Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
1.
Int J Cardiol Heart Vasc ; 41: 101059, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35663621

RESUMO

Background: Mortality following out-of-hospital cardiac arrest (OHCA) is high, and studies on return to work show varying results. It remains uncertain whether mortality and return to work differs between patients with ischaemic heart disease (IHD) and non-ischaemic heart disease (non-IHD). Aim: To investigate all-cause mortality, cardiac death, and return to work among patients admitted after OHCA with IHD and non-IHD. Methods: We included 234 consecutive patients admitted to Aarhus University Hospital with OHCA, who were not declared dead in the prehospital setting or upon arrival. Patients were divided into an IHD and a non-IHD group based on history of myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or signs of obstructive IHD on the admission coronary angiography. Outcome in terms of all-cause mortality, cardiac death, and return to work was evaluated. Results: All-cause mortality after one month, one year, and five years was 41.9%, 49.1%, and 54.3%. There was no difference in all-cause mortality or cardiac death between IHD and non-IHD patients (all-cause mortality: adjusted HR 0.78, 95% CI, 0.53-1.14; P = 0.19) and cardiac death: adjusted HR 0.93, 95% CI, 0.60-1.43; P = 0.73). Among patients working prior to OHCA the cumulative incidence of patients returning to work was 62.3% after five years with no statistically significant difference between groups. Conclusion: A favourable outcome was observed in patients admitted after OHCA with a non-significant trend toward a higher mortality in non-IHD patients, possibly indicating that IHD is a favourable cause of cardiac arrest.

2.
Europace ; 24(12): 2015-2027, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-35726875

RESUMO

AIMS: Variants in SCN5A encoding Nav1.5 are associated with cardiac arrhythmias. We aimed to determine the mechanism by which c.638G>A in SCNA5 resulting in p.Gly213Asp (G213D) in Nav1.5 altered Na+ channel function and how flecainide corrected the defect in a family with multifocal ectopic Purkinje-related premature contractions (MEPPC)-like syndrome. METHODS AND RESULTS: Five patients carrying the G213D variant were treated with flecainide. Gating pore currents were evaluated in Xenopus laevis oocytes. The 638G>A SCN5A variant was introduced to human-induced pluripotent stem cell (hiPSC) by CRISPR-Cas9 gene editing and subsequently differentiated to cardiomyocytes (hiPSC-CM). Action potentials and sodium currents were measured in the absence and presence of flecainide. Ca2+ transients were measured by confocal microscopy. The five patients exhibited premature atrial and ventricular contractions which were suppressed by flecainide treatment. G213D induced gating pore current at potentials negative to -50 mV. Voltage-clamp analysis in hiPSC-CM revealed the activation threshold of INa was shifted in the hyperpolarizing direction resulting in a larger INa window current. The G213D hiPSC-CMs had faster beating rates compared with wild-type and frequently showed Ca2+ waves and alternans. Flecainide applied to G213D hiPSC-CMs decreased window current by shifting the steady-state inactivation curve and slowed the beating rate. CONCLUSION: The G213D variant in Nav1.5 induced gating pore currents and increased window current. The changes in INa resulted in a faster beating rate and Ca2+ transient dysfunction. Flecainide decreased window current and inhibited INa, which is likely responsible for the therapeutic effectiveness of flecainide in MEPPC patients carrying the G213D variant.


Assuntos
Células-Tronco Pluripotentes Induzidas , Miócitos Cardíacos , Canal de Sódio Disparado por Voltagem NAV1.5 , Humanos , Potenciais de Ação/fisiologia , Arritmias Cardíacas/genética , Flecainida/farmacologia , Miócitos Cardíacos/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Fenótipo , Sódio/metabolismo
3.
Eur J Hum Genet ; 26(3): 303-313, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29343803

RESUMO

Aborted sudden cardiac death in the young often is due to inherited heart disease. However, the clinical phenotype in these patients is not always evident. The aim of this study was to identify pathogenic molecular genetic variants in a population with suspected inherited cardiac arrhythmias. Eligible patients were admitted to Aarhus University Hospital, Denmark during the period 1999-2013 with arrhythmias assumed caused by a hereditary heart disease, and in whom no genotype had been established. We used the Danish national pacemaker and ICD registry to identify this cohort. One third (24/80) of the study population had first-line genetic testing with a targeted next-generation sequencing (NGS) panel, and two-third (56/80) of the study population had second-line genetic testing with NGS where prior Sanger sequencing did not reveal a causative variant. Variants were assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines. We included 80 patients. Median age (IQR) was 38 (28-43) years, 54 (68%) were males. First-line genetic testing identified a genetic variant in 33% (8/24) of the cases and second-line genetic testing revealed a variant in 20% (11/56) of the cases. Eleven variants were considered pathogenic, three likely pathogenic and 10 were variants of unknown significance (VUS). Seventeen variants were very rare with a minor allele frequency (MAF) ≤0.02% in all population databases used in the study. Molecular genetic testing of patients with suspected inherited cardiac arrhythmias with NGS identifies a molecular-genetic cause in a significant proportion of patients.


Assuntos
Arritmias Cardíacas/genética , Morte Súbita Cardíaca/etiologia , Frequência do Gene , Mutação , Adulto , Arritmias Cardíacas/complicações , Arritmias Cardíacas/diagnóstico , Feminino , Testes Genéticos , Estudo de Associação Genômica Ampla , Humanos , Canais Iônicos/genética , Masculino , Análise de Sequência de DNA
4.
Heart ; 103(12): 901-909, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28237968

RESUMO

OBJECTIVE: The aim of this study was to characterise disease penetrance, course of disease and use of antiarrhythmic medication and implantable cardioverter-defibrillator (ICD) therapy in a Danish nationwide cohort of patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) due to mutations in the ryanodine receptor-2 (RyR2) gene. METHODS: The study population was identified through the national hereditary heart disease database (Progeny). The study population was divided into three groups: probands, symptomatic and asymptomatic relatives. RESULTS: We identified 23 symptomatic probands, 18 symptomatic and 10 asymptomatic relatives with a RyR2 mutation. Twenty (87%) probands and 10 (36%) relatives had severe presenting symptoms (sudden cardiac death (SCD), aborted SCD (ASCD) or syncope).As compared with symptomatic relatives, probands had lower age at onset of symptoms (16 years (IQR, 10-33) vs 43 years (IQR, 25-54), p<0.0001) and were more prone to fatal or near-fatal events (ASCD, SCD) (16vs5, p<0.0001). Twenty-eight patients had an ICD implanted, and eight experienced appropriate ICD therapy during follow-up (65 months (IQR, 43-175)). Electrical storm was seen in two of the 28 ICD treated patients (7%). No patients receiving treatment died during follow-up (57 months (IQR, 32-139)). Multifocal atrial tachycardia was the predominant symptom in five patients. CONCLUSIONS: In a national cohort of RyR2 mutation-positive CPVT patients, SCD, ASCD and syncope were presenting events in the majority of probands and also occurred in 36% of relatives identified through family screening. Probands were younger at disease onset and more prone to fatal or near-fatal events than relatives.


Assuntos
DNA/genética , Eletrocardiografia , Mutação , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Taquicardia Ventricular/genética , Adolescente , Adulto , Criança , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Estudos Retrospectivos , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/fisiopatologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...