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1.
Eur Heart J ; 43(22): 2127-2135, 2022 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-35171989

RESUMO

AIMS: We aimed to investigate the association of clinically overt and silent brain lesions with cognitive function in atrial fibrillation (AF) patients. METHODS AND RESULTS: We enrolled 1227 AF patients in a prospective, multicentre cohort study (Swiss-AF). Patients underwent standardized brain magnetic resonance imaging (MRI) at baseline and after 2 years. We quantified new small non-cortical infarcts (SNCIs) and large non-cortical or cortical infarcts (LNCCIs), white matter lesions (WML), and microbleeds (Mb). Clinically, silent infarcts were defined as new SNCI/LNCCI on follow-up MRI in patients without a clinical stroke or transient ischaemic attack (TIA) during follow-up. Cognition was assessed using validated tests. The mean age was 71 years, 26.1% were females, and 89.9% were anticoagulated. Twenty-eight patients (2.3%) experienced a stroke/TIA during 2 years of follow-up. Of the 68 (5.5%) patients with ≥1 SNCI/LNCCI, 60 (88.2%) were anticoagulated at baseline and 58 (85.3%) had a silent infarct. Patients with brain infarcts had a larger decline in cognition [median (interquartile range)] changes in Cognitive Construct score [-0.12 (-0.22; -0.07)] than patients without new brain infarcts [0.07 (-0.09; 0.25)]. New WML or Mb were not associated with cognitive decline. CONCLUSION: In a contemporary cohort of AF patients, 5.5% had a new brain infarct on MRI after 2 years. The majority of these infarcts was clinically silent and occurred in anticoagulated patients. Clinically, overt and silent brain infarcts had a similar impact on cognitive decline. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02105844, https://clinicaltrials.gov/ct2/show/NCT02105844.


Assuntos
Fibrilação Atrial , Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Infarto Encefálico , Cognição , Estudos de Coortes , Feminino , Humanos , Ataque Isquêmico Transitório/complicações , Imageamento por Ressonância Magnética , Masculino , Estudos Prospectivos , Acidente Vascular Cerebral/patologia
2.
Rev Med Suisse ; 16(696): 1148-1152, 2020 Jun 03.
Artigo em Francês | MEDLINE | ID: mdl-32496703

RESUMO

The gene SCN5A encodes the cardiac sodium channel which, through the conduction of Na+ current into the cell, generates the fast upstroke of the action potential of cardiomyocytes. Pathogenic variants of SCN5A have been causally associated to several hereditary cardiac diseases including, among others, Brugada syndrome, congenital long QT syndrome and sinus node dysfunction. Recently, overlap syndromes have been described that are characterized by the simultaneous expression of mixed clinical phenotypes among two or more hereditary cardiac diseases associated to the gene SCN5A (HCD-SCN5A). For this reason, it is time to rethink about HCD-SCN5A as different expressions of the same complex spectrum encompassing multiple clinical phenotypes with pronounced overlaps instead of as distinct clinical entities.


Le gène SCN5A code pour le canal sodique cardiaque qui est responsable de la pente de dépolarisation rapide du potentiel d'action. Plusieurs cardiopathies héréditaires (CH) ont été associées à des variants pathogènes du gène SCN5A incluant, entre autres, le syndrome de Brugada, le syndrome du QT long congénital et la dysfonction sinusale. Récemment, des syndromes de chevauchement ont été également décrits, s'exprimant, chez un même patient, par un phénotype clinique mixte comprenant une combinaison des manifestations rapportées ci-dessus. Dans ce contexte, nous devrions donc reconsidérer cliniquement les CH impliquant le gène SCN5A comme des expressions différentes d'un même éventail de phénotypes cliniques avec chevauchements marqués plutôt que comme des entités cliniques distinctes et isolées.


Assuntos
Síndrome de Brugada , Síndrome do QT Longo , Síndrome do Nó Sinusal , Síndrome de Brugada/genética , Humanos , Síndrome do QT Longo/genética , Mutação , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Fenótipo , Síndrome do Nó Sinusal/genética , Síndrome
3.
Rev Med Suisse ; 13(564): 1094-1099, 2017 May 24.
Artigo em Francês | MEDLINE | ID: mdl-28639772

RESUMO

Multidisciplinary cardiogenetic consulting offers a global clinical approach to patients suffering from channelopathies or hereditary cardiomyopathies. Mutation is discovered in around 50 % of the cases. Several experts are working together to bring probands and their families useful and necessary informations to help them understanding causes, consequences and support of their disease. This approach is developped in close collaboration with the treating physician.


La consultation multidisciplinaire de cardiogénétique offre une approche globale spécialisée aux patients souffrant de canalopathies ou de cardiomyopathies héréditaires. Une mutation génétique est identifiée dans près de 50 % des cas. Les différents experts engagés travaillent conjointement pour apporter aux patients et à leurs familles les renseignements utiles et nécessaires pour comprendre les causes, les conséquences et la prise en charge de la maladie concernée. La consultation se fait en étroite collaboration avec les médecins traitants.


Assuntos
Cardiomiopatias/genética , Canalopatias/genética , Aconselhamento Genético/métodos , Cardiomiopatias/fisiopatologia , Canalopatias/fisiopatologia , Humanos , Comunicação Interdisciplinar , Mutação , Relações Médico-Paciente
4.
BMC Cardiovasc Disord ; 14: 140, 2014 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-25291980

RESUMO

BACKGROUND: Sudden cardiac death (SCD) among the young is a rare and devastating event, but its exact incidence in many countries remains unknown. An autopsy is recommended in every case because some of the cardiac pathologies may have a genetic origin, which can have an impact on the living family members. The aims of this retrospective study completed in the canton of Vaud, Switzerland were to determine both the incidence of SCD and the autopsy rate for individuals from 5 to 39 years of age. METHODS: The study was conducted from 2000 to 2007 on the basis of official statistics and analysis of the International Classification of Diseases codes for potential SCDs and other deaths that might have been due to cardiac disease. RESULTS: During the 8 year study period there was an average of 292'546 persons aged 5-39 and there were a total of 1122 deaths, certified as potential SCDs in 3.6% of cases. The calculated incidence is 1.71/100'000 person-years (2.73 for men and 0.69 for women). If all possible cases of SCD (unexplained deaths, drowning, traffic accidents, etc.) are included, the incidence increases to 13.67/100'000 person-years. However, the quality of the officially available data was insufficient to provide an accurate incidence of SCD as well as autopsy rates. The presumed autopsy rate of sudden deaths classified as diseases of the circulatory system is 47.5%. For deaths of unknown cause (11.1% of the deaths), the autopsy was conducted in 13.7% of the cases according to codified data. CONCLUSIONS: The incidence of presumed SCD in the canton of Vaud, Switzerland, is comparable to the data published in the literature for other geographic regions but may be underestimated as it does not take into account other potential SCDs, as unexplained deaths. Increasing the autopsy rate of SCD in the young, better management of information obtained from autopsies as well developing of structured registry could improve the reliability of the statistical data, optimize the diagnostic procedures, and the preventive measures for the family members.


Assuntos
Morte Súbita Cardíaca/epidemiologia , Adolescente , Adulto , Fatores Etários , Autopsia , Causas de Morte , Criança , Pré-Escolar , Atestado de Óbito , Morte Súbita Cardíaca/patologia , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de Risco , Suíça/epidemiologia , Fatores de Tempo , Adulto Jovem
5.
Sci Rep ; 12(1): 2208, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-35140237

RESUMO

Sustained forms of atrial fibrillation (AF) may be associated with a higher risk of adverse outcomes, but few if any long-term studies took into account changes of AF type and co-morbidities over time. We prospectively followed 3843 AF patients and collected information on AF type and co-morbidities during yearly follow-ups. The primary outcome was a composite of stroke or systemic embolism (SE). Secondary outcomes included myocardial infarction, hospitalization for congestive heart failure (CHF), bleeding and all-cause mortality. Multivariable adjusted Cox proportional hazards models with time-varying covariates were used to compare hazard ratios (HR) according to AF type. At baseline 1895 (49%), 1046 (27%) and 902 (24%) patients had paroxysmal, persistent and permanent AF and 3234 (84%) were anticoagulated. After a median (IQR) follow-up of 3.0 (1.9; 4.2) years, the incidence of stroke/SE was 1.0 per 100 patient-years. The incidence of myocardial infarction, CHF, bleeding and all-cause mortality was 0.7, 3.0, 2.9 and 2.7 per 100 patient-years, respectively. The multivariable adjusted (a) HRs (95% confidence interval) for stroke/SE were 1.13 (0.69; 1.85) and 1.27 (0.83; 1.95) for time-updated persistent and permanent AF, respectively. The corresponding aHRs were 1.23 (0.89, 1.69) and 1.45 (1.12; 1.87) for all-cause mortality, 1.34 (1.00; 1.80) and 1.30 (1.01; 1.67) for CHF, 0.91 (0.48; 1.72) and 0.95 (0.56; 1.59) for myocardial infarction, and 0.89 (0.70; 1.14) and 1.00 (0.81; 1.24) for bleeding. In this large prospective cohort of AF patients, time-updated AF type was not associated with incident stroke/SE.


Assuntos
Fibrilação Atrial/complicações , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/mortalidade , Causas de Morte , Estudos de Coortes , Comorbidade , Embolia/complicações , Embolia/epidemiologia , Feminino , Seguimentos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Hemorragia/complicações , Hemorragia/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Suíça/epidemiologia
6.
Ann Noninvasive Electrocardiol ; 16(2): 213-8, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21496174

RESUMO

We report the case of a woman with syncope and persistently prolonged QTc interval. Screening of congenital long QT syndrome (LQTS) genes revealed that she was a heterozygous carrier of a novel KCNH2 mutation, c.G238C. Electrophysiological and biochemical characterizations unveiled the pathogenicity of this new mutation, displaying a 2-fold reduction in protein expression and current density due to a maturation/trafficking-deficient mechanism. The patient's phenotype can be fully explained by this observation. This study illustrates the importance of performing genetic analyses and mutation characterization when there is a suspicion of congenital LQTS. Identifying mutations in the PAS domain or other domains of the hERG1 channel and understanding their effect may provide more focused and mutation-specific risk assessment in this population.


Assuntos
Canais de Potássio Éter-A-Go-Go/genética , Síndrome do QT Longo/genética , Síncope/genética , Diagnóstico Diferencial , Ecocardiografia , Eletrocardiografia , Teste de Esforço , Feminino , Humanos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Mutação de Sentido Incorreto , Síncope/fisiopatologia , Adulto Jovem
7.
Echocardiography ; 28(2): 168-74, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21276073

RESUMO

BACKGROUND: An elevated early (E) to late (A) diastolic filling velocities ratio, typically seen in advanced diastolic dysfunction, has also been observed after cardioversion of atrial fibrillation as a consequence of the depressed left atrial (LA) contractility. We hypothesized that the impaired LA contractile function demonstrated after orthotopic cardiac transplantation (OCT) could also lead to this "pseudorestrictive" pattern. METHOD: E/A ratio related to the tissue Doppler early mitral annular velocity (Ea) as preload-independent index of LV relaxation was evaluated in all consecutive OCT patients between 2005 and 2007. RESULTS: The study population comprised 48 patients 97 ± 77 months after OCT. Thirty-two patients (67%) had an E/A ratio > 2. LV systolic function and myocardial relaxation assessed by the Ea velocity were similar compared to patients with normal ratio (61 ± 6% vs. 60 ± 12%, P = 0.854 and 15 ± 4 cm/s vs. 14 ± 3 cm/s, r = 0.15, P = 0.323, respectively). On the other hand, the proportion of the recipient and donor LA cuffs as estimated by the recipient/global LA area ratio and the LA emptying fraction significantly correlated with the E/A ratio (r = 0.40, P = 0.005 and r =-0.33, P = 0.022, respectively). CONCLUSION: Our study shows that there is a high prevalence of elevated E/A ratio after standard OCT which seems mainly related to reduced LA contractility. Recognition of this "pseudorestrictive" pattern may avoid misdiagnosis of diastolic dysfunction.


Assuntos
Ecocardiografia Doppler/métodos , Átrios do Coração/diagnóstico por imagem , Transplante de Coração/efeitos adversos , Transplante de Coração/diagnóstico por imagem , Estenose da Valva Mitral/diagnóstico por imagem , Estenose da Valva Mitral/etiologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
Int J Cardiol ; 327: 201-208, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33309760

RESUMO

BACKGROUND: Intraventricular conduction disturbances are associated with an increased risk of adverse cardiovascular outcomes. However, data about factors associated with intraventricular conduction disturbances are sparse. We aimed to identify the clinical factors associated with intraventricular conduction disturbances in the general population. METHODS: Cross-sectional study in a sample of 3704 participants (age range 45-86 years, 55.2% women). Intraventricular conduction disturbances were defined as QRS > 110 ms on electrocardiograms, and classified into right bundle branch block (RBBB), left bundle branch block (LBBB), left anterior fascicular block (LAFB) and non-specific intraventricular conduction disturbances (NIVCD). RESULTS: The number of participants, the resulting prevalence (square brackets) and 95% CI (round brackets) of intraventricular conduction disturbances and subtypes (RBBB, LBBB, LAFB and NIVCD) were 187 [5.1% (4.4-5.8%)], 103 [2.9%, (2.3-3.4%)], 29 [0.8% (0.6-1.1%)], 31 (0.9% [0.6-1.2%]), and 47 [1.3% (0.9-1.7)], respectively. Multivariable logistic regression identified male sex [odds ratio and (95% CI): 2.55 (1.34-4.86)] and increasing age (p-value for trend <0.001) as being associated with RBBB; hypertension [3.08 (1.20-7.91)] and elevated NT-proBNP [3.26 (1.43-7.41)] as being associated with LBBB; elevated NT-proBNP [3.14 (1.32-7.46)] as being associated with LFAB; and male sex [5.97 (1.91-18.7)] and increased height [1.31 (1.06-1.63)] as being associated with NIVCD. CONCLUSION: In a sample of the Swiss middle-aged population, the clinical factors associated with intraventricular conduction disturbances differed according to the intraventricular conduction disturbances subtype: male sex and ageing for RBBB; hypertension and elevated NT-proBNP for LBBB; elevated NT-proBNP for LAFB; and male sex and increased height for NIVCD.


Assuntos
Bloqueio de Ramo , Hipertensão , Adulto , Idoso , Idoso de 80 Anos ou mais , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/epidemiologia , Estudos Transversais , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Suíça
10.
J Thromb Haemost ; 19(4): 931-940, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33501722

RESUMO

OBJECTIVE: Balancing bleeding risk and stroke risk in patients with atrial fibrillation (AF) is a common challenge. Though several bleeding risk scores exist, most have not included patients on direct oral anticoagulants (DOACs). We aimed at developing a novel bleeding risk score for patients with AF on oral anticoagulants (OAC) including both vitamin K antagonists (VKA) and DOACs. METHODS: We included patients with AF on OACs from a prospective multicenter cohort study in Switzerland (SWISS-AF). The outcome was time to first bleeding. Bleeding events were defined as major or clinically relevant non-major bleeding. We used backward elimination to identify bleeding risk variables. We derived the score using a point score system based on the ß-coefficients from the multivariable model. We used the Brier score for model calibration (<0.25 indicating good calibration), and Harrel's c-statistics for model discrimination. RESULTS: We included 2147 patients with AF on OAC (72.5% male, mean age 73.4 ± 8.2 years), of whom 1209 (56.3%) took DOACs. After a follow-up of 4.4 years, a total of 255 (11.9%) bleeding events occurred. After backward elimination, age > 75 years, history of cancer, prior major hemorrhage, and arterial hypertension remained in the final prediction model. The Brier score was 0.23 (95% confidence interval [CI] 0.19-0.27), the c-statistic at 12 months was 0.71 (95% CI 0.63-0.80). CONCLUSION: In this prospective cohort study of AF patients and predominantly DOAC users, we successfully derived a bleeding risk prediction model with good calibration and discrimination.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Estudos de Coortes , Feminino , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Hemorragia/epidemiologia , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Suíça
11.
Rev Med Suisse ; 6(251): 1140, 1142-5, 2010 Jun 02.
Artigo em Francês | MEDLINE | ID: mdl-20572358

RESUMO

Idiopathic premature ventricular complexes originating from the ventricular outflow tract: evaluation, prognosis and management The prognosis of ventricular premature complexes (VPC) in the absence of heart disease is considered benign. VPC usually originate from the right or, less commonly, left ventricular outflow tract. QRS complexes therefore usually assume a left bundle branch block and inferior axis morphology. These VPC, particularly if very frequent (> 20,000 per day), may adversely affect left ventricular function and their suppression can restore normal function. Moreover, there is a clinical overlap with arrhythmogenic right ventricular dysplasia and this diagnosis should be considered when facing a left bundle branch block shaped VPC. However, the prognosis of outflow tract VPC is good for appropriately selected patients with normal left ventricular function, absence of syncope or ventricular tachycardia, and no evidence of cardiac disease.


Assuntos
Complexos Ventriculares Prematuros/fisiopatologia , Complexos Ventriculares Prematuros/terapia , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Eletrocardiografia , Humanos , Prognóstico , Síncope/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico , Fibrilação Ventricular/fisiopatologia , Fibrilação Ventricular/terapia , Complexos Ventriculares Prematuros/diagnóstico , Complexos Ventriculares Prematuros/mortalidade , Complexos Ventriculares Prematuros/cirurgia
12.
Clin Cardiol ; 43(6): 614-621, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32329928

RESUMO

BACKGROUND: Prolonged PR interval (PRi) is associated with adverse outcomes. However, PRi determinants are poorly known. We aimed to identify the clinical determinants of the PRi duration in the general population. HYPOTHESIS: Some clinical data are associated with prolonged PRi. METHODS: Cross-sectional study conducted between 2014 and 2017. Electrocardiogram-derived PRi duration was categorized into normal or prolonged (>200 ms). Determinants were identified using stepwise logistic regression, and results were expressed as multivariable-adjusted odds ratio (OR) (95% confidence interval). A further analysis was performed adjusting for antiarrhythmic drugs, P-wave contribution to PRi duration, electrolytes (kalemia, calcemia, and magnesemia), and history of cardiovascular disease. RESULTS: Overall, 3655 participants with measurable PRi duration were included (55.6% females; mean age 62 ± 10 years), and 330 (9.0%) had prolonged PRi. Stepwise logistic regression identified male sex (OR 1.41 [1.02-1.97]); aging (65-74 years: OR 2.29 [1.61-3.24], and ≥ 75 years: OR 4.21 [2.81-6.31]); increased height (per 5 cm, OR 1.15 [1.06-1.25]); hypertension (OR 1.37 [1.06-1.77]); and hs troponin T (OR 1.67 [1.15-2.43]) as significantly and positively associated, and high resting heart rate (≥70 beats/min, OR 0.43 [0.29-0.62]) as negatively associated with prolonged PRi. After further adjustment, male sex, aging and increased height remained positively, and high resting heart rate negatively associated with prolonged PRi. Hypertension and hs troponin T were no longer associated. CONCLUSION: In a sample of the Swiss middle-aged population, male sex, aging and increased height significantly increased the likelihood of a prolonged PRi duration, whereas a high resting heart rate decreased it.


Assuntos
Envelhecimento , Arritmias Cardíacas/fisiopatologia , Eletrocardiografia , Frequência Cardíaca/fisiologia , Adulto , Idoso , Arritmias Cardíacas/epidemiologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Suíça/epidemiologia
13.
Swiss Med Wkly ; 150: w20343, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-33035354

RESUMO

INTRODUCTION: Sudden cardiac death caused by malignant arrhythmia can be prevented by the use of defibrillators. Although the wearable cardioverter defibrillator (WCD) can prevent such an event, its role in clinical practice is ill defined. We investigated the use of the WCD in Switzerland with emphasis on prescription rate, therapy adherence and treatment rate. MATERIALS AND METHODS: The Swiss WCD Registry is a retrospective observational registry including patients using a WCD. Patients were included from the first WCD use in Switzerland until February 2018. Baseline characteristics and data on WCD usage were examined for the total study population, and separately for each hospital. RESULTS: From 1 December 2011 to 18 February 2018, a total of 456 patients (67.1% of all WCDs prescribed in Switzerland and 81.1% of all prescribed in the participating hospitals) were included in the registry. Up to 2017 there was a yearly increase in the number of prescribed WCDs to a maximum of 271 prescriptions per year. The mean age of patients was 57 years (± 14), 81 (17.8%) were female and mean left ventricular ejection fraction (EF) was 32% (± 13). The most common indications for WCD use were new-onset ischaemic cardiomyopathy (ICM) with EF ≤35% (206 patients, 45.2%), new-onset nonischaemic cardiomyopathy (NICM) with EF ≤35% (115 patients, 25.2%), unknown arrhythmic risk (83 patients, 18.2%), bridging to implantable cardioverter-defibrillator implantation or heart transplant (37 patients, 8.1%) and congenital/inherited heart disease (15 patients, 3.3%). Median wear duration was 58 days (interquartile range [IQR] 31–94) with a median average daily wear time of 22.6 hours (IQR 20–23.2). Seventeen appropriate therapies from the WCD were delivered in the whole population (treatment rate: 3.7%) to a total of 12 patients (2.6% of all patients). The most common underlying heart disease in patients with a treatment was ICM (13/17, 76.5%). There were no inappropriate treatments. CONCLUSION: The use of WCDs has increased in Switzerland over the years for a variety of indications. There is high therapy adherence to the WCD, and a treatment rate comparable to previously published registry data.  .


Assuntos
Desfibriladores Implantáveis , Dispositivos Eletrônicos Vestíveis , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores , Cardioversão Elétrica , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Volume Sistólico , Suíça , Função Ventricular Esquerda
14.
Cardiovasc Res ; 78(3): 494-504, 2008 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-18252757

RESUMO

AIMS: Brugada syndrome (BrS) is characterized by arrhythmias leading to sudden cardiac death. BrS is caused, in part, by mutations in the SCN5A gene, which encodes the sodium channel alpha-subunit Na(v)1.5. Here, we aimed to characterize the biophysical properties and consequences of a novel BrS SCN5A mutation. METHODS AND RESULTS: SCN5A was screened for mutations in a male patient with type-1 BrS pattern ECG. Wild-type (WT) and mutant Na(v)1.5 channels were expressed in HEK293 cells. Sodium currents (I(Na)) were analysed using the whole-cell patch-clamp technique at 37 degrees C. The electrophysiological effects of the mutation were simulated using the Luo-Rudy model, into which the transient outward current (I(to)) was incorporated. A new mutation (C1850S) was identified in the Na(v)1.5 C-terminal domain. In HEK293 cells, mutant I(Na) density was decreased by 62% at -20 mV. Inactivation of mutant I(Na) was accelerated in a voltage-dependent manner and the steady-state inactivation curve was shifted by 11.6 mV towards negative potentials. No change was observed regarding activation characteristics. Altogether, these biophysical alterations decreased the availability of I(Na). In the simulations, the I(to) density necessary to precipitate repolarization differed minimally between the two genotypes. In contrast, the mutation greatly affected conduction across a structural heterogeneity and precipitated conduction block. CONCLUSION: Our data confirm that mutations of the C-terminal domain of Na(v)1.5 alter the inactivation of the channel and support the notion that conduction alterations may play a significant role in the pathogenesis of BrS.


Assuntos
Síndrome de Brugada/genética , Sistema de Condução Cardíaco/metabolismo , Frequência Cardíaca , Proteínas Musculares/genética , Mutação , Canais de Sódio/genética , Sódio/metabolismo , Potenciais de Ação , Síndrome de Brugada/metabolismo , Síndrome de Brugada/fisiopatologia , Síndrome de Brugada/terapia , Linhagem Celular , Simulação por Computador , Desfibriladores Implantáveis , Eletrocardiografia , Predisposição Genética para Doença , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Proteínas Musculares/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.5 , Técnicas de Patch-Clamp , Fenótipo , Estrutura Terciária de Proteína , Canais de Sódio/metabolismo , Transfecção
15.
Ther Adv Psychopharmacol ; 9: 2045125319891386, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31853363

RESUMO

BACKGROUND: Psychiatric patients are at risk of cardiovascular diseases, and many psychotropic drugs can prolong QTc interval. Requirements for electrocardiogram (ECG) monitoring have been set up in our psychiatric university hospital. The objective of this study was to determine the proportion of adult patients who had an ECG during their hospitalization, the prevalence of ECG abnormalities, the evolution of the QTc after admission, and the risk factors for QTc prolongation. METHODS: Retrospective analysis of ECGs and clinical data of all patients with a complete hospitalization in 2015. Assessment of the influence of covariates on QTc using linear mixed-effects models. RESULTS: At least one ECG (n = 600) was performed during 37.6% of the stays (n = 1198) and in 45.5% of the patients (n = 871). Among the patients with an ECG, 17.9% had significant ECG abnormalities, including 7.6% with a prolonged QTc. QTc measured at admission and during hospitalization did not change significantly (n = 46, 419.4 ± 29.7 ms, 417.2 ± 27.6 ms, p = 0.71). In the multivariate model (292 patients, 357 ECGs), the covariates significantly associated with the QTc were gender (+15.9 ms if female, p < 0.0001), age (+0.4 ms/year, p = 0.0001), triglyceride levels (+5.7 ms/mmol/l, p = 0.005), and drugs with known risk of torsades de pointes (+6.2 ms if ⩾1 drug, p = 0.028). CONCLUSIONS: The prevalence of hospitalized psychiatric patients with an abnormal ECG indicates that ECGs should be performed systematically in this population. Prescription of psychotropic drugs should be done cautiously, particularly in patients with QTc prolongation risk factors.

16.
Am J Cardiol ; 124(8): 1305-1314, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31455501

RESUMO

Early initiation of reperfusion therapy remains the cornerstone of successful management for ST-elevation myocardial infarction (STEMI). Rapid restoration of coronary blood flow relies on prompt recognition of the typical ST-segment elevation on a 12-lead electrocardiogram (ECG)-a surrogate for coronary occlusion or critical stenosis-allowing timely activation of the STEMI protocol cascade, with a major positive impact in mortality and clinical outcomes. However, atypical, very high risk ECG patterns-known as "STEMI equivalents"-are present in 10% to 25% of patients with ongoing myocardial ischemia in need of urgent primary percutaneous coronary intervention. Though briefly mentioned in the current recommendations, structured clinical data on those specific ECG presentations are lacking. By thoroughly searching MEDLINE and EMBASE we conducted a structured review of non-STEMI, albeit very high risk, ECG patterns of acute coronary syndrome, often associated with coronary occlusion or critical stenosis. After screening 997 studies, we identified the following distinct "STEMI equivalent" ECG patterns: Wellens' syndrome, de Winter sign, hyperacute T waves, left bundle branch block-including paced rhythm-and right bundle branch block. For each pattern, a brief summary of the existing evidence, together with the sensitivity, specificity, and positive predictive value-whenever available-are presented. In conclusion, prompt recognition of "STEMI equivalent" ECG patterns is crucial for every physician or paramedic dealing with acute coronary syndrome patients in the emergency department or the prehospital setting, as misinterpretation of those high risk presentations can lead to reperfusion delays and worse outcomes.


Assuntos
Eletrocardiografia/métodos , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Valor Preditivo dos Testes , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia
17.
J Am Heart Assoc ; 8(20): e012554, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31590581

RESUMO

Background The incidence and predictors of atrial fibrillation (AF) progression are currently not well defined, and clinical AF progression partly overlaps with rhythm control interventions (RCIs). Methods and Results We assessed AF type and intercurrent RCIs during yearly follow-ups in 2869 prospectively followed patients with paroxysmal or persistent AF. Clinical AF progression was defined as progression from paroxysmal to nonparoxysmal or from persistent to permanent AF. An RCI was defined as pulmonary vein isolation, electrical cardioversion, or new treatment with amiodarone. During a median follow-up of 3 years, the incidence of clinical AF progression was 5.2 per 100 patient-years, and 10.9 per 100 patient-years for any RCI. Significant predictors for AF progression were body mass index (hazard ratio [HR], 1.03; 95% CI, 1.01-1.05), heart rate (HR per 5 beats/min increase, 1.05; 95% CI, 1.02-1.08), age (HR per 5-year increase 1.19; 95% CI, 1.13-1.27), systolic blood pressure (HR per 5 mm Hg increase, 1.03; 95% CI, 1.00-1.05), history of hyperthyroidism (HR, 1.71; 95% CI, 1.16-2.52), stroke (HR, 1.50; 95% CI, 1.19-1.88), and heart failure (HR, 1.69; 95% CI, 1.34-2.13). Regular physical activity (HR, 0.80; 95% CI, 0.66-0.98) and previous pulmonary vein isolation (HR, 0.69; 95% CI, 0.53-0.90) showed an inverse association. Significant predictive factors for RCIs were physical activity (HR, 1.42; 95% CI, 1.20-1.68), AF-related symptoms (HR, 1.84; 95% CI, 1.47-2.30), age (HR per 5-year increase, 0.88; 95% CI, 0.85-0.92), and paroxysmal AF (HR, 0.61; 95% CI, 0.51-0.73). Conclusions Cardiovascular risk factors and comorbidities were key predictors of clinical AF progression. A healthy lifestyle may therefore reduce the risk of AF progression.


Assuntos
Fibrilação Atrial/epidemiologia , Frequência Cardíaca/fisiologia , Medição de Risco/métodos , Idoso , Fibrilação Atrial/fisiopatologia , Índice de Massa Corporal , Progressão da Doença , Eletrocardiografia/métodos , Feminino , Seguimentos , Humanos , Incidência , Masculino , Estudos Prospectivos , Fatores de Risco , Suíça/epidemiologia
18.
J Am Coll Cardiol ; 73(9): 989-999, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30846109

RESUMO

BACKGROUND: Patients with atrial fibrillation (AF) have an increased risk of cognitive decline, potentially resulting from clinically unrecognized vascular brain lesions. OBJECTIVES: This study sought to assess the relationships between cognitive function and vascular brain lesions in patients with AF. METHODS: Patients with known AF were enrolled in a multicenter study in Switzerland. Brain magnetic resonance imaging (MRI) and cognitive testing using the Montreal Cognitive Assessment (MoCA) were performed in all participants. Large noncortical or cortical infarcts (LNCCIs), small noncortical infarcts (SNCIs), microbleeds, and white matter lesions were quantified by a central core laboratory. Clinically silent infarcts were defined as infarcts on brain MRI in patients without a clinical history of stroke or transient ischemic attack. RESULTS: The study included 1,737 patients with a mean age of 73 ± 8 years (28% women, 90% taking oral anticoagulant agents). On MRI, LNCCIs were found in 387 patients (22%), SNCIs in 368 (21%), microbleeds in 372 (22%), and white matter lesions in 1715 (99%). Clinically silent infarcts among the 1,390 patients without a history of stroke or transient ischemic attack were found in 201 patients with LNCCIs (15%) and 245 patients with SNCIs (18%). The MoCA score was 24.7 ± 3.3 in patients with and 25.8 ± 2.9 in those without LNCCIs on brain MRI (p < 0.001). The difference in MoCA score remained similar when only clinically silent LNCCIs were considered (24.9 ± 3.1 vs. 25.8 ± 2.9; p < 0.001). In a multivariable regression model including all vascular brain lesion parameters, LNCCI volume was the strongest predictor of a reduced MoCA (ß = -0.26; 95% confidence interval: -0.40 to -0.13; p < 0.001). CONCLUSIONS: Patients with AF have a high burden of LNCCIs and other brain lesions on systematic brain MRI screening, and most of these lesions are clinically silent. LNCCIs were associated with worse cognitive function, even among patients with clinically silent infarcts. Our findings raise the question of MRI screening in patients with AF.


Assuntos
Fibrilação Atrial/complicações , Encéfalo/patologia , Infarto Cerebral/diagnóstico , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico , Imageamento por Ressonância Magnética/métodos , Idoso , Infarto Cerebral/complicações , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Testes Neuropsicológicos , Estudos Prospectivos , Fatores de Risco
19.
Swiss Med Wkly ; 148: w14652, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30378644

RESUMO

OBJECTIVE: Atrial fibrillation (AF) is considered to be a progressive disease, starting with intermittent episodes that progress over time to more sustained events. However, little is known about the prevalence of and predictors for AF type among patients with recent-onset AF. We aimed to address these issues among a selected population of patients with AF. METHODS: The Basel atrial fibrillation cohort (BEAT-AF) study is an ongoing prospective multicentre cohort study among patients with AF. At baseline, we obtained information on the date of AF diagnosis, AF type, comorbidities, medication and lifestyle factors. For this analysis, 486 (31.4%) out of 1550 participants with recent-onset AF (defined as AF duration <24 months) were included. Predictors for AF type (non-paroxysmal vs paroxysmal) were obtained using multivariable adjusted logistic regression models. RESULTS: Mean age was 67 (59-75) years and 136 (28%) were women. Recent-onset paroxysmal AF was observed in 301 (62%) participants, 185 (38%) had non-paroxysmal AF - persistent AF in 148 (30.4%) and permanent AF in 37 (7.6%). In multivariable models, odds ratios for having non-paroxysmal AF around AF diagnosis were 1.03 per year increasing in age (95% confidence interval [CI] 1.01-1.05, p = 0.01); 2.70 (1.5-4.68, p = 0.0004) for history of heart failure; 3.82 (1.05-13.87, p = 0.04) for a history of hyperthyroidism and 1.04 (1.02-1.05, p <0.0001) per beat increase in heart rate. CONCLUSION: We found a substantial proportion of AF patients with the non-paroxysmal form shortly after diagnosis. Predictors for non-paroxysmal AF were increasing age, history of heart failure or hyperthyroidism, and a higher heart rate.


Assuntos
Fibrilação Atrial/epidemiologia , Progressão da Doença , Hipertensão/complicações , Idoso , Eletrocardiografia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , Suíça/epidemiologia , Fatores de Tempo
20.
PLoS One ; 13(2): e0191736, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29394253

RESUMO

BACKGROUND: Patients with atrial fibrillation (AF) have an increased risk for the development of heart failure (HF). In this study, we aimed to detect predictors of HF hospitalizations in an unselected AF population. METHODS: The Basel Atrial Fibrillation Cohort Study is an ongoing observational multicenter cohort study in Switzerland. For this analysis, 1193 patients with documented AF underwent clinical examination, venous blood sampling and resting 12-lead ECG at baseline. Questionnaires about lifestyle and medical history were obtained in person at baseline and during yearly follow-up phone calls. HF hospitalizations were validated by two independent physicians. Cox regression analyses were performed using a forward selection strategy. RESULTS: Overall, 29.8% of all patients were female and mean age was 69 ±12 years. Mean follow-up time was 3.7 ±1.5 years. Hospitalization for HF occurred in 110 patients, corresponding to an incidence of 2.5 events per 100 person years of follow-up. Independent predictors for HF were body mass index (HR 1.40 [95%CI 1.17; 1.66], p = 0.0002), chronic kidney disease (2.27 [1.49; 3.45], p = 0.0001), diabetes mellitus (2.13 [1.41; 3.24], p = 0.0004), QTc interval (1.25 [1.04; 1.49], p = 0.02), brain natriuretic peptide (2.19 [1.73; 2.77], p<0.0001), diastolic blood pressure (0.79 [0.65; 0.96], p = 0.02), history of pulmonary vein isolation or electrical cardioversion (0.54 [0.36; 0.80], p = 0.003) and serum chloride (0.82 [0.70; 0.96], p = 0.02). CONCLUSIONS: In this unselected AF population, several traditional cardiovascular risk factors and arrhythmia interventions predicted HF hospitalizations, providing potential opportunities for the implementation of strategies to reduce HF among AF patients.


Assuntos
Fibrilação Atrial/complicações , Insuficiência Cardíaca/terapia , Hospitalização , Idoso , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
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