RESUMO
Succinate accumulates during myocardial ischemia and is rapidly oxidized during reperfusion, leading to reactive oxygen species (ROS) production through reverse electron transfer (RET) from mitochondrial complex II to complex I, and favoring cell death. Given that connexin 43 (Cx43) modulates mitochondrial ROS production, we investigated whether Cx43 influences RET using inducible knock-out Cx43Cre-ER(T)/fl mice. Oxygen consumption, ROS production, membrane potential and coenzyme Q (CoQ) pool were analyzed in subsarcolemmal (SSM, expressing Cx43) and interfibrillar (IFM) cardiac mitochondria isolated from wild-type Cx43fl/fl mice and Cx43Cre-ER(T)/fl knock-out animals treated with 4-hydroxytamoxifen (4OHT). In addition, infarct size was assessed in isolated hearts from these animals submitted to ischemia-reperfusion (IR), and treated or not with malonate, a complex II inhibitor attenuating RET. Succinate-dependent ROS production and RET were significantly lower in SSM, but not IFM, from Cx43-deficient animals. Mitochondrial membrane potential, a RET driver, was similar between groups, whereas CoQ pool (2.165 ± 0.338 vs. 4.18 ± 0.55 nmol/mg protein, p < 0.05) and its reduction state were significantly lower in Cx43-deficient animals. Isolated hearts from Cx43Cre-ER(T)/fl mice treated with 4OHT had a smaller infarct size after IR compared to Cx43fl/fl, despite similar concentration of succinate at the end of ischemia, and no additional protection by malonate. Cx43 deficiency attenuates ROS production by RET in SSM, but not IFM, and was associated with a decrease in CoQ levels and a change in its redox state. These results may partially explain the reduced infarct size observed in these animals and their lack of protection by malonate.
Assuntos
Conexina 43 , Camundongos Knockout , Mitocôndrias Cardíacas , Espécies Reativas de Oxigênio , Ubiquinona , Animais , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Ubiquinona/metabolismo , Ubiquinona/deficiência , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Conexina 43/metabolismo , Conexina 43/genética , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Transporte de Elétrons/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/genética , MasculinoRESUMO
TRPV4 channels, which respond to mechanical activation by permeating Ca2+ into the cell, may play a pivotal role in cardiac remodeling during cardiac overload. Our study aimed to investigate TRPV4 involvement in pathological and physiological remodeling through Ca2+-dependent signaling. TRPV4 expression was assessed in heart failure (HF) models, induced by isoproterenol infusion or transverse aortic constriction, and in exercise-induced adaptive remodeling models. The impact of genetic TRPV4 inhibition on HF was studied by echocardiography, histology, gene and protein analysis, arrhythmia inducibility, Ca2+ dynamics, calcineurin (CN) activity, and NFAT nuclear translocation. TRPV4 expression exclusively increased in HF models, strongly correlating with fibrosis. Isoproterenol-administered transgenic TRPV4-/- mice did not exhibit HF features. Cardiac fibroblasts (CFb) from TRPV4+/+ animals, compared to TRPV4-/-, displayed significant TRPV4 overexpression, elevated Ca2+ influx, and enhanced CN/NFATc3 pathway activation. TRPC6 expression paralleled that of TRPV4 in all models, with no increase in TRPV4-/- mice. In cultured CFb, the activation of TRPV4 by GSK1016790A increased TRPC6 expression, which led to enhanced CN/NFATc3 activation through synergistic action of both channels. In conclusion, TRPV4 channels contribute to pathological remodeling by promoting fibrosis and inducing TRPC6 upregulation through the activation of Ca2+-dependent CN/NFATc3 signaling. These results pose TRPV4 as a primary mediator of the pathological response.
Assuntos
Calcineurina , Insuficiência Cardíaca , Canais de Cátion TRPV , Remodelação Ventricular , Animais , Camundongos , Calcineurina/metabolismo , Células Cultivadas , Fibrose , Insuficiência Cardíaca/metabolismo , Isoproterenol , Camundongos Transgênicos , Miócitos Cardíacos/metabolismo , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Canal de Cátion TRPC6/genética , Canal de Cátion TRPC6/metabolismo , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Remodelação Ventricular/genéticaRESUMO
Succinate dehydrogenase inhibition with malonate during initial reperfusion reduces myocardial infarct size in both isolated mouse hearts subjected to global ischemia and in in situ pig hearts subjected to transient coronary ligature. However, the long-term effects of acute malonate treatment are unknown. Here, we investigated whether the protective effects of succinate dehydrogenase inhibition extend to a reduction in scar size and adverse left ventricular remodeling 28 days after myocardial infarction. Initially, ten wild-type mice were subjected to 45 min of left anterior descending coronary artery (LAD) occlusion, followed by 24 h of reperfusion, and were infused during the first 15 min of reperfusion with saline with or without disodium malonate (10 mg/kg/min, 120 µL/kg/min). Malonate-treated mice depicted a significant reduction in infarct size (15.47 ± 3.40% of area at risk vs. 29.34 ± 4.44% in control animals, p < 0.05), assessed using triphenyltetrazolium chloride. Additional animals were then subjected to a 45 min LAD ligature, followed by 28 days of reperfusion. Treatment with a single dose of malonate during the first 15 min of reperfusion induced a significant reduction in scar area, measured using Picrosirius Red staining (11.94 ± 1.70% of left ventricular area (n = 5) vs. 23.25 ± 2.67% (n = 9), p < 0.05), an effect associated with improved ejection fraction 28 days after infarction, as determined using echocardiography, and an attenuated enhancement in expression of the pro-inflammatory and fibrotic markers NF-κB and Smad2/3 in remote myocardium. In conclusion, a reversible inhibition of succinate dehydrogenase with a single dose of malonate at the onset of reperfusion has long-term protective effects in mice subjected to transient coronary occlusion.
Assuntos
Malonatos , Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Succinato Desidrogenase , Remodelação Ventricular , Animais , Malonatos/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Camundongos , Succinato Desidrogenase/metabolismo , Succinato Desidrogenase/antagonistas & inibidores , Masculino , Remodelação Ventricular/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/patologia , Cicatriz/patologia , Cicatriz/tratamento farmacológico , Camundongos Endogâmicos C57BLRESUMO
ENA transporters are a group of P-type ATPases that are characterized by actively moving Na+ or K+ out of the cell against their concentration gradient. The existence of these transporters was initially attributed to some fungi, although more recently they have also been identified in mosses, liverworts, and some protozoa. Given the current increase in the number of organisms whose genomes are completely sequenced, we set out to expand our knowledge about the existence of ENA in organisms belonging to other phylogenetic groups. For that, a hidden Markov model profile was constructed to identify homologous sequences to ENA proteins in protein databases. This analysis allowed us to identify the existence of ENA-type ATPases in the most primitive groups of fungi, as well as in other eukaryotic organisms not described so far. In addition, this study has allowed the identification of a possible new group of P-ATPases, initially proposed as ENA but which maintain phylogenetic distances with these proteins. Finally, this work has also addressed this study of the structure of ENA proteins, which remained unknown due to the lack of crystallographic data. For this purpose, a 3D structure prediction of the NcENA1 protein of the fungus Neurospora crassa was performed using AlphaFold2 software v2.3.1. From this structure, the electrostatic potential of the protein was analyzed. With all these data, the protein regions and the amino acids involved in the transport of Na+ or K+ ions across the membrane were proposed for the first time. Targeted mutagenesis of some of these residues has confirmed their relevant participation in the transport function of ENA proteins.
Assuntos
Adenosina Trifosfatases , Neurospora crassa , Adenosina Trifosfatases/genética , Filogenia , Neurospora crassa/genética , Eucariotos , Proteínas de Membrana TransportadorasRESUMO
Introducción y objetivos: Los pacientes con un episodio sincopal inexplicable único (ESU) y bloqueo completo de rama del haz de His (BcR) con frecuencia se tratan de manera más conservadora que aquellos con episodios recurrentes (ESR). El objetivo fue analizar si existen diferencias entre pacientes con ESU o ESR y BcR en cuanto al riesgo arrítmico, el rendimiento diagnóstico de las pruebas y los resultados clínicos. Métodos: Estudio de cohorte de pacientes consecutivos con seguimiento medio de 3 años. Fueron estudiados mediante un protocolo escalonado basado en un estudio electrofisiológico y seguimiento con un monitor cardiaco implantable (MCI). Resultados: De los 503 pacientes incluidos en el estudio, 238 (47,3%) referían un ESU. El riesgo de síncope arrítmico fue similar en ambos grupos (58,8% ESU frente a 57,0% ESR; p=0,68), también tras ajustar por variables de confusión (HR=1,06; IC95%, 0,81-1,38; p=0,674). No se encontraron diferencias significativas en cuanto a los resultados del estudio electrofisiológico y la rentabilidad diagnóstica del monitor cardiaco implantable. Un total de 141 (59,2%) pacientes con ESU y 154 (58,1%) con ESR requirieron el implante de un dispositivo cardiaco (p=0,797). Tras el tratamiento adecuado, 35 (7%) pacientes presentaron recurrencia del síncope. La tasa de recurrencia y la mortalidad también fueron similares. Conclusiones: Los pacientes con BcR y síncope tienen un alto riesgo de tener una etiología arrítmica, aunque solo hayan presentado un episodio aislado. Los pacientes con ESU y ESR tienen un riesgo arrítmico similar y presentan un pronóstico similar, por lo que no existe una justificación clínica para no tratarlos de la misma manera.(AU)
Introduction and objectives: Patients with a single syncopal episode (SSE) and complete bundle branch block (cBBB) are frequently managed more conservatively than patients with recurrent episodes (RSE). The objective of this study was to analyze if there are differences between patients with single or recurrent unexplained syncope and cBBB in arrhythmic risk, the diagnostic yield of tests, and clinical outcomes. Methods: Cohort study of consecutive patients with unexplained syncope and cBBB with a median follow-up time of 3 years. The patients were evaluated via a stepwise workup protocol based on electrophysiological study (EPS) and long-term follow-up with an implantable cardiac monitor. Results: Of the 503 patients included in the study, 238 (47.3%) had had only 1 syncopal episode. The risk of an arrhythmic syncope was similar in both groups (58.8% in SSE vs 57.0% in RSE; P=.68), also after adjustment for possible confounding variables (HR, 1.06; 95%CI, 0.81-1.38; P=.674). No significant differences between the groups were found in the EPS results and implantable cardiac monitor diagnostic yield. A total of 141 (59.2%) patients with SSE and 154 (58.1%) patients with RSE required cardiac device implantation (P=.797). After appropriate treatment, 35 (7%) patients had recurrence of syncope. The recurrence rate and mortality were also similar in both groups. Conclusions: Patients with cBBB and unexplained syncope are at high risk of an arrhythmic etiology, even after the first syncopal episode. Patients with SSE and RSE have a similar arrhythmic risk and similar outcomes, and therefore there is no clinical justification for not managing them in the same manner.(AU)
Assuntos
Humanos , Bloqueio de Ramo , Síncope , Marca-Passo Artificial , Técnicas Eletrofisiológicas Cardíacas , Cardiologia , Doenças Cardiovasculares , Estudos de CoortesRESUMO
Aim: To assess the changes induced by the COVID-19 lockdown on cardiac biometric variables recorded using an implantable cardiac monitor (ICM) in a patient population monitored for syncope work-up, as well to assess whether there has been an effect on arrhythmic events among the patients.MethodsLongitudinal cohort study. We included 245 adult patients monitored with an ICM indicated for the investigation of syncope. The records from days 1 to 12 March 2020 (prior to the institution of lockdown by the state government) with days 16 to 28 March 2020 were compared.ResultsDaily physical exercise reduced markedly after the imposition of lockdown (132 [55233] minutes vs. 78 [21154] minutes). The mean daytime HR prior to lockdown was 77 [6985] bpm, whereas during lockdown it was 74 [6681] bpm. During the lockdown period, a drop in the variability in heart rate (114 [94136] ms vs. 111 [92133] ms) was observed. Although the incidence of AF was similar over both periods, the daily AF burden was significantly higher post-lockdown (405 [391425] minutes vs. 423 [423537] minutes). No differences in the number of other arrhythmias were found.ConclusionsThe establishment of mandatory lockdown has led to a marked drop in daily physical activity in this population which probably explains changes observed in other cardiac biometric variables. Although, in the short term, we have not documented an increased risk of arrhythmia, we cannot rule out an effect in the medium to long term or in other populations of at-risk patients. (AU)
Objetivo: Evaluar los cambios inducidos por el confinamiento durante la pandemia de COVID-19 en las variables biométricas cardiacas registradas, utilizando un monitor cardíaco implantable (ICM) en una población de pacientes monitorizada para el diagnóstico de síncope, así como evaluar si ha habido un efecto sobre los eventos arrítmicos.MétodosEstudio de cohorte prospectivo. Se incluyeron 245 pacientes adultos monitorizados con un ICM indicado para la investigación del síncope. Se compararon los registros de los días uno al 12 de marzo del 2020 (antes del establecimiento del confinamiento por parte del gobierno estatal) con los días 16 al 28 de marzo del 2020.ResultadosEl ejercicio físico diario se redujo notablemente después de la imposición del confinamiento (132 [55 a 233] vs. 78 [21 a 154] min). La frecuencia cardiaca diurna media antes del confinamiento fue de 77 (69 a 85) lpm, mientras que durante el mismo fue de 74 (66 a 81) lpm. Durante el período de confinamiento, se observó una disminución de la variabilidad de la frecuencia cardiaca (114 [94 a 136] vs. 111 [92 a 133] ms). Aunque la incidencia de fibrilación auricular (FA) fue similar en ambos períodos, la carga diaria de FA fue significativamente mayor después del bloqueo (405 [391 a 425] vs. 423 [423 a 537] min). No se encontraron diferencias en el número de otras arritmias.ConclusionesEl establecimiento de un confinamiento obligatorio ha provocado un marcado descenso de la actividad física diaria en esta población, lo que probablemente explica los cambios observados en otras variables biométricas cardiacas. Si bien, a corto plazo, no se ha documentado un aumento del riesgo de arritmia, no podemos descartar un efecto a medio-largo plazo o en otras poblaciones de pacientes de riesgo. (AU)
Assuntos
Humanos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/etiologia , Controle de Doenças Transmissíveis , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Infecções por Coronavirus/epidemiologia , Síncope/diagnóstico , Síncope/epidemiologia , Síncope/etiologia , Estudos Longitudinais , PandemiasRESUMO
El medioambiente es un gran determinante de la salud cardiovascular. La cardiología ambiental estudia la contribución de las exposiciones ambientales con el objetivo de minimizar las influencias nocivas de la contaminación y promover la salud cardiovascular mediante estrategias preventivas o terapéuticas específicas. La presente revisión se centra en el material particulado y los metales, contaminantes con la evidencia científica más sólida, e incluye las posibles intervenciones. La legislación, la mitigación y el control de los contaminantes en el aire, el agua y los alimentos y las políticas ambientales de espacios cardiosaludables son medidas clave para la salud cardiovascular. Entre las estrategias individuales, cabe reseñar la quelación de metales divalentes como el plomo y el cadmio, que solamente pueden eliminarse del cuerpo vía quelación. El ensayo clínico TACT (NCT00044213) demostró el beneficio cardiovascular en pacientes con un infarto de miocardio previo, especialmente en los diabéticos. Actualmente, el ensayo TACT2 (NCT02733185) está reproduciendo los resultados del TACT en personas con diabetes. Datos de Estados Unidos y Argentina también han mostrado la posible utilidad de la quelación en la enfermedad arterial periférica grave. Más investigación y acción en cardiología ambiental podría contribuir sustancialmente a mejorar la prevención y el tratamiento de las enfermedades cardiovasculares.(AU)
The environment is a strong determinant of cardiovascular health. Environmental cardiology studies the contribution of environmental exposures with the aim of minimizing the harmful influences of pollution and promoting cardiovascular health through specific preventive or therapeutic strategies. The present review focuses on particulate matter and metals, which are the pollutants with the strongest level of scientific evidence, and includes possible interventions. Legislation, mitigation and control of pollutants in air, water and food, as well as environmental policies for heart-healthy spaces, are key measures for cardiovascular health. Individual strategies include the chelation of divalent metals such as lead and cadmium, metals that can only be removed from the body via chelation. The TACT (Trial to Assess Chelation Therapy, NCT00044213) clinical trial demonstrated cardiovascular benefit in patients with a previous myocardial infarction, especially in those with diabetes. Currently, the TACT2 trial (NCT02733185) is replicating the TACT results in people with diabetes. Data from the United States and Argentina have also shown the potential usefulness of chelation in severe peripheral arterial disease. More research and action in environmental cardiology could substantially help to improve the prevention and treatment of cardiovascular disease.(AU)
Assuntos
Humanos , Meio Ambiente , Metais , Poluição do Ar , Material Particulado , Doenças Cardiovasculares , Poluentes da Água , Poluentes Atmosféricos , Cardiologia , CardiopatiasRESUMO
No disponible
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Feixe Acessório Atrioventricular/fisiopatologia , Síndromes de Pré-Excitação/complicações , Fibrilação Atrial/complicações , Fatores de Risco , Ablação por CateterRESUMO
Introducción: La disfunción del sistema nervioso autonómico produce alteraciones en la variabilidad de la frecuencia cardiaca y aumenta la incidencia de arritmias. Analizamos este fenómeno fisiopatológico en pacientes con síndrome de apnea/hipoapnea del sueño severo y el impacto sobre el mismo del tratamiento con presión positiva continua en la vía aérea (CPAP). Métodos: Pacientes consecutivos con síndrome de apnea/hipoapnea del sueño severo de reciente diagnóstico fueron prospectivamente considerados para inclusión. Se analizó la incidencia de arritmias y la variabilidad de la frecuencia cardiaca (obtenidos mediante registro Holter de 24 horas) antes de iniciarse tratamiento con CPAP y tras un año del mismo. Resultados: Se incluyeron 26 pacientes. El tiempo de uso de CPAP durante el registro Holter fue de 6,6 ± 1,8 horas. Tras inicio de CPAP, se apreció una reducción marginalmente significativa en la FC media (80 ± 9 a 77 ± 11 lpm, p = 0,05). El uso de CPAP se asoció a una modulación parcial y exclusivamente en horas de vigilia de los parámetros de modulación parasimpáticar-MSSD (p = 0,047) y HF (p = 0,025) y de modulación simpática LF (p = 0,049). Ninguno de estos revirtió completamente a la normalidad (p < 0,001). Se observó una reducción de los episodios no sostenidos de taquicardia auricular (p = 0,024), sin efecto demostrativo sobre otras arritmias. Conclusiones: El tratamiento con CPAP se asocia a una mejora solo parcial y diurna de la variabilidad de la frecuencia cardiaca y disminuye la incidencia de taquicardia auricular. Ambos efectos podrían influir en la morbimortalidad cardiovascular de los pacientes con síndrome de apnea/hipoapnea del sueño
Introduction: Autonomic dysfunction can alter heart rate variability and increase the incidence of arrhythmia. We analyzed the impact of continuous positive airway pressure (CPAP) on this pathophysiological phenomenon in patients with severe sleep apnea-hypopnea syndrome. Methods: Consecutive patients with recently diagnosed severe sleep apnea-hypopnea syndrome were prospectively considered for inclusion. Incidence of arrhythmia and heart rate variability (recorded on a 24-hour Holter monitoring device) were analyzed before starting CPAP therapy and 1 year thereafter. Results: A total of 26 patients were included in the study. CPAP was administered for 6.6 ± 1.8 hours during Holter monitoring. After starting CPAP, we observed a marginally significant reduction in mean HR (80 ± 9 to 77 ± 11 bpm, p = .05). CPAP was associated with partial modulation (only during waking hours) of r-MSSD (p = .047) and HF (p = .025) parasympathetic parameters and LF (p = .049) sympathetic modulation parameters. None of these parameters returned completely to normal levels (p < .001). The number of unsustained episodes of atrial tachycardia diminished (p = .024), but no clear effect on other arrhythmias was observed. Conclusions: CPAP therapy only partially improves heart rate variability, and exclusively during waking hours, and reduces incidence of atrial tachycardia, both of which can influence cardiovascular morbidity and mortality in sleep apnea-hypopnea syndrome patients
Assuntos
Humanos , Masculino , Feminino , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/prevenção & controle , Frequência Cardíaca/fisiologia , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/epidemiologia , Polissonografia/instrumentação , Polissonografia/métodos , Polissonografia , Bloqueio Cardíaco/tratamento farmacológico , Bloqueio Cardíaco/epidemiologiaRESUMO
Introducción y objetivos La ablación de vía lenta nodular es el tratamiento de elección de la taquicardia por reentrada nodular. No hay descritas variables demográficas, anatómicas ni electrofisiológicas que predigan una localización exacta de la vía lenta dentro del nódulo auriculoventricular ni su proximidad a la vía rápida. El objetivo es estudiar estas variables. Métodos Se incluyó prospectivamente a 54 pacientes (17 varones; media de edad, 55 ± 16 años) sometidos a ablación efectiva de vía lenta. Se midieron los periodos refractarios de ambas vías y su tiempo de conducción diferencial. Se calculó las distancias desde la región hisiana (correspondiente a la localización de la vía rápida) hasta el ostium del seno coronario (con lo que se obtuvo una estimación de la longitud anteroposterior del triángulo de Koch) y también hasta la zona de la vía lenta. Resultados El tiempo de conducción diferencial (139 ± 98 ms) no se correlacionó con las distancias His-seno coronario (19 ± 6 mm; p = 0,6) ni His-vía lenta (14 ± 4 mm; p = 0,4). A mayor distancia His-seno coronario, se estableció mayor distancia His-vía lenta (r = 0,652; p < 0,01) y se confirmó la correlación anatómica entre las dimensiones del triángulo y la separación entre ambas vías. En los pacientes mayores de 70 años, se observaron menor tamaño del triángulo y menor distancia entre ambas vías (p < 0,001). Conclusiones Una mayor dimensión anteroposterior del triángulo de Koch se asocia a una localización de vía lenta más alejada de la rápida, encontrándose ambas más próximas entre sí (mayor riesgo de bloqueo auriculoventricular) en los pacientes de edad avanzada (AU)
Introduction and objectives: Nodal slow pathway ablation is the treatment of choice for nodal reentrant tachycardia. No demographic, anatomic, or electrophysiologic variables have been reported to predict an exact location of the slow pathway in the atrioventricular node or its proximity to the fast pathway. The purpose of this study was to analyze these variables. Methods: The study prospectively included 54 patients (17 men; mean age, 55 [16] years) who had undergone successful slow pathway ablation. The refractory periods of both pathways and their differential conduction time were measured, and calculations were performed to obtain the distance from the His-bundle region (location of the fast pathway) to the coronary sinus ostium (to estimate the anteroposterior length of the triangle of Koch) and to the slow pathway area. Results: The differential conduction time (139 [98] ms) did not correlate with the His-coronary sinus distance (19 [6] mm; P = .6) or the His-slow pathway distance (14 [4] mm; P = .4). When the Hiscoronary sinus distance was larger, the His-slow pathway distance was also larger (r = 0.652; P < .01) and the anatomic correlation between the triangle dimensions and the separation between the two pathways was confirmed. In patients older than 70 years, smaller triangle sizes and a shorter distance between both pathways were observed (P < .001). Conclusions: A greater anteroposterior dimension of the triangle of Koch is associated with a slow pathway location farther from the fast pathway. In elderly patients the two pathways are closer together (higher risk of atrioventricular block) (AU)
Assuntos
Humanos , Ablação por Cateter/métodos , Taquicardia por Reentrada no Nó Atrioventricular/diagnóstico , Estudos Prospectivos , Taquicardia Reciprocante/diagnóstico , Tratamento por Radiofrequência Pulsada/métodosRESUMO
El síndrome de QT largo, el síndrome de QT corto, el síndrome de Brugada y la taquicardia ventricular polimórfica catecolaminérgica son trastornos eléctricos primarios que predisponen a muerte súbita en ausencia de cardiopatía estructural. La estratificación del riesgo en estas enfermedades es fundamental para identificar a los pacientes con peor pronóstico. En el síndrome de QT largo y el síndrome de Brugada, numerosos estudios han establecido que los principales factores pronósticos son clínicos y se basan en la presencia de síntomas previos, los hallazgos del ECG, el sexo y, en el caso del síndrome de Brugada, la inducibilidad de arritmias en el estudio electrofisiológico. Por el escaso número de casos descritos, actualmente disponemos de poca información acerca de las variables implicadas en el pronóstico del síndrome de QT corto y la taquicardia ventricular polimórfica catecolaminérgica. Esta revisión resume nuestro conocimiento actual sobre la estratificación del riesgo en estos cuatro trastornos hereditarios arritmogénicos (AU)
Long-QT syndrome, short-QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia are all primary electrical disorders that predispose patients to sudden death in the absence of structural heart disease. Risk stratification in these conditions is essential for identifying those patients with a poor prognosis. In long-QT and Brugada syndromes, a number of studies have shown that the main prognostic factors are clinical, namely the presence of previous symptoms, ECG findings, sex and, in the case of Brugada syndrome, the inducibility of ventricular arrhythmias during electrophysiologic investigations. Because very few cases have been described, little information is currently available about prognostic variables in short-QT syndrome or catecholaminergic polymorphic ventricular tachycardia. This article reviews what is currently known about risk stratification in these four hereditary arrhythmogenic disorders (AU)
Assuntos
Humanos , Morte Súbita Cardíaca/epidemiologia , Eletrocardiografia/métodos , Fatores de Risco , Síndrome do QT Longo/complicações , Taquicardia Ventricular/complicações , Síndrome de Brugada/complicaçõesRESUMO
El tratamiento antiarrítmico crónico de la fibrilación auricular ha experimentado pocos cambios en los últimos años hasta la irrupción de la dronedarona. Su papel probablemente quedará restringido a pacientes con fibrilación auricular paroxística o persistente sin clínica de insuficiencia cardiaca asociada. La decisión más importante que debe adoptar el cardiólogo sigue siendo si luchar por mantener el ritmo cardiaco o simplemente mantener una frecuencia cardiaca adecuada. La primera opción es más recomendable para pacientes sintomáticos sin demasiada cardiopatía estructural; la segunda, para pacientes poco sintomáticos o asintomáticos, de edad avanzada y con cardiopatía estructural asociada que haga previsible que el ritmo sinusal no se mantenga. La combinación con tratamientos no farmacológicos, como la ablación, actualmente es una realidad que probablemente será más notable aún en un futuro cercano (AU)
Long-term pharmacologic treatment of atrial fibrillation underwent few changes in the years before the recent introduction of dronedarone. Use of this drug is restricted to patients with paroxysmal or persistent atrial fibrillation who are scheduled for electrical cardioversion and who show no signs of associated heart failure. The most important decision facing the cardiologist is still whether to attempt to maintain sinus rhythm or simply to maintain an adequate heart rate. The first option is preferred for symptomatic patients without substantial structural heart disease; the second is preferred for patients with no or few symptoms and those of advanced age who have associated structural heart disease which makes it unlikely that sinus rhythm can be maintained. The combination of pharmacologic treatment with nonpharmacologic treatment, such as ablation, is today a real option that will probably become more widely used in the near future (AU)
Assuntos
Humanos , Fibrilação Atrial/tratamento farmacológico , Anticoagulantes/uso terapêutico , Antiarrítmicos/uso terapêutico , Nó Atrioventricular , Doença Crônica/tratamento farmacológico , Flecainida/farmacocinética , Propafenona/farmacocinética , Sotalol/farmacocinética , Amiodarona/farmacocinética , Benzofuranos/farmacocinética , Frequência CardíacaRESUMO
Las arritmias ventriculares contribuyen de manera importante en la morbilidad y mortalidad de los pacientes con enfermedad coronaria. La fibrilación ventricular es la causa de la mayor parte de las muertes que se producen en la fase aguda de la isquemia, mientras que la taquicardia ventricular monomorfa sostenida, debida a una reentrada generada en el tejido cicatrizal aparece sobre todo en el contexto de un infarto de miocardio cicatrizado, principalmente en pacientes con una fracción de eyección ventricular izquierda más baja. A pesar de los importantes avances que se han producido en la educación sanitaria de la población y en el tratamiento del infarto de miocardio, el riesgo de taquicardia ventricular en la población global con enfermedad coronaria continúa siendo un problema importante en la práctica clínica. La evaluación inicial del paciente que presenta una taquicardia ventricular requiere un electrocardiograma de 12 derivaciones, que puede ser útil para confirmar el diagnóstico, sugerir la presencia de una posible cardiopatía subyacente, e identificar la localización del circuito de taquicardia ventricular. El estudio electrofisiológico invasivo suele ser crucial para determinar el mecanismo de la arritmia una vez inducida, y para guiar la ablación. El abordaje utilizado para la ablación de la taquicardia ventricular depende de varios factores, como la inducibilidad, la sostenibilidad y la tolerancia clínica a la taquicardia ventricular. Este artículo revisa también otras opciones terapéuticas para los pacientes con taquicardia ventricular asociada a la enfermedad coronaria, como el tratamiento farmacológico antiarrítmico, la ablación quirúrgica y las indicaciones actuales de desfibrilador automático implantable (AU)
Ventricular arrhythmias are important contributors to morbidity and mortality in patients with coronary artery disease. Ventricular fibrillation accounts for the majority of deaths occurring in the acute phase of ischemia, whereas sustained, monomorphic ventricular tachycardia due to reentry generated in the scar tissue develops most often in the setting of healed myocardial infarction, especially in patients with lower left ventricular ejection fraction. Despite determinant advances in population education and myocardial infarction management, the ventricular tachycardia risk in the overall population with coronary artery disease continues to be a major problem in clinical practice. The initial evaluation of a patient presenting with ventricular tachycardia requires a 12-lead electrocardiogram, which can be helpful to confirm the diagnosis, suggest the presence of potential underlying heart disease, and identify the location of the ventricular tachycardia circuit. An invasive electrophysiologic study is usually crucial to determine the mechanism of the arrhythmia once induced and to provide guidance for ablation. The approach for ventricular tachycardia ablation depends on several factors, including inducibility, sustainability, and clinical tolerance of ventricular tachycardia. The paper also reviews other therapeutic options for patients with ventricular tachycardia associated with coronary artery disease, including antiarrhythmic drug therapy, surgical ablation, and current implantable cardioverter-defibrillator indications (AU)
Assuntos
Humanos , Masculino , Feminino , Arritmias Cardíacas/epidemiologia , Taquicardia Ventricular/complicações , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/mortalidade , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Eletrofisiologia/métodos , Infarto do Miocárdio/terapia , Eletrocardiografia/métodos , Desfibriladores Implantáveis/tendências , Arritmias Cardíacas/mortalidade , Eletrofisiologia/normas , Eletrocardiografia/instrumentação , Taquicardia Ventricular/epidemiologia , Taquicardia Ventricular/fisiopatologia , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/patologia , Eletrofisiologia Cardíaca/instrumentação , Eletrofisiologia Cardíaca/métodos , Eletrofisiologia Cardíaca/organização & administraçãoRESUMO
El síndrome de Brugada, descrito por primera vez en 1992, se caracteriza por un patrón electrocardiográfico característico en precordiales derechas y la predisposición a presentar arritmias ventriculares y muerte súbita. El síndrome de Brugada se incluye entre las canalopatías, trastornos eléctricos primarios que característicamente no asocian cardiopatía estructural concomitante. En los últimos años, gracias a una intensa labor científica tanto básica como clínica, hemos podido identificar múltiples mutaciones causales, y asimismo comprender cuáles son los mecanismos implicados en la aparición del fenotipo característico y los determinantes del pronóstico clínico en los pacientes. Sin embargo, todavía persisten múltiples preguntas sin resolver que mantienen activa la investigación sobre el tema. Este artículo revisa nuestro conocimiento actual sobre el síndrome de Brugada y trata de recoger los principales estudios básicos y clínicos que han contribuido más significativamente a avanzar en nuestra comprensión de esta enfermedad (AU)
First described in 1992, Brugada syndrome is characterized by a specific electrocardiographic pattern in the right precordial leads and susceptibility to ventricular arrhythmias and sudden death. Brugada syndrome is included among the channelopathies, primary electrical disorders that, characteristically, are not associated with concomitant structural cardiac abnormalities. In recent years, substantial preclinical and clinical research has led to the identification of multiple causative mutations and to understanding of the mechanisms underlying the development of the characteristic phenotype and of the factors that determine clinical prognosis in patients. Nevertheless, there remain numerous unresolved questions which provide an impetus for ongoing active research into the condition. This article provides a summary of what is currently known about Brugada syndrome and an overview of the principal preclinical and clinical studies that have made the most significant contributions to our understanding of the condition (AU)
Assuntos
Humanos , Síndrome de Brugada/epidemiologia , Morte Súbita Cardíaca/epidemiologia , Canalopatias/epidemiologia , Síndrome de Brugada/genética , Canais Iônicos/genética , Fibrilação Ventricular/genéticaRESUMO
Fundamento y objetivo: La hiperglucemia en el momento del ingreso se ha asociado con mal pronóstico en pacientes con infarto de miocardio (IM). El beneficio clínico del tratamiento intensivo con insulina se ha evaluado en pacientes diabéticos ingresados en unidades de cuidados intensivos. Nuestro objetivo ha sido evaluar los efectos a corto plazo y la seguridad del control glucémico estricto en pacientes con IM e hiperglucemia sin diabetes conocida. Pacientes y método: Se aleatorizó a un total de 28 pacientes sin diabetes conocida que habían ingresado con IM e hiperglucemia a 2 grupos de tratamiento durante las primeras 48 h: a) grupo de tratamiento intensivo (n = 13), que recibió insulina intravenosa con el objetivo de mantener la glucemia entre 80 y 110 mg/dl, y b) grupo de tratamiento convencional (n = 15), que recibió insulina subcutánea sólo si la glucemia era mayor o igual a 160 mg/dl. La proteína C reactiva ultrasensible se determinó a las 48 h del ingreso y al alta. Se realizó un test de tolerancia oral a la glucosa al cabo de un mes. Resultados: Durante las primeras 48 h la glucemia fue significativamente menor en el grupo de tratamiento intensivo, con una media (desviación estándar) de 104 (8) mg/dl, frente a 153 (54) mg/dl en el grupo de tratamiento convencional (p = 0,002), sin episodios de hipoglucemias sintomáticas. A las 48 h la proteína C reactiva ultrasensible fue significativamente menor en el grupo de tratamiento intensivo que en el de tratamiento convencional media de 44,3 (35,7) y 20,3 (20,3) mg/ml, respectivamente (p = 0,04). Al cabo de 4 semanas sólo el 28,6% de los pacientes presentaba tolerancia normal a la glucosa. Conclusiones: El tratamiento intensivo con insulina con valores cercanos a la normoglucemia en pacientes no diabéticos con IM e hiperglucemia es factible, seguro y más efectivo que el tratamiento convencional. Además, atenúa la respuesta inflamatoria. El estudio confirma la alta prevalencia de alteraciones de la tolerancia a la glucosa no conocidas en pacientes con IM
Background and objective: Hyperglycemia at admission has been associated with bad prognosis in patients with myocardial infarction (MI). The clinical benefit of intensive insulin treatment has been evaluated in diabetic patients admitted to intensive care units. The aim of our study was to assess the short-term effects and the safety of strict glycemic control in subjects with MI and hyperglycemia without a previous history of diabetes. Patients and method: Twenty-eight non-previously diabetic patients admitted with MI and hyperglycemia were randomized to 2 treatment arms during the first 48 h: a) the intensive group (n = 13) received intravenous insulin with target glycemia levels of 80-110 mg/dl, and b) the conventional group (n = 15) received subcutaneous insulin only when glycemia was 160 mg/dl. High-sensitivity C-reactive protein was determined at 48 h and before discharge. An oral glucose tolerance test was performed after one month. Results: During the first 48 h, glycemia was significantly lower in the intensive than in the conventional group mean (standard deviation): 104 (8) and 153 (54) mg/dl, respectively (p = 0.002), without any clinically significanyt hypoglycemic episodes. At 48 h, high-sensitivity C-reactive protein was significantly lower in the intensive group 44.3 (35.7) and 20.3 (20.3) mg/ml, respectively (p = 0.04). After 4 weeks, only 28.6% of patients showed normal response in the oral glucose tolerance test. Conclusions: Intensive treatment with insulin to maintain near normoglycemia in non-diabetic patients with MI and hyperglycemia is feasible, safe and more effective than conventional treatment. In addition, it produces attenuation of inflammatory response. Our study also confirms the high prevalence of unknown abnormalities in glucose tolerance in subjects with MI
Assuntos
Humanos , Masculino , Feminino , Infarto do Miocárdio/tratamento farmacológico , Insulina/uso terapêutico , Infarto do Miocárdio/complicações , Hiperglicemia/complicações , Infarto do Miocárdio/diagnóstico , Hiperglicemia/diagnóstico , Estudos Prospectivos , Estudo de AvaliaçãoRESUMO
El intervencionismo percutáneo genera una rotura de la placa aterosclerótica y una denudación del endotelio que estimulan la agregación plaquetaria y la coagulación. Por ello, los agentes antitrombóticos son la base del tratamiento farmacológico coadyuvante al cateterismo intervencionista. Además de la aspirina, fármaco de beneficio indiscutible en la cardiopatía isquémica, el clopidogrel, administrado antes y después del cateterismo, ha demostrado su utilidad en la reducción de las tasas de trombosis tras la implantación de stent. A su vez, la introducción de los inhibidores de la glucoproteína IIb/IIIa ha mejorado los resultados de la revascularización percutánea, especialmente en los pacientes de mayor riesgo. Por su parte, los fármacos anticoagulantes son indispensables para evitar las complicaciones trombóticas agudas derivadas de las características invasivas del procedimiento. Las heparinas de bajo peso molecular, los inhibidores directos de la trombina (hirudina y derivados) y los inhibidores directos del factor X son las nuevas alternativas a la heparina no fraccionada clásica, que han demostrado reducir las complicaciones hemorrágicas sin requerir una monitorización tan exhaustiva. Finalmente, con objeto de reducir la reestenosis coronaria a medio plazo, se han ensayado fármacos con actividad antiproliferativa. Es el caso de la rapamicina oral
All percutaneous interventions disrupt atherosclerotic plaque and denude the endothelium. These processes stimulate both platelet aggregation and the coagulation cascade. Therefore, pharmacological treatment during percutaneous intervention is based on the use of antithrombotic agents. In addition to aspirin, whose benefit has been clearly demonstrated in all forms of ischemic heart disease, clopidogrel, given before and after cardiac catheterization, also reduces the rate of thrombosis after stent placement. Moreover, the introduction of glycoprotein IIb/IIIa inhibitors has improved the results of percutaneous revascularization, especially in high-risk patients. On the other hand, anticoagulants are essential for preventing the acute thrombotic complications that result from the invasive nature of the procedure. Low-molecular-weight heparins, direct thrombin inhibitors (e.g., hirudin and its derivatives), and recently developed pentasaccharides, which inhibit factor X, provide new alternatives to classical unfractionated heparin. These novel compounds lead to fewer hemorrhagic complications than unfractionated heparin and do not require such extensive monitoring. Finally, new antiproliferative agents, such as oral rapamycin, have been introduced to reduce the rate of coronary restenosis during follow-up