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2.
Ann Acad Med Singap ; 48(3): 86-94, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30997477

RESUMEN

INTRODUCTION: Numerous heart failure risk scores have been developed but there is none for Asians. We aimed to develop a risk calculator, the Singapore Heart Failure Risk Score, to predict 1- and 2-year survival in Southeast Asian patients hospitalised for heart failure. MATERIALS AND METHODS: Consecutive patients admitted for heart failure were identified from the Singapore Cardiac Databank Heart Failure registry. The follow-up was 2 to 4 years and mortality was obtained from national registries. RESULTS: The derivation (2008-2009) and 2 validation cohorts (2008-2009, 2013) included 1392, 729 and 804 patients, respectively. Ten variables were ultimately included in the risk model: age, prior myocardial infarction, prior stroke, atrial fibrillation, peripheral vascular disease, systolic blood pressure, QRS duration, ejection fraction and creatinine and sodium levels. In the derivation cohort, predicted 1- and 2-year survival was 79.1% and 68.1% compared to actual 1- and 2-year survival of 78.2% and 67.9%. There was good agreement between the predicted and observed mortality rates (Hosmer-Lemeshow statistic = 14.36, P = 0.073). C-statistics for 2-year mortality in the derivation and validation cohorts were 0.73 (95% CI, 0.70-0.75) and 0.68 (95% CI, 0.64-0.72), respectively. CONCLUSION: We provided a risk score based on readily available clinical characteristics to predict 1- and 2-year survival in Southeast Asian patients hospitalised for heart failure via a simple online risk calculator, the Singapore Heart Failure Risk Score.


Asunto(s)
Pueblo Asiatico , Insuficiencia Cardíaca/mortalidad , Factores de Edad , Anciano , Anciano de 80 o más Años , Asia Sudoriental , Fibrilación Atrial/epidemiología , Creatinina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Enfermedades Vasculares Periféricas/epidemiología , Medición de Riesgo , Factores de Riesgo , Singapur/epidemiología , Sodio/sangre , Accidente Cerebrovascular/epidemiología , Volumen Sistólico , Tasa de Supervivencia
3.
Sci Rep ; 8(1): 11246, 2018 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-30050137

RESUMEN

Brugada syndrome (BrS) is an inherited cardiac arrhythmia commonly associated with SCN5A mutations, yet its ionic mechanisms remain unclear due to a lack of cellular models. Here, we used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a BrS patient (BrS1) to evaluate the roles of Na+ currents (INa) and transient outward K+ currents (Ito) in BrS induced action potential (AP) changes. To understand the role of these current changes in repolarization we employed dynamic clamp to "electronically express" IK1 and restore normal resting membrane potentials and allow normal recovery of the inactivating currents, INa, ICa and Ito. HiPSC-CMs were generated from BrS1 with a compound SCN5A mutation (p. A226V & p. R1629X) and a healthy sibling control (CON1). Genome edited hiPSC-CMs (BrS2) with a milder p. T1620M mutation and a commercial control (CON2) were also studied. CON1, CON2 and BrS2, had unaltered peak INa amplitudes, and normal APs whereas BrS1, with over 75% loss of INa, displayed a loss-of-INa basal AP morphology (at 1.0 Hz) manifested by a reduced maximum upstroke velocity (by ~80%, p < 0.001) and AP amplitude (p < 0.001), and an increased phase-1 repolarization pro-arrhythmic AP morphology (at 0.1 Hz) in ~25% of cells characterized by marked APD shortening (~65% shortening, p < 0.001). Moreover, Ito densities of BrS1 and CON1 were comparable and increased from 1.0 Hz to 0.1 Hz by ~ 100%. These data indicate that a repolarization deficit could be a mechanism underlying BrS.


Asunto(s)
Síndrome de Brugada/fisiopatología , Potenciales de la Membrana , Miocitos Cardíacos/patología , Potasio/metabolismo , Sodio/metabolismo , Diferenciación Celular , Humanos , Mutación , Canal de Sodio Activado por Voltaje NAV1.5/genética , Técnicas de Placa-Clamp , Células Madre Pluripotentes/fisiología
5.
Medicine (Baltimore) ; 96(6): e6080, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28178165

RESUMEN

The efficacy of a completely zero-fluoroscopy (ZF) approach for the catheter ablation of idiopathic ventricular arrhythmias (VAs) and whether it has advantages over the conventional fluoroscopy (F) approach are still unknown. The aim of this study was to compare the safety and efficacy of a completely ZF approach with those of the conventional F approach in the ablation of idiopathic VAs.We conducted a prospective study involving 7 centers in China. Consecutive patients (n = 489, mean age 45.3 ±â€Š15.3 years, 44.8% male) with idiopathic VAs were recruited. Eligible participants were assigned to either a ZF (n = 163) or F (n = 326) approach at a ratio of 1:2. The completely ZF approach was successful in 163 (100%) patients for electrophysiological study, and in 151 patients (94.4%) for arrhythmia ablation with 9 cases having to switch to the F approach due to the need for coronary angiography. There was no significant difference between the ZF approach and F approach in procedural success rate (84.1% vs 85.4%, respectively), arrhythmia recurrence (1.9% vs 2.2%), or severe complications (0.6% vs 0.9%). The medical staffs using the ZF approach did not wear heavy protective apparels, thus experienced significantly less fatigue compared with those using the F approach (2.1 ±â€Š0.7 vs 3.9 ±â€Š1.6, P < 0.05).The completely ZF approach is as safe and efficient as the conventional F approach for the electrophysiological study and the ablation of idiopathic VAs. The medical staffs using ZF approach felt less fatigue and received less exposure to radiation.


Asunto(s)
Arritmias Cardíacas/cirugía , Ablación por Catéter/métodos , Fluoroscopía/métodos , Adulto , Anciano , Ablación por Catéter/efectos adversos , China , Fatiga/etiología , Femenino , Fluoroscopía/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Estudios Prospectivos
6.
Europace ; 18(12): 1829-1836, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27733459

RESUMEN

AIMS: This study was aimed to report the characteristics and treatment of ventricular tachycardia (VT) following surgical treatment of pulmonary stenosis with intact ventricular septum. METHODS AND RESULTS: Five patients underwent radiofrequency catheter ablation for sustained monomorphic left bundle branch block (LBBB) type VT who previously underwent surgical treatment of pulmonary stenosis. Except stimulation, voltage and activation mapping was performed using three-dimensional (3D) electro-anatomic mapping and ablation was applied accordingly. Four VTs were induced during EP study. Two VTs were focal and the earliest activity was targeted in the right ventricular apex (RVA). The other two VTs were reentrant and the critical isthmus located in the mid-lateral wall and anterior wall of right ventricle, respectively. Ablation abolished all inducible VTs in four patients. In the patient whose VT was non-inducible, radiofrequency (RF) energy was delivered to the RVA where pacing mapping matched the clinical VT. One focal VT recurred 60 months after the initial RF ablation. Repeat mapping and ablation was performed and no VT recurred over a 24-month period. CONCLUSIONS: The mechanism of VT following surgical treatment of pulmonary stenosis can be either focal or reentrant. Ablation of this subgroup of VT is feasible.


Asunto(s)
Estimulación Cardíaca Artificial/métodos , Ablación por Catéter/métodos , Complicaciones Posoperatorias/terapia , Estenosis de la Válvula Pulmonar/cirugía , Taquicardia Ventricular/terapia , Procedimientos Quirúrgicos Torácicos/efectos adversos , Adulto , Antiarrítmicos/uso terapéutico , Bloqueo de Rama/fisiopatología , Electrocardiografía , Femenino , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Taquicardia Ventricular/etiología
7.
Eur J Prev Cardiol ; 23(12): 1339-49, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-26780920

RESUMEN

BACKGROUND: In western populations, high-sensitivity C-reactive protein (hsCRP), and to a lesser degree serum creatinine and haemoglobin A1c, predict risk of coronary heart disease (CHD). However, data on Asian populations that are increasingly affected by CHD are sparse and it is not clear whether these biomarkers can be used to improve CHD risk classification. DESIGN AND METHODS: We conducted a nested case-control study within the Singapore Chinese Health Study cohort, with incident 'hard' CHD (myocardial infarction or CHD death) as an outcome. We used data from 965 men (298 cases, 667 controls) and 528 women (143 cases, 385 controls) to examine the utility of hsCRP, serum creatinine and haemoglobin A1c in improving the prediction of CHD risk over and above traditional risk factors for CHD included in the ATP III model. For each sex, the performance of models with only traditional risk factors used in the ATP III model was compared with models with the biomarkers added using weighted Cox proportional hazards analysis. The impact of adding these biomarkers was assessed using the net reclassification improvement index. RESULTS: For men, loge hsCRP (hazard ratio 1.25, 95% confidence interval: 1.05; 1.49) and loge serum creatinine (hazard ratio 4.82, 95% confidence interval: 2.10; 11.04) showed statistically significantly associations with CHD risk when added to the ATP III model. We did not observe a significant association between loge haemoglobin A1c and CHD risk (hazard ratio 1.83, 95% confidence interval: 0.21; 16.06). Adding hsCRP and serum creatinine to the ATP III model improved risk classification in men with a net gain of 6.3% of cases (p-value = 0.001) being reclassified to a higher risk category, while it did not significantly reduce the accuracy of classification for non-cases. For women, squared hsCRP was borderline significantly (hazard ratio 1.01, 95% confidence interval: 1.00; 1.03) and squared serum creatinine was significantly (hazard ratio 1.81, 95% confidence interval: 1.49; 2.21) associated with CHD risk. However, the association between squared haemoglobin A1c and CHD risk was not significant (hazard ratio 1.05, 95% confidence interval: 0.99; 1.12). The addition of hsCRP and serum creatinine to the ATP III model resulted in 3.7% of future cases being reclassified to a higher risk category (p-value = 0.025), while it did not significantly reduce the accuracy of classification for non-cases. CONCLUSION: Adding hsCRP and serum creatinine, but not haemoglobin A1c, to traditional risk factors improved CHD risk prediction among non-diabetic Singaporean Chinese. The improved risk estimates will allow better identification of individuals at high risk of CHD than existing risk calculators such as the ATP III model.


Asunto(s)
Proteína C-Reactiva/metabolismo , Enfermedad Coronaria/sangre , Creatinina/sangre , Hemoglobina Glucada/metabolismo , Medición de Riesgo , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Enfermedad Coronaria/epidemiología , Diabetes Mellitus , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Riesgo , Singapur/epidemiología
8.
J Cardiovasc Electrophysiol ; 27(5): 531-5, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26773415

RESUMEN

BACKGROUND: Whether patients with asymptomatic atrial fibrillation (AF) could benefit from radiofrequency catheter ablation (RFCA) remains unclear. This study aimed to compare the outcomes of RFCA between asymptomatic and symptomatic AF. METHODS: Sixty-six patients with asymptomatic persistent AF who underwent the primary ablation for AF were enrolled; 132 patients with symptomatic persistent AF were matched using propensity score matching. All patients underwent circumferential pulmonary vein isolation in combination with linear ablation using AF termination as the primary procedural endpoint. RESULTS: Sinus rhythm (SR) was restored by ablation in 18 (27.3%) patients in the asymptomatic group and 93 (70.5%) in the symptomatic group (P < 0.001). Combined with intravenous infusion of ibutilide (1 mg), the numbers were 45 (68.2%) and 116 (87.8%), respectively (P = 0.001). At 1-year follow-up, SR was present in 23 (34.8%) patients in the asymptomatic group and 78 (59.1%) in the symptomatic group without any antiarrhythmic medication after a single procedure (P = 0.001). Of the 43 patients experiencing recurrence in the asymptomatic group, 16 (37.2%) had recurrent atrial tachycardia (AT)-related symptoms. Multivariate analysis showed that asymptomatic AF was independently associated with AF failed to be terminated by ablation (OR: 7.1; 95% CI: 3.4 to 14.9; P < 0.001) and recurrence (OR: 2.2; 95% CI: 1.1 to 4.4; P = 0.018). Patients with asymptomatic AF showed less improvement in quality of life postablation than those with symptoms. CONCLUSION: Current catheter ablation techniques showed worse outcomes in asymptomatic AF patients than in those with symptoms. Recurrent AT could cause significant symptoms in previously asymptomatic patients.


Asunto(s)
Fibrilación Atrial/cirugía , Ablación por Catéter , Venas Pulmonares/cirugía , Enfermedades Asintomáticas , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Ablación por Catéter/efectos adversos , Distribución de Chi-Cuadrado , Femenino , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Puntaje de Propensión , Venas Pulmonares/fisiopatología , Calidad de Vida , Recuperación de la Función , Recurrencia , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
9.
J Cardiovasc Electrophysiol ; 26(9): 969-977, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26031652

RESUMEN

BACKGROUND: The aim of this study was to describe the electrocardiogram (ECG) morphology and electroanatomical characteristics of counterclockwise tricuspid annular atrial flutter (CCWTA-AFL) in the patients with prior atriotomy. METHODS AND RESULTS: This retrospective study included 34 patients with CCWTA-AFL after cardiac surgery and 20 patients with typical CCWTA-AFL without prior surgery. For patients in the postsurgical group, 19 had single-loop CCWTA-AFL and 15 had a double loop CCWTA-AFL. For single loop CCWTA-AFL the F-wave in lead I was very flat in l7 of 19 patients. The F-wave morphology in the inferior leads and V1 were found to be similar to typical AFL in 14 of 19 patients. For double loop CCWTA-AFL, F-waves were positive in lead I in 13 out of 15 patients. A long isoelectric activation was measured between F-waves in most of the patients. The presence of isoelectric segments between F-waves suggested a double loop AFL, which had a sensitivity of 86.7% and a specificity of 100%. Moreover, flat F-waves in lead I suggested a single loop AFL, which had a sensitivity of 89.5% and specificity of 86.7%. All patients in the group without prior cardiac surgery had typical ECGs features of CCWTA-AFL. None of the patients showed isoelectric segments between F-waves in the inferior leads. The amplitudes of most of the leads were higher than those for single loop CCWTA-AFL in patients with prior surgery.

10.
Stem Cell Res Ther ; 6: 39, 2015 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-25889101

RESUMEN

INTRODUCTION: Type 1 long QT syndrome (LQT1) is a common type of cardiac channelopathy associated with loss-of-function mutations of KCNQ1. Currently there is a lack of drugs that target the defected slowly activating delayed rectifier potassium channel (IKs). With LQT1 patient-specific human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs), we tested the effects of a selective IKs activator ML277 on reversing the disease phenotypes. METHODS: A LQT1 family with a novel heterozygous exon 7 deletion in the KCNQ1 gene was identified. Dermal fibroblasts from the proband and her healthy father were reprogrammed to hiPSCs and subsequently differentiated into hiPSC-CMs. RESULTS: Compared with the control, LQT1 patient hiPSC-CMs showed reduced levels of wild type KCNQ1 mRNA accompanied by multiple exon skipping mRNAs and a ~50% reduction of the full length Kv7.1 protein. Patient hiPSC-CMs showed reduced IKs current (tail current density at 30 mV: 0.33±0.02 vs. 0.92±0.21, P<0.05) and prolonged action potential duration (APD) (APD 50 and APD90: 603.9±39.2 vs. 319.3±13.8 ms, P<0.005; and 671.0±41.1 vs. 372.9±14.2 ms, P<0.005). ML277, a small molecule recently identified to selectively activate KV7.1, reversed the decreased IKs and partially restored APDs in patient hiPSC-CMs. CONCLUSIONS: From a LQT1 patient carrying a novel heterozygous exon7 deletion mutation of KCNQ1, we generated hiPSC-CMs that faithfully recapitulated the LQT1 phenotypes that are likely associated with haploinsufficiency and trafficking defect of KCNQ1/Kv7.1. The small molecule ML277 restored IKs function in hiPSC-CMs and could have therapeutic value for LQT1 patients.


Asunto(s)
Células Madre Pluripotentes Inducidas/citología , Canal de Potasio KCNQ1/genética , Miocitos Cardíacos/citología , Canales de Potasio con Entrada de Voltaje/efectos de los fármacos , Síndrome de Romano-Ward/genética , Potenciales de Acción/fisiología , Adulto , Diferenciación Celular , Línea Celular , Técnicas de Reprogramación Celular , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Técnicas de Placa-Clamp , Piperidinas/uso terapéutico , Canales de Potasio con Entrada de Voltaje/genética , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Eliminación de Secuencia/genética , Tiazoles/uso terapéutico , Compuestos de Tosilo/uso terapéutico , Adulto Joven
11.
Int J Cardiol ; 183: 33-8, 2015 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-25662051

RESUMEN

INTRODUCTION: Mortality in patients with heart failure and preserved ejection fraction (HFpEF) remains high. Data from Asia is lacking. We aim to study the impact of ethnicity and other predictors of mortality in patients admitted for HFpEF in a multi-ethnic Asian country. MATERIAL AND METHODS: Consecutive patients admitted to two local institutions with heart failure and ejection fraction ≥50% on transthoracic echocardiogram from Jan 2008 to Dec 2009 were included. All patients were followed-up for 2 years. Overall mortality was obtained from the national registry of deaths in our country. RESULTS: A total of 1960 patients with heart failure were included. 751 (38.3%) patients had HFpEF. Overall mortality at two years was 26.6% (n=200) compared to 37.1% (n=449) in patients with reduced ejection fraction (HR 0.618 (95% CI 0.508-0.753), p<0.001). Ethnicity did not predict mortality. On multivariable Cox regression analysis, significant predictors of two-year mortality in HFpEF patients were older age (HR 1.027 (1.011-1.044)), prior myocardial infarction (HR 1.577 (1.104-2.253)), prior stroke (HR 1.475 (1.055-2.061)), smoking (HR 1.467 (1.085-1.985)), higher creatinine levels (HR 1.002 (1.001-1.003)) and use of mineralocorticoid receptor antagonists (HR 1.884 (1.226-2.896)). Use of warfarin (HR 0.506 (0.304-0.842)) and statins (HR 0.585 (0.435-0.785)) were associated with significantly lower mortality. CONCLUSIONS: In our Asian population presenting with HFpEF, two-year mortality was 26.6%. Ethnicity did not predict mortality. Older age, prior myocardial infarction, prior stroke, smoking, and higher creatinine levels were found to be significant predictors of mortality.


Asunto(s)
Insuficiencia Cardíaca/mortalidad , Volumen Sistólico/fisiología , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/etnología , Electrocardiografía , Femenino , Insuficiencia Cardíaca/etnología , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Singapur/epidemiología
12.
Eur Cardiol ; 10(2): 118-122, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30310436

RESUMEN

Sudden cardiac death (SCD) remains a major public health problem worldwide, yet current methods to identify those at greatest risk are inadequate. High-risk individuals may benefit from potentially life-saving treatment, such as insertion of an implantable-cardioverter defibrillator (ICD). However, such treatments are expensive and have their own associated risks. Furthermore, most cases of SCD occur in the general adult population who may be relatively asymptomatic but yet have an underlying predisposition to SCD. Hence, there is great interest and clinical need in improving methods for risk stratification of SCD to identify those at greatest risk and implement the most appropriate treatment. This review provides an update on current risk-stratification methods for SCD in high-risk groups, in particular patients with reduced left ventricular function following acute myocardial infarction and those with non-ischaemic dilated cardiomyopathy, and highlights some novel methods that may have a role to play in future risk-stratification schemes. Approaches and challenges for SCD risk stratification among the general public are also discussed.

13.
BMC Cardiovasc Disord ; 14: 122, 2014 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-25245139

RESUMEN

BACKGROUND: The optimal timing of pulmonary homograft valve replacement (PVR) is uncertain. Cardiopulmonary exercise testing (CPET) and cardiac magnetic resonance (CMR) are often used to guide the clinical decision for PVR in operated tetralogy of Fallot (TOF) patients with significant pulmonary regurgitation (PR). We aim to study the relationship between exercise capacity and CMR in these patients. METHODS: The study is a single-centre retrospective analysis of 36 operated TOF patients [median 21.4 (interquartile range 16.4, 26.4) years post-repair; 30 NYHA I, 6 NYHA II; median age 25.2 (interquartile range 19.5-31.7) years, 29 males] with significant PR on CMR who underwent CPET within 15 [median 2.0 (interquartile range 0.8-7.2)] months from CMR. CPET parameters were compared with 30 age- and sex-matched healthy controls [median age 27.8 (interquartile range 21.0-32.8) years; 24 males]. RESULTS: Peak systolic blood pressure (177 versus 192 mmHg, p = 0.007), Mets (7.3 versus 9.9, p < 0.001), peak oxygen consumption (VO2max) (29.2 versus 34.5 ml/kg/min, p < 0.001) and peak oxygen pulse (11.0 versus 13.7 ml/beat, p = 0.003) were significantly lower in TOF group versus control. Univariate analyses showed negative correlation between PR fraction and anaerobic threshold. There was a positive correlation between indexed left (LV) and right (RV) ventricular end-diastolic volumes, as well as indexed LV and effective RV stroke volumes, on CMR and VO2max and Mets achieved on CPET. These remained significant after adjustment for age and sex. CONCLUSIONS: TOF subjects have near normal exercise capacity but significantly lower Mets, VO2max and peak oygen pulse achieved compared to controls. Increased PR fraction in TOF subjects was associated with lower anaerobic threshold. Higher indexed effective RV stroke volume, a measure of LV preload, was associated with higher VO2max and Mets achieved, and may potentially be used as a predictor of exercise capacity.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos/efectos adversos , Tolerancia al Ejercicio , Imagen por Resonancia Cinemagnética , Insuficiencia de la Válvula Pulmonar/diagnóstico , Tetralogía de Fallot/cirugía , Función Ventricular Izquierda , Adolescente , Adulto , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Consumo de Oxígeno , Valor Predictivo de las Pruebas , Insuficiencia de la Válvula Pulmonar/etiología , Insuficiencia de la Válvula Pulmonar/fisiopatología , Estudios Retrospectivos , Singapur , Tetralogía de Fallot/diagnóstico , Tetralogía de Fallot/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Función Ventricular Derecha , Adulto Joven
14.
Rev. urug. cardiol ; 29(2): 250-266, ago. 2014.
Artículo en Español | LILACS-Express | LILACS | ID: lil-754310

RESUMEN

En los últimos años se han hecho importantes avances en el campo de la electrofisiología cardíaca clínica y la estimulación cardíaca. Tanto los investigadores como los médicos comprenden mejor ahora los mecanismos fisiopatológicos que constituyen la base de la fibrilación auricular (FA), que ha trascendido en una mejora de los métodos de detección, la estratificación del riesgo y los tratamientos. Asimismo, la introducción de nuevos anticoagulantes orales ha muñido a los médicos de distintas opciones alternativas para el manejo de pacientes con FA con riesgo moderado o alto de tromboembolia, y han ido apareciendo otros datos sobre el uso de la ablación con catéter para el tratamiento de la FA sintomática. Otra área de investigación intensa en el campo de las arritmias y la estimulación cardíaca es en el uso de la terapia de resincronización cardíaca (TRC) para el tratamiento de pacientes con insuficiencia cardíaca. Tras la publicación de ensayos controlados aleatorizados señeros que informaron la ventaja que confiere la TRC en términos de supervivencia en pacientes con insuficiencia cardíaca severa y en mejora de los síntomas, se han realizado muchos estudios posteriores para perfeccionar la selección de pacientes candidatos a TRC y para determinar las características clínicas asociadas con una respuesta favorable. El campo de la muerte súbita cardíaca y los desfibriladores automáticos implantables también continúa siendo investigado activamente, y van surgiendo datos epidemiológicos y clínicos nuevos e importantes en la mejora de los métodos de selección y manejo de los pacientes, y la estratificación del riesgo. Esta revisión abarca los principales avances recientes en estas áreas relacionados con las arritmias cardíacas y la estimulación cardíaca.

15.
Eur J Heart Fail ; 16(11): 1183-9, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24903314

RESUMEN

AIM: The aim of this study was to test the hypothesis that diabetes modifies the risk of mortality in acute heart failure patients, especially in patients with impaired LVEF, and that impaired LVEF in turn modifies the risk of mortality in diabetic patients. METHODS AND RESULTS: We studied 2121 patients with acute heart failure admitted at two centres in Singapore from 1 January 2008 to 31 December 2009. The date of the last follow-up was 31 December 2011, with a median follow-up time (interquartile range) of 914 (442-1190) days. Cox regression was used to estimate hazard ratios for all-cause mortality in patients with LVEF ≥50%, LVEF 30-49%, and LVEF <30% relative to diabetic status. Impaired LVEF (<50%) in the presence of diabetes substantially increased the risk of mortality compared with non-diabetics with LVEF <50%. The adjusted hazard ratio (aHR) and 95% confidence interval (CI) for diabetic patients with an LVEF of 30-49% (1.46, 95% 1.18-1.81) was not statistically different from the aHR in non-diabetic patients with severely impaired LVEF of <30% (1.38, 95% CI 1.09-1.75) (P = 0.644). The deleterious effects of diabetes seemed to be confined to acute heart failure patients with impaired LVEF, as the mortality rate in patients with LVEF >50% was not increased. Other clinical predictors of mortality were ageing, prior myocardial infarction, systolic blood pressure >140 mmHg, creatinine ≥250 µmol/L, haemoglobin <9.0 g/dL, and prior stroke/transient ischaemic attack. CONCLUSION: The interaction of diabetes and impaired LVEF in acute heart failure patients significantly amplifies the deleterious effects of each as distinct disease entities.


Asunto(s)
Complicaciones de la Diabetes/mortalidad , Complicaciones de la Diabetes/fisiopatología , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Disfunción Ventricular Izquierda/mortalidad , Disfunción Ventricular Izquierda/fisiopatología , Enfermedad Aguda , Anciano , Causas de Muerte , Estudios de Seguimiento , Humanos , Valor Predictivo de las Pruebas , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Singapur/epidemiología , Volumen Sistólico/fisiología
16.
Acta Cardiol ; 69(2): 222-34, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24783482

RESUMEN

Important advances have been made in the past few years in the fields of clinical cardiac electrophysiology and pacing. Researchers and clinicians have a greater understanding of the pathophysiological mechanisms underlying atrial fibrillation (AF), which has transpired into improved methods of detection, risk stratification, and treatments. The introduction of novel oral anticoagulants has provided clinicians with alternative options in managing patients with AF at moderate to high thromboembolic risk and further data has been emerging on the use of catheter ablation for the treatment of symptomatic AF. Another area of intense research in the field of cardiac arrhythmias and pacing is in the use of cardiac resynchronisation therapy (CRT) for the treatment of patients with heart failure. Following the publication of major landmark randomised controlled trials reporting that CRT confers a survival advantage in patients with severe heart failure and improves symptoms, many subsequent studies have been performed to further refine the selection of patients for CRT and determine the clinical characteristics associated with a favourable response. The field of sudden cardiac death and implantable cardioverter defibrillators also continues to be actively researched, with important new epidemiological and clinical data emerging on improved methods for patient selection, risk stratification, and management.This review covers the major recent advances in these areas related to cardiac arrhythmias and pacing.


Asunto(s)
Arritmias Cardíacas/terapia , Desfibriladores Implantables , Marcapaso Artificial , Administración Oral , Almanaques como Asunto , Anticoagulantes/uso terapéutico , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/fisiopatología , Fibrilación Atrial/terapia , Terapia de Resincronización Cardíaca , Cardiología , Ablación por Catéter , Ensayos Clínicos como Asunto , Sistema de Conducción Cardíaco/fisiopatología , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Singapur/epidemiología , Factores de Tiempo , Resultado del Tratamiento
17.
Cardiovasc Res ; 102(3): 497-506, 2014 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-24623279

RESUMEN

AIMS: Long QT syndrome 2 (LQTS2) caused by missense mutations in hERG channel is clinically associated with abnormally prolonged ventricular repolarization and sudden cardiac deaths. Modelling monogenic arrhythmogenic diseases using human-induced pluripotent stem cells (hiPSCs) offers unprecedented mechanistic insights into disease pathogenesis. We utilized LQTS2-hiPSC-derived cardiomyocytes (CMs) to elucidate pathological changes and to demonstrate reversal of LQTS2 phenotype in a therapeutic intervention using a pharmacological agent, (N-[N-(N-acetyl-l-leucyl)-l-leucyl]-l-norleucine) (ALLN). METHODS AND RESULTS: We generated LQTS2-specific CMs (A561V missense mutation in KCNH2) from iPSCs using the virus-free reprogramming method. These CMs recapitulate dysfunction of hERG potassium channel with diminished IKr currents, prolonged repolarization durations, and elevated arrhythmogenesis due to reduced membrane localization of glycosylated/mature hERG. Dysregulated expression of folding chaperones and processing proteasomes coupled with sequestered hERG in the endoplasmic reticulum confirmed trafficking-induced disease manifestation. Treatment with ALLN, not only increased membrane localization of mature hERG but also reduced repolarization, increased IKr currents and reduced arrhythmogenic events. Diverged from biophysical interference of hERG channel, our results show that modulation of chaperone proteins could be therapeutic in LQTS2 treatment. CONCLUSION: Our in vitro study shows an alternative approach to rescue diseased LQTS2 phenotype via corrective re-trafficking therapy using a small chemical molecule, such as ALLN. This potentially novel approach may have ramifications in other clinically relevant trafficking disorders.


Asunto(s)
Canales de Potasio Éter-A-Go-Go/fisiología , Células Madre Pluripotentes Inducidas/citología , Leupeptinas/uso terapéutico , Síndrome de QT Prolongado/tratamiento farmacológico , Miocitos Cardíacos/metabolismo , Animales , Canal de Potasio ERG1 , Canales de Potasio Éter-A-Go-Go/genética , Humanos , Síndrome de QT Prolongado/fisiopatología , Masculino , Ratones , Mutación , Fenotipo , Transporte de Proteínas
18.
J Cell Mol Med ; 18(2): 355-62, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24467431

RESUMEN

Telocytes (TCs) with exceptionally long cellular processes of telopodes have been described in human epicardium to act as structural supporting cells in the heart. We examined myocardial chamber-specific TCs identified in atrial and ventricular fibroblast culture using immunocytochemistry and studied their electrophysiological property by whole-cell patch clamp. Atrial and ventricular TCs with extended telopodes and alternating podoms and podomers that expressed CD34, c-Kit and PDGFR-ß were identified. These cells expressed large conductance Ca²âº-activated K⁺ current (BK(Ca)) and inwardly rectifying K⁺ current (IK(ir)), but not transient outward K⁺ current (I(to)) and ATP-sensitive potassium current (K(ATP)). The active channels were functionally competent with demonstrated modulatory response to H2 S and transforming growth factor (TGF)-ß1 whereby H2S significantly inhibited the stimulatory effect of TGF-ß1 on current density of both BKCa and IK(ir). Furthermore, H2S attenuated TGF-ß1-stimulated KCa1.1/Kv1.1 (encode BK(Ca)) and Kir2.1 (encode IK(ir)) expression in TCs. Our results show that functionally competent K⁺ channels are present in human atrial and ventricular TCs and their modulation may have significant implications in myocardial physiopathology.


Asunto(s)
Atrios Cardíacos/citología , Ventrículos Cardíacos/citología , Subunidades alfa de los Canales de Potasio de Gran Conductancia Activados por Calcio/metabolismo , Miocardio/citología , Canales de Potasio de Rectificación Interna/metabolismo , Células del Estroma/fisiología , Antígenos CD34/genética , Antígenos CD34/metabolismo , Separación Celular , Células Cultivadas , Fibroblastos/citología , Fibroblastos/fisiología , Expresión Génica , Atrios Cardíacos/metabolismo , Ventrículos Cardíacos/metabolismo , Humanos , Sulfuro de Hidrógeno/farmacología , Subunidades alfa de los Canales de Potasio de Gran Conductancia Activados por Calcio/genética , Potenciales de la Membrana/efectos de los fármacos , Miocardio/metabolismo , Técnicas de Placa-Clamp , Canales de Potasio de Rectificación Interna/genética , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Células del Estroma/citología , Células del Estroma/efectos de los fármacos , Factor de Crecimiento Transformador beta1/farmacología
19.
J Cardiovasc Electrophysiol ; 25(3): 324-7, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24303874

RESUMEN

We report a case of pectus excavatum associated with ventricular tachycardia provoked by exercise in a 19-year-old man. Although this chest deformity has been associated with supraventricular dysrhythmias, documented ventricular tachycardia has only been reported once. Our patient's ventricular dysrhythmia was treated by surgical correction of his pectus excavatum only, and at 3 years follow-up he has had no recurrence of his ventricular tachycardia.


Asunto(s)
Tórax en Embudo/complicaciones , Tórax en Embudo/diagnóstico , Ventrículos Cardíacos/patología , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiología , Tórax en Embudo/cirugía , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/cirugía , Humanos , Masculino , Taquicardia Ventricular/cirugía , Adulto Joven
20.
Turk Kardiyol Dern Ars ; 41(8): 765-79, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24351955

RESUMEN

Important advances have been made in the past few years in the fields of clinical cardiac electrophysiology and pacing. Researchers and clinicians have a greater understanding of the pathophysiological mechanisms underlying atrial fibrillation (AF), which has transpired into improved methods of detection,risk stratification, and treatments. The introduction of novel oral anticoagulants has provided clinicians with alternative options in managing patients with AF at moderate to high thromboembolic risk and further data has been emerging on the use of catheter ablation for the treatment of symptomatic AF.Another area of intense research in the field of cardiac arrhythmias and pacing is in the use of cardiac resynchronisation therapy (CRT) for the treatment of patients with heart failure. Following the publication of major landmark randomised controlled trials reporting that CRT confers a survival advantage in patients with severe heart failure and improves symptoms,many subsequent studies have been performed to further refine the selection of patients for CRT and determine the clinical characteristics associated with a favourable response. The field of sudden cardiac death and implantable cardioverter defibrillators also continues to be actively researched, with important new epidemiological and clinical data emerging on improved methods for patient selection, risk stratification, and management. This review covers the major recent advances in these areas related to cardiac arrhythmias and pacing.


Asunto(s)
Estimulación Cardíaca Artificial , Fibrilación Atrial/terapia , Cardiología/métodos , Cardiología/normas , Ablación por Catéter , Humanos , Guías de Práctica Clínica como Asunto
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