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BACKGROUND: A lower cut-off of the oesophageal temperature (ET) during catheter ablation of atrial fibrillation (AF) should be safer, but its durability may become in question. We evaluated an ET cut-off of 38°C with an output of 25W on the posterior wall. METHODS: In 636 consecutive patients (age: 60±10years, male: 542, paroxysmal AF: 405, CHADS2 score: 0.7±0.9), an ET probe was utilised in 303 patients (259 pulmonary vein isolations [PVIs] and 44 simultaneous isolations of the posterior wall and all PVs box isolations [BOXIs]). When the ET increased to >38°C, the radiofrequency delivery was switched off and the ablation point was tagged as an "EsoTag" by the CARTO™ system (Biosense Webster, Irvine, CA, USA). We analysed the characteristics of the ablation lesions at the EsoTags with respect to the dormant conduction, gaps in the redo-session, and ablation outcome. RESULTS: EsoTags were identified in 94.6% of the left PVIs and all BOXIs, and dormant conduction at the EsoTags was identified in 12.0% and 6.8%, respectively. In 10,796 ablation points, the ablation at the EsoTags that were associated with dormant conduction had a significantly shorter duration, smaller force-time integral, and smaller Δimpedance. The duration of an ET of >38°C was significantly and positively correlated with the body mass index and negatively with the left atrial appendage flow velocity. During the redo-sessions in a 10.5±6.0months of follow-up (PVI: 14.7%, BOXI: 11.4%), reconnections at the EsoTags with dormant conduction were observed only in two patients after the PVI. The AF survival rate did not significantly differ in the presence of dormant conduction at the EsoTags (83.1% vs. 75.0%, p=0.696). There were no patients hospitalised for gastroparesis. CONCLUSIONS: Atrial fibrillation ablation utilising an oesophageal temperature cut-off of 38°C might be safe and durable.
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Fibrilación Atrial , Temperatura Corporal , Ablación por Catéter , Esófago/fisiopatología , Anciano , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/cirugía , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Differences in the methodologies for evaluating atrial fibrillation (AF) ablation outcomes should be evaluated. In the present study, we compared the AF ablation outcomes among periodic clinic electrocardiography (ECG), 24-h Holter ECG, and telemonitoring ECG to evaluate the differences among these methods. In addition, we evaluated the AF-free survival rate for each method with different durations of the blanking period. A total of 30 AF patients were followed up for 6 months after initial catheter ablation, with clinic ECG on every clinic visit, monthly 24-h Holter ECG, and telemonitoring ECG twice daily and upon symptoms. AF relapse was defined as AF or atrial tachycardia detected with any of the methods. Two patients dropped out of the study, and 28 patients were followed up for 8.8 ± 2.7 months. Patients underwent 3.6 ± 0.8 clinic ECG, 5.1 ± 0.8 Holter ECG, and 273 ± 68 telemonitoring ECG examinations. During the first, second, third, fourth, fifth, and sixth months of follow-up, Holter ECG detected relapses in 11.1, 8.3, 11.5, 15.4, 4.2, and 4.8 % of patients and telemonitoring ECG detected relapses in 32.1, 25.0, 25.0, 17.9, 28.6, and 17.9 % of patients, respectively. When no duration was set for the blanking period, the AF-free survival rate was significantly lower with telemonitoring ECG (46.4 %) than with Holter ECG (78.6 %, P = 0.013) or clinic ECG (85.7 %, P = 0.002). In addition, when the duration of the blanking period was set to 3 months, the AF-free survival rate was significantly lower with telemonitoring ECG than with clinic ECG (92.9 vs. 71.4 %, P = 0.041). The AF ablation outcomes with twice-daily telemonitoring ECG might differ from those with clinic ECG when the duration of the blanking period is 0-3 months. A follow-up based solely on clinic ECG might underestimate AF recurrence.
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Fibrilación Atrial/cirugía , Ablación por Catéter/efectos adversos , Electrocardiografía Ambulatoria/métodos , Anciano , Femenino , Estudios de Seguimiento , Humanos , Japón , Masculino , Persona de Mediana Edad , Venas Pulmonares/cirugía , Recurrencia , Tasa de Supervivencia , Telemedicina , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIMS: With the new era of multi-tip radiofrequency or balloon ablation catheters replacing the point-to-point ablation strategy, we aimed to determine the feasibility of a ring-laser catheter ablation technology to electrically isolate the superior vena cava (SVC) by exploring the advantages of the limitless catheter tip size possibly with the photodynamic therapy (PDT)-mediated ablation. METHODS AND RESULTS: We developed a first-generation prototype of a circular-laser-mapping catheter by fitting a 7 cm plastic optical fibre onto a circular variable-loop Lasso™ mapping catheter. Following SVC venography, both the laser catheter and another ring catheter for monitoring the SVC potentials were placed at the SVC. After the systemic infusion of a photosensitizer (talaporfin sodium), we initiated the irradiation with an output of 1 W in three canines and 0.3 W in four. The creation of electrical isolation as well as occurrence of phrenic nerve injury, sinus node injury, and SVC stenosis were evaluated before, immediately after, and 1 month after the procedure. A PDT-mediated SVC isolation was successfully performed in all seven canines. The isolation was completed with a laser irradiation of 70.4 ± 71.4 J/cm under 30.9 ± 5.0 µg/mL of a photosensitizer without any sinus node injury, phrenic nerve palsy, or SVC stenosis in both the acute and chronic evaluations. The minimum isolation time of 270 s was not correlated with the laser input power or the photosensitizer concentration. CONCLUSION: The electrical SVC isolation was successfully and instantly achieved using the PDT laser-ring catheter without any complications.
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Ablación por Catéter/métodos , Fotoquimioterapia/métodos , Vena Cava Superior/cirugía , Potenciales de Acción , Animales , Ablación por Catéter/efectos adversos , Ablación por Catéter/instrumentación , Catéteres , Perros , Electrocardiografía , Diseño de Equipo , Estudios de Factibilidad , Rayos Láser , Modelos Animales , Flebografía , Fotoquimioterapia/efectos adversos , Fotoquimioterapia/instrumentación , Fármacos Fotosensibilizantes/administración & dosificación , Porfirinas/administración & dosificación , Factores de Tiempo , Vena Cava Superior/diagnóstico por imagenRESUMEN
The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cell cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle.
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Corazón Fetal/citología , Miocardio/citología , Miocitos Cardíacos/citología , Miocitos Cardíacos/fisiología , Animales , Puntos de Control del Ciclo Celular/genética , Movimiento Celular , Proliferación Celular , Femenino , Corazón Fetal/embriología , Regulación del Desarrollo de la Expresión Génica , Genes Reporteros , Corazón/crecimiento & desarrollo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Miocardio/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , EmbarazoRESUMEN
BACKGROUND: Catheter ablation (CA) benefits atrial fibrillation (AF) patients with heart failure (HF). Brain natriuretic peptide (BNP), a marker of left-ventricular pressure load, may serve as a potential surrogate for predicting quality of life (QOL) in a broader range of patients. METHODS: Within the multicenter KiCS-AF registry, 491 AF patients underwent CA without clinical HF (e.g., documented history of HF, left ventricular ejection fraction ≤ 40%, or BNP levels ≥ 100 pg/mL). Participants, aged 61 ± 10 years, were categorized by baseline BNP quartiles. Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaire assessments were assessed at baseline and 1 year. RESULTS: A lower baseline BNP correlated with reduced AFEQT scores. Post CA, all groups showed significant AFEQT score improvements. The lower-BNP group displayed notable enhancements (18.2 ± 1.2, 15.0 ± 1.1, 12.6 ± 1.2, 13.6 ± 1.2, p < 0.005), especially in symptom and treatment concern areas. Even those with normal BNP levels (≤18.4 pg/mL) exhibited significant QOL improvements. Comparing paroxysmal AF (PAF) and non-PAF groups, the PAF group, especially with higher BNP levels, showed greater AFEQT score improvements. CONCLUSIONS: This study establishes BNP as a predictive marker for QOL enhancement in non-HF patients undergoing CA for AF. BNP levels represent AF stages, with individuals in earlier stages, especially within normal BNP levels, experiencing greater QOL improvements.
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Failure of the right ventricle plays a critical role in any type of heart failure. However, the mechanism remains unclear, and there is no specific therapy. Here, we show that the right ventricle predominantly expresses alternative complement pathway-related genes, including Cfd and C3aR1. Complement 3 (C3)-knockout attenuates right ventricular dysfunction and fibrosis in a mouse model of right ventricular failure. C3a is produced from C3 by the C3 convertase complex, which includes the essential component complement factor D (Cfd). Cfd-knockout mice also show attenuation of right ventricular failure. Moreover, the plasma concentration of CFD correlates with the severity of right ventricular failure in patients with chronic right ventricular failure. A C3a receptor (C3aR) antagonist dramatically improves right ventricular dysfunction in mice. In summary, we demonstrate the crucial role of the C3-Cfd-C3aR axis in right ventricular failure and highlight potential therapeutic targets for right ventricular failure.
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Insuficiencia Cardíaca , Disfunción Ventricular Derecha , Animales , Complemento C3/genética , Convertasas de Complemento C3-C5 , Factor D del Complemento , Insuficiencia Cardíaca/genética , Ratones , Ratones Noqueados , Remodelación VentricularRESUMEN
OBJECTIVES: This study sought to isolate arrhythmogenic Marshall bundles (MBs) by radiofrequency (RF) catheter ablation. BACKGROUND: The vein of Marshall (VOM) is surrounded by a muscular bundle called the MB. The MB is 1 of the arrhythmogenic sources of atrial fibrillation (AF) and electrically connects to either the left atrial (LA) myocardium or coronary sinus (CS) musculature. By eliminating such electric connections using RF catheter ablation, the MB might be electrically isolated. METHODS: This retrospective study included 20 patients (64 ± 10 years old, 5 women) who underwent an MB isolation for nonparoxysmal AF. After pulmonary vein isolation, we performed venography of the VOM and inserted a 2-F electrode catheter into the VOM. RF applications were delivered to eliminate the MB electrograms from both the LA and CS when the MB was considered arrhythmogenic. RESULTS: MB isolation was achieved in 14 patients (70%). Of them, complete or partial MB isolation was accomplished in 7 patients (35%) each. The average number of RF applications in the LA (35 W, 30 s) and CS (25 W, 30 s) was 15 ± 14 and 4 ± 3, respectively. No severe adverse events were observed. During a follow-up of 23 ± 11 months, 18 patients (90%) maintained sinus rhythm. CONCLUSIONS: RF applications targeting recordings from an electrode catheter in the VOM were feasible, and the MB could be electrically isolated. Elimination of the MB potentials would be a clear endpoint for patients with an arrhythmogenic MB.
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Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Fibrilación Atrial/cirugía , Niño , Femenino , Atrios Cardíacos , Humanos , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/cirugía , Estudios RetrospectivosRESUMEN
OBJECTIVES: This randomized study compared uninterrupted rivaroxaban therapy with warfarin therapy as prophylaxis against catheter ablation (CA)-induced asymptomatic cerebral infarction (ACI) and identified the risk factors of rivaroxaban. BACKGROUND: The reported incidence of ACI during CA for atrial fibrillation (AF) remains at 10% to 30%, and periprocedural oral anticoagulation could affect this incidence. METHODS: Patients with nonvalvular AF undergoing radiofrequency CA were randomly assigned to receive either uninterrupted rivaroxaban or warfarin as periprocedural anticoagulation therapy. CA was performed after at least 1 month of adequate anticoagulation. Cerebral magnetic resonance imaging (MRI) was performed within 2 weeks before and 1 day after CA to detect ACI. RESULTS: A total 132 patients were enrolled; 127 (median: 60.0 years of age; 83.5% males; 64.6% incidence of paroxysmal AF) complied with the study protocol and were analyzed; 64 patients received rivaroxaban, and 63 patients received warfarin. The rates of CA-induced ACI in the rivaroxaban group (15.6% [10 of 64 patients]) were similar to those in the warfarin group (15.9% [10 of 63 patients]; p = 1.000). No thromboembolic events developed; no differences in major or nonmajor bleeding rates were observed between the 2 drug groups (3.1% vs. 1.6%, respectively, or 18.8% vs. 19.0%, respectively). Multiple regression analysis indicated that the presence of deep and subcortical white matter hyperintensity (p = 0.002; odds ratio [OR]: 5.323) and the frequency of cardioversions (p = 0.016; OR: 1.250) were associated with the incidence of ACI. CONCLUSIONS: No notable differences were found between the incidence of CA-induced ACI in the rivaroxaban group and that in the warfarin group in this randomized study.
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Anticoagulantes/uso terapéutico , Fibrilación Atrial/cirugía , Ablación por Catéter/efectos adversos , Infarto Cerebral , Rivaroxabán/uso terapéutico , Warfarina/uso terapéutico , Anciano , Enfermedades Asintomáticas/epidemiología , Encéfalo/diagnóstico por imagen , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/tratamiento farmacológico , Infarto Cerebral/epidemiología , Infarto Cerebral/etiología , Femenino , Humanos , Incidencia , Complicaciones Intraoperatorias/epidemiología , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
INTRODUCTION: We aimed to study the prevalence and types of sleep apnea (SA) as well as their clinical characteristics in atrial fibrillation (AF) ablation candidates in Japan. METHODS: Before catheter ablation, 197 consecutive AF patients (age: 60⯱â¯9â¯years, body mass index; 25.0⯱â¯3.0) were evaluated with portable polygraphy. We compared the clinical characteristics, according to the severity of SA as well as its types, as defined by the presence of obstruction and the mixed vs. central apnea indices. RESULTS: The mean apnea-hypopnea index (AHI) was 17.7⯱â¯11.9, with 135 AF patients having an AHI ≥10 (68.5%). Patients with an AHI ≥10 had a significantly higher body mass index, plasma brain natriuretic peptide (BNP) level, prevalence of hypertension, and larger left atrial size. Among patients with an AHI ≥10, the incidence of obstructive-dominant SA was 60.9% and that of central-dominant SA was 7.6%. The prevalence of hypertension was significantly higher in obstructive-dominant SA patients (obstructive vs. central: 48.3% vs. 20.0%, Pâ¯=â¯0.038). The obstructive apnea index correlated with plasma BNP level and age, but the central and mixed apnea indices did not. CONCLUSIONS: The prevalence of SA was common in AF ablation candidates, even without an obesity epidemic, and the SA type was predominantly obstructive. Portable polygraphy was useful for detecting undiagnosed SA patients in AF ablation candidates.
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Fibrilación Atrial/epidemiología , Ablación por Catéter/tendencias , Apnea Central del Sueño/epidemiología , Apnea Obstructiva del Sueño/epidemiología , Anciano , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Estudios Transversales , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Apnea Central del Sueño/fisiopatología , Apnea Central del Sueño/cirugía , Apnea Obstructiva del Sueño/fisiopatología , Apnea Obstructiva del Sueño/cirugíaRESUMEN
BACKGROUND: We aimed to clarify the cost-effectiveness of an expensive combination therapy for atrial fibrillation (AF) using both catheter ablation and dabigatran compared with warfarin at each CHADS2 score for patients in Japan. METHODS: A Markov model was constructed to analyze costs and quality-adjusted life years associated with AF therapeutic options with a time horizon of 10 years. The target population was 60-year-old patients with paroxysmal AF. The indication for anticoagulation was determined according to the Japanese guideline. Anticoagulation-related data were derived from the RE-LY study and the AF recurrence rate was set at 2.7% per month during the first 12 months and at 0.40% per month afterwards. Stroke risk was determined according to AF recurrence, anticoagulation, and CHADS2 score. The risks for stroke recurrence and stroke death were also considered. Costs were calculated from the healthcare payer's perspective, and only direct medical costs were included. RESULTS: Warfarin was the most preferred option for patients with a CHADS2 score of 0 from a health economics aspect. Ablation under warfarin was preferred for a CHADS2 score of 1-3, while ablation under dabigatran was preferred for a CHADS2 score ≥4. The quality of life score for AF had the largest impact on the incremental cost-effectiveness ratios in the analysis between the anticoagulation arm and the anticoagulation+ablation arm for a CHADS2 score of 2. Within the range of the Japanese willingness-to-pay threshold (¥5,000,000), the ablation+warfarin arm became the best option with its probability of 81.7% for a CHADS2 score of 2; the dabigatran+ablation arm was the most preferred option with its probability of 56.1% for a CHADS2 score of 4. CONCLUSIONS: Ablation under dabigatran therapy is an expensive therapeutic option, but it might benefit patients with a low quality of life and a high CHADS2 score.
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Antitrombinas/economía , Fibrilación Atrial/terapia , Ablación por Catéter/economía , Dabigatrán/economía , Índice de Severidad de la Enfermedad , Warfarina/economía , Antitrombinas/uso terapéutico , Fibrilación Atrial/economía , Terapia Combinada , Análisis Costo-Beneficio , Dabigatrán/uso terapéutico , Humanos , Japón , Cadenas de Markov , Persona de Mediana Edad , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Warfarina/uso terapéuticoRESUMEN
BACKGROUND: The monitoring of the effects of direct oral anticoagulants may be beneficial during emergencies and adverse events. We aimed to explore direct oral anticoagulant monitoring in "real-world" settings, in which monitoring methods are limited and loading time can be estimated based on only patient reports. METHODS: In 164 patients, plasma anti-Xa activity was assessed using a STA®-Liquid Anti-Xa reagent (Diagnostica Stago, Asnieres, France), and prothrombin time was measured using HemosIL® RecombiPlasTin 2G (Instrumentation Laboratory, Bedford, MA, USA). The loading time was calculated according to the previous dosing time reported by the patient. In the clinic setting, rivaroxaban and apixaban were administered to 103 patients with atrial fibrillation and a blood sample was tested once during a clinic visit. In the hospitalization setting, edoxaban was administered to 61 patients undergoing arthroplasty for prophylaxis of a venous thrombosis and blood samples were tested 3 and 18 h after the last intake. RESULTS: Plasma Xa activity in the clinical setting ranged widely (rivaroxaban: 1.1-424.4 ng/mL, apixaban: 15.4-469.2 ng/mL) during the 11.7 ± 7.0 h following the previous dose. The values varied over a wide range (up to a factor of 2) at the same loading time, especially around the peak period. The plasma anti-Xa activity of rivaroxaban and apixaban showed linear correlations with prothrombin time (R2 = 0.828 and 0.717, respectively). Edoxaban administration prolonged the prothrombin time by only 1.6 ± 1.1 s from the trough to the peak, to a degree that was negatively correlated with age, but not with plasma creatinine level, creatinine clearance, or body mass index. CONCLUSION: In real-world settings, plasma anti-Xa monitoring should be interpreted considering the wide variations in data, reflecting the variability in patient-reported loading time and interpatient variability.
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BACKGROUND: For perimitral atrial flutter (PMFL) developing after catheter ablation of atrial fibrillation (AF), to create a complete conduction block at the mitral isthmus (MI) is mandatory to terminate it, however, it is still challenging. METHODS: This study consisted of 80 patients (74 male, 61 ± 8.1 years) undergoing MI ablation. After a circular mapping catheter was positioned at the neck of the left atrial appendage (LAA), the MI ablation was performed on the MI line just below the LAA neck targeting the earliest activation recording site of the LAA catheter during pacing from the coronary sinus (CS). When ablation during CS pacing was not successful, an RF delivery during LAA pacing was applied targeting the earliest activation site just below the MI line. If the endocardial approach failed, an RF application inside the CS was attempted. RESULTS: With the endocardial approach, acute success was achieved in 51/80 patients (64%). Additional epicardial ablation from the CS was performed in 26/29 (90%) endocardially unsuccessful patients and conduction block at the MI was achieved in 21/26 (81%). Overall, complete conduction block at the MI was achieved in 72/80 patients (90%). At a mean follow-up of 16 ± 6 months, 20 patients (25%) had recurrence of atrial arrhythmias (AT: 12, AF: 8), and 10 (AT: 7, AF : 3) underwent a second procedure in which an LMI block line was completed in 3 (33%). PMFL was diagnosed in 6 out of 7 AT patients. No complications were observed. CONCLUSIONS: Creating linear lesions just beneath the neck of the LAA was highly successful under the guidance of a circular mapping catheter in the LAA using a steerable sheath. An RF application from the CS was needed in less than half of the cases.
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The expression of pluripotency genes fluctuates in a population of embryonic stem (ES) cells and the fluctuations in the expression of some pluripotency genes correlate. However, no correlation in the fluctuation of Pou5f1, Zfp42, and Nanog expression was observed in ES cells. Correlation between Pou5f1 and Zfp42 fluctuations was demonstrated in ES cells containing a knockout in the NuRD component Mbd3. ES cells containing a triple knockout in the DNA methyltransferases Dnmt1, Dnmt3a, and Dnmt3b showed correlation between the fluctuation of Pou5f1, Zfp42, and Nanog gene expression. We suggest that an epigenetic barrier is key to preventing the propagation of fluctuating pluripotency gene expression in ES cells.
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Células Madre Embrionarias/metabolismo , Animales , Epigenómica , Expresión Génica/genética , Ratones , Proteína Homeótica Nanog/genética , Factor 3 de Transcripción de Unión a Octámeros/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción SOXB1/genéticaRESUMEN
Alteration of the nuclear Ca2+ transient is an early event in cardiac remodeling. Regulation of the nuclear Ca2+ transient is partly independent of the cytosolic Ca2+ transient in cardiomyocytes. One nuclear membrane protein, emerin, is encoded by EMD, and an EMD mutation causes Emery-Dreifuss muscular dystrophy (EDMD). It remains unclear whether emerin is involved in nuclear Ca2+ homeostasis. The aim of this study is to elucidate the role of emerin in rat cardiomyocytes by means of hypertrophic stimuli and in EDMD induced pluripotent stem (iPS) cell-derived cardiomyocytes in terms of nuclear structure and the Ca2+ transient. The cardiac hypertrophic stimuli increased the nuclear area, decreased nuclear invagination, and increased the half-decay time of the nuclear Ca2+ transient in cardiomyocytes. Emd knockdown cardiomyocytes showed similar properties after hypertrophic stimuli. The EDMD-iPS cell-derived cardiomyocytes showed increased nuclear area, decreased nuclear invagination, and increased half-decay time of the nuclear Ca2+ transient. An autopsied heart from a patient with EDMD also showed increased nuclear area and decreased nuclear invagination. These data suggest that Emerin plays a crucial role in nuclear structure and in the nuclear Ca2+ transient. Thus, emerin and the nuclear Ca2+ transient are possible therapeutic targets in heart failure and EDMD.
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Calcio/metabolismo , Cardiomegalia/genética , Proteínas de la Membrana/genética , Distrofia Muscular de Emery-Dreifuss/genética , Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Membrana Nuclear/metabolismo , Proteínas Nucleares/genética , Transporte Activo de Núcleo Celular/efectos de los fármacos , Angiotensina II/farmacología , Compuestos de Anilina/química , Animales , Remodelación Atrial , Cardiomegalia/metabolismo , Cardiomegalia/patología , Citoplasma/efectos de los fármacos , Citoplasma/metabolismo , Citoplasma/ultraestructura , Modelos Animales de Enfermedad , Endotelina-1/farmacología , Colorantes Fluorescentes/química , Regulación de la Expresión Génica , Compuestos Heterocíclicos con 3 Anillos/química , Humanos , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/metabolismo , Distrofia Muscular de Emery-Dreifuss/metabolismo , Distrofia Muscular de Emery-Dreifuss/patología , Miocardio/patología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/ultraestructura , Membrana Nuclear/efectos de los fármacos , Membrana Nuclear/ultraestructura , Proteínas Nucleares/antagonistas & inhibidores , Proteínas Nucleares/metabolismo , Fenilefrina/farmacología , Cultivo Primario de Células , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Ratas , Ratas Sprague-Dawley , Remodelación Ventricular , Xantenos/químicaRESUMEN
Embryonic stem cells (ESCs) are a hallmark of ideal pluripotent stem cells. Epigenetic reprogramming of induced pluripotent stem cells (iPSCs) has not been fully accomplished. iPSC generation is similar to somatic cell nuclear transfer (SCNT) in oocytes, and this procedure can be used to generate ESCs (SCNT-ESCs), which suggests the contribution of oocyte-specific constituents. Here, we show that the mammalian oocyte-specific linker histone H1foo has beneficial effects on iPSC generation. Induction of H1foo with Oct4, Sox2, and Klf4 significantly enhanced the efficiency of iPSC generation. H1foo promoted in vitro differentiation characteristics with low heterogeneity in iPSCs. H1foo enhanced the generation of germline-competent chimeric mice from iPSCs in a manner similar to that for ESCs. These findings indicate that H1foo contributes to the generation of higher-quality iPSCs.
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Reprogramación Celular , Epigénesis Genética , Histonas/genética , Células Madre Pluripotentes Inducidas/metabolismo , Oocitos/metabolismo , Animales , Quimerismo , Embrión de Mamíferos , Femenino , Fibroblastos/citología , Fibroblastos/metabolismo , Expresión Génica , Histonas/metabolismo , Células Madre Pluripotentes Inducidas/citología , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Ratones , Ratones Transgénicos , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Oocitos/citología , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismoRESUMEN
BACKGROUND: Although automated external defibrillators (AEDs) have contributed to a better survival of out-of-hospital cardiac arrests, there have been reports of their malfunctioning. We investigated the diagnostic accuracy of commercially available AEDs using surface ECGs of ventricular fibrillation (VF), ventricular tachycardia (VT), and supraventricular tachycardia (SVT). METHODS AND RESULTS: ECGs(VF 31, VT 48, SVT 97) were stored during electrophysiological studies and transmitted to 4 AEDs, the LifePak CR Plus (CR Plus), HeartStart FR3 (FR3), and CardioLife AED-2150 (CL2150) and -9231 (CL9231), through the pad electrode cables. For VF, the CL2150 and CL9231 advised shocks in all cases, and the CR Plus and FR3 advised shocks in all but one VF case. For VTs faster than 180 bpm, the ratios for advising shocks were 79%, 36%, 89%, and 96% for the CR Plus, FR3, CL2150, and CL9231, respectively. The FR3 and CR Plus did not advise shocks for narrow QRS SVTs, whereas the CL9231 tended to treat high-rate tachycardias faster than 180 bpm even with narrow QRS complexes. The characteristics of the shock advice for the FR3 differed from that for the CL9231 (kappa coefficient [κ]=0.479, P<0.001), and the CR Plus and CL2150 had characteristics somewhere between the 2 former AEDs (κ=0.818, P<0.001). CONCLUSIONS: Commercially available AEDs diagnosed VF almost always correctly. For VT and SVT diagnoses, a discrepancy was evident among the 4 investigated AEDs. The differences in the arrhythmia diagnosis algorithms for differentiating SVT from VT were thought to account for these differences.
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Desfibriladores , Taquicardia Supraventricular/diagnóstico , Taquicardia Ventricular/diagnóstico , Fibrilación Ventricular/diagnóstico , Desfibriladores/normas , Cardioversión Eléctrica/instrumentación , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Taquicardia Supraventricular/fisiopatología , Taquicardia Supraventricular/terapia , Taquicardia Ventricular/fisiopatología , Taquicardia Ventricular/terapia , Fibrilación Ventricular/fisiopatología , Fibrilación Ventricular/terapiaRESUMEN
BACKGROUND: The mechanism underlying the associations of sleep-disordered breathing (SDB) with stroke and atrial fibrillation (AF) is not well established. We explored the relationship between nocturnal intermittent hypoxia, a marker of SDB, and left atrial (LA)/LA appendage (LAA) function among AF patients. METHODS: We evaluated 134 consecutive AF candidates for catheter ablation (age, 59.6 ± 9.4 years; body mass index [BMI], 24.8 ± 3.2; Congestive Heart Failure, Hypertension, Age (≥75 years), Diabetes, Stroke/Transient Ischemic Attack, Vascular Disease, Age (65-74 years), Sex (Female) (CHA2DS2-VASc) score, 1.2 ± 1.1, paroxysmal AF, n = 83) using nocturnal pulse oximetry, a noninvasive screening method for nocturnal intermittent hypoxia. Based on 3% oxygen desaturation index (3% ODI), patients were divided into nocturnal intermittent hypoxia (3% ODI > 15; n = 32) and control groups (3% ODI ≤ 15; n = 102). RESULTS: The nocturnal intermittent hypoxia group demonstrated significantly higher weight, BMI, Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack (CHADS2) and CHA2DS2-VASc scores, serum hemoglobin A1c and plasma brain natriuretic peptide levels, LA size, and prevalence of hypertension, vascular disease, and sick sinus syndrome. Echocardiographically, nocturnal intermittent hypoxia was associated with a higher grade of spontaneous echo contrast and low LAA flow velocity. Multiple regression analysis adjusted for type of AF, CHA2DS2-VASc score, BMI, plasma brain natriuretic peptide level, LA size, and rhythm on echocardiography revealed that 3% ODI was a factor independently associated with LAA flow velocity (ß = -0.184; 95% confidence interval, -0.818 to -0.006). CONCLUSIONS: Nocturnal intermittent hypoxia was an independent determinant for low LAA flow velocity in patients with AF, suggesting that the connection between SDB and LAA function might underlie the association of AF with stroke.
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Apéndice Atrial/fisiopatología , Fibrilación Atrial/complicaciones , Función del Atrio Izquierdo/fisiología , Hipoxia/etiología , Flujo Sanguíneo Regional/fisiología , Medición de Riesgo , Síndromes de la Apnea del Sueño/complicaciones , Anciano , Apéndice Atrial/diagnóstico por imagen , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Hipoxia/epidemiología , Hipoxia/fisiopatología , Incidencia , Japón/epidemiología , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Estudios Retrospectivos , Factores de Riesgo , Síndromes de la Apnea del Sueño/fisiopatología , UltrasonografíaRESUMEN
INTRODUCTION: Lead failures (LFs) are one of the most common complications in patients implanted with cardiovascular implantable electronic devices. LFs often cause serious secondary complications such as inappropriate ICD shocks or asystole. This study aimed to identify the clinical factors associated with the occurrence of LFs. METHODS: A total of 735 consecutive device implantations (mean age 67±15years, males 64%) performed at a single university hospital setting from 1997 to 2014 were included. The implanted devices consisted of 421 pacemakers, 250 implantable cardioverter defibrillators (ICD), 9 cardiac resynchronization therapy pacemakers (CRT-P), and 55 CRT defibrillators (CRT-D). The primary endpoint was the development of an LF. RESULTS: During a mean duration of 5.8±4.3years, 38 LFs developed in 31 patients (mean age 56±14years). LFs included 32 ICD (7 Sprint Fidelis, 2 Riata), and 6 pacing leads. Nine patients received inappropriate ICD shocks and 1 had syncope due to an LF. All patients underwent lead reinsertions with device replacements. Eight patients required opposite site implantations due to venous occlusions. The predictive factors of LFs were the age, male sex, taller body length, ICD vs. pacemaker, lesser lead number, extra-thoracic puncture of the axillary vein vs. a cut-down of the cephalic vein, use of recalled leads and patients with idiopathic ventricular fibrillation (IVF) and Brugada syndrome (BrS). CONCLUSION: LFs occurred mainly with ICD leads. A lesser age, the puncture method, lead model, and diagnosis of IVF/BrS were associated with the development of LFs.
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Arritmias Cardíacas/terapia , Desfibriladores Implantables/efectos adversos , Marcapaso Artificial/efectos adversos , Anciano , Remoción de Dispositivos , Falla de Equipo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de TiempoRESUMEN
Mitochondrial diseases are heterogeneous disorders, caused by mitochondrial dysfunction. Mitochondria are not regulated solely by nuclear genomic DNA but by mitochondrial DNA. It is difficult to develop effective therapies for mitochondrial disease because of the lack of mitochondrial disease models. Mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the major mitochondrial diseases. The aim of this study was to generate MELAS-specific induced pluripotent stem cells (iPSCs) and to demonstrate that MELAS-iPSCs can be models for mitochondrial disease. We successfully established iPSCs from the primary MELAS-fibroblasts carrying 77.7% of m.3243A>G heteroplasmy. MELAS-iPSC lines ranged from 3.6% to 99.4% of m.3243A>G heteroplasmy levels. The enzymatic activities of mitochondrial respiratory complexes indicated that MELAS-iPSC-derived fibroblasts with high heteroplasmy levels showed a deficiency of complex I activity but MELAS-iPSC-derived fibroblasts with low heteroplasmy levels showed normal complex I activity. Our data indicate that MELAS-iPSCs can be models for MELAS but we should carefully select MELAS-iPSCs with appropriate heteroplasmy levels and respiratory functions for mitochondrial disease modeling.