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BACKGROUND: High shock impedance is associated with conversion failure among patients with subcutaneous implantable cardioverter defibrillators (S-ICD). Currently, there is no preoperative assessment method for predicting high shock impedance. This study examined the efficacy of chest computed tomography (CT) as a preoperative evaluation tool to assess the shock impedance of S-ICDs. METHODSâANDâRESULTS: The amount of adipose tissue adjacent to the device and anteroposterior diameter at the basal heart region were measured preoperatively using chest CT. We examined the correlation between these measurements and shock impedance at the conversion test. We enrolled 43 patients with S-ICDs (mean [±SD] age 54±15 years; body mass index 23±4 kg/m2; PRAETORIAN score 30-270 points; amount of adipose tissue 1,250±716 cm3), who underwent intraoperative conversion tests by inducing ventricular fibrillation, which was terminated with a 65-J shock. A sufficient concordance correlation coefficient was observed between the shock impedance and the amount of adipose tissue (r=0.616, P<0.01) and anteroposterior diameter (r=0.645, P<0.01). In multiple regression analysis, the amount of adipose tissue (ß=0.439, P=0.009) and anteroposterior diameter (ß=0.344, P=0.038) were identified as independent predictive factors of shock impedance. CONCLUSIONS: The preoperative CT-measured amount of adipose tissue and basal heart anteroposterior diameter are independent predictors of shock impedance. These parameters may be more accurate in identifying higher shock impedance in patients with S-ICDs.
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Desfibriladores Implantáveis , Impedância Elétrica , Tomografia Computadorizada por Raios X , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Adulto , Tecido Adiposo/diagnóstico por imagem , Fibrilação Ventricular/terapia , Fibrilação Ventricular/diagnóstico por imagem , Fibrilação Ventricular/fisiopatologia , Valor Preditivo dos TestesRESUMO
Environmental changes such as seasonality, decadal oscillation, and anthropogenic forcing may shape the dynamics of lower trophic-level organisms. In this study, 9-years (2010-2018) of monitoring data on microscopic protists such as diatoms and dinoflagellates, and environmental variables were analyzed to clarify the relationships between plankton and local/synoptic environmental changes. We found that time-series temperature increased in May, whereas it decreased in August and November. Nutrients (e.g., phosphate) decreased in May, remained unchanged in August, and increased in November from 2010 to 2018. The partial pressure of CO2 increased in May, August, and November over time. It is notable that the change in seawater temperature (-0.54 to 0.32 °C per year) and CO2 levels (3.6-5.7 µatm CO2 per year) in the latest decade in the eastern Tsugaru Strait were highly dynamic than the projected anthropogenic climate change. Protist abundance generally increased or stayed unchanged during the examined period. In August and November, when cooling and decreases in pH occurred, diatoms such as Chaetoceros subgenus Hyalochaete spp. and Rhizosoleniaceae temporally increased from 2010 to 2018. During the study period, we found that locally aquacultured scallops elevated soft tissue mass relative to the total weight as diatom abundance increased, and the relative scallop soft tissue mass was positively related to the Pacific Decadal Oscillation index. These results indicate that decadal climatic forcing in the ocean modifies the local physical and chemical environment, which strongly affects phytoplankton dynamics rather than the effect of anthropogenic climate change in the eastern Tsugaru Strait.
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Dióxido de Carbono , Diatomáceas , Japão , Meteorologia , Água do Mar/química , AquiculturaRESUMO
OBJECTIVES: Inguinal hernia (IH) is a common postoperative complication after robot-assisted radical prostatectomy (RARP). We developed a novel clipping technique for the prevention of IH developing after RARP. METHODS: This cohort included 759 consecutive patients who underwent RARP for prostate cancer at the University of Tokyo Hospital between January 2011 and December 2018. We reviewed clinical parameters and identified the risk factors of postoperative IH. The prophylactic preventive procedure of IH development was performed by clipping the peritoneum and underlying tissue around the internal inguinal ring using Hem-o-Lok clip to prevent the prolapse of the intestine through the internal inguinal ring. RESULTS: In total, 236 patients received the clipping procedure. The median follow-up time was 50 months. The incidence rate of IH was 10.8% (78/720). The median time to the diagnosis of IH was 10 months. Univariate analysis revealed that patients with higher age (age ≥ 63), low BMI (BMI < 25 kg/m2), and lower number of surgical experiences (Surgical experience < 40) showed a significantly higher odds ratio of developing IH. Multivariate analysis showed that "BMI < 25 kg/m2" and "Surgical experience < 40" were independent predictive factors of IH. Among the patients with a high risk of IH due to receiving surgery from inexperienced surgeons, there was a statistically significant preventive effect for the patients with "BMI ≥ 25 kg/m2" by the novel clipping procedure. CONCLUSIONS: The novel clipping procedure reduced the risk of post-operative IH in obese patients when the RARP was performed by inexperienced surgeons.
RESUMO
BACKGROUND: Predictors of worsening atrioventricular valve regurgitation and left ventricular (LV) systolic function after implantation of a leadless pacemaker (LPM) remain unclear compared with those of a transvenous pacemaker (TPM). METHODS: We retrospectively analyzed 205 patients who were newly implanted with a permanent pacemaker (119 LPMs and 86 TPMs) and underwent transthoracic echocardiography before and 8 ± 5 months after implantation. We evaluated the worsening of tricuspid and mitral regurgitation (TR and MR), defined as at least one-grade aggravation in severity, and changes in LV ejection fraction (LVEF). RESULTS: Worsening TR occurred more frequently in the LPM group compared to the TPM group (33% vs. 20%, p = .04); however, there was no significant difference between the two groups regarding worsening MR (26% vs. 18%, p = .18) and LVEF change (-2 ± 10% vs. -3 ± 8%, p = .40). In multivariable analysis, independent predictors for worsening TR, MR, and LVEF after implantation were found to be (1) the change from sinus rhythm at baseline to atrioventricular asynchronous right ventricular (RV) pacing (odds ratio [OR]: 5.68, 95% confidence interval [CI]: 1.94-16.70, p < .01); (2) the change from non-pacing ventricular contraction at baseline to RV pacing (OR: 2.42, 95% CI: 1.12-5.24, p = .02); and (3) a higher RV pacing burden (ß: -0.05, 95% CI: -0.08--0.02, p < .01), respectively. CONCLUSION: Worsening TR, MR, and LVEF after pacemaker implantation were not associated with the type of pacing device but loss of atrioventricular synchrony or dependency on RV pacing.
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Insuficiência da Valva Mitral , Marca-Passo Artificial , Insuficiência da Valva Tricúspide , Humanos , Estimulação Cardíaca Artificial , Estudos Retrospectivos , Função Ventricular Esquerda , Insuficiência da Valva Mitral/terapiaRESUMO
PURPOSE: To compare the characteristics of reimplantation (RI) using grafts with sinuses and remodeling (RM) with/without external suture annuloplasty using a pulsatile flow simulator. METHODS: Porcine aortic roots were obtained from an abattoir, and six models of RM and RI with sinuses were prepared. External suture annuloplasty (ESA) was performed in the RM models to decrease the root diameter to 22 mm (RM-AP22) and 18 mm (RM-AP18). Valve models were tested at mean pulsatile flow and aortic pressure of 5.0 L/min and 120/80 (100) mmHg, respectively, at 70 beats/min. The forward flow, regurgitation, leakage, backflow rates, valve-closing time, and mean and peak pressure gradient (p-PG) were evaluated. Root configurations were examined using micro-computed tomography (micro-CT). RESULTS: The backflow rate was larger in the RM models than in the RI models (RI: 8.56% ± 0.38% vs. RM: 12.64% ± 0.79%; p < 0.01). The RM-AP and RI models were comparable in terms of the forward flow, regurgitation, backflow rates, p-PG, and valve-closing time. The analysis using a micro-CT showed a larger dilatation of the sinus of the Valsalva in the RM groups than in the RI group (Valsalva: RI, 26.55 ± 0.40 mm vs. RM-AP22, 31.22 ± 0.55 mm [p < 0.05]; RM-AP18, 31.05 ± 0.85 mm [p < 0.05]). CONCLUSIONS: RM with ESA and RI with neo-sinuses showed comparable hemodynamics. ESA to RM reduced regurgitation.
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Insuficiência da Valva Aórtica , Valva Aórtica , Hemodinâmica , Reimplante , Animais , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/cirurgia , Fluxo Pulsátil , Suínos , Microtomografia por Raio-XRESUMO
A 59-year-old man who had been diagnosed with human immunodeficiency virus-associated cardiomyopathy was referred for catheter ablation of ventricular tachycardia (VT). An electrocardiogram (ECG) waveform revealed that the clinical VT originated from the epicardium. A deceleration zone (DZ) was identified on an isochronal late activation map. Moreover, 2 forms of monomorphic VT were induced by different cycle length burst pacings from near the DZ. The morphologies of the 2 VTs with an identical cycle length were very likely to use a shared common pathway with bi-directional conduction around the slow conduction area in the left ventricle posterolateral small epicardial surface area. After ablation of the DZ, the VT was uninducible.
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Cardiomiopatias , Ablação por Cateter , Taquicardia Ventricular , Masculino , Humanos , Pessoa de Meia-Idade , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/cirurgia , Arritmias Cardíacas/cirurgia , Frequência Cardíaca/fisiologia , Cardiomiopatias/complicações , Cardiomiopatias/diagnóstico , Resultado do TratamentoRESUMO
BACKGROUND: Implanting a ventricular demand leadless pacemaker (VVI-LPM) for patients with non-atrial fibrillation (AF) bradyarrhythmias such as sick sinus syndrome (SSS) or high-grade (i.e., second- or third-degree) atrioventricular (AV) block is not recommended unless they have limited vascular access or a high infection risk; nevertheless, an unexpectedly high number of VVI-LPM implantations have been performed. This study investigated the clinical outcomes of these unusual uses.MethodsâandâResults:This study retrospectively analyzed 193 patients who were newly implanted with a VVI-LPM or an atrioventricular synchronous transvenous pacemaker (DDD-TPM) for non-AF bradyarrhythmias at a high-volume center in Japan from September 2017 to September 2020. Propensity score-matching produced 2 comparable cohorts treated with a VVI-LPM or DDD-TPM (n=58 each). Each group had 20 (34%) patients with SSS and 38 (66%) patients with high-grade AV block. During a median follow up of 733 (interquartile range 395-997) days, there were no significant differences between the VVI-LPM and DDD-TPM groups regarding late device-related adverse events (0% vs. 4%, log-rank P=0.155), but the VVI-LPM group had a significantly increased readmission rate for heart failure (HF) (29% vs. 2%, log-rank P=0.001) and a tendency to have higher all-cause mortality (28% vs. 4%, log-rank P=0.059). CONCLUSIONS: The implantation of a VVI-LPM for non-AF bradyarrhythmias increased the incidence of HF-related rehospitalization at the mid-term follow up compared to the use of a DDD-TPM.
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Bloqueio Atrioventricular , Insuficiência Cardíaca , Marca-Passo Artificial , Bloqueio Atrioventricular/etiologia , Bloqueio Atrioventricular/terapia , Bradicardia/terapia , Estimulação Cardíaca Artificial/métodos , Seguimentos , Insuficiência Cardíaca/etiologia , Humanos , Marca-Passo Artificial/efeitos adversos , Pontuação de Propensão , Estudos RetrospectivosRESUMO
PURPOSE: Osteoporosis is a well-known adverse effect of androgen deprivation therapy for prostate cancer. This study aimed to reveal the factors associated with the diagnosis of osteoporosis in prostate cancer patients undergoing androgen deprivation therapy. METHODS: This retrospective cross-sectional study included 106 prostate cancer patients treated with androgen deprivation therapy. Patients with bone metastasis at the initiation of androgen deprivation therapy and those with castration-resistant prostate cancer were excluded. Bone mineral density was measured at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry. Osteoporosis was defined as bone mineral density equal to or below either -2.5 SD or 70% of the mean in young adults. The association between clinicopathological variables and bone mineral density or diagnosis of osteoporosis was investigated. RESULTS: Thirty-six (34%) patients were found to have osteoporosis. The incidence of osteoporosis increased in a stepwise manner depending on the duration of androgen deprivation therapy. Multivariate logistic regression analysis identified a longer duration of androgen deprivation therapy (months, odd's ratio = 1.017, P = 0.006), lower body mass index (kg/m2, odd's ratio = 0.801, P = 0.005) and higher serum alkaline phosphatase value (U/l, odd's ratio 1.007, P = 0.014) as the factors independently associated with the diagnosis of osteoporosis. Eleven out of 50 (22%), 14 out of 35 (40%) and 11 out of 20 patients (55%) were osteoporotic in the patients with serum alkaline phosphatase values <238 U/l, 238-322 U/l and >322 U/l, respectively (P = 0.022). CONCLUSIONS: Osteoporosis is common in prostate cancer patients undergoing androgen deprivation therapy; furthermore, its incidence increases depending on the duration of androgen deprivation therapy. Bone mineral density testing should be considered for all patients on androgen deprivation therapy, especially for those with a lower body mass index and higher serum alkaline phosphatase value.
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Antagonistas de Androgênios , Neoplasias da Próstata , Fosfatase Alcalina , Antagonistas de Androgênios/efeitos adversos , Androgênios , Densidade Óssea , Estudos Transversais , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Estudos RetrospectivosRESUMO
PURPOSE: The low anterior resection syndrome (LARS) score (LS) has been widely validated and has become an international tool for evaluating postoperative bowel dysfunction. However, many physicians still use the conventional incontinence scores in LARS treatment. Moreover, interpretation of LS and its relationship with conventional incontinence scores are not yet well understood. Here we compared the LS with the Cleveland Clinic Incontinence Score (CCIS) to clarify the clinical utility and characteristics of the LARS score. METHODS: We performed a multicentre observational study, recruiting 246 rectal cancer patients following sphincter-preserving surgery. Patients completed the LS, CCIS, and SF36 questionnaires. RESULTS: The response rate was 76.4%, and a total of 180 patients were analysed. The LS was strongly correlated with the CCIS (P < 0.001, rs = 0.727). However, among 116 patients determined to not have incontinence (CCIS 0-5), 51 (44%) were diagnosed with LARS (29 with minor LARS and 22 with major LARS). Among 68 patients without LARS, only 3 were diagnosed as having incontinence (CCIS > 6). In comparison with background factors, aging and elapsed time were associated with only LS. High LS and CCIS both showed significant quality-of-life impairment as assessed by the SF-36. CONCLUSION: This is the first study to determine the difference in the numeric values between the CCIS and LS. The LS can be a convenient tool for LARS screening, identifying a wide range of patients with LARS, including those with incontinence evaluated by CCIS. Assessment using the CCIS may often underestimate LARS.
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Complicações Pós-Operatórias , Neoplasias Retais , Humanos , Complicações Pós-Operatórias/diagnóstico , Qualidade de Vida , Neoplasias Retais/diagnóstico , Neoplasias Retais/cirurgia , Inquéritos e Questionários , SíndromeRESUMO
BACKGROUND: The optimum cut-off value of premature atrial contraction (PAC) burden (CV-PACb) in 24-h Holter electrocardiography (24-h ECG) for predicting atrial fibrillation (AF) is debatable, with few validation data.MethodsâandâResults:We retrospectively analyzed 61 patients already diagnosed with AF (AD-AF) and 147 patients never diagnosed with AF (ND-AF), aged ≥50 years, free of heart disease, and who had undergone 24-h ECG and transthoracic echocardiography (TTE). Receiver operating characteristic analysis demonstrated that 0.4% was the optimal CV-PACb differentiating AD-AF from ND-AF, with 69% sensitivity and 72% specificity (area under the curve [AUC] 0.72; 95% confidence interval [CI] 0.65-0.79); however, the left atrial volume index was not significant (AUC 0.60; 95% CI 0.51-0.68). To verify the CV-PACb, new propensity-matched cohorts (i.e., subjects with a PAC burden ≥0.4% and <0.4%; n=69 in each group) were compared based on new detection of AF at a median follow-up of 50 months (interquartile range 12-60 months) Multivariable Cox regression analysis revealed that among 24-h ECG and TTE findings, only PAC burden ≥0.4% was independently associated with incident AF (hazard ratio 5.28; 95% CI 1.28-26.11; P=0.023). CONCLUSIONS: A high PAC burden (≥0.4%) in 24-h ECG was a reliable indicator to identify undiagnosed AF, whereas TTE parameters did not show any predictive value.
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Fibrilação Atrial , Fibrilação Atrial/diagnóstico , Complexos Atriais Prematuros/diagnóstico , Eletrocardiografia , Eletrocardiografia Ambulatorial , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Fatores de RiscoRESUMO
The differences in aortic root geometry associated with various valve-sparing root replacement (VSRR) techniques have not fully been understood. We evaluated the root configuration of current VSRR techniques by developing in vitro test apparatus. Six fresh porcine hearts were used for each model. The aortic root remodeling control group involved replacement of the ascending aorta with diameter reduction of sino-tubular junction (STJ) (C1). The aortic valve reimplantation control group involved replacement of the ascending aorta alone (C2). VSRR included remodeling without (RM) or with annuloplasty (RM + A) and reimplantation with a tube (RI) or a handmade neo-Valsalva graft (RI + V). The root geometry of each model in response to closing hydraulic pressures of 80 and 120 mmHg was investigated using echocardiography. Among the VSRR models, RM yielded the largest aorto-ventricular junction (AVJ), which was similar to those in non-VSRR models [mean AVJ diameter (mm) at 80 mmHg; RM = 25.1 ± 1.5, RM + A = 20.9 ± 0.7, RI = 20.7 ± 0.9, RI + V = 20.8 ± 0.4]. RI + V yielded the largest Valsalva size and largest ratio of Valsalva/AVJ, which was similar to the control group [mean Valsalva diameter (mm) at 80 mmHg; RM = 28.4 ± 1.4, RM + A = 25.8 ± 1.3, RI = 23.6 ± 1.0, RI + V = 30.5 ± 0.8, ratio of Valsalva/AVJ at 80 mmHg; RM = 1.14 ± 0.06, RM + A = 1.24 ± 0.06, RI = 1.15 ± 0.06, RI + V = 1.47 ± 0.05]. The STJ diameter at 80 mmHg was numerically smaller with RM + A (22.4 ± 1.2 mm) than with RM (24.8 ± 2.3 mm, p = 0.11). There were no significant differences in AVJ, Valsalva, or STJ distensibility or ellipticity between procedures. Current modifications, including annuloplasty for remodeling or reimplantation in the setting of neo-Valsalva graft, yield near-physiological root geometries.
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Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca , Reimplante , Remodelação Ventricular/fisiologia , Animais , Aorta/patologia , Aorta/cirurgia , Valva Aórtica/patologia , Insuficiência da Valva Aórtica/patologia , Insuficiência da Valva Aórtica/cirurgia , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/métodos , Modelos Biológicos , Pressão , Reoperação/métodos , Suínos , Resultado do Tratamento , Valva Tricúspide/cirurgiaRESUMO
BACKGROUND: Although left bundle-branch block (LBBB) is a known conduction disorder that occurs after transcatheter aortic valve implantation (TAVI), its clinical impact in the Japanese population remains unclear.MethodsâandâResults:Of the 298 consecutive patients who underwent TAVI from January 2016 to December 2018 in a high-volume center in Japan, 68 with prior or periprocedural permanent pacemaker implantation (PPI), pre-existing LBBB, death during hospitalization, aborted procedure, or incomplete data were excluded. Among the final cohort of 230 patients, new-onset LBBB occurred in 90 (39%) after TAVI and persisted at 1-month follow up in 29 patients (13%; persistent new-onset LBBB, PN-LBBB). On multivariable analysis, self-expandable valve (SEV) use was found to be the only predictor of PN-LBBB (odds ratio: 4.39, 95% confidence interval: 1.69-11.41, P=0.002). There were no differences between patients with and without PN-LBBB in terms of overall mortality (18.8% vs. 26.0%, log-rank P=0.90) or need for late PPI (4.0% vs. 3.5%, log-rank P=0.74), yet there was an increased re-admission rate for heart failure (HF) in the PN-LBBB group (15.6% vs. 8.0%, log-rank P=0.046) at a median follow up of 431 (interquartile range, 271-733) days. CONCLUSIONS: PN-LBBB following TAVI was not associated with mortality or late PPI, but with a higher incidence of HF-related re-hospitalization at the mid-term follow up.
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Estenose da Valva Aórtica/cirurgia , Bloqueio de Ramo/epidemiologia , Hospitais com Alto Volume de Atendimentos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/mortalidade , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/mortalidade , Bloqueio de Ramo/terapia , Estimulação Cardíaca Artificial , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Incidência , Japão/epidemiologia , Masculino , Readmissão do Paciente , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: Surgical site infection (SSI) occurs at a high rate after ileostomy closure. The effect of preventive negative-pressure wound therapy (NPWT) on SSI development in closed wounds remains controversial. We conducted a prospective multicenter study to evaluate the usefulness of preventive NPWT for SSI after ileostomy closure. METHODS: From January 2018 to November 2018, 50 patients who underwent closure of ileostomy created after surgery for colorectal cancer participated in this study. An NPWT device was applied to each wound immediately after surgery and then treatment was continued for 3 days. The primary endpoint was 30-day SSI, and the secondary endpoints were the incidence of seroma, hematoma, and adverse events related to NPWT. RESULTS: No patients developed SSI, seroma, or hematoma. Adverse events that may have been causally linked with NPWT were contact dermatitis in two patients and wound pain in one patient, and there were no cases of discontinuation or decompression of NPWT. CONCLUSION: The use of NPWT following ileostomy closure may be useful for reducing the development of SSI in colorectal cancer patients. This is a prospective multicenter pilot study and we are planning a comparative study based on these successful results. TRAIL REGISTRATION: Registration number: UMIN000032053 ( https://www.umin.ac.jp/ ).
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Neoplasias Colorretais/cirurgia , Ileostomia/efeitos adversos , Tratamento de Ferimentos com Pressão Negativa/métodos , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/terapia , Técnicas de Fechamento de Ferimentos/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Ileostomia/métodos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Resultado do TratamentoRESUMO
Calmodulin is a ubiquitous Ca2+ sensor molecule encoded by three distinct calmodulin genes, CALM1-3. Recently, mutations in CALM1-3 have been reported to be associated with severe early-onset long-QT syndrome (LQTS). However, the underlying mechanism through which heterozygous calmodulin mutations lead to severe LQTS remains unknown, particularly in human cardiomyocytes. We aimed to establish an LQTS disease model associated with a CALM2 mutation (LQT15) using human induced pluripotent stem cells (hiPSCs) and to assess mutant allele-specific ablation by genome editing for the treatment of LQT15. We generated LQT15-hiPSCs from a 12-year-old boy with LQTS carrying a CALM2-N98S mutation and differentiated these hiPSCs into cardiomyocytes (LQT15-hiPSC-CMs). Action potentials (APs) and L-type Ca2+ channel (LTCC) currents in hiPSC-CMs were analyzed by the patch-clamp technique and compared with those of healthy controls. Furthermore, we performed mutant allele-specific knockout using a CRISPR-Cas9 system and analyzed electrophysiological properties. Electrophysiological analyses revealed that LQT15-hiPSC-CMs exhibited significantly lower beating rates, prolonged AP durations, and impaired inactivation of LTCC currents compared with control cells, consistent with clinical phenotypes. Notably, ablation of the mutant allele rescued the electrophysiological abnormalities of LQT15-hiPSC-CMs, indicating that the mutant allele caused dominant-negative suppression of LTCC inactivation, resulting in prolonged AP duration. We successfully recapitulated the disease phenotypes of LQT15 and revealed that inactivation of LTCC currents was impaired in CALM2-N98S hiPSC model. Additionally, allele-specific ablation using the latest genome-editing technology provided important insights into a promising therapeutic approach for inherited cardiac diseases.
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Calmodulina/genética , Calmodulina/metabolismo , Células-Tronco Pluripotentes Induzidas/fisiologia , Síndrome do QT Longo/genética , Potenciais de Ação , Alelos , Arritmias Cardíacas/genética , Diferenciação Celular/genética , Linhagem Celular , Fenômenos Eletrofisiológicos , Sistema de Condução Cardíaco , Humanos , Síndrome do QT Longo/metabolismo , Masculino , Mutação de Sentido Incorreto , Miócitos Cardíacos/citologia , Técnicas de Patch-ClampRESUMO
BACKGROUND: The entirely subcutaneous implantable cardioverter defibrillator (S-ICD) was introduced as a new alternative to conventional transvenous ICD (TV-ICD) in Japan in February 2016, but its safety and efficacy are unclear.MethodsâandâResults:A total of 60 patients (48 men, median age, 60 years; IQR, 44-67 years; primary prevention, n=24) underwent S-ICD implantation between February 2016 and August 2017. The device pocket was formed in the intermuscular space between the serratus anterior muscle and the latissimus dorsi muscle, and the parasternal S-ICD lead was placed according to pre-implant screening. Defibrillation test was performed in 56 patients (93%). Ventricular fibrillation (VF) was induced in 55 patients and terminated by a single 65-J shock in all patients. The median time to shock therapy was 13.4 s (IQR, 12.1-14.9 s) and the median post-shock impedance of the S-ICD lead was 64 Ω (IQR, 58-77 Ω). There were no operation-related complications or subsequent infectious complications. During follow-up (median, 275 days; IQR, 107-421 days), 1 patient (1.7%) had appropriate shock for VF with successful termination, whereas 5 patients (8.3%) had inappropriate shock due to oversensing of myopotential (n=3) or T-wave (n=1), and detection of supraventricular tachycardia (n=1). CONCLUSIONS: S-ICD is a safe and effective alternative to conventional TV-ICD. The long-term safety and efficacy of the S-ICD need further investigation.
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Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis/normas , Fibrilação Ventricular/terapia , Adulto , Idoso , Desfibriladores Implantáveis/efeitos adversos , Cardioversão Elétrica/métodos , Cardioversão Elétrica/normas , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Prevenção Primária/métodos , Prevenção Primária/normas , Prevenção Secundária/métodos , Prevenção Secundária/normas , Taquicardia/diagnóstico , Resultado do Tratamento , Fibrilação Ventricular/diagnósticoRESUMO
BACKGROUND: There is a scarcity of reports on the clinical characteristics and management practice in contemporary all-comer patients with acute decompensated heart failure (ADHF). MethodsâandâResults: The Kyoto Congestive Heart Failure (KCHF) registry is a prospective observational cohort study enrolling 4,056 consecutive patients who had hospital admission due to ADHF without any exclusion criteria between October 2014 and March 2016 in the 19 participating hospitals in Japan. Baseline characteristics, clinical presentations, management, and in-hospital outcomes were compared between heart failure (HF) with reduced left ventricular ejection fraction (LVEF; HFrEF, LVEF <40%), HF with mid-range LVEF (HFmrEF, LVEF 40-49%), and HF with preserved LVEF (HFpEF, LVEF ≥50%). Of the 4,041 patients with documented LVEF, 1,744 (43%) had HFpEF; 746 (19%), HFmrEF; and 1,551 (38%), HFrEF. The median age was 80 years (IQR, 72-86 years) in the entire population, and was higher with increasing LVEF (P<0.001). The in-hospital mortality rate was higher in the HFrEF than in the HFmrEF and HFpEF groups (9.2%, 4.8%, and 5.1%, respectively, P<0.001). CONCLUSIONS: This registry elucidated the clinical features and clinically relevant in-hospital outcomes in contemporary consecutive patients with ADHF in real-world clinical practice in Japan. When classified by LVEF, significant differences in characteristics and in-hospital outcomes existed between patients with HFrEF, HFmrEF, and HFpEF.
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Insuficiência Cardíaca , Mortalidade Hospitalar , Hospitalização , Volume Sistólico , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Japão/epidemiologia , Masculino , Estudos Prospectivos , Sistema de Registros , Taxa de Sobrevida , SíndromeRESUMO
We report the case of an 84-year-old female with symptomatic bradycardia due to a complete atrioventricular block, who carried absent right and persistent left superior vena cava (SVC). Implantation of a pacing lead, particularly within the right ventricle (RV) in a patient with this venous anomaly is accompanied by technical difficulties. However, the apparatus consisting of a fixed-curve sheath (Model C315-S10, Medtronic, Inc., Minneapolis, MN, USA) and a lumenless fixed-screw pacing lead (Model 3830, Medtronic), allowed a rapid delivery into the RV without any complications. By rotating the Model C315-S10 sheath in the counterclockwise direction in the right atrium, its tip faced the tricuspid orifice, advanced across the tricuspid valve and confronted the RV lower septum near the apex. Then the RV-lead was fixed with acceptable pacing and sensing parameters. Utilizing a lumenless pacing lead and a preformed sheath to deliver it is a novel approach that could be helpful in pacemaker implantation in patients with absent right and persistent left SVC.
RESUMO
BACKGROUND: Variability in the international normalized ratio (INR) of prothrombin time has been suggested to be related to outcome in patients with atrial fibrillation (AF) under warfarin therapy, but its determinants remain unclear.MethodsâandâResults:The study population consisted of 626 AF patients under warfarin therapy in the Shinken Database (n=22,230). INR variability was calculated by Fihn's method. Determinants of high log INR variability (defined as over mean+standard deviation) were determined by logistic regression analyses. Symptomatic heart failure (odds ratio [OR] 3.974, 95% confidence interval [CI] 2.510-6.292), older age (≥75 years old; OR 2.984, 95% CI 1.844-4.826) and severe renal dysfunction (eGFR <30 mL/min/1.73 m2; OR 3.918, 95% CI 1.742-8.813) were identified as independent predictors of high INR variability on multivariate logistic regression analysis. CONCLUSIONS: The determinants of INR variability in AF patients under warfarin therapy could assist Japanese clinicians in identifying patients likely to show unstable warfarin control irrespective of the definition of the target INR range.
Assuntos
Fibrilação Atrial/diagnóstico , Coeficiente Internacional Normatizado , Varfarina/uso terapêutico , Idoso , Fibrilação Atrial/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Japão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: TheSCN5Agene encodes the α subunit of the cardiac voltage-gated sodium channel, NaV1.5. The missense mutation, D1275N, has been associated with a range of unusual phenotypes associated with reduced NaV1.5 function, including cardiac conduction disease and dilated cardiomyopathy. Curiously, the reported biophysical properties ofSCN5A-D1275N channels vary with experimental system.MethodsâandâResults:First, using a human embryonic kidney (HEK) 293 cell-based heterologous expression system, theSCN5A-D1275N channels showed similar maximum sodium conductance but a significantly depolarizing shift of activation gate (+10 mV) compared to wild type. Second, we generated human-induced pluripotent stem cells (hiPSCs) from a 24-year-old female who carried heterozygousSCN5A-D1275N and analyzed the differentiated cardiomyocytes (CMs). AlthoughSCN5Atranscript levels were equivalent between D1275N and control hiPSC-CMs, both the total amount of NaV1.5 and the membrane fractions were reduced approximately half in the D1275N cells, which were rescued by the proteasome inhibitor MG132 treatment. Electrophysiological assays revealed that maximum sodium conductance was reduced to approximately half of that in control hiPSC-CMs in the D1275N cells, and maximum upstroke velocity of action potential was lower in D1275N, which was consistent with the reduced protein level of NaV1.5. CONCLUSIONS: This study successfully demonstrated diminished sodium currents resulting from lower NaV1.5 protein levels, which is dependent on proteasomal degradation, using a hiPSC-based model forSCN5A-D1275N-related sodium channelopathy.
Assuntos
Canalopatias/genética , Células-Tronco Pluripotentes Induzidas/citologia , Mutação de Sentido Incorreto , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Eletrofisiologia Cardíaca , Células HEK293 , Humanos , Miócitos Cardíacos/citologia , Canal de Sódio Disparado por Voltagem NAV1.5/análise , Complexo de Endopeptidases do Proteassoma/metabolismo , Sódio/metabolismoRESUMO
BACKGROUNDS: Postpacing interval (PPI) measured after entrainment pacing describes the distance between pacing site and reentrant circuit. However, the influential features to PPI remain to be elucidated. METHODS AND RESULTS: This study included 22 cases with slow/fast atrioventricular (AV) nodal reentrant tachycardia (AVNRT), 14 orthodromic AV reciprocating tachycardia (AVRT) using an accessary pathway, 22 typical atrial flutter (AFL), and 18 other macroreentrant atrial tachycardia (atypical AFL). Rapid pacing at a pacing cycle length (PCL) 5% shorter than tachycardia cycle length (TCL) was done from a site on or close to the reentry circuit. Pacing sites included the coronary sinus ostium in AVNRT, earliest atrial activation site in AVRT, and cavotricuspid isthmus in typical AFL. In atypical AFL, tachycardia circuit was determined on the basis of CARTO mapping, and then the pacing site was. TCL was significantly longer in AVNRT and AVRT than in typical AFL and atypical AFL (both P < 0.05). PCL minus TCL value was similar among the 4 groups. PPI minus TCL value (milliseconds) was significantly longer in AVNRT (median, 40 [IQR, 29-60.8]) and AVRT (34 [20-47]) than in typical AFL (0 [0-4]) and atypical AFL (3.5 [0-8]) (both P < 0.05). Furthermore, PPI minus TCL was prolonged with shortening of PCL in AVNRT and AVRT (both P < 0.05), whereas it was unchanged in typical AFL (P = 0.50). CONCLUSION: PPI after concealed entrainment is prolonged compared with TCL when the reentry circuit involves a slow conduction zone with a decremental conduction property such as the AV node.