RESUMEN
Group 2 innate lymphoid cells (ILC2 cells) are important for type 2 immune responses and are activated by the epithelial cytokines interleukin 33 (IL-33), IL-25 and thymic stromal lymphopoietin (TSLP). Here we demonstrated that IL-1ß was a critical activator of ILC2 cells, inducing proliferation and cytokine production and regulating the expression of epithelial cytokine receptors. IL-1ß also governed ILC2 plasticity by inducing low expression of the transcription factor T-bet and the cytokine receptor chain IL-12Rß2, which enabled the conversion of these cells into an ILC1 phenotype in response to IL-12. This transition was marked by an atypical chromatin landscape characterized by the simultaneous transcriptional accessibility of the locus encoding interferon-γ (IFN-γ) and the loci encoding IL-5 and IL-13. Finally, IL-1ß potentiated ILC2 activation and plasticity in vivo, and IL-12 acted as the switch that determined an ILC2-versus-ILC1 response. Thus, we have identified a previously unknown role for IL-1ß in facilitating ILC2 maturation and plasticity.
Asunto(s)
Plasticidad de la Célula , Inmunidad Innata , Interleucina-12/metabolismo , Interleucina-1beta/metabolismo , Linfocitos/inmunología , Animales , Diferenciación Celular , Plasticidad de la Célula/inmunología , Células Cultivadas , Citocinas/metabolismo , Humanos , Interferón gamma/metabolismo , Interleucina-17/metabolismo , Interleucina-33/metabolismo , Ratones , Ratones SCID , Receptores de Interleucina-12/genética , Receptores de Interleucina-12/metabolismo , Transducción de Señal , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismo , Células TH1/inmunología , Balance Th1 - Th2 , Células Th2/inmunología , Linfopoyetina del Estroma TímicoRESUMEN
Innate lymphoid cells (ILCs) are critical mediators of mucosal immunity, and group 1 ILCs (ILC1 cells) and group 3 ILCs (ILC3 cells) have been shown to be functionally plastic. Here we found that group 2 ILCs (ILC2 cells) also exhibited phenotypic plasticity in response to infectious or noxious agents, characterized by substantially lower expression of the transcription factor GATA-3 and a concomitant switch to being ILC1 cells that produced interferon-γ (IFN-γ). Interleukin 12 (IL-12) and IL-18 regulated this conversion, and during viral infection, ILC2 cells clustered within inflamed areas and acquired an ILC1-like phenotype. Mechanistically, these ILC1 cells augmented virus-induced inflammation in a manner dependent on the transcription factor T-bet. Notably, IL-12 converted human ILC2 cells into ILC1 cells, and the frequency of ILC1 cells in patients with chronic obstructive pulmonary disease (COPD) correlated with disease severity and susceptibility to exacerbations. Thus, functional plasticity of ILC2 cells exacerbates anti-viral immunity, which may have adverse consequences in respiratory diseases such as COPD.
Asunto(s)
Infecciones por Haemophilus/inmunología , Haemophilus influenzae/inmunología , Virus de la Influenza A/inmunología , Pulmón/inmunología , Linfocitos/inmunología , Infecciones por Orthomyxoviridae/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Infecciones Estafilocócicas/inmunología , Staphylococcus aureus/inmunología , Células TH1/inmunología , Células Th2/inmunología , Anciano , Animales , Diferenciación Celular , Plasticidad de la Célula/inmunología , Células Cultivadas , Citocinas/metabolismo , Femenino , Factor de Transcripción GATA3/genética , Factor de Transcripción GATA3/metabolismo , Regulación de la Expresión Génica , Humanos , Inmunidad Innata , Mediadores de Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Fenotipo , Fumar/efectos adversos , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismoRESUMEN
INTRODUCTION: In hypertrophic cardiomyopathy (HCM), atrial fibrillation (AF) has historically been regarded to have a deleterious impact on clinical course, strongly associated with progressive heart failure (HF) symptoms. However, there is a paucity of information regarding the impact of AF on HCM employing validated quality of life (QoL) surveys. Therefore, we evaluated the impact of AF on QoL utilizing patient reported outcome measures (PROMs). METHODS: 218 consecutive HCM patients with or without AF at the Lahey HCM center in 2022 completed PROMs at their most recent visit evaluating HF (Kansas City Cardiomyopathy Questionnaire [KCCQ]) and AF symptoms (AF Effect on QoL [AFEQT]). RESULTS: Among the 218 patients, 50 (23%) had a history of AF and comprise the primary study cohort. AF was diagnosed at 55 ± 10 years of age, median of 5.5 years before PROM, with 66% of patients treated with a rhythm control strategy with antiarrhythmic drug and/or AF ablation. AFEQT indicated that 52% of patients experienced no or minimal AF-related disability, mild to moderate in 22%, and severe in 26%. There was no substantial difference in HCM phenotype in patients with no or minimal AF disability compared to those with severe disability. HF symptoms for most HCM patients with prior AF history was consistent with no or minimal (59%) or only mild (27%) disability as measured by KCCQ overall summary scores. In addition, with multivariate analysis, AF history was associated with less HF symptoms and improved QoL (OR 0.4, p = 0.02). CONCLUSION: In contrast to prior perceptions, HCM patients with prior AF history were less likely to incur HF symptoms impairing QoL compared to HCM patients without AF. After treatment, prior history of AF did not substantially impact current QoL. These data provide a realistic appraisal for the impact that AF has on HCM patients and also offers a measure of reassurance for this patient subgroup.
Asunto(s)
Fibrilación Atrial , Cardiomiopatía Hipertrófica , Enfermedades Vasculares , Humanos , Calidad de Vida , Antiarrítmicos/uso terapéutico , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/terapia , Enfermedades Vasculares/complicacionesRESUMEN
Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease and is presumed to be central to the altered responsiveness to recurrent infection in these patients. We examined the effects of smoke priming underlying the exacerbated response to viral infection in mice. Lack of interleukin-33 (IL-33) signaling conferred complete protection during exacerbation and prevented enhanced inflammation and exaggerated weight loss. Mechanistically, smoke was required to upregulate epithelial-derived IL-33 and simultaneously alter the distribution of the IL-33 receptor ST2. Specifically, smoke decreased ST2 expression on group 2 innate lymphoid cells (ILC2s) while elevating ST2 expression on macrophages and natural killer (NK) cells, thus altering IL-33 responsiveness within the lung. Consequently, upon infection and release, increased local IL-33 significantly amplified type I proinflammatory responses via synergistic modulation of macrophage and NK cell function. Therefore, in COPD, smoke alters the lung microenvironment to facilitate an alternative IL-33-dependent exaggerated proinflammatory response to infection, exacerbating disease.
Asunto(s)
Inmunidad Innata/efectos de los fármacos , Interleucinas/inmunología , Infecciones por Orthomyxoviridae/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Receptores de Interleucina/inmunología , Humo/efectos adversos , Animales , Femenino , Regulación de la Expresión Génica , Humanos , Virus de la Influenza A/inmunología , Proteína 1 Similar al Receptor de Interleucina-1 , Interleucina-33 , Interleucinas/deficiencia , Interleucinas/genética , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/patología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Linfocitos/patología , Macrófagos/inmunología , Macrófagos/patología , Ratones Transgénicos , Infecciones por Orthomyxoviridae/etiología , Infecciones por Orthomyxoviridae/genética , Infecciones por Orthomyxoviridae/patología , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/patología , Receptores de Interleucina/deficiencia , Receptores de Interleucina/genética , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/patología , Transducción de Señal , Nicotiana/química , Pérdida de PesoRESUMEN
Interferon-γ (IFN-γ) promotes a population of T-bet(+) CXCR3(+) regulatory T (Treg) cells that limit T helper 1 (Th1) cell-mediated pathology. Our studies demonstrate that interleukin-27 (IL-27) also promoted expression of T-bet and CXCR3 in Treg cells. During infection with Toxoplasma gondii, a similar population emerged that limited T cell responses and was dependent on IFN-γ in the periphery but on IL-27 at mucosal sites. Transfer of Treg cells ameliorated the infection-induced pathology observed in Il27(-/-) mice, and this was dependent on their ability to produce IL-10. Microarray analysis revealed that Treg cells exposed to either IFN-γ or IL-27 have distinct transcriptional profiles. Thus, IFN-γ and IL-27 have different roles in Treg cell biology and IL-27 is a key cytokine that promotes the development of Treg cells specialized to control Th1 cell-mediated immunity at local sites of inflammation.
Asunto(s)
Interferón gamma/farmacología , Interleucina-17/farmacología , Salmonelosis Animal/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Toxoplasmosis Animal/inmunología , Animales , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/inmunología , Células Cultivadas , Femenino , Citometría de Flujo , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/inmunología , Factores de Transcripción Forkhead/metabolismo , Perfilación de la Expresión Génica , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-17/genética , Interleucina-17/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Noqueados , Ratones Transgénicos , Análisis de Secuencia por Matrices de Oligonucleótidos , Receptores CXCR3/genética , Receptores CXCR3/inmunología , Receptores CXCR3/metabolismo , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/inmunología , Factor de Transcripción STAT1/metabolismo , Salmonelosis Animal/microbiología , Salmonelosis Animal/patología , Salmonella typhimurium/inmunología , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/inmunología , Proteínas de Dominio T Box/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Toxoplasma/inmunología , Toxoplasmosis Animal/parasitología , Toxoplasmosis Animal/patologíaRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by frequent exacerbation phenotypes independent of disease stage. Increasing evidence shows that the microbiota plays a role in disease progression and severity, but long-term and international multicenter assessment of the variations in viral and bacterial communities as drivers of exacerbations are lacking. METHODS: Two-hundred severe COPD patients from Europe and North America were followed longitudinally for 3 years. We performed nucleic acid detection for 20 respiratory viruses and 16S ribosomal RNA gene sequencing to evaluate the bacterial microbiota in 1179 sputum samples collected at stable, acute exacerbation and follow-up visits. RESULTS: Similar viral and bacterial taxa were found in patients from the USA compared to Bulgaria and Czech Republic but their microbiome diversity was significantly different (P < 0.001) and did not impact exacerbation rates. Virus infection was strongly associated with exacerbation events (P < 5E-20). Human rhinovirus (13.1%), coronavirus (5.1%) and influenza virus (3.6%) constitute the top viral pathogens in triggering exacerbation. Moraxella and Haemophilus were 5-fold and 1.6-fold more likely to be the dominating microbiota during an exacerbation event. Presence of Proteobacteria such as Pseudomonas or Staphylococcus amongst others, were associated with exacerbation events (OR > 0.17; P < 0.02) but more strongly associated with exacerbation frequency (OR > 0.39; P < 4E-10), as confirmed by longitudinal variations and biotyping of the bacterial microbiota, and suggesting a role of the microbiota in sensitizing the lung. CONCLUSIONS: This study highlights bacterial taxa in lung sensitization and viral triggers in COPD exacerbations. It provides a global overview of the diverse targets for drug development and explores new microbiome analysis methods to guide future patient management applications.
Asunto(s)
Bacterias/aislamiento & purificación , Pulmón/microbiología , Pulmón/virología , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Enfermedad Pulmonar Obstructiva Crónica/virología , Virus/aislamiento & purificación , Anciano , Anciano de 80 o más Años , Bacterias/genética , Carga Bacteriana , Progresión de la Enfermedad , Europa (Continente)/epidemiología , Femenino , Humanos , Incidencia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Esputo/microbiología , Esputo/virología , Factores de Tiempo , Estados Unidos/epidemiología , Carga Viral , Virus/genéticaRESUMEN
Interleukin 10 (IL-10) has a prominent function in regulating the balance between protective and pathological T cell responses. Consistent with that activity, many sources of this cytokine are found in vivo, including from myeloid cells and a variety of T cell subsets. However, although there are many pathways that regulate innate production of IL-10, the factors that govern its synthesis by the adaptive response are poorly understood. Here we report that IL-27 and IL-6 induced T helper type 1 and type 2 cells, as well as T helper cells that produce IL-17, to secrete IL-10. This effect was dependent on the transcription factors STAT1 and STAT3 for IL-27 and on STAT3 for IL-6. Our studies identify a previously unknown pathway that allows the immune system to temper inflammatory responses.
Asunto(s)
Interleucina-10/biosíntesis , Interleucina-17/fisiología , Interleucina-6/fisiología , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT3/fisiología , Linfocitos T/inmunología , Animales , Humanos , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Factor de Transcripción STAT3/metabolismo , Linfocitos T Colaboradores-InductoresRESUMEN
T follicular cells help B cells generate high-affinity antibodies. Two papers in this issue of Immunity (Nurieva et al., 2008, and Vogelzang et al., 2008) have identified a role for interleukin-21 in the development of these specialized cells and highlight questions about how this dedicated population is generated.
Asunto(s)
Linfocitos B/inmunología , Interleucinas/inmunología , Cooperación Linfocítica/inmunología , Subgrupos de Linfocitos T/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Animales , Centro Germinal/citología , Centro Germinal/inmunología , Activación de Linfocitos/inmunologíaRESUMEN
BACKGROUND: The relationship of life-threatening ventricular arrhythmias to specific patterns of adverse LV remodeling has not been reported. We examined the relationship of ventricular tachycardia and/or fibrillation (VT/VF) to the pattern of left ventricular (LV) structural remodeling and to the degree of LV dysfunction in patients with a low ejection fraction (EF). METHODS AND RESULTS: Data from 127 patients with a low EF (≤0.45) and an implantable cardioverter-defibrillator (ICD) were examined and VT/VF identified by means of ICD device interrogation. Echocardiographic data were used to define LV structural remodeling (eccentric hypertrophy, concentric remodeling/hypertrophy, and normal geometry). VT/VF occurred in 26% of the 127 patients. VT/VF was more common in the 60 patients with LV hypertrophy versus the 67 with normal LV mass (40% vs 13%; P = .001) and in the 61 patients with LV enlargement versus the 66 with a normal chamber size (34% vs 18%; P = .04). When LV chamber size, wall mass, and geometry were assessed in a combinatorial fashion, a Kaplan-Meier analysis indicated that the occurrence of VT/VF was highest in the patients with eccentric hypertrophy (43%), intermediate in those with concentric remodeling/hypertrophy (30%), and lowest (12%) in those with normal geometry (all P < .02). The EFs were similar (P = ns) in these 3 groups of distinctly different patterns of remodeling. CONCLUSIONS: Life-threatening ventricular arrhythmias in patients with a low EF are related to the pattern of LV remodeling, not the degree of LV dysfunction. Risk stratification of such patients might be improved by a consideration of the pattern of LV remodeling.
Asunto(s)
Volumen Sistólico/fisiología , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatología , Remodelación Ventricular/fisiología , Anciano , Anciano de 80 o más Años , Desfibriladores Implantables/tendencias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Taquicardia Ventricular/terapiaRESUMEN
IL-6 and IL-27 are closely related cytokines that play critical but distinct roles during infection with Toxoplasma gondii. Thus, IL-6 is required for the development of protective immunity to this pathogen, whereas IL-27 is required to limit infection-induced pathology. Paradoxically, these factors both signal through gp130, but little is known about how the signals downstream of gp130 are integrated to coordinate the immune response to infection. To better understand these events, gp130 Y757F mice that have a mutation in gp130 at the binding site for suppressor of cytokine signaling 3, a critical negative regulator of gp130 signaling, were infected with T. gondii. These mutant mice were acutely susceptible to this challenge, characterized by an early defect in the production of IL-12 and IFN-γ and increased parasite burdens. Consistent with the reduced IL-12 levels, IL-6, but not other gp130 cytokines, was a potent antagonist of IL-12 production by gp130 Y757F macrophages and dendritic cells in vitro. Moreover, in gp130 Y757F mice, blocking IL-6 in vivo, or administration of rIL-12, during infection restored IFN-γ production and protective immunity. Collectively, these studies highlight that a failure to abbreviate IL-6-mediated gp130 signaling results in a profound anti-inflammatory signal that blocks the generation of protective immunity to T. gondii.
Asunto(s)
Receptor gp130 de Citocinas/antagonistas & inhibidores , Mediadores de Inflamación/antagonistas & inhibidores , Interleucina-6/fisiología , Transducción de Señal/inmunología , Toxoplasma/crecimiento & desarrollo , Toxoplasma/inmunología , Animales , Células Cultivadas , Receptor gp130 de Citocinas/fisiología , Predisposición Genética a la Enfermedad , Inmunidad Innata/genética , Mediadores de Inflamación/fisiología , Interleucina-6/antagonistas & inhibidores , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Noqueados , Transducción de Señal/genética , Toxoplasma/patogenicidad , Toxoplasmosis/genética , Toxoplasmosis/inmunología , Toxoplasmosis/parasitologíaRESUMEN
Follicular helper T (T(FH)) cells are critical for germinal center (GC) formation. The processes that drive their generation and effector potential remain unclear. In this study, we define requirements for MHC class II APCs in murine T(FH) cell formation by either transiently ablating or restricting Ag presentation to dendritic cells (DCs). We find that cognate interactions with DCs are necessary and sufficient to prime CD4(+) T cells toward a CXCR5(+)ICOS(+)Bcl6(+) T(FH) cell intermediate. However, in the absence of additional APCs, these T(FH) cells fail to produce IL-21. Furthermore, in vitro priming of naive T cells by B cells engenders optimal production of IL-21, which induces a GC B cell transcriptional profile. These results support a multistep model for effector T(FH) cell priming and GC initiation, in which DCs are necessary and sufficient to induce a T(FH) cell intermediate that requires additional interactions with distinct APCs for full effector function.
Asunto(s)
Presentación de Antígeno/inmunología , Comunicación Celular/inmunología , Diferenciación Celular/inmunología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Activación de Linfocitos/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/patología , Traslado Adoptivo , Animales , Linfocitos B/inmunología , Comunicación Celular/genética , Diferenciación Celular/genética , Inmunofenotipificación , Activación de Linfocitos/genética , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/patología , Subgrupos de Linfocitos T/trasplante , Linfocitos T Colaboradores-Inductores/clasificaciónAsunto(s)
Aleteo Atrial/microbiología , Bloqueo Atrioventricular/microbiología , Bradicardia/microbiología , Enfermedad de Lyme/complicaciones , Enfermedad de Lyme/diagnóstico , Anciano , Antibacterianos/uso terapéutico , Aleteo Atrial/fisiopatología , Aleteo Atrial/cirugía , Bloqueo Atrioventricular/fisiopatología , Bradicardia/fisiopatología , Ceftriaxona/uso terapéutico , Diagnóstico Diferencial , Doxiciclina/uso terapéutico , Ecocardiografía , Electrocardiografía , Prueba de Esfuerzo , Femenino , Humanos , Enfermedad de Lyme/tratamiento farmacológicoRESUMEN
B cell responses are required for resistance to Toxoplasma gondii; however, the events that lead to production of class-switched antibodies during T. gondii infection have not been defined. Indeed, mice challenged with the parasite exhibited an expansion of T follicular helper cells and germinal center B cells in the spleen. Unexpectedly, this was not associated with germinal center formation and was instead accompanied by profound changes in splenic organization. This phenomenon was transient and was correlated with a decrease in expression of effector proteins that contribute to splenic organization, including lymphotoxins α and ß. The importance of lymphotoxin was confirmed, as the use of a lymphotoxin ß receptor agonist results in partial restoration of splenic structure. Splenectomized mice were used to test the splenic contribution to the antibody response during T. gondii infection. Analysis of splenectomized mice revealed delayed kinetics in the production of parasite-specific antibody, but the mice did eventually develop normal levels of parasite-specific antibody. Together, these studies provide a better understanding of how infection with T. gondii impacts the customized structures required for the optimal humoral responses to the parasite and the role of lymphotoxin in these events.
Asunto(s)
Linfotoxina-alfa/metabolismo , Bazo/patología , Bazo/parasitología , Toxoplasma , Toxoplasmosis Animal/metabolismo , Toxoplasmosis Animal/patología , Animales , Anticuerpos Antiprotozoarios/sangre , Regulación de la Expresión Génica/inmunología , Regulación de la Expresión Génica/fisiología , Inmunoglobulina G/sangre , Inmunoglobulina G/clasificación , Inmunoglobulina M/sangre , Linfotoxina-alfa/genética , Ratones , Ratones Endogámicos C57BL , Transducción de Señal , Organismos Libres de Patógenos Específicos , Bazo/citologíaRESUMEN
Previous studies have implicated T cell production of IL-17 in resistance to Toxoplasma gondii as well as the development of immune-mediated pathology during this infection. Analysis of C57BL/6 and C57BL/6 RAG(-/-) mice challenged with T. gondii-identified NK cells as a major innate source of IL-17. The ability of soluble Toxoplasma Ag to stimulate NK cells to produce IL-17 was dependent on the presence of accessory cells and the production of IL-6, IL-23, and TGF-beta. In contrast, these events were inhibited by IL-2, IL-15, and IL-27. Given that IL-6 was one of the most potent enhancers of NK cell production of IL-17, further studies revealed that only a subset of NK cells expressed both chains of the IL-6R, IL-6 upregulated expression of the Th17-associated transcription factor RORgammat, and that IL-6(-/-) mice challenged with T. gondii had a major defect in NK cell production of IL-17. Together, these data indicate that many of the same cytokines that regulate Th17 cells are part of a conserved pathway that also control innate production of IL-17 and identify a major role for IL-6 in the regulation of NK cell responses.
Asunto(s)
Interleucina-17/biosíntesis , Interleucina-6/fisiología , Células Asesinas Naturales/inmunología , Toxoplasmosis Animal/inmunología , Enfermedad Aguda , Animales , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Células Cultivadas , Proteínas de Homeodominio/genética , Inmunidad Innata/genética , Células Asesinas Naturales/metabolismo , Células Asesinas Naturales/parasitología , Células Asesinas Naturales/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Toxoplasma/inmunología , Toxoplasmosis Animal/metabolismo , Toxoplasmosis Animal/patologíaRESUMEN
We present the case of a 57-year-old man with a primary prevention internal cardioverter-defibrillator for severe nonischemic cardiomyopathy. At the time of elective replacement indicator, systolic function had fully recovered, and his generator was not changed. Nearly 5 years post-elective replacement indicator he received appropriate internal cardioverter-defibrillator therapies during a myocardial infarction. (Level of Difficulty: Intermediate.).
RESUMEN
BACKGROUND: The limited effectiveness of endocardial catheter ablation (CA) for persistent and long-standing persistent atrial fibrillation (AF) treatment led to the development of a minimally invasive epicardial/endocardial ablation approach (Hybrid Convergent) to achieve a more comprehensive lesion set with durable transmural lesions. The multicenter randomized controlled CONVERGE trial (Convergence of Epicardial and Endocardial Ablation for the Treatment of Symptomatic Persistent AF) evaluated the safety of Hybrid Convergent and compared its effectiveness to CA for persistent and long-standing persistent AF treatment. METHODS: One-hundred fifty-three patients were randomized 2:1 to Hybrid Convergent versus CA. Primary effectiveness was freedom from AF/atrial flutter/atrial tachycardia absent new/increased dosage of previously failed/intolerant class I/III antiarrhythmic drugs through 12 months. Primary safety was major adverse events through 30 days. CONVERGE permitted left atrium size up to 6 cm and imposed no limits on AF duration, making it the only ablation trial to substantially include long-standing persistent-AF, that is, 42% patients with long-standing persistent-AF. RESULTS: Of 149 evaluable patients at 12 months, primary effectiveness was achieved in 67.7% (67/99) patients with Hybrid Convergent and 50.0% (25/50) with CA (P=0.036) on/off previously failed antiarrhythmic drugs and in 53.5% (53/99) versus 32.0% (16/50; P=0.0128) respectively off antiarrhythmic drugs. At 18 months using 7-day Holter, 74.0% (53/72) Hybrid Convergent and 55% (23/42) CA patients experienced ≥90% AF burden reduction. A total of 2.9% (3/102) patients had primary safety events within 7 days, and 4.9% (5/102) between 8 and 30 days postprocedure. No deaths, cardiac perforations, or atrioesophageal fistulas occurred. All but one primary safety event resolved. CONCLUSIONS: The Hybrid Convergent procedure has superior effectiveness compared to the CA for the treatment of persistent and long-standing persistent atrial fibrillation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01984346.
Asunto(s)
Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Venas Pulmonares/cirugía , Anciano , Antiarrítmicos/uso terapéutico , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Ablación por Catéter/efectos adversos , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Venas Pulmonares/fisiopatología , Recurrencia , Factores de Tiempo , Resultado del Tratamiento , Reino Unido , Estados UnidosRESUMEN
T-wave oversensing represents a common cause of inappropriate shocks in patients with implanted cardiac defibrillators. This case report demonstrates a strategy of device programming using V-V pace delay (sequential rather than simultaneous biventricular pacing) to eliminate T-wave oversensing without decreasing sensitivity to detect true tachyarrhythmia.