terminating ICD shock. RESULTS: Overall, 1615 patients (mean age 53.7 ± 15.2 years; 943 males, 58.4%) were assessed, with mean follow-up 2.46 years and 110 SCD events. Via logistic regression (n = 820), the odds of SCD increased with increasing number of conventional risk factors. With one risk factor the OR was 4.88 (p < .0001; CI 2.22-10.74), two risk factors the OR was 6.922 (p < .0001; CI 2.94-16.28) and three or more risk factors, the OR was 13.997 (p < .0001; CI 5.649-34.68). Adding QTc > 450 to this logistic regression model had OR 1.722 (p = .04, CI 1.01-2.937) to predict SCD. QTc ≥ 450 was a significant predictor for death (HR 1.88, p = .021, CI 1.10-3.20). There was no correlation between sinus bradycardia, sinus tachycardia, first degree AV block, atrial fibrillation, left bundle branch block, right bundle branch block, premature atrial complexes, premature ventricular complexes, supraventricular tachycardia, PR interval, QRS interval and SCD. CONCLUSIONS: Prolonged QTc was a risk factor for SCD and death even when controlling for typical risk factors.


Assuntos
Cardiomiopatia Hipertrófica/complicações , Morte Súbita Cardíaca/etiologia , Previsões , Síndrome do QT Longo/etiologia , Medição de Risco/métodos , Idoso , Cardiomiopatia Hipertrófica/fisiopatologia , Morte Súbita Cardíaca/epidemiologia , Eletrocardiografia Ambulatorial , Feminino , Seguimentos , Humanos , Incidência , Síndrome do QT Longo/epidemiologia , Síndrome do QT Longo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
14.
Horm Mol Biol Clin Investig ; 36(1)2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30427780

RESUMO

Background Severe mental disorders, i.e. psychotic disorders, unipolar and bipolar disorders are associated with increased morbidity and mortality from cardiovascular and metabolic disorders. The underlying cause of this association is complex and comprises disorder specific alterations such as dysfunctions of immunological and hormonal systems, body-composition changes and health associated behaviors (smoking, sedentary lifestyle, alcohol intake and treatment compliance). Furthermore, some psychopharmacological drugs may exert unwanted side effects that impact the cardiovascular system. Methods This paper reviews studies concerning commonly used antidepressant and antipsychotics drugs with a particular focus on direct and indirect cardiovascular side effects. Results Newer antidepressant drugs have a favorable cardiovascular safety profile compared to tricyclic antidepressants. However, QTc prolongation, increased blood pressure and potentially higher risks of bleeding have been observed in some newer antidepressants. Some second generation (atypical) antipsychotics have raised concern because of indirect cardiovascular, metabolic side effects such as weight gain and disturbances in lipid and glucose metabolism. Conclusions Psychiatrists need to be aware of potential direct and indirect cardiovascular side effects and to include them in the risk/benefit assessment when choosing a specific individualized treatment.


Assuntos
Antidepressivos Tricíclicos/efeitos adversos , Antipsicóticos/efeitos adversos , Síndrome do QT Longo/etiologia , Animais , Cardiotoxicidade , Humanos , Ganho de Peso
15.
Iran J Kidney Dis ; 12(5): 293-298, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30367021

RESUMO

INTRODUCTION: Acute nephritic syndrome (ANS) is the most common cause of hypertensive heart failure in pediatric population. There are few publications on myocardial evaluation using electrocardiographic and echocardiographic data in pediatric patients with ANS. This study aimed to evaluate myocardial function by electrocardiography and 2-dimensional echocardiography in Egyptian pediatric patients with ANS. MATERIALS AND METHODS: Sixty children with ANS were included and subjected to clinical, laboratory, electrocardiography for corrected QT interval, and 2-dimensional echocardiographic study on admission, and repeated at 6 and 12 weeks to measure left ventricular ejection fraction, left atrium-aorta ratio, and the ratio of peak early filling (E wave) to late diastolic filling (A wave) velocities (E/A ratio). RESULTS: Prolonged corrected QT interval was reported in 22 patients (36.7%), of whom 18 had hypertension. Fourteen patients (23.3%) had left ventricular ejection fraction below 60%. The same children also had left atrium-aorta ratios more than 2 and E/A ratios more than 2. Left ventricular ejection fraction became within normal values by 6 weeks in 12 patients, and 2 become normal by 3 months of follow-up. 4 of 14 children with low left ventricular ejection fraction (28.6%) had normal arterial blood pressure. All of the 14 children completely recovered within 3 months. CONCLUSIONS: Myocardial dysfunction in the acute phase of ANS was alleviated in almost all children within 12 weeks. Although elevated blood pressure was the commonest etiology of congestive heart failure in children with ANS, the impact of primary myocardial functional disturbance could also be put into consideration.


Assuntos
Coração/fisiopatologia , Hipertensão/diagnóstico , Síndrome do QT Longo/diagnóstico , Síndrome Nefrótica/complicações , Disfunção Ventricular Esquerda/diagnóstico , Doença Aguda , Pressão Sanguínea , Criança , Pré-Escolar , Ecocardiografia Doppler , Egito , Eletrocardiografia , Feminino , Seguimentos , Humanos , Hipertensão/etiologia , Lactente , Síndrome do QT Longo/etiologia , Masculino , Volume Sistólico , Disfunção Ventricular Esquerda/etiologia
16.
Br J Clin Pharmacol ; 84(12): 2824-2835, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30112769

RESUMO

AIMS: QTc prolongation is a complex problem linked with multiple risk factors. The RISQ-PATH score was previously developed to identify high-risk patients for QTc prolongation. The aim of this study was to optimize and validate this risk score in a large patient cohort, and to propose an algorithm to generate smart QT signals in the electronic medical record. METHODS: A retrospective study was performed in the Nexus hospital network (n = 17) in Belgium. All electrocardiograms performed in 2015 in both ambulatory and hospitalized patients were collected together with risk factors for QTc prolongation (training database). Multiple logistic regression was performed to obtain the optimal prediction (RISQ-PATH) model. The model was tested in a validation database (electrocardiograms between January and April 2016). RESULTS: In total, 60 208 patients (52.8% males, mean age 63 ± 18 years) were included; 3543 patients (5.9%) had a QTc ≥ 450(♂)/470(♀) ms and 453 (0.8%) a QTc ≥ 500 ms. The optimized RISQ-PATH model has an area under the ROC-curve of 0.772 [95% CI 0.763-0.780] to predict QTc ≥ 450(♂)/470(♀)ms. A predicted probability of ≥0.035 was set as cutoff for a high risk of QTc prolongation. This cutoff resulted in a sensitivity of 87.4% [95% CI 86.2-88.5] and a specificity of 46.2% [95% CI 45.8-46.6]. These results could be confirmed for QTc ≥ 500 ms and in the validation database (n = 28 400). CONCLUSIONS: The RISQ-PATH model, with a cutoff probability of 0.035, predicted a prolonged QTc interval ≥ 450/470 ms or ≥500 ms with a sensitivity of ±87% and a specificity of ±45%. This RISQ-PATH model can be used in clinical decision support systems to create smart QT alerts.


Assuntos
Síndrome do QT Longo/prevenção & controle , Gestão de Riscos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Estudos Transversais , Sistemas de Apoio a Decisões Clínicas , Eletrocardiografia , Feminino , Humanos , Modelos Logísticos , Síndrome do QT Longo/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
17.
BMJ Open ; 8(7): e020036, 2018 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-29982199

RESUMO

OBJECTIVES: Poisoning is a frequent cause of admission to the emergency department (ED) and may involve drugs known to prolong the QT interval. This study aims to describe the prevalence of QTc prolongation among ED patients with suspected poisoning and to calculate the absolute and relative risk of mortality or cardiac arrest associated with a prolonged QTc interval. METHODS: We performed a register-based cohort study, including all adult first-time contacts with suspected poisoning to the ED of two Swedish hospitals (January 2010-December 2014) and two Danish hospitals (March 2013-April 2014). We used propensity score matching to calculate HRs for all-cause mortality or cardiac arrest (combined endpoint) within 30 days after contact comparing patients with a prolonged QTc interval (≥450 ms men, ≥460 ms women) with patients with a QTc interval of <440 ms. RESULTS: Among all first-time contacts with suspected poisoning that had an ECG recorded within 4 hours after arrival (n=3869), QTc prolongation occurred in 6.5%. The overall mortality after a 30-day follow-up period was 0.8% (95% CI 0.6 to 1.2), with an absolute risk of mortality or cardiac arrest in patients with QTc prolongation of 3.2% (95% CI 1.4 to 6.1). A prolonged QTc interval on arrival was associated with a HR of 3.6 (95% CI 1.0 to 12.2). CONCLUSION: In the ED, a prolonged QTc interval in patients arriving with suspected poisoning seems to be associated with a threefold increased risk of 30-day all-cause mortality or cardiac arrest.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Síndrome do QT Longo/mortalidade , Envenenamento/epidemiologia , Adolescente , Adulto , Idoso , Comorbidade , Estudos Transversais , Eletrocardiografia , Feminino , Humanos , Síndrome do QT Longo/etiologia , Masculino , Pessoa de Meia-Idade , Envenenamento/complicações , Prevalência , Pontuação de Propensão , Fatores de Risco , Análise de Sobrevida , Suécia/epidemiologia , Fatores de Tempo , Adulto Jovem
18.
PLoS One ; 13(6): e0199028, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29898002

RESUMO

PURPOSE: To investigate the prevalence and risk factors of acquired long QT syndrome (LQTS) on admission to a general Intensive Care Unit (ICU), and to assess the risk of LQTS associated with prescribed medications. METHODS: Prospective observational, cross-sectional study approved by the Institutional Review Board. Between May 2014 and July 2016, 412 patients >18 years-old consecutively admitted to the ICU of a university hospital were included. LQTS was defined as a QT interval on the admission electrocardiogram corrected using Bazett's formula (QTc) >460 ms for men and >470 ms for women. All medications administered within 24 hours before admission were recorded. Logistic regression was used. RESULTS: LQTS prevalence was 27.9%. In LQTS patients, 70.4% had ≥ 1 LQTS-inducing drug prescribed in the 24 hours prior to ICU admission versus 70.4% in non-LQTS patients (p = 0.99). Bradycardia and Charlson morbidity index score are independent risk factors for LQTS. Haloperidol (OR 4.416), amiodarone (OR 2.509) and furosemide (OR 1.895) were associated with LQTS, as well as another drug not yet described, namely clopidogrel (OR 2.241). CONCLUSIONS: The LQTS is highly prevalent in critically ill patients, ICU patients are often admitted with LQTS-inducing medications, and patients with slow heart rate or with high Charlson comorbidity index should be evaluated for LQTS.


Assuntos
Amiodarona/efeitos adversos , Clopidogrel/efeitos adversos , Furosemida/efeitos adversos , Haloperidol/efeitos adversos , Síndrome do QT Longo/etiologia , Adulto , Idoso , Amiodarona/uso terapêutico , Clopidogrel/uso terapêutico , Estado Terminal , Estudos Transversais , Eletrocardiografia , Feminino , Furosemida/uso terapêutico , Haloperidol/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Estudos Prospectivos , Fatores de Risco
19.
Neurologist ; 23(4): 135-137, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29953038

RESUMO

INTRODUCTION: Acute cerebral injuries, such as cerebral ischemic or hemorrhagic events, have been repeatedly correlated with sudden electrocardiogram (ECG) changes, such as cardiac arrhythmias, QT prolongation, and T-wave inversion (the "cerebral T-wave"). Injuries to the insular cortex have been reported in the literature to result in such changes, possibly due to increased sympathetic tone to the cardiac system. CASE REPORT: A 65-year-old gentleman presented with an acute right middle cerebral artery territory infarction, and was found to have ECG abnormalities and left ventricular dysfunction, which improved after the acute phase of the stroke. CONCLUSIONS: Acute ischemic infarcts, particularly to the right insular cortex, can result in ECG abnormalities, such as QT prolongation and T-wave inversion, as well as acute systolic heart failure; all of which may be reversible after the acute phase of the stroke.


Assuntos
Insuficiência Cardíaca Sistólica/diagnóstico , Infarto da Artéria Cerebral Média/diagnóstico , Síndrome do QT Longo/diagnóstico , Disfunção Ventricular Esquerda/diagnóstico , Doença Aguda , Idoso , Eletrocardiografia , Insuficiência Cardíaca Sistólica/etiologia , Humanos , Infarto da Artéria Cerebral Média/complicações , Síndrome do QT Longo/etiologia , Masculino , Disfunção Ventricular Esquerda/etiologia
20.
Cancer Chemother Pharmacol ; 81(6): 1129-1141, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29603015

RESUMO

PURPOSE: The aim of this analysis was to investigate the potential for ulixertinib (BVD-523) to prolong cardiac repolarization. The mean prolongation of the corrected QT (QTc) interval was predicted at the mean maximum drug concentrations of the recommended phase 2 dose (RP2D; 600 mg BID) and of higher concentrations. In addition, the effect of ulixertinib on other quantitative ECG parameters was assessed. METHODS: In a two-part, phase 1, open-label study in adults with advanced solid tumors, 105 patients [24 in Part 1 (dose escalation) and 81 in Part 2 (cohort expansion)] were included in a QT prolongation analysis. Electrocardiograms (ECGs) extracted from 12-lead Holter monitors, along with time-matched pharmacokinetic blood samples, were collected over 12 h on cycle 1 day 1 and cycle 1 day 15 and analyzed by a core ECG laboratory. RESULTS: A small increase in heart rate was observed on both study days (up to 5.6 bpm on day 1 and up to 7 bpm on day 15). The estimated mean changes from baseline in the study-specific QTc interval (QTcSS), at the ulixertinib Cmax, were - 0.529 ms (90% CI - 6.621, 5.562) on day 1 and - 9.202 ms (90% CI - 22.505, 4.101) on day 15. The concentration: QTc regression slopes were mildly positive but not statistically significant [0.53 (90% CI - 1.343, 2.412) and 1.16 (90% CI - 1.732, 4.042) ms per µg/mL for days 1 and 15, respectively]. Ulixertinib had no meaningful effect on PR or QRS intervals. CONCLUSIONS: Ulixertinib administered to patients with solid tumors at clinically relevant doses has a low risk for QT/QTc prolongation or any other effects on ECG parameters. REGISTRATION: The study is registered at Clinicaltrials.gov (NCT01781429) and was sponsored by BioMed Valley Discoveries.


Assuntos
Aminopiridinas/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Síndrome do QT Longo/etiologia , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Pirróis/administração & dosagem , Idoso , Aminopiridinas/efeitos adversos , Relação Dose-Resposta a Droga , Eletrocardiografia Ambulatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Inibidores de Proteínas Quinases/efeitos adversos , Pirróis/efeitos adversos
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