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BACKGROUND AND AIMS: In transcatheter aortic valve replacement (TAVR) recipients, the optimal management of concomitant chronic obstructive coronary artery disease (CAD) remains unknown. Some advocate for pre-TAVR percutaneous coronary intervention, while others manage it expectantly. The aim of this study was to assess the impact of varying degrees and extent of untreated chronic obstructive CAD on TAVR and longer-term outcomes. METHODS: The authors conducted a retrospective cohort study of TAVR recipients from January 2015 to November 2021, separating patients into stable non-obstructive or varying degrees of obstructive CAD. The major outcomes of interest were procedural all-cause mortality and complications, major adverse cardiovascular events, and post-TAVR unplanned coronary revascularization. RESULTS: Of the 1911 patients meeting inclusion, 75%, 6%, 10%, and 9% had non-obstructive, intermediate-risk, high-risk, and extreme-risk CAD, respectively. Procedural complication rates overall were low (death 0.4%, shock 0.1%, extracorporeal membrane oxygenation 0.1%), with no difference across groups. At a median follow-up of 21 months, rates of acute coronary syndrome and unplanned coronary revascularization were 0.7% and 0.5%, respectively, in the non-obstructive population, rising in incidence with increasing severity of CAD (P < .001 for acute coronary syndrome/unplanned coronary revascularization). Multivariable analysis did not yield a significantly greater risk of all-cause mortality or major adverse cardiovascular events across groups. One-year acute coronary syndrome and unplanned coronary revascularization rates in time-to-event analyses were significantly greater in the non-obstructive (98%) vs. obstructive (94%) subsets (Plog-rank< .001). CONCLUSIONS: Transcatheter aortic valve replacement can be performed safely in patients with untreated chronic obstructive CAD, without portending higher procedural complication rates and with relatively low rates of unplanned coronary revascularization and acute coronary syndrome at 1 year.
Assuntos
Estenose da Valva Aórtica , Doença da Artéria Coronariana , Complicações Pós-Operatórias , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/mortalidade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Idoso , Intervenção Coronária Percutânea , Resultado do Tratamento , Fatores de RiscoRESUMO
BACKGROUND: The newest-generation balloon-expandable valve, SAPIEN 3 Ultra (S3U), is expected to function well with the enhanced sealing skirt compared with SAPIEN 3 (S3). However, current literature on the comparison between these two valves is limited to short-term follow-ups. Therefore, we aimed to evaluate the 1-year outcomes and echocardiographic changes of S3U compared with S3. METHODS: We retrospectively identified patients who underwent transfemoral-transcatheter aortic valve replacement with S3U or S3 (20/23/26 mm) at our institution in 2018-2020. Outcomes were 1-year clinical events and echocardiographic parameters, and were compared between S3U and S3 after adjustment with inverse probability of treatment weighting. RESULTS: The S3U and S3 groups included 297 (25.7%) and 858 (74.3%) patients, respectively. There were no significant differences between the two groups in clinical events (death 5.8% vs. 5.5%, hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.81-1.90; death or heart failure hospitalization 10.3% vs. 10.1%, HR 1.04, 95% CI 0.67-1.62). The S3U group had a lower prevalence of mild paravalvular leakage (PVL) (13.7% vs. 22.3%, p = 0.044), with similar moderate PVL (0.7% vs. 1.2%, p > 0.99). No significant differences were observed in aortic valve mean gradient and Doppler velocity index at 1 year. However, the S3U group had a larger increase in mean gradient from implantation to 1 year (median +4.70 vs. +1.63 mmHg, p < 0.001). CONCLUSIONS: S3U and S3 carried similarly favorable clinical event risks. Nonetheless, S3U was associated with less frequent mild PVL but a larger increase in transprosthetic gradient. Further studies are needed to determine the prognostic impact of these hemodynamic differences.
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BACKGROUND: The cerebral embolic protection (CEP) device captures embolic debris during transcatheter aortic valve replacement (TAVR). However, the impact of CEP on stroke severity following TAVR remains unclear. Therefore, we aimed to examine whether CEP was associated with reduced severity of stroke following TAVR. METHODS: This was a retrospective cohort study of 2839 consecutive patients (mean age: 79.2 ± 9.5 years, females: 41.5%) who underwent transfemoral TAVR at our institution between 2013 and 2020. We categorized patients into Sentinel CEP users and nonusers. Neuroimaging data were reviewed and the final diagnosis of a cerebrovascular event was adjudicated by a neurologist blinded to the CEP use or nonuse. We compared the incidence and severity (assessed by the National Institutes of Health Stroke Scale [NIHSS]) of stroke through 72 h post-TAVR or discharge between the two groups using stabilized inverse probability of treatment weighting (IPTW) of propensity scores. RESULTS: Of the eligible patients, 1802 (63.5%) received CEP during TAVR and 1037 (36.5%) did not. After adjustment for patient characteristics by stabilized IPTW, the rate of overall stroke was numerically lower in CEP users than in CEP nonusers, but the difference did not reach statistical significance (0.49% vs. 1.18%, p = 0.064). However, CEP users had significantly lower rates of moderate-or-severe stroke (NIHSS ≥ 6: 0.11% vs. 0.69%, p = 0.013) and severe stroke (NIHSS ≥ 15: 0% vs. 0.29%, p = 0.046). Stroke following CEP use (n = 8), compared with stroke following CEP nonuse (n = 15), tended to carry a lower NIHSS (median [IQR], 4.0 [2.0-7.0] vs. 7.0 [4.5-19.0], p = 0.087). Four (26.7%) out of 15 patients with stroke following CEP nonuse died within 30 days, with no death after stroke following CEP use. CONCLUSIONS: CEP use may be associated with attenuated severity of stroke despite no significant difference in overall stroke incidence compared with CEP nonuse. This finding is considered hypothesis-generating and needs to be confirmed in large prospective studies.
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Estenose da Valva Aórtica , Dispositivos de Proteção Embólica , Embolia Intracraniana , Acidente Vascular Cerebral , Substituição da Valva Aórtica Transcateter , Feminino , Humanos , Idoso , Idoso de 80 Anos ou mais , Substituição da Valva Aórtica Transcateter/efeitos adversos , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/epidemiologia , Embolia Intracraniana/etiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Fatores de RiscoRESUMO
BACKGROUND: We previously reported beneficial effects of prone positioning during ex vivo lung perfusion (EVLP) using porcine lungs. In this study, we sought to determine if prone positioning during EVLP was beneficial in human donor lungs rejected for clinical use. METHODS: Human double lung blocs were randomized to prone EVLP (n = 5) or supine EVLP (n = 5). Following 16 h of cold storage at 4°C and 2 h of cellular EVLP in either the prone or supine position. Lung function, compliance, and weight were evaluated and transplant suitability determined after 2 h of EVLP. RESULTS: Human lungs treated with prone EVLP had significantly higher partial pressure of oxygen/fraction of inspired oxygen (P/F) ratio [348 (291-402) vs. 199 (191-257) mm Hg, p = 0.022] and significantly lower lung weight [926(864-1078) vs. 1277(1029-1483) g, p = 0.037] after EVLP. 3/5 cases in the prone group were judged suitable for transplant after EVLP, while 0/5 cases in the supine group were suitable. When function of upper vs. lower lobes was evaluated, prone EVLP lungs showed similar P/F ratios and inflammatory cytokine levels in lower vs. upper lobes. In contrast, supine EVLP lungs showed significantly lower P/F ratios [68(59-150) vs. 467(407-515) mm Hg, p = 0.012] and higher tissue tumor necrosis factor alpha levels [100.5 (46.9-108.3) vs. 39.9 (17.0-61.0) ng/ml, p = 0.036] in lower vs. upper lobes. CONCLUSIONS: Prone lung positioning during EVLP may optimize the outcome of EVLP in human donor lungs, possibly by improving lower lobe function.
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Transplante de Pulmão , Traumatismo por Reperfusão , Animais , Humanos , Pulmão , Transplante de Pulmão/efeitos adversos , Oxigênio , Perfusão , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/patologia , SuínosRESUMO
OBJECTIVES: This study sought to investigate the incidence and outcomes of surgical bailout (SB) after transcatheter mitral valve repair (TMVr) with MitraClip. BACKGROUND: TMVr poses a risk of serious procedural complications, possibly requiring urgent open surgery for SB. However, little is known about the risk of SB cases after TMVr. METHODS: We retrospectively identified patients who underwent TMVr using the Nationwide Readmissions Database 2014-2017. SB was defined as open thoracotomy for heart and aorta during the same hospitalization. Annual hospital volume was defined as the annual number of TMVr cases in each hospital in each year. RESULTS: Among 15,032 eligible patients, SB was required in 214 (1.42%), of whom 134 (62.6%) underwent mitral valve surgery (113 replacements; 21 repairs). The incidence of SB was decreasing significantly over the 4 years (5.26% in 2014; 0.43% in 2017; ptrend < .001). There was a significant nonlinear, inverse association of annual hospital volume with the incidence of SB. In-hospital death (15.0 vs. 2.1%; p < .001) and other in-hospital adverse events were significantly more frequent in patients with than without SB, whereas the 30-day readmission rate was similar (13.2 vs. 15.1%; p = .572). After adjustment for patient and hospital characteristics, SB was significantly associated with higher in-hospital mortality (odds ratio = 6.67, 95% confidence interval = 4.35, 10.23, p < .001). CONCLUSIONS: This study suggests that although the incidence of SB after TMVr is decreasing, SB is required more frequently in lower-volume hospitals and carries high in-hospital mortality. Further efforts are needed to understand the reasons for SB and improve outcomes in patients needing SB.
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Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Cateterismo Cardíaco/efeitos adversos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Mortalidade Hospitalar , Humanos , Incidência , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/epidemiologia , Insuficiência da Valva Mitral/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Ex vivo lung perfusion (EVLP) permits extended evaluation of donor lungs for transplant. However, the optimal EVLP duration of Lund protocol is unclear. Using human lungs rejected for clinical transplant, we sought to compare the results of 1 versus 2 h of EVLP using the Lund protocol. METHODS: Twenty-five pairs of human lungs rejected for clinical transplant were perfused with the Lund EVLP protocol. Blood gas analysis, lung compliance, bronchoscopy assessment, and perfusate cytokine analysis were performed at both 1 and 2 h. Recruitment was performed at both time points. Donor lung transplant suitability was determined at both time points. RESULTS: All cases were divided into four groups based on transplant suitability assessment at 1 h and 2 h of EVLP. In group A (n = 10), lungs were judged suitable for transplant at both 1 and 2 h of EVLP. In group B (n = 6), lungs were suitable at 1 h but nonsuitable at 2 h. In group C (n = 2), lungs were nonsuitable at 1 h but suitable at 2 h. Finally, in group D (n = 7), lungs were nonsuitable for transplant at both time points. In both groups B and C (n = 8), the transplant suitability assessment changed between 1 and 2 h of EVLP. CONCLUSIONS: In human lungs rejected for transplant, transplant suitability differed at 1 versus 2 h of EVLP in 32% of lungs studied. Evaluation of lungs with Lund protocol EVLP beyond 1 h may improve donor organ assessment.
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Seleção do Doador/métodos , Transplante de Pulmão/normas , Pulmão/fisiologia , Perfusão , Transplantes/fisiologia , Adulto , Broncoscopia , Seleção do Doador/normas , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Troca Gasosa Pulmonar/fisiologia , Fatores de Tempo , Transplantes/diagnóstico por imagemRESUMO
BACKGROUND: Recent reports describe increases in the case volume of surgical aortic valve replacement (SAVR) after centers establish a transcatheter aortic valve replacement (TAVR) program. We investigate contemporary temporal trends in SAVR and TAVR case volumes and risk profiles at a high volume academic medical center. METHODS: We conducted a retrospective, descriptive evaluation of consecutive patients who underwent TAVR (n = 538) or SAVR (n = 657) in 2011-2016. The STS predicted risk of mortality (PROM) for isolated SAVR was used to calculate PROM for both SAVR and TAVR patients. Patients were stratified based on STS PROM as follows: low risk (<4%), intermediate risk (4-8%), and high risk (≥8%). Temporal changes in patient risk-profile were characterized descriptively. RESULTS: Median STS PROM for the study period was 6.3% and 2.0% for TAVR and SAVR cohorts, respectively (P < 0.001). Since 2011, TAVR volume consistently increased, while SAVR volume increased initially, peaking in 2013 and steadily declined. The STS PROM for SAVR remained stable during the entire study period, while that for TAVR showed a steady decline. The proportions of intermediate and low STS PROM patients undergoing TAVR increased. Proportions of each risk category in SAVR cohort remained stable over time. CONCLUSIONS: SAVR volume increased initially but declined eventually following the implementation of TAVR program. The distribution of the STS PROM in TAVR cohort changed dramatically with increasing proportion of patients in lower risk categories. These findings suggest the converging patient populations in TAVR and SAVR, which may be associated with the decline in the overall SAVR volume.
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Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/tendências , Padrões de Prática Médica/tendências , Substituição da Valva Aórtica Transcateter/tendências , Centros Médicos Acadêmicos/tendências , Idoso , Idoso de 80 Anos ou mais , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/mortalidade , Hospitais com Alto Volume de Atendimentos/tendências , Humanos , Masculino , Medidas de Resultados Relatados pelo Paciente , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/mortalidade , Resultado do TratamentoRESUMO
INTRODUCTION: Surgical management for tricuspid valve (TV) endocarditis is usually TV repair or replacement. When repair is not feasible, and concerns for patient recidivism preclude TV replacement, tricuspid valvectomy without replacement is an option to alleviate symptoms and allow time for addiction management. METHODS: We reviewed our institution's experience with isolated tricuspid valvectomy for cases of intravenous drug use (IVDU)-associated endocarditis (n = 7) from 2009 to 2017. RESULTS: The decision for tricuspid valvectomy was based on each patient's comorbid condition and realization of active IVDU. This intervention resulted in 100% perioperative and mid-term survival with a mean follow-up of 25.4 months. One patient required a valve replacement in the long term only after appropriate substance abuse management was completed. CONCLUSION: Cardiac surgeons increasingly encounter patients with active endocarditis who suffer from IVDU addiction. Drug addiction increases the risk for recurrent endocarditis and requires an effective management plan. Multidisciplinary endocarditis care teams may play a pivotal role in improving outcomes by better addressing addiction treatment.
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Procedimentos Cirúrgicos Cardíacos , Endocardite Bacteriana/cirurgia , Abuso de Substâncias por Via Intravenosa/reabilitação , Valva Tricúspide/cirurgia , Adulto , Antibacterianos/uso terapêutico , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/fisiopatologia , Feminino , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Recuperação de Função Fisiológica , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/diagnóstico , Fatores de Tempo , Resultado do Tratamento , Valva Tricúspide/microbiologia , Valva Tricúspide/fisiopatologia , Adulto JovemRESUMO
RATIONALE: Transplantation, the most effective therapy for end-stage organ failure, is markedly limited by early-onset cardiovascular disease (CVD) and premature death of the host. The mechanistic basis of this increased CVD is not fully explained by known risk factors. OBJECTIVE: To investigate the role of alloimmune responses in promoting CVD of organ transplant recipients. METHODS AND RESULTS: We established an animal model of graft-exacerbated host CVD by combining murine models of atherosclerosis (apolipoprotein E-deficient recipients on standard diet) and of intra-abdominal graft rejection (heterotopic cardiac transplantation without immunosuppression). CVD was absent in normolipidemic hosts receiving allogeneic grafts and varied in severity among hyperlipidemic grafted hosts according to recipient-donor genetic disparities, most strikingly across an isolated major histocompatibility complex class II antigen barrier. Host disease manifested as increased atherosclerosis of the aorta that also involved the native coronary arteries and new findings of decreased cardiac contractility, ventricular dilatation, and diminished aortic compliance. Exacerbated CVD was accompanied by greater levels of circulating cytokines, especially interferon-γ and other Th1-type cytokines, and showed both systemic and intralesional activation of leukocytes, particularly T-helper cells. Serological neutralization of interferon-γ after allotransplantation prevented graft-related atherosclerosis, cardiomyopathy, and aortic stiffening in the host. CONCLUSIONS: Our study reveals that sustained activation of the immune system because of chronic allorecognition exacerbates the atherogenic diathesis of hyperlipidemia and results in de novo cardiovascular dysfunction in organ transplant recipients.
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Doenças Cardiovasculares/etiologia , Rejeição de Enxerto/complicações , Transplante de Coração/efeitos adversos , Hiperlipidemias/complicações , Mediadores da Inflamação/sangue , Interferon gama/sangue , Aloenxertos , Animais , Doenças da Aorta/sangue , Doenças da Aorta/etiologia , Doenças da Aorta/imunologia , Doenças da Aorta/prevenção & controle , Apolipoproteínas E , Aterosclerose/sangue , Aterosclerose/etiologia , Aterosclerose/imunologia , Aterosclerose/prevenção & controle , Cardiomiopatias/sangue , Cardiomiopatias/etiologia , Cardiomiopatias/imunologia , Cardiomiopatias/prevenção & controle , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Modelos Animais de Doenças , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Hemodinâmica , Antígenos de Histocompatibilidade Classe II/imunologia , Hiperlipidemias/sangue , Hiperlipidemias/genética , Mediadores da Inflamação/imunologia , Interferon gama/imunologia , Ativação Linfocitária , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais , Células Th1/imunologia , Células Th1/metabolismo , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/imunologia , Disfunção Ventricular Esquerda/prevenção & controle , Função Ventricular EsquerdaRESUMO
BACKGROUND: A lack of donor hearts remains a major limitation of heart transplantation. Hearts from Centers for Disease Control (CDC) high-risk donors can be utilized with specific recipient consent. However, outcomes of heart transplantation with CDC high-risk donors are not well known. We sought to define outcomes, including posttransplant hepatitis and human immunodeficiency virus (HIV) status, in recipients of CDC high-risk donor hearts at our institution. METHODS: All heart transplant recipients from August 2010 to December 2014 (n = 74) were reviewed. Comparison of 1) CDC high-risk donor (HRD) versus 2) standard-risk donor (SRD) groups were performed using chi-squared tests for nominal data and Wilcoxon two-sample tests for continuous variables. Survival was estimated with Kaplan-Meier curves. RESULTS: Of 74 heart transplant recipients reviewed, 66 (89%) received a SRD heart and eight (11%) received a CDC HRD heart. We found no significant differences in recipient age, sex, waiting list 1A status, pretransplant left ventricular assist device (LVAD) support, cytomegalovirus (CMV) status, and graft ischemia times (p = NS) between the HRD and SRD groups. All of the eight HRD were seronegative at the time of transplant. Postoperatively, there was no significant difference in rejection rates at six and 12 months posttransplant. Importantly, no HRD recipients acquired hepatitis or HIV. Survival in HRD versus SRD recipients was not significantly different by Kaplan-Meier analysis (log rank p = 0.644) at five years posttransplant. CONCLUSION: Heart transplants that were seronegative at the time of transplant had similar posttransplant graft function, rejection rates, and five-year posttransplant survival versus recipients of SRD hearts. At our institution, no cases of hepatitis or HIV occurred in HRD recipients in early follow-up.
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Centers for Disease Control and Prevention, U.S. , Transplante de Coração , Medição de Risco/estatística & dados numéricos , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Transplantados , Adulto , Distribuição de Qui-Quadrado , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Transplante de Coração/mortalidade , Transplante de Coração/estatística & dados numéricos , Hepatite/epidemiologia , Hepatite/prevenção & controle , Humanos , Estimativa de Kaplan-Meier , Masculino , Risco , Medição de Risco/métodos , Taxa de Sobrevida , Doadores de Tecidos/estatística & dados numéricos , Transplantados/estatística & dados numéricos , Resultado do Tratamento , Estados Unidos , Adulto JovemRESUMO
The tumor microenvironment strongly influences cancer development, progression, and metastasis. The role of carcinoma-associated fibroblasts (CAFs) in these processes and their clinical impact has not been studied systematically in non-small cell lung carcinoma (NSCLC). We established primary cultures of CAFs and matched normal fibroblasts (NFs) from 15 resected NSCLC. We demonstrate that CAFs have greater ability than NFs to enhance the tumorigenicity of lung cancer cell lines. Microarray gene-expression analysis of the 15 matched CAF and NF cell lines identified 46 differentially expressed genes, encoding for proteins that are significantly enriched for extracellular proteins regulated by the TGF-ß signaling pathway. We have identified a subset of 11 genes (13 probe sets) that formed a prognostic gene-expression signature, which was validated in multiple independent NSCLC microarray datasets. Functional annotation using protein-protein interaction analyses of these and published cancer stroma-associated gene-expression changes revealed prominent involvement of the focal adhesion and MAPK signaling pathways. Fourteen (30%) of the 46 genes also were differentially expressed in laser-capture-microdissected corresponding primary tumor stroma compared with the matched normal lung. Six of these 14 genes could be induced by TGF-ß1 in NF. The results establish the prognostic impact of CAF-associated gene-expression changes in NSCLC patients.
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Carcinoma Pulmonar de Células não Pequenas/metabolismo , Fibroblastos/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/biossíntese , Animais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Transformada , Intervalo Livre de Doença , Feminino , Fibroblastos/patologia , Perfilação da Expressão Gênica , Humanos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos SCID , Análise de Sequência com Séries de Oligonucleotídeos , Transdução de Sinais , Taxa de SobrevidaRESUMO
BACKGROUND: Real-time lung weight (LW) measurement is a simple and non-invasive technique for detecting extravascular lung water during ex vivo lung perfusion (EVLP). We investigated the feasibility of real-time LW measurement in clinical EVLP as a predictor of transplant suitability and post-transplant outcomes. METHODS: In our clinical acellular EVLP protocol, real-time LW was measured in 117 EVLP cases from June 2019 to June 2022. The estimated LW gain at each timepoint was calculated using a scale placed under the organ chamber. The lungs were classified into four categories based on LW adjusted for height and compared between suitable and unsuitable cases. The relationship between estimated LW gain and primary graft dysfunction was also investigated. RESULTS: The estimated LW gain during the EVLP significantly correlated with the LW gain (post EVLP LW - pre EVLP LW) measured on the back table (R2=0.61, P<0.01). In the adjusted LW categories 2-4, the estimated LW gain at 0-1 h after EVLP was significantly higher in unsuitable cases than in suitable cases. The area under the curve for the estimated LW gain was ≥0.80. Primary graft dysfunction grade 0-1 had a significantly lower estimated LW gain at 60 min than grades 2-3 (-43 vs. 1 g, P<0.01). CONCLUSIONS: Real-time lung measurements can predict transplant suitability and post-transplant outcomes by the early detection of extravascular lung water during the initial 1 h of EVLP.
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BACKGROUND: Ex vivo lung perfusion expands the lung transplant donor pool and extends preservation time beyond cold static preservation. We hypothesized that repeated regular ex vivo lung perfusion would better maintain lung grafts. METHODS: Ten pig lungs were randomized into 2 groups. The control underwent 16 h of cold ischemic time and 2 h of cellular ex vivo lung perfusion. The intermittent ex vivo lung perfusion group underwent cold ischemic time for 4 h, ex vivo lung perfusion (first) for 2 h, cold ischemic time for 10 h, and 2 h of ex vivo lung perfusion (second). Lungs were assessed, and transplant suitability was determined after 2 h of ex vivo lung perfusion. RESULTS: The second ex vivo lung perfusion was significantly associated with better oxygenation, limited extravascular water, higher adenosine triphosphate, reduced intraalveolar edema, and well-preserved mitochondria compared with the control, despite proinflammatory cytokine elevation. No significant difference was observed in the first and second perfusion regarding oxygenation and adenosine triphosphate, whereas the second was associated with lower dynamic compliance and higher extravascular lung water than the first. Transplant suitability was 100% for the first and 60% for the second ex vivo lung perfusion, and 0% for the control. CONCLUSIONS: The second ex vivo lung perfusion had a slight deterioration in graft function compared to the first. Intermittent ex vivo lung perfusion created a better condition for lung grafts than cold static preservation, despite cytokine elevation. These results suggested that intermittent ex vivo lung perfusion may help prolong lung preservation.
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Transplante de Pulmão , Preservação de Órgãos , Suínos , Animais , Preservação de Órgãos/métodos , Pulmão , Perfusão/efeitos adversos , Perfusão/métodos , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/métodos , Citocinas , Trifosfato de AdenosinaRESUMO
BACKGROUND: Candidates for transcatheter aortic valve replacement (TAVR) occasionally have a "borderline-size" aortic annulus between 2 transcatheter heart valve sizes, based on the manufacturer's sizing chart. Data on TAVR outcomes in such patients are limited. METHODS: We retrospectively reviewed 1816 patients who underwent transfemoral-TAVR with balloon-expandable valve (BEV) at our institution between 2016 and 2020. We divided patients into borderline and non-borderline groups based on computed tomography-derived annular measurements and compared outcomes. Furthermore, we analyzed procedural characteristics and compared outcomes between the smaller- and larger-valve strategies in patients with borderline-size annulus. RESULTS: During a median follow-up of 23.3 months, there was no significant difference between the borderline (n = 310, 17.0 %) and non-borderline (n = 1506) groups in mortality (17.3 % vs. 19.5 %; hazard ratio [HR] = 0.86 [95% CI = 0.62-1.20], p = 0.39), major adverse cardiac/cerebrovascular events (MACCE: death/myocardial infarction/stroke, 21.2 % vs. 21.5 %; HR = 0.97 [0.71-1.32], p = 0.85), paravalvular leak (PVL: mild 21.8 % vs. 20.6 %, p = 0.81; moderate 0 % vs. 1.2 %; p = 0.37), or mean gradient (12.9 ± 5.8 vs. 12.6 ± 5.2 mmHg, p = 0.69) at 1 year. There was no significant difference between the larger-(n = 113) and smaller-valve(n = 197) subgroups in mortality (23.7 % vs. 15.2 %; HR = 1.57 [0.89-2.77], p = 0.12), MACCE (28.1 % vs. 18.4 %; HR = 1.52 [0.91-2.54], p = 0.11), mild PVL (13.3 % vs. 25.9 %; p = 0.12), or mean gradient (12.3 ± 4.5 vs. 13.6 ± 5.3 mmHg, p = 0.16); however, the rate of permanent pacemaker implantation (PPI) was higher in the larger-valve subgroup (15.9 % vs. 2.6 %, p < 0.001). CONCLUSION: Borderline-size annulus is not associated with higher risk of adverse outcomes after BEV-TAVR. However, the larger-valve strategy for borderline-size annulus is associated with higher PPI risk, suggesting a greater risk of injury to the conduction system.
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BACKGROUND: Heparin is routinely administered to brain-dead donors before cardiac arrest, although it is not universally allowed for donation after cardiac death (DCD) donors due to concerns that death may be hastened. The lack of heparin may lead to thrombosis and compromised graft function. We evaluated the impact of timing of heparin administration and thrombi formation in a DCD pig model. METHODS: Eight domestic adult pigs were administered systemic heparin (30,000 IU): four prior to cardiac arrest through intravenous injection (prearrest heparin) and four after cardiac arrest via injection into the right atrium followed by open cardiac massage (postarrest heparin). Pigs were euthanized with potassium chloride and a minimum of 5 minutes of cardiac silence allowed before organ procurement. Lungs were flushed with antegrade and retrograde Perfadex, and pulmonary preservation solution effluent was evaluated for gross thrombi. Organs were fixed in formalin, sagittally sectioned, and evaluated by a pulmonary pathologist blinded to treatment. RESULTS: Antegrade and retrograde flushes demonstrated no significant thrombi. Gross pathologic evaluation revealed no occlusive central thrombi. Scant peripheral thrombi were detected in both treatment groups. No microscopic thrombi were noted in either treatment group. CONCLUSIONS: Delayed heparin administration after cardiac death does not affect thrombus formation in an animal model of lung procurement after cardiac death. Concern about clinically significant thrombosis occurring when heparin is not given before cardiac arrest appears unfounded. These findings suggest that DCD lungs can be used regardless of antemortem heparin administration.
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Morte Súbita Cardíaca , Heparina/administração & dosagem , Transplante de Pulmão , Trombose/prevenção & controle , Doadores de Tecidos , Animais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esquema de Medicação , Heparina/efeitos adversos , Prognóstico , Suínos , Trombose/sangue , Trombose/etiologia , Fatores de TempoRESUMO
The objective of this study was to explain step by step how to achieve a complete resection of an intravascular leiomyoma. A 48-year-old woman was referred to our institution with progressive dyspnea on exertion, lightheadedness, and previous history of total abdominal hysterectomy and bilateral salpingo-oophorectomy for a uterine leiomyoma echocardiography, computed tomography, and magnetic resonance imaging of the heart and abdomen/pelvis were performed and an intracaval mass with extension into the right heart and pulmonary artery was identified. After multidisciplinary review, a single-stage sternotomy-laparotomy procedure on cardiopulmonary bypass (with beating heart, mild hypothermia, and no deep hypothermic circulatory arrest) ensured complete resection of a giant intravenous leiomyoma (IVL). Multidisciplinary approach, multimodality imaging, and single-stage sternotomy-laparotomy procedure on cardiopulmonary bypass (with heart beating and mild hypothermia) ensure complete resection of IVL.
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Background Peripheral vascular intervention (PVI) is occasionally required to facilitate delivery system insertion or to treat vascular complications during transfemoral transcatheter aortic valve replacement (TF-TAVR). However, the impact of PVI on outcomes is not well understood. Therefore, we aimed to compare outcomes between TF-TAVR with versus without PVI and between TF-TAVR with PVI versus non-TF-TAVR. Methods and Results We retrospectively reviewed 2386 patients who underwent TAVR with a balloon-expandable valve at a single institution from 2016 to 2020. The primary outcomes were death and major adverse cardiac/cerebrovascular event (MACCE), defined as death, myocardial infarction, or stroke. Of 2246 TF-TAVR recipients, 136 (6.1%) required PVI (89% bailout treatment). During follow-up (median 23.0 months), there were no significant differences between TF-TAVR with and without PVI in death (15.4% versus 20.7%; adjusted HR [aHR], 0.96 [95% CI, 0.58-1.58]) or MACCE (16.9% versus 23.0%; aHR, 0.84 [95% CI, 0.52-1.36]). However, compared with non-TF-TAVR (n=140), TF-TAVR with PVI carried significantly lower rates of death (15.4% versus 40.7%; aHR, 0.42 [95% CI, 0.24-0.75]) and MACCE (16.9% versus 45.0%; aHR, 0.40 [95% CI, 0.23-0.68]). Landmark analyses demonstrated lower outcome rates following TF-TAVR with PVI than non-TF-TAVR both within 60 days (death 0.7% versus 5.7%, P=0.019; MACCE 0.7% versus 9.3%; P=0.001) and thereafter (death 15.0% versus 38.9%, P=0.014; MACCE 16.5% versus 41.3%, P=0.013). Conclusions The need for PVI during TF-TAVR is not uncommon, mainly due to the bailout treatment for vascular complications. PVI is not associated with worse outcomes in TF-TAVR recipients. Even when PVI is required, TF-TAVR is associated with better short- and intermediate-term outcomes than non-TF-TAVR.
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Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/métodos , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/etiologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Artéria Femoral/cirurgiaRESUMO
Aims: Conduction abnormalities necessitating permanent pacemaker (PPM) implantation remain the most frequent complication post-transcatheter aortic valve implantation (TAVI), yet reliance on PPM function varies. We evaluated the association of right-ventricular (RV)-stimulation rate post-TAVI with 1-year major adverse cardiovascular events (MACE) (all-cause mortality and heart failure hospitalization). Methods and results: This retrospective cohort study of patients undergoing TAVI in two high-volume centers included patients with existing PPM pre-TAVI or new PPM post-TAVI. There was a bimodal distribution of RV-stimulation rates stratifying patients into two groups of either low [≤10%: 1.0 (0.0, 3.6)] or high [>10%: 96.0 (54.0, 99.9)] RV-stimulation rate post-TAVI. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated comparing MACE in patients with high vs. low RV-stimulation rates post-TAVI. Of 4659 patients, 408 patients (8.6%) had an existing PPM pre-TAVI and 361 patients (7.7%) underwent PPM implantation post-TAVI. Mean age was 82.3 ± 8.1 years, 39% were women. A high RV-stimulation rate (>10%) development post-TAVI is associated with a two-fold increased risk for MACE [1.97 (1.20, 3.25), P = 0.008]. Valve implantation depth was an independent predictor of high RV-stimulation rate [odds ratio (95% CI): 1.58 (1.21, 2.06), P=<0.001] and itself associated with MACE [1.27 (1.00, 1.59), P = 0.047]. Conclusion: Greater RV-stimulation rates post-TAVI correlate with increased 1-year MACE in patients with new PPM post-TAVI or in those with existing PPM but low RV-stimulation rates pre-TAVI. A shallower valve implantation depth reduces the risk of greater RV-stimulation rates post-TAVI, correlating with improved patient outcomes. These data highlight the importance of a meticulous implant technique even in TAVI recipients with pre-existing PPMs.
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Pulmonary arterial hypertension (PAH) is a progressive fatal disease. Although medical therapies have improved the outlook for these patients, there still exists a cohort of patients with PAH who are refractory to these therapies. Lung transplantation (LT), and in certain cases heart-lung transplantation (HLT), is a therapeutic option for patients with severe PAH who are receiving optimal therapy yet declining. ECMO may serve as a bridge to transplant or recovery in appropriate patients. Although, the mortality within the first 3 months after transplant is higher in PAH recipients than the other indications for LT, and the long-term survival after LT is excellent for this group of individuals. In this review, we discuss the indications for LT in PAH patients, when to refer and list patients for LT, the indications for double lung transplant (DLT) versus HLT for PAH patients, types of advanced circulatory support for severe PAH, and short and long-term outcomes in transplant recipients with PAH.
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Transplante de Coração-Pulmão , Hipertensão Pulmonar , Transplante de Pulmão , Humanos , Hipertensão Pulmonar/cirurgia , Resultado do TratamentoRESUMO
Background: In the absence of randomized data, an expert panel recently proposed an algorithm for conduction disturbance management in transcatheter aortic valve implantation (TAVI) recipients. However, external validations of its recommendations are limited. Methods: We retrospectively identified 808 patients without a pre-existing pacing device who underwent transfemoral TAVI with the Sapien 3 valve at our institution in 2018-2019. Patients were grouped based on pre-existing conduction disturbance and immediate post-TAVI electrocardiogram. Timing of temporary pacemaker (TPM) removal and hospital discharge were compared with those of the expert panel recommendations to evaluate the associated risk of TPM reinsertion and permanent pacemaker (PPM) implantation. Results: In most group 1 patients (no electrocardiogram changes without pre-existing right bundle branch block), the timing of TPM removal and discharge were concordant with those of the expert panel recommendations, with low TPM reinsertion (0.8%) and postdischarge PPM (0.8%) rates. In the majority of group 5 patients (procedural high-degree/complete atrioventricular block), TPM was maintained, followed by PPM implantation, compatible with the expert panel recommendations. In contrast, in groups 2-4 (pre-existing/new conduction disturbances), earlier TPM removal than recommended by the expert panel (mostly, immediately after procedure) was feasible in 97.5%-100% of patients, with a low TPM reinsertion rate (0.0%-1.8%); earlier discharge was also feasible in 50.0%-65.5%, with a low 30-day postdischarge PPM rate (0.0%-2.8%) and no 30-day death. Conclusions: Early TPM removal and discharge after TAVI appear safe and feasible in the majority of cases. These data may provide a framework for an early, streamlined hospital discharge plan for TAVI recipients, optimizing both cost savings and patient safety.