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BACKGROUND: Based on the results of a clinical trial in Japan, transcatheter aortic valve replacement (TAVR) for hemodialysis (HD) patients gained approval; however, mid-term TAVR outcomes and transcatheter aortic valve (TAV) durability in HD patients remain unexplored.MethodsâandâResults: We analyzed background, procedural, in-hospital outcome, and follow-up data for 101 HD patients and 494 non-HD patients who underwent TAVR using balloon-expandable valves (SAPIEN XT or SAPIEN 3) retrieved from Osaka University Hospital TAVR database. Periprocedural mortality and TAVR-related complications were comparable between HD and non-HD patients. However, Kaplan-Meier analysis revealed that HD patients had significantly lower survival rates (log-rank test, P<0.001). In addition, HD patients had significantly higher rates of severe structural valve deterioration (SVD) than non-HD patients (Gray test, P=0.038). CONCLUSIONS: TAVR in HD patients had comparable periprocedural mortality but inferior mid-term survival and TAV durability than in non-HD patients. Indications for TAVR in younger HD patients should be carefully determined, considering the possibility of a TAV-in-TAV procedure when early SVD occurs.
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Advance care planning (ACP) is essential in managing serious and chronic illnesses to ensure that patients receive care aligned with their personal values, goals, and preferences. This review focuses on integrating ACP in the treatment of patients receiving implantable left ventricular assist devices (VADs). The heart failure palliative care team developed a unique advance directive form and pamphlet to facilitate ACP discussions, emphasizing not only medical treatment preferences but also patients' values and life goals.The study highlights the distinction between bridge to transplantation (BTT) and destination therapy (DT) in VAD patients, with different goals and considerations for ACP. The use of decision aids developed especially for DT candidates as a communication tool helps in sharing patients' wishes and facilitates shared decision-making, particularly in the complex decisions surrounding DT therapy.Challenges in implementing ACP, such as time constraints due to urgent medical conditions, difficulties in patient communication, and the recent COVID-19 pandemic, are addressed. The need for a comprehensive healthcare system capable of supporting patients' ACP wishes, especially in the community setting, is also pointed out.Future directions include not only developing materials to ease ACP discussions and ensuring that ACP content is shared among healthcare providers to foster collaborative and detailed planning, but also a call for widespread adoption of ACP in Japan.This is a translation of a paper written in Japanese Journal of Artificial Organs (Vol. 52, No. 1, pp. 89-92) with additions and corrections.
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Planejamento Antecipado de Cuidados , Coração Auxiliar , Humanos , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/cirurgia , COVID-19/epidemiologia , Japão , População do Leste AsiáticoRESUMO
We examined the number of patients abandoning cardiac replacement therapy due to the inability to secure a designated caregiver. At Osaka University Hospital Heart Center, when we receive a consultation for a patient with severe heart failure from another hospital, a heart failure team makes a visit to the referring hospital as soon as possible. We retrospectively analyzed this hospital-visit database. We received 199 severe heart failure consultations from 2016-2023. Issues identified during hospital visits included age ≥ 65 years (8%), inability to confirm the patient's intention (8.5%), and explicit refusal of therapy (2.5%). Medical problems included multiple organ failure (18.1%), obesity (13.1%), diabetes (9.5%), malignancy (5.5%), chronic dialysis (1.0%), and other systemic diseases (12.6%). Adherence problems included poor medication compliance (3.5%), history of heavy drinking (2.5%), and smoking (2.0%). Social problems included inadequate family support in 16.1% of patients. Of the 199 patients, 95 (48.0%) proceeded to a heart transplant and LVAD indication review meeting at Osaka University Hospital. The remaining 104 patients (52.0%) did not proceed to the meeting. Reasons included improvement of heart failure with conservative treatment in 37 cases (35.6%), death before discussion in 21 cases (20.2%), medical contraindications in 18 cases (18.3%), lack of caregivers in 18 cases (18.3%; 9.5% of 199 cases), and patient refusal in 5 cases (4.8%). Approximately 10% of patients consulted at Osaka University Hospital Heart Center for severe heart failure abandoned cardiac replacement therapy due to the lack of caregivers.
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The arrival of modern humans into previously unoccupied island ecosystems is closely linked to widespread extinction, and a key reason cited for Pleistocene megafauna extinction is anthropogenic overhunting. A common assumption based on late Holocene records is that humans always negatively impact insular biotas, which requires an extrapolation of recent human behavior and technology into the archaeological past. Hominins have been on islands since at least the early Pleistocene and Homo sapiens for at least 50 thousand y (ka). Over such lengthy intervals it is scarcely surprising that significant evolutionary, behavioral, and cultural changes occurred. However, the deep-time link between human arrival and island extinctions has never been explored globally. Here, we examine archaeological and paleontological records of all Pleistocene islands with a documented hominin presence to examine whether humans have always been destructive agents. We show that extinctions at a global level cannot be associated with Pleistocene hominin arrival based on current data and are difficult to disentangle from records of environmental change. It is not until the Holocene that large-scale changes in technology, dispersal, demography, and human behavior visibly affect island ecosystems. The extinction acceleration we are currently experiencing is thus not inherent but rather part of a more recent cultural complex.
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Extinção Biológica , Fósseis/história , Hominidae/psicologia , Tecnologia/história , Animais , Arqueologia/métodos , Evolução Biológica , Ecossistema , História Antiga , Hominidae/fisiologia , Humanos , Paleontologia/métodosRESUMO
PURPOSE: Culture of extracted drains or epicardial pacing wires is an easy and noninvasive method for detecting mediastinitis after open-heart surgery, although studies on its sensitivity and specificity are limited. We, therefore, investigated the usefulness of this approach for diagnosing mediastinitis. METHODS: We retrospectively studied the culture results of drains and epicardial pacing wires extracted from 3308 patients. Prediction models of mediastinitis with and without culture results added to clinical risk factors identified by a logistic regression analysis were compared. RESULTS: The incidence of mediastinitis requiring surgery was 1.89% (n = 64). Staphylococcus was the causative bacterium in 64.0% of cases. The sensitivity, specificity, and positive and negative predictive values of positive culture results were 50.8%, 91.8%, 10.7%, and 99.0%, respectively. Methicillin-resistant Staphylococcus aureus had the highest positive predictive value (61.5%). A multivariate analysis identified preoperative hemodialysis (OR 5.40 [2.54-11.5], p < 0.01), long operative duration (p < 0.01), postoperative hemodialysis (OR 2.25 [1.01-4.98], p < 0.05), and positive culture result (OR 10.2 [5.88-17.7], p < 0.01) as independent risk factors. The addition of culture results to pre- and postoperative hemodialysis and a lengthy operative time improved the prediction of mediastinitis. CONCLUSIONS: A culture survey using extracted drains and epicardial pacing wires may provide useful information for diagnosing mediastinitis.
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Procedimentos Cirúrgicos Cardíacos , Mediastinite , Staphylococcus aureus Resistente à Meticilina , Humanos , Estudos Retrospectivos , Mediastinite/diagnóstico , Mediastinite/etiologia , Mediastinite/terapia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , StaphylococcusRESUMO
The world's first clinical cardiac xenotransplantation, using a genetically engineered pig heart with 10 gene modifications, prolonged the life of a 57-year-old man with no other life-saving options, by 60 days. It is foreseeable that xenotransplantation will be introduced in clinical practice in the United States. However, little clinical or regulatory progress has been made in the field of xenotransplantation in Japan in recent years. Japan seems to be heading toward a "device lag", and the over-importation of medical devices and technology in the medical field is becoming problematic. In this review, we discuss the concept of pig-heart xenotransplantation, including the pathobiological aspects related to immune rejection, coagulation dysregulation, and detrimental heart overgrowth, as well as genetic modification strategies in pigs to prevent or minimize these problems. Moreover, we summarize the necessity for and current status of xenotransplantation worldwide, and future prospects in Japan, with the aim of initiating xenotransplantation in Japan using genetically modified pigs without a global delay. It is imperative that this study prompts the initiation of preclinical xenotransplantation research using non-human primates and leads to clinical studies.
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Animais Geneticamente Modificados , Transplante de Coração , Transplante Heterólogo , Animais , Suínos , Japão , Humanos , Rejeição de Enxerto , Masculino , Pessoa de Meia-Idade , Engenharia Genética , Coagulação Sanguínea , CoraçãoRESUMO
BACKGROUND: The use of hybrid operating rooms (HOR) for transcatheter aortic valve implantation (TAVI) has increased, so radiation exposure during procedures that use X-ray fluoroscopy is a fundamental problem not only for patients but also for surgeons and interventional cardiologists, increasing the risk of cataracts among operators. We investigated the efficacy of leaded glasses and protective sheets for ocular radiation protection.MethodsâandâResults: Between January 2020 and February 2021 we enrolled 54 TAVI procedures using the transfemoral approach. The subjects were divided into a curtain protection group (Group C, n=20), glass protection group (Group G, n=17), and sheet protection group (Group S, n=17). The cumulative dose (CD) of the operators showed a decreasing trend in Group S compared with the other two groups. The CD normalized by dose area product (CD/DAP) of the operators was significantly reduced in Group S compared with Group C. However, Group G showed no significant difference compared with Group C. Regarding the distribution of CD/DAP, Group S had a significantly lower distribution than that in groups C and G. CONCLUSIONS: Protective sheets provide more stable radiation protection than conventional curtains or leaded glasses.
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Estenose da Valva Aórtica , Exposição à Radiação , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/métodos , Estenose da Valva Aórtica/cirurgia , Doses de Radiação , Fatores de Risco , Exposição à Radiação/efeitos adversos , Exposição à Radiação/prevenção & controle , Fluoroscopia/efeitos adversos , Valva Aórtica/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: The superiority of a fully magnetically levitated centrifugal-flow left ventricular assist device (LVAD) in terms of overall survival, stroke events and pump thrombosis has been demonstrated in previous international analyses, so we evaluated a Japanese cohort for the same.MethodsâandâResults: This retrospective observational study was conducted at Osaka University Medical Hospital and the National Cerebral and Cardiovascular Center in Japan. A total of 75 consecutive patients who underwent HeartMate3 (HM3) implantation were included. The primary endpoint was on-device survival, and the secondary endpoint was the incidence of LVAD-related complications at 2 years. All parameters were compared with those of the previously performed HeartMate II (HMII) implantation in 197 cases. The on-device survival rates were 94.7% and 92.3% in the HM3 and HMII groups, respectively, at the 2-year follow-up (P=0.62). The rehospitalization-free rate after implantation was 61.8% in the HM3 group, which was significantly higher than that in the HMII group (relative risk, 0.35; 95% confidence interval [CI], 0.23-0.55; P<0.0001). Event-free survival rates from cerebral cerebrovascular events and pump thrombosis in the HM3 group were significantly higher than those in the HMII group, at 97.2% and 100%, respectively (relative risk, 0.14; 95% CI 0.03-0.58); P=0.0015 and relative risk, not calculated; P=0.049, respectively). CONCLUSIONS: Satisfactory short-term outcomes were observed after HM3 implantation in a Japanese cohort.
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Insuficiência Cardíaca , Coração Auxiliar , Acidente Vascular Cerebral , Trombose , Humanos , Coração Auxiliar/efeitos adversos , Japão/epidemiologia , Acidente Vascular Cerebral/complicações , Trombose/etiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
We evaluated the cardiac function recovery following skeletal myoblast cell-sheet transplantation and the long-term outcomes after applying this treatment in 23 patients with ischemic cardiomyopathy. We defined patients as "responders" when their left ventricular ejection fraction remained unchanged or improved at 6 months after treatment. At 6 months, 16 (69.6%) patients were defined as responders, and the average increase in left ventricular ejection fraction was 4.9%. The responders achieved greater improvement degrees in left ventricular and hemodynamic function parameters, and they presented improved exercise capacity. During the follow-up period (56 ± 28 months), there were four deaths and the overall 5-year survival rate was 95%. Although the responders showed higher freedom from mortality and/or heart failure admission (5-year, 81% versus 0%; p = 0.0002), both groups presented an excellent 5-year survival rate (5-year, 93% versus 100%; p = 0.297) that was higher than that predicted using the Seattle Heart Failure Model. The stepwise logistic regression analysis showed that the preoperative estimated glomerular filtration rate and the left ventricular end-systolic volume index were independently associated with the recovery progress. Approximately 70% of patients with "no-option" ischemic cardiomyopathy responded well to the cell-sheet transplantation. Preoperative renal and left ventricular function might predict the patients' response to this treatment.
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Cardiomiopatias/terapia , Insuficiência Cardíaca/terapia , Mioblastos/transplante , Isquemia Miocárdica/terapia , Cardiomiopatias/genética , Cardiomiopatias/patologia , Feminino , Coração/crescimento & desenvolvimento , Coração/fisiopatologia , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/patologia , Ventrículos do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/genética , Isquemia Miocárdica/patologia , Volume Sistólico/genética , Transplante Autólogo/efeitos adversos , Transplante Autólogo/métodos , Função Ventricular Esquerda/genéticaRESUMO
Thrombus formation is a troublesome and sometimes lethal complication occurring in patients with severe heart failure and supported by a left ventricular assist device (LVAD). Appropriate treatment for pump thrombosis especially in emergency cases with severe pump failure is difficult to choose. Herein, we present important findings of a case of unexpected LVAD pump thrombosis that rapidly developed into serious pump failure and circulatory arrest due to total obstruction of the LVAD inflow tract by a huge thrombus.
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Insuficiência Cardíaca , Coração Auxiliar , Trombose , Humanos , Coração Auxiliar/efeitos adversos , Cânula/efeitos adversos , Valva Aórtica , Trombose/etiologia , Trombose/cirurgia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/cirurgiaRESUMO
A pump infection is a fatal complication specific to left ventricular assist devices. Infection recurrence is a major concern when device exchange is indicated for pump infection. In the present case, we used the Impella 5.0 to maintain proper hemodynamics and to treat the infection in the absence of an implantable device. We demonstrate that the Impella 5.0 can serve as an effective bridge for device exchange by controlling infection and minimizing organ dysfunction, despite prolonged management.
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Coração Auxiliar , Humanos , Hemodinâmica , Resultado do Tratamento , Choque Cardiogênico/terapiaRESUMO
Women with implantable left-ventricular assist devices (LVADs) experience gynecological bleeding (GYN-bleeding). However, a few studies have investigated female-specific problems. Therefore, this study aimed to identify the risk factors for adverse GYN-bleeding after LVAD implantation. We retrospectively analyzed 59 women (mean age: 41 ± 15 years) with long-term implantable LVAD support (≥ 6 months) at our institution between 2005 and 2018. The history of GYN-bleeding before implantation was defined as abnormal utero-ovarian bleeding, excessive menstruation, uterine fibroids, and endometrial lesions. GYN-bleeding after implantation was defined as a requirement of emergency outpatient visits and/or hospitalization, blood transfusions, hormonal therapy, and/or surgery. Additionally, risk factors for GYN-bleeding were identified using the Cox regression model. Twenty-four GYN-bleeding cases were seen in 15 patients (two times: five patients, three times: two patients, 0.18 events per patient-year). The 1- and 2-year GYN-bleeding-free rates were 84% and 73%, respectively. Twelve patients (17 events) required RBC ≥ 4 units, and five patients (7 events) required FFP ≥ 4 units. Seven patients required pseudomenopausal treatment after blood transfusion, and four patients required surgical treatment. Fifteen patients with GYN-bleeding after implantation were significantly younger than the remaining 44 patients without GYN-bleeding (34 ± 12 years vs. 43 ± 16 years, P = 0.02). Multivariable risk analysis showed a history of GYN-bleeding before implantation was a significant risk factor (hazard ratio 3.7 [1.2-10.6], P = 0.004). Patients with a history of GYN-bleeding before LVAD implantation have a high risk of developing GYN-bleeding after implantation. We should identify the high-risk population and prepare for the management of GYN-bleeding.
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Insuficiência Cardíaca , Coração Auxiliar , Adulto , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/cirurgia , Coração Auxiliar/efeitos adversos , Hemorragia/etiologia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
In this article, we analyzed 114 adult heart transplantation( HTx) cases from 1999 to 2021. Of these cases, 94% of patients underwent left ventricular assist device ( LVAD) implantation before HTx. The mean period of LVAD support was 3.0 ±1.2 years. Thirty-day mortality was 0.8% and the 10-year survival rate was 89% after HTx. Preoperative and postoperative renal function was the prognostic factors. Long LVAD support was not associated with the long-term survival after HTx.
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Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Adulto , Insuficiência Cardíaca/cirurgia , Humanos , Estudos Retrospectivos , Resultado do Tratamento , UniversidadesRESUMO
BACKGROUND: In patients with severe left ventricular (LV) dysfunction requiring coronary artery bypass grafting (CABG), the association between diabetic status and outcomes after surgery, as well as with survival benefit following bilateral internal thoracic artery (ITA) grafting, remain largely unknown.MethodsâandâResults:Patients (n=188; mean [±SD] age 67±9 years) with LV ejection fraction ≤40% who underwent isolated initial CABG were classified into non-diabetic (n=64), non-insulin-dependent diabetic (NIDM; n=74), and insulin-dependent diabetic (IDM; n=50) groups. During follow-up (mean [±SD] 68±47 months), the 5-year survival rate was 84% and 65% among non-diabetic and diabetic patients, respectively (P=0.034). After adjusting for all covariates, both NIDM and IDM were associated with increased mortality, with hazard ratios (HRs) of 1.9 (95% confidence interval [CI] 1.0-3.7; P=0.049) and 2.4 (95% CI 1.2-4.8; P=0.016), respectively. Among non-diabetic patients, there was no difference in the 5-year survival rate between single and bilateral ITA grafting (86% vs. 80%, respectively; P=0.95), whereas bilateral ITA grafting increased survival among diabetic patients (57% vs. 81%; P=0.004). Multivariate analysis revealed that bilateral ITA was significantly associated with a decreased risk of mortality (HR 0.3; 95% CI 0.1-0.8; P=0.024). CONCLUSIONS: NIDM and IDM were significantly associated with worse long-term clinical outcome after CABG for severe LV dysfunction. Bilateral ITA grafting has the potential to improve survival in diabetic patients with severe LV dysfunction.
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Doença da Artéria Coronariana , Diabetes Mellitus , Artéria Torácica Interna , Disfunção Ventricular Esquerda , Idoso , Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Disfunção Ventricular Esquerda/cirurgiaRESUMO
Infection is a major complication in patients with a left ventricular assist device (LVAD). Once a driveline exit-site infection (DLI) reaches the LVAD component, LVAD exchange may become necessary for radical treatment, although clinical results are not satisfactory. In this report, we describe two cases of LVAD infection successfully treated with pump exchange. During LVAD support, the DLI extended into the pump pocket and the outflow graft despite aggressive surgical debridement and negative pressure wound therapy. These two patients required LVAD exchange for radical treatment, because the estimated waiting period for heart transplantation was at least more than 1 year. The LVAD exchange was performed through median re-sternotomy, and the infected HeartWare ventricular assist device (HVAD) was completely removed under cardiopulmonary bypass. Then, a new LVAD covered with the omentum flap was implanted. These two patients were successfully bridged to heart transplantation after 10 months and 2 years of support without recurrence of infection. These two cases may suggest that the driveline of the HVAD needs to be kept away from the outflow graft to prevent refractory outflow graft infection.
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Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Insuficiência Cardíaca/cirurgia , Coração Auxiliar/efeitos adversos , Humanos , Complicações Pós-Operatórias , Estudos RetrospectivosRESUMO
We report an effective therapeutic approach of mechanical circulatory support for a patient with cardiogenic shock and respiratory insufficiency due to fulminant myocarditis. An Impella® 5.0 was utilized as a left ventricular assist device (VAD) and percutaneous veno-pulmonary extracorporeal membrane oxygenation (ECMO) as a right VAD. These devices were implanted without sternotomy or thoracotomy. Although a combination of Impella and veno-arterial ECMO has been reported as percutaneous biventricular support, there are concerns that this combination is not beneficial for myocardial recovery in patients with respiratory insufficiency, because Impella expels insufficiently oxygenated blood from the left ventricle to the coronary arteries. Our approach took advantage of percutaneous implantation of ECMO and temporary VAD, eliminating the drawbacks of both devices, thus providing a more effective and less invasive form of temporary biventricular support.
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Oxigenação por Membrana Extracorpórea/instrumentação , Implante de Prótese de Valva Cardíaca , Coração Auxiliar , Miocardite/terapia , Choque Cardiogênico/terapia , Terapia Combinada , Desenho de Equipamento , Oxigenação por Membrana Extracorpórea/métodos , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/instrumentação , Implante de Prótese de Valva Cardíaca/métodos , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/cirurgia , Coração Auxiliar/efeitos adversos , Hemodinâmica , Humanos , Pessoa de Meia-Idade , Miocardite/complicações , Miocardite/patologia , Miocardite/fisiopatologia , Choque Cardiogênico/etiologia , Choque Cardiogênico/patologia , Choque Cardiogênico/fisiopatologia , Esternotomia , Resultado do TratamentoRESUMO
Significant aortic regurgitation (AR) is a common complication after continuous-flow left ventricular assist device (LVAD) implantation. Using machine-learning algorithms, this study was designed to examine valuable predictors obtained from LVAD sound and to provide models for identifying AR. During a 2-year follow-up period of 13 patients with Jarvik2000 LVAD, sound signals were serially obtained from the chest wall above the LVAD using an electronic stethoscope for 1 min at 40,000 Hz, and echocardiography was simultaneously performed to confirm the presence of AR. Among the 245 echocardiographic and acoustic data collected, we found 26 episodes of significant AR, which we categorized as "present"; the other 219 episodes were characterized as "none". Wavelet (time-frequency) analysis was applied to the LVAD sound and 19 feature vectors of instantaneous spectral components were extracted. Important variables for predicting AR were searched using an iterative forward selection method. Seventy-five percent of 245 episodes were randomly assigned as training data and the remaining as test data. Supervised machine learning for predicting concomitant AR involved an ensemble classifier and tenfold stratified cross-validation. Of the 19 features, the most useful variables for predicting concomitant AR were the amplitude of the first harmonic, LVAD rotational speed during intermittent low speed (ILS), and the variation in the amplitude during normal rotation and ILS. The predictive accuracy and area under the curve were 91% and 0.73, respectively. Machine learning, trained on the time-frequency acoustic spectra, provides a novel modality for detecting concomitant AR during follow-up after LVAD.
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Acústica , Insuficiência da Valva Aórtica/diagnóstico , Coração Auxiliar/efeitos adversos , Adolescente , Adulto , Idoso , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Insuficiência da Valva Aórtica/etiologia , Insuficiência da Valva Aórtica/fisiopatologia , Inteligência Artificial , Ecocardiografia , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Aprendizado de Máquina Supervisionado , Adulto JovemRESUMO
Severe aortic insufficiency (AI) after implantation of continuous-flow left ventricular-assist device (LVAD) affects device performance and outcomes. However, the mechanism for the occurrence and progression of AI has not been elucidated. We investigated the impact of nonphysiological retrograde blood flow in the aortic root on AI after LVAD implantation. Blood flow pattern was analyzed in patients with and without AI (n = 3 each) who underwent LVAD implantation, by computational fluid dynamics with patient-specific geometries, which were reproduced using electrocardiogram-gated 320-slice computed tomographic images. The total volume of retrograde blood flow during one cardiac cycle (716 ± 88 mL) was higher and the volume of slow blood flow (<0.1 cm/s) (0.16 ± 0.04 cm3 ) was lower in patients with AI than in those without AI (360 ± 111 mL, P = .0495, and 0.49 ± 0.08 cm3 , P = .0495, respectively). No significant difference in wall shear stress on the aortic valve was observed between the groups. Patients with AI had a perpendicular anastomosis at the distal ascending aorta and the simulation in the modified anastomosis model of patients with AI showed that the retrograde blood flow pattern depended on the angle and position of anastomosis. Computational fluid dynamics revealed strong retrograde blood flow in the ascending aorta and aortic root in patients with AI after LVAD implantation. The angle and position of LVAD outflow anastomosis might impact retrograde blood flow and de novo AI after LVAD implantation.
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Insuficiência da Valva Aórtica/etiologia , Circulação Sanguínea/fisiologia , Coração Auxiliar/efeitos adversos , Adolescente , Adulto , Aorta/fisiopatologia , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/fisiopatologia , Eletrocardiografia , Feminino , Humanos , Masculino , Tomografia Computadorizada Multidetectores , Fluxo Pulsátil/fisiologia , Estudos RetrospectivosRESUMO
The expression of immune checkpoint proteins such as programmed cell death protein 1 (PD-1) and its ligand (PD-L1) has been shown to correlate with patient prognosis in many malignant cancers. The expression of PD-L1 is controlled by c-Myc; however, further upstream regulation of PD-L1 expression is largely unknown. We have previously shown that atypical protein kinase C lambda/iota (aPKCλ) phosphorylates the Forkhead box protein O1 (FoxO1) transcription factor at Ser218 to suppress its DNA-binding ability, thereby regulating c-Myc expression and controlling physiologic and pathologic endothelial proliferation. The presence of phosphorylation of FoxO1 at Ser218 (pSer218 FoxO1) in cutaneous angiosarcoma (CAS) strongly correlates with poor patient prognosis. Here, we reported that patients with PD-L1+ cells in CAS lesions showed significantly worse prognosis compared to those that were PD-L1- . Expression of PD-L1 correlated with that of aPKCλ or the presence of pSer218FoxO1. Moreover, suppression of aPKCλ expression or inhibition of its activity in HUVECs or AS-M, an established human angiosarcoma cell line, resulted in decreased PD-L1 expression. Our results suggest that combined treatment with immune checkpoint inhibitors and aPKCλ inhibitors could be a novel treatment strategy for CAS patients.
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Antígeno B7-H1/metabolismo , Proteína Forkhead Box O1/metabolismo , Hemangiossarcoma/metabolismo , Isoenzimas/metabolismo , Proteína Quinase C/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Neoplasias Cutâneas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Feminino , Proteína Forkhead Box O1/química , Regulação Neoplásica da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Fosforilação , Prognóstico , Serina/metabolismoRESUMO
OBJECTIVES: The purpose of this study was to compare the stent deformation, obstruction of stent struts at a jailed side branch (SB) ostium, and stent strut malapposition after a repetitive proximal optimizing technique (re-POT) sequence between bifurcation lesions with and without stent links at SB ostia in ex vivo experimental setting. METHODS: A flexible urethane coronary bifurcation bench model was used, and crossover single stent implantation was performed from main branch (MB) with re-POT sequence. Under videoscope observation, presence (link group, n = 12) or absence (no-link group, n = 12) of stent link at distal semicircle of SB ostium was intentionally set, and rewiring was performed through distal cell in four different stent platforms. RESULTS: There were no significant differences in the rate of malapposed struts and in SB jailing ratio after the re-POT sequence between the link and no-link groups. SB jailing ratio increased significantly from 8.0% to 9.6% during the second POT procedure (P < 0.001). SB jailing ratio after the second POT procedure differed among stent platforms. CONCLUSIONS: The presence of a stent link at an SB ostium was not associated with a rate of malapposed struts and SB jailing ratio after the re-POT sequence. SB jailing ratio was significantly increased after second POT procedure, but was different among stent platforms. The Xience stent might minimize the change of SB jailing ratio and be suitable for coronary bifurcation stenting using re-POT sequence.