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1.
Europace ; 26(7)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38970395

RESUMO

AIMS: Although electrical activity of the normal human heart is well characterized by the electrocardiogram, detailed insights into within-subject and between-subject variations of ventricular activation and recovery by noninvasive electroanatomic mapping are lacking. We characterized human epicardial activation and recovery within and between normal subjects using non-invasive electrocardiographic imaging (ECGI) as a basis to better understand pathology. METHODS AND RESULTS: Epicardial activation and recovery were assessed by ECGI in 22 normal subjects, 4 subjects with bundle branch block (BBB) and 4 with long-QT syndrome (LQTS). We compared characteristics between the ventricles [left ventricle (LV) and right ventricle (RV)], sexes, and age groups (<50/≥50years). Pearson's correlation coefficient (CC) was used for within-subject and between-subject comparisons. Age of normal subjects averaged 49 ± 14 years, 6/22 were male, and no structural/electrical heart disease was present. The average activation time was longer in LV than in RV, but not different by sex or age. Electrical recovery was similar for the ventricles, but started earlier and was on average shorter in males. Median CCs of between-subject comparisons of the ECG signals, activation, and recovery patterns were 0.61, 0.32, and 0.19, respectively. Within-subject beat-to-beat comparisons yielded higher CCs (0.98, 0.89, and 0.82, respectively). Activation and/or recovery patterns of patients with BBB or LQTS contrasted significantly with those found in the normal population. CONCLUSION: Activation and recovery patterns vary profoundly between normal subjects, but are stable individually beat to beat, with a male preponderance to shorter recovery. Individual characterization by ECGI at baseline serves as reference to better understand the emergence, progression, and treatment of electrical heart disease.


Assuntos
Potenciais de Ação , Bloqueio de Ramo , Eletrocardiografia , Síndrome do QT Longo , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Bloqueio de Ramo/fisiopatologia , Bloqueio de Ramo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Síndrome do QT Longo/diagnóstico , Frequência Cardíaca , Valor Preditivo dos Testes , Idoso , Estudos de Casos e Controles , Fatores de Tempo , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Fatores Etários , Mapeamento Epicárdico
3.
Inn Med (Heidelb) ; 65(8): 787-797, 2024 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-38977442

RESUMO

Genetic arrhythmia disorders are rare diseases; however, they are a common cause of sudden cardiac death in children, adolescents, and young adults. In principle, a distinction can be made between channelopathies and cardiomyopathies in the context of genetic diseases. This paper focuses on the channelopathies long and short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia (CPVT). Early diagnosis of these diseases is essential, as drug therapy, behavioral measures, and if necessary, implantation of a cardioverter defibrillator can significantly improve the prognosis and quality of life of patients. This paper highlights the pathophysiological and genetic basis of these channelopathies, describes their clinical manifestations, and comments on the principles of diagnosis, risk stratification and therapy.


Assuntos
Arritmias Cardíacas , Síndrome de Brugada , Canalopatias , Humanos , Arritmias Cardíacas/genética , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/terapia , Arritmias Cardíacas/fisiopatologia , Canalopatias/genética , Canalopatias/diagnóstico , Canalopatias/terapia , Síndrome de Brugada/genética , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/fisiopatologia , Síndrome de Brugada/terapia , Taquicardia Ventricular/genética , Taquicardia Ventricular/terapia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Adolescente , Criança , Síndrome do QT Longo/genética , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/terapia , Síndrome do QT Longo/fisiopatologia , Morte Súbita Cardíaca/prevenção & controle , Morte Súbita Cardíaca/etiologia , Adulto , Desfibriladores Implantáveis , Eletrocardiografia
4.
J Am Heart Assoc ; 13(14): e033619, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38979841

RESUMO

BACKGROUND: Few small-sample studies have quantified the T-wave alternans (TWA) value by 24-hour ambulatory recordings or exercise stress tests in patients with long QT syndrome (LQTS). The cutoff point of TWA ≥47 µV was based on patients with myocardial infarction. In our study, we aimed to (1) evaluate the association of TWA with life-threatening arrhythmic events (LAEs); (2) compare the predictive model of LAEs according to the TWA value measured by 24-hour ambulatory recordings and exercise stress tests; and (3) propose a cutoff point for the high risk of LAEs in patients with LQTS. METHODS AND RESULTS: The study cohort included 110 patients with LQTS referred to our hospital, and the primary outcome was LAEs. Thirty-one patients with LQTS (31/110 [28.2%]) developed LAEs during the following 24 (12-47) months. Peak TWA value quantified from 12 leads by 24-hour ambulatory recordings in patients with LQTS with LAEs (LQTS-LAEs group) was significantly higher than LQTS without LAEs (LQTS-non-LAEs group) (64.0 [42.0-86.0] µV versus 43.0 [36.0-53.0] µV; P<0.01). There was no statistical difference in TWA value measured by exercise stress tests between the 2 groups (69.0 [54.5-127.5] µV versus 68.5 [53.3-99.8] µV; P=0.871). The new cutoff point of the peak TWA value measured by 24-hour ambulatory recordings was 55.5 µV, with a sensitivity of 75.0% and a specificity of 78.6%. A univariate Cox regression analysis revealed that TWA value ≥55.5 µV was a strong predictor of LAEs (hazard ratio [HR], 4.5 [2.1-9.6]; P<0.001]. A multivariate Cox regression analysis indicated that TWA value ≥55.5 µV remained significant (HR, 2.7 [1.1-6.8]; P=0.034). CONCLUSIONS: Peak TWA measured by 24-hour ambulatory recordings was a more favorable risk stratification marker than exercise stress tests for patients with LQTS.


Assuntos
Eletrocardiografia Ambulatorial , Teste de Esforço , Síndrome do QT Longo , Humanos , Feminino , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Masculino , Teste de Esforço/métodos , Medição de Risco/métodos , Adulto , Eletrocardiografia Ambulatorial/métodos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Adulto Jovem , Prognóstico , Fatores de Tempo , Estudos Retrospectivos , Frequência Cardíaca/fisiologia
5.
JAMA Netw Open ; 7(6): e2415576, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38848063

RESUMO

Importance: Rifampin-resistant tuberculosis treatment regimens require electrocardiographic (ECG) monitoring due to the use of multiple QTc-prolonging agents. Formal 12-lead ECG devices represent a significant burden in resource-constrained clinics worldwide and a potential barrier to treatment scale-up in some settings. Objective: To evaluate the diagnostic accuracy of a handheld 6-lead ECG device within resource-constrained clinics. Design, Setting, and Participants: This diagnostic study was performed within a multicenter, pragmatic (broad eligibility criteria with no exclusions for randomized participants), phase 3 rifampin-resistant tuberculosis treatment trial (BEAT Tuberculosis [Building Evidence for Advancing New Treatment for Tuberculosis]) in South Africa. A total of 192 consecutive trial participants were assessed, and 191 were recruited for this substudy between January 21, 2021, and March 27, 2023. A low proportion (3 of 432 [0.7%]) of all screened trial participants were excluded due to a QTc interval greater than 450 milliseconds. Triplicate reference standard 12-lead ECG results were human calibrated with readers blinded to 6-lead ECG results. Main Outcomes and Measures: Diagnostic accuracy, repeatability, and feasibility of a 6-lead ECG device. Results: A total of 191 participants (median age, 36 years [IQR, 28-45 years]; 81 female participants [42.4%]; 91 participants [47.6%] living with HIV) with a median of 4 clinic visits (IQR, 3-4 visits) contributed 2070 and 2015 12-lead and 6-lead ECG assessments, respectively. Across 170 participants attending 489 total clinic visits where valid triplicate QTc measurements were available for both devices, the mean 12-lead QTc measurement was 418 milliseconds (range, 321-519 milliseconds), and the mean 6-lead QTc measurement was 422 milliseconds (range, 288-574 milliseconds; proportion of variation explained, R2 = 0.4; P < .001). At a QTc interval threshold of 500 milliseconds, the 6-lead ECG device had a negative predictive value of 99.8% (95% CI, 98.8%-99.9%) and a positive predictive value of 16.7% (95% CI, 0.4%-64.1%). The normal expected range of within-individual variability of the 6-lead ECG device was high (±50.2 milliseconds [coefficient of variation, 6.0%]) relative to the 12-lead ECG device (±22.0 milliseconds [coefficient of variation, 2.7%]). The mean (SD) increase in the 12-lead QTc measurement during treatment was 10.1 (25.8) milliseconds, with 0.8% of clinic visits (4 of 489) having a QTc interval of 500 milliseconds or more. Conclusions and Relevance: This study suggests that simplified, handheld 6-lead ECG devices are effective triage tests that could reduce the need to perform 12-lead ECG monitoring in resource-constrained settings.


Assuntos
Eletrocardiografia , Humanos , Feminino , Masculino , Adulto , Eletrocardiografia/instrumentação , Eletrocardiografia/métodos , África do Sul , Pessoa de Meia-Idade , Síndrome do QT Longo/diagnóstico , Reprodutibilidade dos Testes , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Região de Recursos Limitados
6.
Int Heart J ; 65(3): 580-585, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38825499

RESUMO

Cardiac ryanodine receptor (RyR2) gain-of-function mutations cause catecholaminergic polymorphic ventricular tachycardia (CPVT). Conversely, RyR2 loss-of-function mutations cause a new disease entity, termed calcium release deficiency syndrome (CRDS), which may include RYR2-related long QT syndrome (LQTS). Importantly, unlike CPVT, patients with CRDS do not always exhibit exercise- or epinephrine-induced ventricular arrhythmias, which precludes a diagnosis of CRDS. Here we report a boy and his father, who both experienced exercise-induced cardiac events and harbor the same RYR2 E4107A variant. In the boy, an exercise stress test (EST) and epinephrine provocation test (EPT) did not induce any ventricular arrhythmias. QTc was slightly prolonged (QTc: 474 ms), and an EPT induced QTc prolongation (QTc-baseline: 466 ms, peak: 532 ms, steady-state: 527 ms). In contrast, in his father, QTc was not prolonged (QTc: 417 ms), and neither an EST nor EPT induced QTc prolongation. However, an EST induced multifocal premature ventricular contraction (PVC) bigeminy and bidirectional PVC couplets. Thus, they exhibited distinct clinical phenotypes: the boy exhibited LQTS (or CRDS) phenotype, whereas his father exhibited CPVT phenotype. These findings suggest that, in addition to the altered RyR2 function, other unidentified factors, such as other genetic, epigenetic, and environmental factors, and aging, may be involved in the diverse phenotypic manifestations. Considering that a single RYR2 variant can cause both CPVT and LQTS (or CRDS) phenotypes, in cascade screening of patients with CPVT and CRDS, an EST and EPT are not sufficient and genetic analysis is required to identify individuals who are at increased risk for life-threatening arrhythmias.


Assuntos
Síndrome do QT Longo , Fenótipo , Canal de Liberação de Cálcio do Receptor de Rianodina , Taquicardia Ventricular , Humanos , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Masculino , Síndrome do QT Longo/genética , Síndrome do QT Longo/diagnóstico , Taquicardia Ventricular/genética , Taquicardia Ventricular/diagnóstico , Eletrocardiografia , Linhagem , Adulto , Teste de Esforço , Mutação
8.
Br J Gen Pract ; 74(suppl 1)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902083

RESUMO

BACKGROUND: Opioid Agonist Treatment (OAT) is the gold standard for managing Opioid Use Disorder (OUD). It is highly effective at reducing all-cause mortality and drug-related harms. Prescribing OAT, particularly methadone, is becoming increasingly complex as Scotland's OUD population ages. Older patients, with increased polypharmacy and multimorbidity, are more susceptible to QTc interval prolongation associated with methadone use. Therefore, adherence to ECG monitoring guidelines for patients prescribed methadone is crucial, though insights from substance use services indicate suboptimal compliance. Medically Assisted Treatment guidelines established by the Scottish Government advocate for shared care agreements, thus transferring OAT prescribing responsibilities to primary care. Understanding ECG monitoring guideline implementation in non-specialist services is vital for developing safe OAT services in primary care. AIM: This audit assessed adherence to NICE guidelines for ECG monitoring in OUD patients prescribed methadone in a Scottish primary care practice. METHOD: The notes of patients prescribed methadone were assessed using NICE criteria to determine eligibility for ECG monitoring. Eligible patients' medical records were reviewed to identify previous ECG investigations. RESULTS: Of 21 patients prescribed methadone, 16 qualified for ECG monitoring. Only 25% of eligible patients received ECG monitoring per NICE guideline, meaning 75% did not. CONCLUSION: These findings highlight that the issue of poor compliance with ECG monitoring guidelines is not limited to specialist services, but also affects primary care. Further exploration of barriers to guideline implementation is essential. Perhaps more resources are needed to integrate OAT services into primary care, which has taken on increased responsibilities without corresponding investment.


Assuntos
Eletrocardiografia , Fidelidade a Diretrizes , Metadona , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides , Atenção Primária à Saúde , Humanos , Metadona/uso terapêutico , Escócia , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Feminino , Masculino , Tratamento de Substituição de Opiáceos/métodos , Adulto , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/diagnóstico , Analgésicos Opioides/uso terapêutico , Analgésicos Opioides/efeitos adversos
9.
Card Electrophysiol Clin ; 16(2): 203-210, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38749642

RESUMO

Bidirectional ventricular tachycardia is a unique arrhythmia that can herald lethal arrhythmia syndromes. Using cases based on real patient stories, this article examines 3 different presentations to help clinicians learn the differential diagnosis associated with this condition. Each associated genetic disorder will be briefly discussed, and valuable tips for distinguishing them from each other will be provided.


Assuntos
Taquicardia Ventricular , Criança , Humanos , Masculino , Arritmias Cardíacas/genética , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Diagnóstico Diferencial , Eletrocardiografia , Síndrome do QT Longo/genética , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/genética , Taquicardia Ventricular/fisiopatologia , Adolescente
10.
Clin Transl Sci ; 17(5): e13808, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38700272

RESUMO

Sitravatinib (MGCD516) is an orally available, small molecule, tyrosine kinase inhibitor that has been evaluated in patients with advanced solid tumors. Concentration-corrected QT interval (QTc; C-QTc) modeling was undertaken, using 767 matched concentration-ECG observations from 187 patients across two clinical studies in patients with advanced solid malignancies, across a dose range of 10-200 mg, via a linear mixed-effects (LME) model. The effect on heart rate (HR)-corrected QT interval via Fridericia's correction method (QTcF) at the steady-state maximum concentration (Cmax,ss) for the sitravatinib proposed therapeutic dosing regimen (100 mg malate once daily [q.d.]) without and with relevant intrinsic and extrinsic factors were predicted. No significant changes in HR from baseline were observed. Hysteresis between sitravatinib plasma concentration and change in QTcF from baseline (ΔQTcF) was not observed. There was no significant relationship between sitravatinib plasma concentration and ΔQTcF. The final C-QTc model predicted a mean (90% confidence interval [CI]) ΔQTcF of 3.92 (1.95-5.89) ms and 2.94 (0.23-6.10) ms at the proposed therapeutic dosing regimen in patients with normal organ function (best case scenario) and patients with hepatic impairment (worst-case scenario), respectively. The upper bounds of the 90% CIs were below the regulatory threshold of concern of 10 ms. The results of the described C-QTc analysis, along with corroborating results from nonclinical safety pharmacology studies, indicate that sitravatinib has a low risk of QTc interval prolongation at the proposed therapeutic dose of 100 mg malate q.d.


Assuntos
Eletrocardiografia , Frequência Cardíaca , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Relação Dose-Resposta a Droga , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/diagnóstico , Modelos Biológicos , Idoso de 80 Anos ou mais , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacocinética , Adulto Jovem , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética
11.
JACC Clin Electrophysiol ; 10(5): 956-966, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38703162

RESUMO

BACKGROUND: Prediction of drug-induced long QT syndrome (diLQTS) is of critical importance given its association with torsades de pointes. There is no reliable method for the outpatient prediction of diLQTS. OBJECTIVES: This study sought to evaluate the use of a convolutional neural network (CNN) applied to electrocardiograms (ECGs) to predict diLQTS in an outpatient population. METHODS: We identified all adult outpatients newly prescribed a QT-prolonging medication between January 1, 2003, and March 31, 2022, who had a 12-lead sinus ECG in the preceding 6 months. Using risk factor data and the ECG signal as inputs, the CNN QTNet was implemented in TensorFlow to predict diLQTS. RESULTS: Models were evaluated in a held-out test dataset of 44,386 patients (57% female) with a median age of 62 years. Compared with 3 other models relying on risk factors or ECG signal or baseline QTc alone, QTNet achieved the best (P < 0.001) performance with a mean area under the curve of 0.802 (95% CI: 0.786-0.818). In a survival analysis, QTNet also had the highest inverse probability of censorship-weighted area under the receiver-operating characteristic curve at day 2 (0.875; 95% CI: 0.848-0.904) and up to 6 months. In a subgroup analysis, QTNet performed best among males and patients ≤50 years or with baseline QTc <450 ms. In an external validation cohort of solely suburban outpatient practices, QTNet similarly maintained the highest predictive performance. CONCLUSIONS: An ECG-based CNN can accurately predict diLQTS in the outpatient setting while maintaining its predictive performance over time. In the outpatient setting, our model could identify higher-risk individuals who would benefit from closer monitoring.


Assuntos
Inteligência Artificial , Eletrocardiografia , Síndrome do QT Longo , Redes Neurais de Computação , Humanos , Feminino , Masculino , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/diagnóstico , Pessoa de Meia-Idade , Idoso , Adulto , Fatores de Risco
12.
Card Electrophysiol Clin ; 16(2): 195-202, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38749641

RESUMO

The case series reviews differential diagnosis of a genetic arrhythmia syndrome when evaluating a patient with prolonged QTc. Making the correct diagnosis requires: detailed patient history, family history, and careful review of the electrocardiogram (ECG). Signs and symptoms and ECG characteristics can often help clinicians make the diagnosis before genetic testing results return. These skills can help clinicians make an accurate and timely diagnosis and prevent life-threatening events.


Assuntos
Arritmias Cardíacas , Eletrocardiografia , Síndrome do QT Longo , Humanos , Diagnóstico Diferencial , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/genética , Arritmias Cardíacas/fisiopatologia , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/genética , Síndrome do QT Longo/fisiopatologia , Criança , Masculino , Feminino , Adolescente , Testes Genéticos
13.
J Cardiovasc Electrophysiol ; 35(7): 1370-1381, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38725227

RESUMO

INTRODUCTION: Although prior studies indicate that a QTc > 500 ms on a single baseline 12-lead electrocardiogram (ECG) is associated with significantly increased risk of arrhythmic events in long QT syndrome (LQTS), less is known about the risk of persistent QT prolongation. We sought to determine QTc persistence and its prognostic effect on breakthrough cardiac events (BCEs) among pediatric patients treated for LQTS. METHODS: We performed a retrospective analysis of 433 patients with LQTS evaluated, risk-stratified, and undergoing active guideline-based LQTS treatment between 1999 and 2019. BCEs were defined as arrhythmogenic syncope/seizure, sudden cardiac arrest (SCA), appropriate VF-terminating ICD shock, and sudden cardiac death (SCD). RESULTS: During the median follow-up of 5.5 years (interquartile range [IQR] = 3-9), 32 (7%) patients experienced a total of 129 BCEs. A maximum QTc threshold of 520 ms and median QTc threshold of 490 ms were determined to be strong predictors for BCEs. A landmark analysis controlling for age, sex, genotype, and symptomatic status demonstrated models utilizing both the median QTc and maximum QTc demonstrated the highest discriminatory value (c-statistic = 0.93-0.95). Patients in the high-risk group (median QTc > 490 ms and maximum QTc > 520 ms) had a significantly lower BCE free survival (70%-81%) when compared to patients in both medium-risk (93%-97%) and low-risk (98%-99%) groups. CONCLUSIONS: The risk of BCE among patients treated for LQTS increases not only based upon their maximum QTc, but also their median QTc (persistence of QTc prolongation). Patients with a maximum QTc > 520 ms and median QTc > 490 ms over serial 12-lead ECGs are at the highest risk of BCE while on guideline-directed medical therapy.


Assuntos
Potenciais de Ação , Morte Súbita Cardíaca , Eletrocardiografia , Frequência Cardíaca , Síndrome do QT Longo , Valor Preditivo dos Testes , Humanos , Masculino , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Feminino , Estudos Retrospectivos , Criança , Medição de Risco , Fatores de Risco , Adolescente , Morte Súbita Cardíaca/prevenção & controle , Morte Súbita Cardíaca/etiologia , Pré-Escolar , Fatores de Tempo , Fatores Etários , Lactente , Resultado do Tratamento , Sistema de Condução Cardíaco/fisiopatologia
14.
PLoS One ; 19(5): e0297914, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38691546

RESUMO

Inherited cardiovascular diseases are rare diseases that are difficult to diagnose by non-expert professionals. Genetic analyses play a key role in the diagnosis of these diseases, in which the identification of a pathogenic genetic variant is often a diagnostic criterion. Therefore, genetic variant classification and routine reinterpretation as data become available represent one of the main challenges associated with genetic analyses. Using the genetic variants identified in an inherited cardiovascular diseases unit during a 10-year period, the objectives of this study were: 1) to evaluate the impact of genetic variant reinterpretation, 2) to compare the reclassification rates between different cohorts of cardiac channelopathies and cardiomyopathies, and 3) to establish the most appropriate periodicity for genetic variant reinterpretation. All the evaluated cohorts (full cohort of inherited cardiovascular diseases, cardiomyopathies, cardiac channelopathies, hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic cardiomyopathy, Brugada syndrome, long QT syndrome and catecholaminergic polymorphic ventricular tachycardia) showed reclassification rates above 25%, showing even higher reclassification rates when there is definitive evidence of the association between the gene and the disease in the cardiac channelopathies. Evaluation of genetic variant reclassification rates based on the year of the initial classification showed that the most appropriate frequency for the reinterpretation would be 2 years, with the possibility of a more frequent reinterpretation if deemed convenient. To keep genetic variant classifications up to date, genetic counsellors play a critical role in the reinterpretation process, providing clinical evidence that genetic diagnostic laboratories often do not have at their disposal and communicating changes in classification and the potential implications of these reclassifications to patients and relatives.


Assuntos
Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/diagnóstico , Canalopatias/genética , Canalopatias/diagnóstico , Testes Genéticos/métodos , Variação Genética , Cardiomiopatias/genética , Cardiomiopatias/diagnóstico , Síndrome do QT Longo/genética , Síndrome do QT Longo/diagnóstico , Síndrome de Brugada/genética , Síndrome de Brugada/diagnóstico
15.
Cardiovasc Toxicol ; 24(7): 700-709, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38819736

RESUMO

Cardiovascular disease is a major global burden and a leading cause of premature death among patients with severe mental illness. Over time, research and clinical practice have paid increased attention to the impact of psychiatric medications on cardiac repolarization. In a resource-limited setting, it is common for psychotropic medications to be initiated and maintained in an outpatient setting without baseline or follow up ECG. This study evaluated the determinants and predictors of QT abnormalities among patient taking psychotropic drugs. We conducted a cross-sectional study in a population of 150 psychiatric patients on psychotropics and 75 controls. We studied the effects of various psychotropic drugs on QT dispersion (QTd) and corrected QT interval (QTc) as well as correlation with the types and dosages of psychotropic drugs used. All the subjects had detailed clinical examination and resting electrocardiogram (ECG) at 25 mm/sec done. QTc was determined using Bazett formula and QTd was determined by subtracting shortest from longest QT in 12-lead ECG. The prevalence of prolonged QTc and QTd as well as the mean QTc and QTd were significantly higher in patients than the control group. The mean QTc was significantly higher in patient on typical antipsychotics compared to those on atypical antipsychotics. Age, heart rate and antipsychotic dose in chlorpromazine equivalent were predictors of QTc with the heart rate being the most powerful predictor among them. Psychotropic drugs use is associated with QTc and QTd prolongation with age, heart rate and antipsychotic dose as predictors of QTc.


Assuntos
Antipsicóticos , Eletrocardiografia , Frequência Cardíaca , Síndrome do QT Longo , Centros de Atenção Terciária , Humanos , Nigéria/epidemiologia , Masculino , Feminino , Estudos Transversais , Adulto , Frequência Cardíaca/efeitos dos fármacos , Pessoa de Meia-Idade , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/fisiopatologia , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/epidemiologia , Fatores de Risco , Antipsicóticos/efeitos adversos , Estudos de Casos e Controles , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/fisiopatologia , Psicotrópicos/efeitos adversos , Medição de Risco , Prevalência , Adulto Jovem , Potenciais de Ação/efeitos dos fármacos , Fatores Etários
16.
Clin Pharmacol Ther ; 116(1): 106-116, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38709223

RESUMO

The ICH E14/S7B Q&As highlighted the need for best practices concerning the design, execution, analysis, interpretation, and reporting of the in vivo non-rodent QT assay as a component of the integrated risk assessment to potentially support a TQT waiver or substitute. We conducted a dog telemetry study to assess the effects on QTc of six reference compounds (five positive and one negative) previously evaluated by Darpo et al. (2015) in humans. The sensitivity of the assay to detect QTc increases was determined, and exposure-response analysis was performed, as done in clinical practice. By-timepoint analysis showed QTc prolongation induced by moxifloxacin, dofetilide, dolasetron, ondansetron, and quinine within human relevant plasma exposures ranges. Moreover, a hysteresis was observed for quinine. As expected, levocetirizine showed no statistically significant effect on QTc across a range of exposure, well exceeding the therapeutic Cmax. Power analyses confirmed the study ability to detect statistically significant QTc changes of less than 10 milliseconds with 80% probability, even with a sample size as low as n = 4 animals. Finally, concentration-QTc modeling enabled to predict the minimal plasma concentration needed to detect a 10 milliseconds QTc prolongation, including for quinine. The comparison with clinical available data supported the relevance of dogs under these experimental conditions as a robust translational predictor of drug-induced QTc prolongation in humans as a key pillar of the integrated risk assessment.


Assuntos
Eletrocardiografia , Síndrome do QT Longo , Cães , Animais , Estudos Prospectivos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/diagnóstico , Eletrocardiografia/efeitos dos fármacos , Masculino , Feminino , Telemetria/métodos , Medição de Risco/métodos , Humanos , Frequência Cardíaca/efeitos dos fármacos
17.
Arch Cardiovasc Dis ; 117(5): 313-320, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38704288

RESUMO

BACKGROUND: In patients with congenital long QT syndrome (LQTS), the risk of ventricular arrhythmia is correlated with the duration of the corrected QT interval and the changes in the ST-T wave pattern on the 12-lead surface electrocardiogram (12L-ECG). Remote monitoring of these variables could be useful. AIM: To evaluate the abilities of two wearable electrocardiogram devices (Apple Watch and KardiaMobile 6L) to provide reliable electrocardiograms in terms of corrected QT interval and ST-T wave patterns in patients with LQTS. METHODS: In a prospective multicentre study (ClinicalTrials.gov identifier: NCT04728100), a 12L-ECG, a 6-lead KardiaMobile 6L electrocardiogram and two single-lead Apple Watch electrocardiograms were recorded in patients with LQTS. The corrected QT interval and ST-T wave patterns were evaluated manually. RESULTS: Overall, 98 patients with LQTS were included; 12.2% were children and 92.8% had a pathogenic variant in an LQTS gene. The main genotypes were LQTS type 1 (40.8%), LQTS type 2 (36.7%) and LQTS type 3 (7.1%); rarer genotypes were also represented. When comparing the ST-T wave patterns obtained with the 12L-ECG, the level of agreement was moderate with the Apple Watch (k=0.593) and substantial with the KardiaMobile 6L (k=0.651). Regarding the corrected QT interval, the correlation with 12L-ECG was strong for the Apple Watch (r=0.703 in lead II) and moderate for the KardiaMobile 6L (r=0.593). There was a slight overestimation of corrected QT interval with the Apple Watch and a subtle underestimation with the KardiaMobile 6L. CONCLUSIONS: In patients with LQTS, the corrected QT interval and ST-T wave patterns obtained with the Apple Watch and the KardiaMobile 6L correlated with the 12L-ECG. Although wearable electrocardiogram devices cannot replace the 12L-ECG for the follow-up of these patients, they could be interesting additional monitoring tools.


Assuntos
Frequência Cardíaca , Síndrome do QT Longo , Valor Preditivo dos Testes , Dispositivos Eletrônicos Vestíveis , Humanos , Síndrome do QT Longo/fisiopatologia , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/congênito , Síndrome do QT Longo/genética , Feminino , Masculino , Estudos Prospectivos , Criança , Adolescente , Adulto , Reprodutibilidade dos Testes , Adulto Jovem , Eletrocardiografia Ambulatorial/instrumentação , Potenciais de Ação , Pré-Escolar , Desenho de Equipamento , Fatores de Tempo , Pessoa de Meia-Idade , Eletrocardiografia/instrumentação , Sistema de Condução Cardíaco/fisiopatologia
18.
Ann Noninvasive Electrocardiol ; 29(3): e13116, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38627955

RESUMO

PURPOSE: Acquired QT prolongation is frequent and leads to a higher mortality rate in critically ill patients. KardiaMobile 1L® (KM1L) is a portable, user-friendly single lead, mobile alternative to conventional 12-lead electrocardiogram (12-L ECG) that could be more readily available, potentially facilitating more frequent QTc assessments in intensive care units (ICU); however, there is currently no evidence to validate this potential use. METHODS: We conducted a prospective diagnostic test study comparing QT interval measurement using KM1L with conventional 12-L ECG ordered for any reason in patients admitted to an ICU. We compared the mean difference using a paired t-test, agreement using Bland-Altman analysis, and Lin's concordance coefficient, numerical precision (proportion of QT measurements with <10 ms difference between KM1L and conventional 12-L ECG), and clinical precision (concordance for adequate discrimination of prolonged QTc). RESULTS: We included 114 patients (61.4% men, 60% cardiovascular etiology of hospitalization) with 131 12-L ECG traces. We found no statistical difference between corrected QT measurements (427 ms vs. 428 ms, p = .308). Lin's concordance coefficient was 0.848 (95% CI 0.801-0.894, p = .001). Clinical precision was excellent in males and substantial in females (Kappa 0.837 and 0.781, respectively). Numerical precision was lower in patients with vasoactive drugs (-13.99 ms), QT-prolonging drugs (13.84 ms), antiarrhythmic drugs (-12.87 ms), and a heart rate (HR) difference of ≥5 beats per minute (bpm) between devices (-11.26 ms). CONCLUSION: Our study validates the clinical viability of KM1L, a single-lead mobile ECG device, for identifying prolonged QT intervals in ICU patients. Caution is warranted in patients with certain medical conditions that may affect numerical precision.


Assuntos
Eletrocardiografia , Síndrome do QT Longo , Masculino , Feminino , Humanos , Estado Terminal , Estudos Prospectivos , Síndrome do QT Longo/diagnóstico , Frequência Cardíaca/fisiologia
19.
J Electrocardiol ; 84: 91-94, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38579636

RESUMO

A 69-year-old woman was admitted after a cardiac arrest. She developed status epilepticus and was later found to have variable morphologies of a "spiked helmet sign" (SHS) on ECGs in the setting of prolonged QT interval, raising the question of whether this sign is a manifestation of QT prolongation.


Assuntos
Eletrocardiografia , Síndrome do QT Longo , Humanos , Feminino , Idoso , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Diagnóstico Diferencial , Estado Epiléptico/etiologia , Estado Epiléptico/diagnóstico , Parada Cardíaca/etiologia
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