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1.
Heart Vessels ; 36(2): 267-276, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32902701

RESUMO

Atrial fibrillation (AF) is known to aggregate within family and might be associated with a lower quality-of-life (QoL). We evaluated the association between a family history (FHx) of AF and patient-reported symptom burden and perception towards treatment. We performed a retrospective analysis in a cohort of 1285 newly diagnosed patients with AF. Patients completed the atrial fibrillation effect on quality of life (AFEQT) questionnaire at the time of registration and at the 1-year follow-up. Patients who had a first-degree relative with AF were classified into the FHx group. Baseline characteristics and AFEQT scores were compared between groups, and a multivariate analysis was used to evaluate the independent association between FHx and QoL. Overall, 15.9% of patients (n = 204) had a positive AF FHx. Compared to the non-FHx group, the FHx group had an earlier onset of AF (60.2 ± 12.0 years vs. 64.5 ± 12.1 years; P < 0.05) and lower AFEQT overall summary (AFEQT-OS) score at baseline (73.9 ± 17.8 vs. 77.0 ± 16.8; P < 0.05). After adjustment for clinical background, a positive FHx was independently associated with a worse QoL (changes in AFEQT-OS score = - 3.18; 95% confidence interval: - 5.67 to - 0.69; P = 0.012). No between-group difference in AFEQT-OS scores was noted at the 1-year follow-up. An FHx of AF was associated with a lower QoL, which could be improved by therapeutic intervention in patients with AF. Recognizing the presence of an FHx of AF is important to predict patient's symptom load and treatment acceptance.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Percepção , Qualidade de Vida/psicologia , Sistema de Registros , Idoso , Fibrilação Atrial/psicologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários
2.
Am Heart J ; 226: 240-249, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32517853

RESUMO

Our aim was to investigate the variability in physician recognition of atrial fibrillation (AF)-related symptoms, which greatly contributes to the management of AF patients. METHODS AND RESULTS: A total of 1493 newly-referredAF patients (67 ±â€¯11 y/o, 1057 men) consecutively registered in an outpatient-based Japanese multicenter database (KiCS-AF) from September 2012 to December 2016 were analyzed. Self-reportedAF symptom burden was assessed via symptom and daily activities domains within the Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) questionnaire. Physician symptom under-recognition (UR) was defined as no subjective complaints recorded in the medical records despite AFEQT score of <80; and physician's apparent over-recognition (OvR) was defined as documentation of subjective complaints despite total AFEQT score of ≥80. There was poor agreement between patient-reported and physicians-estimated symptom burden (kappa 0.28, 95% CI 0.23 to 0.33). In the logistic regression analysis, age> 75 (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.13-2.62), male sex (OR, 1.82; 95% CI, 1.22-2.74), and persistent/permanent AF (OR 2.54/3.36; CI, 1.63-3.99/1.91-5.89, respectively) were predictors of UR. Conversely, heart failure (OR, 2.46; 95% CI, 1.44-4.25) and treatment in an ablation facility (OR, 1.43; 95% CI, 1.02-2.02) were associated with greater odds of OvR in addition to age, sex, and type of AF. CONCLUSIONS: Discordance in recognition of AF symptom burden by physicians was frequent in AF patients seen in outpatient management and involved both patient- and physician-related factors.


Assuntos
Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Estudos Prospectivos , Sistema de Registros , Índice de Gravidade de Doença , Avaliação de Sintomas
3.
Biochem Biophys Res Commun ; 511(3): 711-717, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30827508

RESUMO

Immunogenicity of immature pluripotent stem cells is a topic of intense debate. Immunogenic antigens, which are specific in pluripotent states, have not been described previously. In this study, we identified glypican-3 (GPC3), a known carcinoembryonic antigen, as a pluripotent state-specific immunogenic antigen. Additionally, we validated the applicability of human leukocyte antigen (HLA)-class I-restricted GPC3-reactive cytotoxic T lymphocytes (CTLs) in the removal of undifferentiated pluripotent stem cells (PSCs) from human induced pluripotent stem cell (hiPSC)-derivatives. HiPSCs uniquely express GPC3 in pluripotent states and were rejected by GPC3-reactive CTLs, which were sensitized with HLA-class I-restricted GPC3 peptides. Furthermore, GPC3-reactive CTLs selectively removed undifferentiated PSCs from hiPSC-derivatives in vitro and inhibited tumor formation in vivo. Our results demonstrate that GPC3 works as a pluripotent state-specific immunogenic antigen in hiPSCs and is applicable to regenerative medicine as a method of removing undifferentiated PSCs, which are the main cause of tumor formation.


Assuntos
Glipicanas/imunologia , Células-Tronco Pluripotentes Induzidas/imunologia , Linfócitos T Citotóxicos/imunologia , Animais , Diferenciação Celular , Linhagem Celular , Glipicanas/análise , Antígeno HLA-A2/imunologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Camundongos Endogâmicos NOD , Camundongos SCID , Modelos Moleculares , Neoplasias/imunologia
4.
Pacing Clin Electrophysiol ; 42(6): 617-624, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30779354

RESUMO

BACKGROUND: Epicardiac conduction via the vein of Marshall (VOM) can bypass the mitral isthmus (MI) line, making MI ablation difficult. This study aimed to assess the contribution of the VOM in achieving MI conduction block. METHODS: This study included 143 consecutive patients with nonparoxysmal atrial fibrillation who underwent initial MI ablation. They were retrospectively classified into two groups, a VOM-guided group (n = 28) and a conventional group (n = 115), according to the use of a 2-Fr electrode catheter inserted in the VOM. The acute success rate of achieving MI block and the ablation data were assessed. When the bidirectional block was verified exclusively in the VOM or coronary sinus (CS) electrodes, we defined it as a pseudo MI block. In the VOM-guided group, we ascertained the complete MI block, verified both in the VOM and CS electrodes. RESULTS: In the VOM-guided group, the pseudoblock was observed in 33.3% of the patients during MI ablation. With significantly less radiofrequency energy (19 322.6 ± 11 352.8 vs 25 389.3 ± 19 951.9, P = 0.04), we achieved a similar level of success rate in MI ablation in the VOM-guided group (96.4% vs 91.3%, P = 0.36). Notably, after achieving complete MI block, atrial burst pacing induced two perimitral flutters in the VOM-guided group, which were successfully terminated by the additional radiofrequency application. CONCLUSIONS: Assessment of electrical conduction through the VOM could clarify the existence of a pseudo MI conduction block. However, the existence of a slow conduction through the MI could be detected only after induction of perimitral atrial tachycardia with atrial programmed stimulation.


Assuntos
Fibrilação Atrial/cirurgia , Vasos Coronários/cirurgia , Sistema de Condução Cardíaco/cirurgia , Valva Mitral/cirurgia , Ablação por Radiofrequência/métodos , Fibrilação Atrial/fisiopatologia , Cateterismo Cardíaco , Angiografia Coronária , Feminino , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/fisiopatologia , Estudos Retrospectivos
5.
Heart Lung Circ ; 28(7): 1050-1058, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31178023

RESUMO

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.


Assuntos
Fibrilação Atrial , Temperatura Corporal , Ablação por Cateter , Esôfago/fisiopatologia , Idoso , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
Heart Vessels ; 32(3): 317-325, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27385021

RESUMO

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.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Eletrocardiografia Ambulatorial/métodos , Idoso , Feminino , Seguimentos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Veias Pulmonares/cirurgia , Recidiva , Taxa de Sobrevida , Telemedicina , Fatores de Tempo , Resultado do Tratamento
7.
Europace ; 18(2): 294-300, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25825457

RESUMO

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.


Assuntos
Ablação por Cateter/métodos , Fotoquimioterapia/métodos , Veia Cava Superior/cirurgia , Potenciais de Ação , Animais , Ablação por Cateter/efeitos adversos , Ablação por Cateter/instrumentação , Catéteres , Cães , Eletrocardiografia , Desenho de Equipamento , Estudos de Viabilidade , Lasers , Modelos Animais , Flebografia , Fotoquimioterapia/efeitos adversos , Fotoquimioterapia/instrumentação , Fármacos Fotossensibilizantes/administração & dosagem , Porfirinas/administração & dosagem , Fatores de Tempo , Veia Cava Superior/diagnóstico por imagem
8.
Heart Vessels ; 31(9): 1579-82, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26747439

RESUMO

Endomyocardial fibrosis (EMF) is a progressive type of obliterative/restrictive cardiomyopathy characterized by fibrosis of the apical endomyocardium of the ventricles. Although the prognosis of EMF patients is poor in tropical regions, the exact clinical course and pathogenesis of patients with EMF are not known. Here, we report the rare case with EMF in the seventh decade, who showed the disappearance of papillary muscles, chordae tendineae, and part of the tricuspid valves due to massive right ventricular thrombus. Because of those unusual findings of the isolated RV involvement, we observed continuous forward pulmonary artery flow, as occurring in a Fontan circulation.


Assuntos
Fibrose Endomiocárdica/complicações , Artéria Pulmonar/fisiopatologia , Circulação Pulmonar , Trombose/etiologia , Valva Tricúspide , Autopsia , Cordas Tendinosas/diagnóstico por imagem , Progressão da Doença , Ecocardiografia Doppler em Cores , Fibrose Endomiocárdica/diagnóstico por imagem , Fibrose Endomiocárdica/fisiopatologia , Evolução Fatal , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculos Papilares/diagnóstico por imagem , Artéria Pulmonar/diagnóstico por imagem , Trombose/diagnóstico por imagem , Trombose/fisiopatologia , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/fisiopatologia
9.
Int J Cardiol Heart Vasc ; 47: 101241, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37576084

RESUMO

Aim: During percutaneous coronary intervention (PCI), complicated lesions in the target coronary artery often hinder device delivery. Fluid lubricants have commonly been used to reduce friction between adjacent solid materials in manufacturing, thus achieving smoother action. This ex vivo experimental study examined whether a contrast medium could function as a fluid lubricant during PCI. Methods and results: We used two different coronary artery lesion models with distinct complexities made from silicon. Each model was fit into the ex vivo PCI-simulation system. This ex vivo laboratory equipment consisted of ordinary PCI instruments and an aorta model from the Valsalva sinus to the descending aorta. A Wolverine™ cutting balloon catheter was advanced through each lesion model via a guide catheter set into the system. The maximum force required to push the catheter through the lesion models was measured while the vessel system was filled with either normal saline or contrast medium. The maximum force required was significantly lower with the contrast medium (1.38 ± 0.21 N in the normal-saline condition vs. 0.92 ± 0.05 N in the contrast-medium condition in the lesion model A, p < 0.001; 1.30 ± 0.07 N in the normal-saline condition vs. 1.14 ± 0.04 N in the contrast-medium condition in the lesion model B, p < 0.001). Conclusions: The contrast medium for vessel system filling reduced the force required to push the devices through the lesion models. This contrast medium represents a potential candidate for a liquid lubricant to facilitate device delivery for complicated coronary lesions.

10.
iScience ; 24(2): 102090, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33615198

RESUMO

Human pluripotent stem cells (hPSCs) have a unique metabolic signature for maintenance of pluripotency, self-renewal, and survival. Although hPSCs could be potentially used in regenerative medicine, the prohibitive cost associated with large-scale cell culture presents a major barrier to the clinical application of hPSC. Moreover, without a fully characterized metabolic signature, hPSC culture conditions are not optimized. Here, we performed detailed amino acid profiling and found that tryptophan (TRP) plays a key role in the proliferation with maintenance of pluripotency. In addition, metabolome analyses revealed that intra- and extracellular kynurenine (KYN) is decreased under TRP-supplemented conditions, whereas N-formylkynurenine (NFK), the upstream metabolite of KYN, is increased thereby contributing to proliferation promotion. Taken together, we demonstrate that TRP is indispensable for survival and proliferation of hPSCs. A deeper understanding of TRP metabolism will enable cost-effective large-scale production of hPSCs, leading to advances in regenerative medicine.

11.
JACC Basic Transl Sci ; 6(3): 239-254, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33778211

RESUMO

The severe shortage of donor hearts hampered the cardiac transplantation to patients with advanced heart failure. Therefore, cardiac regenerative therapies are eagerly awaited as a substitution. Human induced pluripotent stem cells (hiPSCs) are realistic cell source for regenerative cardiomyocytes. The hiPSC-derived cardiomyocytes are highly expected to help the recovery of heart. Avoidance of teratoma formation and large-scale culture of cardiomyocytes are definitely necessary for clinical setting. The combination of pure cardiac spheroids and gelatin hydrogel succeeded to recover reduced ejection fraction. The feasible transplantation strategy including transplantation device for regenerative cardiomyocytes are established in this study.

13.
Oxf Med Case Reports ; 2020(7): omaa044, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32728447

RESUMO

We report the case of a 48-year-old man who was unexpectedly found by abdominal ultrasonography to have large retroperitoneal masses accompanied by Graves' disease. Computed tomography and magnetic resonance imaging further demonstrated giant fat-rich soft masses arising within both renal sinuses. Histopathological examination of the mass was performed twice at 5-year intervals, with both examinations indicating fatty tissue cells with chronic fibrous panniculitis. Intravenous pulse therapy and successive oral glucocorticoid therapy were ineffective against Graves' ophthalmopathy or mass lesion. An antithyroid hormone regimen was followed by subtotal thyroid resection, leading to improvements in hyperthyroidism. Mass growth then attenuated slowly as the thyroid hormones returned to normal levels. The long-term follow-up of this patient should carefully monitor the appearance of warning signs such as mass effects.

14.
Circ Rep ; 2(11): 657-664, 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33693192

RESUMO

Background: The relationship between left ventricular diastolic dysfunction (LVDD) and paroxysmal atrial fibrillation (PAF) remains unclear because of a lack of standard measures to evaluate LVDD. Accordingly, we examined the association between the prevalence of PAF and each LVDD grade determined according to the latest American Society of Echocardiography guidelines. Methods and Results: In all, 2,063 patients without persistent AF who underwent echocardiography at Saitama Municipal Hospital from July 2016 to June 2017 were included in the study. Patients were divided into LVDD 6 categories: No-LVDD (n=1,107), Borderline (n=392), Grade 1 (n=204), Indeterminate (n=62), Grade 2 (n=254), and Grade 3 (n=44). PAF was documented in 111 (10.0%), 81 (20.7%), 28 (13.7%), 6 (9.7%), 52 (20.5%), and 24 (54.5%) patients in the No-LVDD, Borderline, Grade 1, Indeterminate, Grade 2, and Grade 3 categories, respectively. PAF prevalence was higher in patients with Grade 3 LVDD across the whole study population. Subgroup analyses showed that the prevalence of PAF increased with increased LVDD grade in patients with reduced left ventricular ejection fraction. This relationship was significant in multivariate analysis including various patient characteristics. Conclusions: LVDD severity determined on the basis of the latest echocardiographic criteria was associated with the prevalence of PAF. The present findings shed light on the development of new therapeutic markers for PAF.

15.
JACC Clin Electrophysiol ; 6(13): 1647-1657, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33334443

RESUMO

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.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Fibrilação Atrial/cirurgia , Criança , Feminino , Átrios do Coração , Humanos , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia , Estudos Retrospectivos
16.
iScience ; 23(9): 101535, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33083764

RESUMO

The role of lipid metabolism in human pluripotent stem cells (hPSCs) is poorly understood. We have used large-scale targeted proteomics to demonstrate that undifferentiated hPSCs express different fatty acid (FA) biosynthesis-related enzymes, including ATP citrate lyase and FA synthase (FASN), than those expressed in hPSC-derived cardiomyocytes (hPSC-CMs). Detailed lipid profiling revealed that inhibition of FASN resulted in significant reduction of sphingolipids and phosphatidylcholine (PC); moreover, we found that PC was the key metabolite for cell survival in hPSCs. Inhibition of FASN induced cell death in undifferentiated hPSCs via mitochondria-mediated apoptosis; however, it did not affect cell survival in hPSC-CMs, neurons, or hepatocytes as there was no significant reduction of PC. Furthermore, we did not observe tumor formation following transplantation of FASN inhibitor-treated cells. Our findings demonstrate the importance of de novo FA synthesis in the survival of undifferentiated hPSCs and suggest applications for FASN inhibition in regenerative medicine.

17.
Keio J Med ; 68(4): 87-94, 2019 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-30606897

RESUMO

Some patients with hypertrophic cardiomyopathy (HCM) develop systolic dysfunction, called the dilated phase of HCM (d-HCM), which is associated with increased morbidity and mortality. We conducted a retrospective study using an HCM database to clarify the incidence, clinical characteristics, and long-term outcomes of d-HCM. We analyzed an HCM cohort consisting of 434 patients (273 with apical HCM and 161 with non-apical HCM; 18 had obstructive HCM, 16 had dilated HCM, and 127 had other HCM) diagnosed by echocardiography in our hospital between 1991 and 2010. The follow-up period was 8.4 ± 6.7 years. The mean age at final follow-up was 67 ± 14 years, and 304 patients (70%) were men. The mean age of the 16 d-HCM patients at the initial visit was 45 ± 17 years, the age at final follow-up was 59 ± 18 years, and 13 were men. Thirteen d-HCM patients developed atrial fibrillation and six patients developed ischemic stroke. Twelve d-HCM patients were implanted with cardiac devices: one pacemaker, nine implantable cardioverter-defibrillators, and two cardiac resynchronization therapy with defibrillator. Five patients died of progressive heart failure at the age of 61 ± 23 years. The age at the initial visit and final follow-up were lower and the NYHA class, brain natriuretic peptide levels, and left ventricular function at initial evaluation were worse in the d-HCM group. Univariate analysis demonstrated that a lower age at the initial visit was associated with d-HCM (hazard ratio 0.955/1 year increase; 95% CI 0.920-0.991, P = 0.015). In our HCM cohort, the incidence of d-HCM was 4%. A high prevalence of atrial fibrillation and cerebral infarction and poor prognosis were noted in this group, despite patients undergoing medication and device implantation.


Assuntos
Fibrilação Atrial/fisiopatologia , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Hipertrófica/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/mortalidade , Fibrilação Atrial/terapia , Biomarcadores/sangue , Terapia de Ressincronização Cardíaca/métodos , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/terapia , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/mortalidade , Cardiomiopatia Hipertrófica/terapia , Cardiotônicos/uso terapêutico , Desfibriladores Implantáveis , Ecocardiografia , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Marca-Passo Artificial , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/terapia , Análise de Sobrevida , Função Ventricular Esquerda/fisiologia
18.
Case Rep Genet ; 2019: 9056596, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30729048

RESUMO

A 62-year-old female had suffered from recurrent syncopal episodes triggered by physical and emotional stress since childhood. She had no family history of sudden death. An intensive examination could not detect any structural disease, and exercise stress testing provoked polymorphic ventricular ectopy followed by polymorphic ventricular tachycardia accompanied with syncope leading to a diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT). A genetic analysis with a next generation sequencer identified a homozygous W361X mutation in the CASQ2 gene. Careful history taking disclosed that her parents had a consanguineous marriage. Here we present a Japanese patient with a recessive form of CPVT.

19.
J Heart Lung Transplant ; 38(2): 203-214, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30691596

RESUMO

BACKGROUND: Induced pluripotent stem cell (iPSC)‒based regenerative therapy is a promising strategy for cardiovascular disease treatment; however, the method is limited by the myocardial retention of grafted iPSCs. Thus, an injection protocol that efficiently introduces and retains human iPSC-derived cardiomyocytes (hiPSC-CMs) within the myocardium is urgently needed. The objective of the present study was to develop a method to improve the retention of hiPSCs in the myocardium for cardiac therapy. METHODS: We efficiently produced hiPSC-CM spheroids in 3-dimensional (3D) culture using microwell plates, and developed an injection device for optimal 3D distribution of the spheroids in the myocardial layer. Device biocompatibility was assessed with purified hiPSC-CM spheroids. Device effectiveness was evaluated in 10- to 15-month-old farm pigs (n = 15) and 5- to 24-month-old micro-minipigs (n = 20). The pigs were euthanized after injection, and tissues were harvested for retention and histologic analysis. RESULTS: We demonstrated an injection device for direct intramyocardial transplantation of hiPSC-CM spheroids from large-scale culture. The device had no detrimental effects on cell viability, spheroid shape, or size. Direct epicardial injection of spheroids mixed with gelatin hydrogel into beating porcine hearts using this device resulted in better distribution and retention of transplanted spheroids in a layer within the myocardium than did conventional needle injection procedures. CONCLUSIONS: The combination of the newly developed transplant device and spheroid formation promotes the retention of transplanted CMs. These findings support the clinical application of hiPSC-CM spheroid‒based cardiac regenerative therapy in patients with heart failure.


Assuntos
Insuficiência Cardíaca/terapia , Células-Tronco Pluripotentes Induzidas/transplante , Miócitos Cardíacos/citologia , Transplante de Células-Tronco/instrumentação , Animais , Materiais Biocompatíveis , Diferenciação Celular , Modelos Animais de Doenças , Desenho de Equipamento , Feminino , Insuficiência Cardíaca/patologia , Humanos , Injeções/instrumentação , Esferoides Celulares , Suínos , Porco Miniatura
20.
Int J Cardiol ; 260: 99-102, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29622460

RESUMO

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€¯9 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%, P = 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.


Assuntos
Fibrilação Atrial/epidemiologia , Ablação por Cateter/tendências , Apneia do Sono Tipo Central/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Idoso , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Estudos Transversais , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Apneia do Sono Tipo Central/fisiopatologia , Apneia do Sono Tipo Central/cirurgia , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/cirurgia
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