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BACKGROUND: Chronic kidney disease (CKD) accelerates atherosclerosis, but the mechanisms remain unclear. Tyrosine sulfation has been recognized as a key post-translational modification (PTM) in regulation of various cellular processes, and the sulfated adhesion molecules and chemokine receptors have been shown to participate in the pathogenesis of atherosclerosis via enhancement of monocyte/macrophage function. The levels of inorganic sulfate, the essential substrate for the sulfation reaction, are dramatically increased in patients with CKD, which indicates a change of sulfation status in CKD patients. Thus, in the present study, we detected the sulfation status in CKD patients and probed into the impact of sulfation on CKD-related atherosclerosis by targeting tyrosine sulfation function. RESULTS: PBMCs from individuals with CKD showed higher amounts of total sulfotyrosine and tyrosylprotein sulfotransferase (TPST) type 1 and 2 protein levels. The plasma level of O-sulfotyrosine, the metabolic end product of tyrosine sulfation, increased significantly in CKD patients. Statistically, O-sulfotyrosine and the coronary atherosclerosis severity SYNTAX score positively correlated. Mechanically, more sulfate-positive nucleated cells in peripheral blood and more abundant infiltration of sulfated macrophages in deteriorated vascular plaques in CKD ApoE null mice were noted. Knockout of TPST1 and TPST2 decreased atherosclerosis and peritoneal macrophage adherence and migration in CKD condition. The sulfation of the chemokine receptors, CCR2 and CCR5, was increased in PBMCs from CKD patients. CONCLUSIONS: CKD is associated with increased sulfation status. Increased sulfation contributes to monocyte/macrophage activation and might be involved in CKD-related atherosclerosis. Inhibition of sulfation may suppress CKD-related atherosclerosis and is worthy of further study.
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Aterosclerose , Sulfotransferases , Camundongos , Animais , Sulfotransferases/química , Sulfotransferases/genética , Sulfotransferases/metabolismo , Proteínas/metabolismo , Tirosina/metabolismo , Camundongos Knockout , Receptores de Quimiocinas/metabolismo , Aterosclerose/complicações , Processamento de Proteína Pós-TraducionalRESUMO
PURPOSE: To assess predictive value of 68Ga-labeled fibroblast activation protein inhibitor-04 ([68Ga]Ga-DOTA-FAPI-04) PET/MR for late left ventricular (LV) remodeling in patients with ST-segment elevated myocardial infarction (STEMI). METHODS: Twenty-six patients with STEMI were included in the study. [68Ga]Ga-DOTA-FAPI-04 PET/MR was performed at baseline and at average 12 months after STEMI. LV remodeling was defined as >10% increase in LV end-systolic volume (LVESV) from baseline to 12 months. RESULTS: The LV remodeling group demonstrated higher [68Ga]Ga-DOTA-FAPI-04 uptake volume (UV) at baseline than the non-LV remodeling group (p < 0.001). [68Ga]Ga-DOTA-FAPI-04 UV at baseline was a significant predictor (OR = 1.048, p = 0.011) for LV remodeling at 12 months after STEMI. Compared to clinical information, MR imaging and cardiac function parameters at baseline, [68Ga]Ga-DOTA-FAPI-04 UV demonstrated better predictive ability (AUC = 0.938, p < 0.001) for late LV remodeling, with sensitivity of 100.0% and specificity of 81.3%. CONCLUSIONS: [68Ga]Ga-DOTA-FAPI-04 PET/MR is an effective tool to non-invasively quantify myocardial fibroblasts activation, and baseline [68Ga]Ga-DOTA-FAPI-04 UV may have potential predictive value for late LV remodeling.
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Infarto do Miocárdio , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Radioisótopos de Gálio , Remodelação Ventricular , Função Ventricular Esquerda , Infarto do Miocárdio/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Tomografia por Emissão de Pósitrons combinada à Tomografia ComputadorizadaRESUMO
BACKGROUND: This is first-in-man investigation of an implantable Heartech left ventricular partitioning device (LVPD) therapy for chronic heart failure (HF) after a myocardial infarction. METHODS AND RESULTS: Initially, 16 patients were chosen from 3 cardiac centers within China. All patients were treated with percutaneous ventricular restoration involving the Heartech LVPD implantation. Major adverse cardiovascular and cerebrovascular events were documented. Functional status, echocardiograph evaluation, European five-dimensional health scale, 6-minute walk test before the procedure and at postoperative follow-ups were recorded. We demonstrated successful implantation and device function with a success rate of 93.75%. One patient suffered a fatal myocardial infarction within the 12 ± 1 month follow-up. However, other patients did not report any major adverse cardiovascular and cerebrovascular events at their 12 ± 1 month follow-ups. After the operation, the average left ventricular end-systolic volume index decreased dramatically (66.00 mL/m2, interquartile range [IQR] 63.00-89.00 mL/m2 vs 48.00 mL/m2, IQR 32.25-68.25 mL/m2, Pâ¯=â¯.001), along with the left ventricular end-diastolic volume index (105.00 mL/m2, IQR 90.00-130.00 mL/m2 vs 76.50 mL/m2, IQR 57.75-120.25 mL/m2, Pâ¯=â¯.002). The left ventricular ejection fraction (35.00%, IQR 27.00-38.00% vs 42.50%, IQR 34.75-50.25%, Pâ¯=â¯.003), 6-minute walk test (383.13 ± 108.70 m vs 491.17 ± 118.44 m, Pâ¯=â¯.01), and European five-dimensional health scale (65.93 ± 11.25 vs 82.50 ± 5.44, P < .001), in turn, improved significantly. CONCLUSIONS: In our study, the Heartech LVPD was demonstrated as both safe and effective in reducing LV volume, enhancing LV function after implantation. These results remain constant at least till the 12 month follow-up. (Trial Registration: NCT02938637.).
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Insuficiência Cardíaca , Infarto do Miocárdio , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/cirurgia , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda , Remodelação VentricularRESUMO
OBJECTIVES: This study presents 1-year follow-up data of echocardiographic outcomes in patients who received the Heartech® left ventricular (LV) partitioning device (LVPD) (Xinrui Medical Equipment Co. Ltd., Shanghai, China). BACKGROUND: Our first-in-man study of the Heartech® LVPD confirmed its safety and efficacy in patients with chronic heart failure (HF) post-myocardial infarction (MI) 1 month post-implantation. This subsequent study reports the echocardiographic outcomes of these patients at 1 year of follow-up. METHODS: Fifteen patients with HF post-MI from three cardiac intervention centers in China were successfully implanted with the Heartech® LVPD via percutaneous ventricular restoration procedures. Echocardiographic parameters-including LV systolic function, diastolic function, two-dimensional speckle-tracking analysis, and right ventricular systolic function-were obtained before device implantation and at 1 month and 1 year postoperatively. RESULTS: There was no deterioration of LV diastolic function, specific strain parameters, or right ventricular function at 1 year. Relative to the echocardiographic parameters recorded before the procedure, the LV ejection fraction (32.47 ± 6.98% vs. 42.5 ± 7.41%; p = .001) was significantly improved at 1 year, while the LV end-diastolic volume index (106.29 ± 28.01 vs. 83.30 ± 31.71; p = .005) and end-systolic volume index were significantly reduced (72.47 ± 22.77 vs. 50.00 ± 19.70; p = .001). CONCLUSIONS: One-year echocardiographic follow-up results confirmed that no deterioration of LV diastolic function or specific strain parameters was observed and LV systolic function was significantly improved in patients with HF post-MI who were implanted with the Heartech® LVPD.
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Insuficiência Cardíaca , Infarto do Miocárdio , Disfunção Ventricular Esquerda , China , Seguimentos , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico por imagem , Volume Sistólico , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/terapia , Função Ventricular EsquerdaRESUMO
RATIONALE: Macrophages are critically involved in wound healing following myocardial infarction (MI). Lgr4, a member of LGR (leucine-rich repeat-containing G protein-coupled receptor) family, is emerging as a regulator of macrophage-associated immune responses. However, the contribution of Lgr4 to macrophage phenotype and function in the context of MI remains unclear. OBJECTIVE: To determine the role of macrophage Lgr4 in MI and to dissect the underlying mechanisms. METHODS AND RESULTS: During early inflammatory phase of MI, infarct macrophages rather than neutrophils expressed high level of Lgr4. Macrophage-specific Lgr4 knockout mice had no baseline cardiovascular defects but manifested improved heart function, modestly reduced infarct size, decreased early mortality due to cardiac rupture, and ameliorated adverse remodeling after MI. Improved outcomes in macrophage-specific Lgr4 knockout mice subjected to MI were associated with mitigated ischemic injury and optimal infarct healing, as determined by reduction of cardiac apoptosis in the peri-infarct zone, attenuation of local myocardial inflammatory response, decrease of matrix metalloproteinase expression in the infarct, enhancement of angiogenesis, myofibroblast proliferation, and collagen I deposition in reparative granulation tissue as well as formation of collagen-rich scar. More importantly, macrophage-specific Lgr4 knockout infarcts had reduced numbers of infiltrating leukocytes and inflammatory macrophages but harbored abundant reparative macrophage subsets. Lgr4-null infarct macrophages exhibited a less inflammatory transcriptional signature. These findings were further supported by transcriptomic profiling data showing repression of multiple pathways and broad-spectrum genes associated with proinflammatory responses in macrophage-specific Lgr4 knockout infarcts. Notably, we discovered that Lgr4-mediated functional phenotype programing in infarct macrophages was at least partly attributed to regulation of AP (activator protein)-1 activity. We further demonstrated that the synergistic effects of Lgr4 on AP-1 activation in inflammatory macrophages occurred via enhancing CREB (cAMP response element-binding protein)-mediated c-Fos, Fosl1, and Fosb transactivation. CONCLUSIONS: Together, our data highlight the significance of Lgr4 in governing proinflammatory phenotype of infarct macrophages and postinfarction repair.
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Mediadores da Inflamação/metabolismo , Inflamação/metabolismo , Macrófagos/metabolismo , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Função Ventricular Esquerda , Remodelação Ventricular , Idoso , Animais , Apoptose , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Inflamação/genética , Inflamação/patologia , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/patologia , Fenótipo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Células RAW 264.7 , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais , Fator de Transcrição AP-1/metabolismoRESUMO
BACKGROUND: Sulfation of tyrosine, yielding O-sulfotyrosine, is a common but fixed post-translational modification in eukaryotes. Patients with increased circulating O-sulfotyrosine levels experience a faster decline in renal function with progression to end-stage renal disease (ESRD). In the present study, we measured serum O-sulfotyrosine levels in individuals with chronic kidney disease (CKD) and acute kidney injury (AKI) to explore its ability to differentiate AKI from CKD. METHODS: A total of 135 patients (20 with AKI and 115 with CKD) were recruited prospectively for liquid chromatography-mass spectrometry assessment of circulating O-sulfotyrosine. We also studied C57BL/6 mice with CKD after 5/6 nephrectomy (Nx). Blood samples were drawn from the tail vein on Day 1, 3, 5, 7, 14, 30, 60, and 90 after CKD. Serum separation and characterization of creatinine, blood urea nitrogen (BUN), and O-sulfotyrosine was performed. Thus, the time-concentration curves of the O-sulfotyrosine level demonstrate the variation of kidney dysfunction. RESULTS: The serum levels of O-sulfotyrosine were markedly increased in patients with CKD compared with AKI. Median O-sulfotyrosine levels in CKD patients versus AKI, respectively, were as follows:243.61 ng/mL(interquartile range [IQR] = 171.90-553.86) versus 126.55 ng/mL (IQR = 48.19-185.03, P = 0.004). In patients with CKD, O-sulfotyrosine levels were positively correlated with creatinine, BUN, and Cystatin C (r = 0.63, P < 0.001; r = 0.49, P < 0.001; r = 0.61, P < 0.001, respectively) by the multivariate linear regression analysis (ß = 0.71, P < 0.001; ß = 0.40, P = 0.002; ß = 0.73, P < 0.001, respectively). However, this association was not statistically significant in patients with AKI (r = - 0.17, P = 0.472; r = 0.11, P = 0.655; r = 0.09, P = 0.716, respectively). The receiver operating characteristic (ROC) analysis illustrated that the area under the curve was 0.80 (95% confidence interval [CI] 0.71-0.89; P < 0.001) and the optimal cut-off value of serum O-sulfotyrosine suggesting AKI was < 147.40 ng/mL with a sensitivity and specificity of 80.90 and 70.00% respectively. In animal experiments, serum levels of O-sulfotyrosine in mice were elevated on Day 7 after 5/6 nephrectomy (14.89 ± 1.05 vs. 8.88 ± 2.62 ng/mL, P < 0.001) until Day 90 (32.65 ± 5.59 vs. 8.88 ± 2.62 ng/mL, P < 0.001). CONCLUSION: Serum O-sulfotyrosine levels were observed correlated with degrading renal function and in CKD patients substantially higher than those in AKI patients. Thus serum O-sulfotyrosine facilitated the differential diagnosis of AKI from CKD.
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Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Tirosina/análogos & derivados , Idoso , Animais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Tirosina/sangueRESUMO
BACKGROUND: Chronic kidney disease (CKD) is associated with an increased risk of the progression of coronary artery disease (CAD). However, there are few data on the relationship between CAD severity and the duration of CKD. This study assessed the predictive value of the duration of kidney dysfunction in CKD patients with CAD severity. METHODS: In 145 patients (63.4% male, n = 92; mean age, 68.8 ± 12.8 years) with CKD, severity of CAD was assessed by coronary angiography and quantified by SYNTAX scores, and duration of kidney dysfunction was either assessed by checking historical biochemical parameters of individuals or was based on enquiries. RESULTS: Patients with high SYNTAX scores (≥ 22) had a greater prevalence of cardiovascular risk factors including age, gender, history of heart failure and smoking. In CKD patients, SYNTAX scores were positively correlated to duration of CKD and serum uric acid (UA), and negatively correlated to high-density lipoprotein-cholesterol (HDL-C) and ApoA1 levels. Univariate binary logistic regression and multivariate logistic analyses showed that SYNTAX scores correlated significantly with CKD duration, UA, and HDL-C. Receiver-operating characteristic analysis was used to explore a time point when coronary angiography application was economical and effective and yielded a Youden index of 6.5 years. CONCLUSIONS: Together, our results demonstrated that the duration of kidney dysfunction was an independent correlate of the severity of CAD in patients with CKD. Our findings suggest that coronary angiography should be considered for CKD patients with renal insufficiency having lasted for more than 6.5 years.
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Angiografia Coronária/estatística & dados numéricos , Doença da Artéria Coronariana/diagnóstico , Insuficiência Renal Crônica/complicações , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/patologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Progressão da Doença , Feminino , Taxa de Filtração Glomerular/fisiologia , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de TempoRESUMO
OBJECTIVE: This first-in-man (FIM) study aimed to determine the safety and efficacy of the Heartech® left ventricular partitioning device (LVPD) in patients with chronic heart failure (HF) postmyocardial infarction. METHODS: Sixteen patients were enrolled from three cardiac intervention centers in China. All patients underwent percutaneous ventricular restoration (PVR) procedures with implantation of the Heartech® LVPD. Safety and immediate success rates were recorded. Major adverse cardiovascular and cerebrovascular events (MACCEs) including all-cause mortality, myocardial infarction, stroke, emergent or selective surgery or interventional therapy, renal failure requiring hemodialysis, and major bleeding were recorded. Efficacy features included functional status, echocardiographic characteristics, life quality characteristics including peak oxygen consumption of cardiopulmonary exercise testing (CPET), European five-dimensional health scale (EQ-5D), 6-min walk test (6MWT) at baseline and during follow-up (NCT02938637). RESULTS: The device success rate was 93.75% (15 successes in 16 patients) with 100% safety. During follow-up of 36 ± 4.5 days, no MACCEs were found. The left ventricular end-systolic volume index decreased significantly (LVESVi, 72.47 ± 22.77 mL/m2 vs. 50.13 ± 13.36 mL/m2 , p < .001) as did left ventricular end diastolic volume index (LVEDVi, 106.27 ± 28.01 mL/m2 vs. 83.20 ± 16.87 mL/m2 , p = .001). Left ventricular ejection fraction (LVEF, 32.47 ± 6.98% vs. 40.41 ± 6.15, p < .001), 6MWT (383.13 ± 108.70 vs. 453.47 ± 88.24, p < 0.001) and EQ-5D (65.93 ± 11.25 vs. 78.67 ± 8.35, p < .001) improved significantly. CONCLUSIONS: Heartech® LVPD appeared to be safe and effective for treatment of HF postmyocardial infarction.
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Cateterismo Cardíaco/instrumentação , Insuficiência Cardíaca/terapia , Infarto do Miocárdio/complicações , Volume Sistólico , Função Ventricular Esquerda , Idoso , Cateterismo Cardíaco/efeitos adversos , China , Doença Crônica , Tolerância ao Exercício , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Estudos Prospectivos , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do TratamentoRESUMO
Renal fibrosis is a significant threat to public health globally. Diverse primary aetiologies eventually result in chronic kidney disease (CKD) and immune cells influence this process. The roles of monocytes/macrophages, T cells, and mast cells have been carefully examined, whilst only a few studies have focused on the effect of B cells. We investigated B-cell function in tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO), using genetic B-cell-deficient µMT mice or CD20 antibody-mediated B-cell-depleted mice. Obstructed kidneys of µMT and anti-CD20-treated mice showed lower levels of monocyte/macrophage infiltration and collagen deposition compared to wild-type mice. Mechanistically, anti-CD20 attenuated UUO-induced alterations of renal tumour necrosis factor-α (TNF-α), vascular cell adhesion molecule 1 (VCAM-1) pro-inflammatory genes, and CC chemokine ligand-2 (CCL2) essential for monocyte recruitment; B cells were one of the main sources of CCL2 in post-UUO kidneys. Neutralization of CCL2 reduced monocyte/macrophage influx and fibrotic changes in obstructed kidneys. Therefore, early-stage accumulation of B cells in the kidney accelerated monocyte/macrophage mobilization and infiltration, aggravating the fibrosis resulting from acutely induced kidney nephropathy. © 2016 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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Linfócitos B/imunologia , Nefropatias/imunologia , Monócitos/imunologia , Obstrução Ureteral/imunologia , Animais , Movimento Celular/imunologia , Quimiocina CCL2/antagonistas & inibidores , Quimiocina CCL2/imunologia , Quimiotaxia de Leucócito/imunologia , Fibrose , Mediadores da Inflamação/metabolismo , Nefropatias/etiologia , Túbulos Renais/imunologia , Túbulos Renais/patologia , Masculino , Camundongos Endogâmicos C57BL , Obstrução Ureteral/complicaçõesRESUMO
In high-risk patients with pure native aortic regurgitation (PNAR), transcatheter aortic valve replacement (TAVR) remains an off-label intervention. Due to anatomical variations in the aortic root and technical challenges unique to PNAR, the transfemoral approach (TF-TAVR) requires continued accumulation of experience and technological refinement. In this context, we successfully and safely performed a snare-assisted TF-TAVR procedure for a patient with PNAR, characterized by significant aortic angulation. We introduced an innovative technique termed "snare-assisted coaxiality optimized technique" (SACOT) during valve deployment. SACOT played a crucial role in optimizing valve positioning, enhancing coaxiality, and achieving the ideal implantation depth for PNAR. Post-procedure assessments demonstrated stability and the absence of paravalvular regurgitation (PVR).
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PURPOSE: The fibroblast activation protein inhibitor-04 (FAPI-04) specifically binds to the FAP of activated myocardial fibroblasts, which makes 68Ga-labelled FAPI-04 (68Ga-FAPI-04) positron emission tomography (PET)/magnetic resonance (MR) a new potential imaging technique for the evaluation of myocardial fibrosis. This study aimed to evaluate the potential value of 68Ga-FAPI-04 PET/MR in assessing and predicting changes in renal function in patients with acute ST-elevation myocardial infarction (STEMI). METHODS: Thirty-three patients with STEMI were included in this study. 68Ga-FAPI-04 PET/MR and cardiac magnetic resonance were performed before discharge in all patients. Worsening renal function(WRF) was defined as ≥20% decrease in estimated glomerular filtration rate(eGFR) from baseline to 12 months. RESULTS: The WRF group demonstrated higher 68Ga-FAPI-04 uptake volume (UV) at baseline than the non-WRF group(P = 0.009). 68Ga-FAPI-04 UV at baseline was correlated with follow-up eGFR (r = -0.493, P = 0.004). 68Ga-FAPI-04 UV at baseline was a significant predictor of WRF (OR = 1.014, P = 0.029) at 12 months after STEMI. CONCLUSIONS: As an effective tool to non-invasively quantify myocardial fibroblast activation, 68Ga-FAPI-04 PET/MR has potential value for assessing and predicting worsening renal function in patients with STEMI.
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STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with acute nocturnal hemodynamic and neurohormonal abnormalities that may increase the risk of coronary events, especially during the nighttime. This study sought to investigate the day-night pattern of acute ST-segment elevation myocardial infarction (STEMI) onset in patients with OSA and its impact on cardiovascular adverse events. METHODS: We prospectively enrolled 397 patients with STEMI, for which the time of onset of chest pain was clearly identified. All participants were categorized into non-OSA (n = 280) and OSA (n = 117) groups. The association between STEMI onset time and major adverse cardiovascular and cerebrovascular events was estimated by Cox proportional hazards regression. RESULTS: STEMI onset occurred from midnight to 5:59 am in 33% of patients with OSA, as compared with 15% in non-OSA patients (P < .01). For individuals with OSA, the relative risk of STEMI from midnight to 5:59 am was 2.717 [95% confidence interval (CI) 1.616 - 4.568] compared with non-OSA patients. After a median of 2.89 ± 0.78 years follow-up, symptom onset time was found to be significantly associated with risk of major adverse cardiovascular and cerebrovascular events in patients with OSA, while there was no significant association observed in non-OSA patients. Compared with STEMI presenting during noon to 5:59 pm, the hazard ratios for major adverse cardiovascular and cerebrovascular events in patients with OSA were 4.683 (95% CI 2.024 - 21.409, P = .027) for midnight to 5:59 am and 6.964 (95% CI 1.379 - 35.169, P = .019) for 6 pm to midnight, whereas the hazard ratios for non-OSA patients were 1.053 (95% CI 0.394 - 2.813, P = .917) for midnight to 5:59 am and 0.745 (95% CI 0.278 - 1.995, P = .558) for 6 pm to midnight. CONCLUSIONS: Patients with OSA exhibited a peak incidence of STEMI between midnight and 5:59 am, which showed an independent association with cardiovascular adverse events. CITATION: Wang Y, Buayiximu K, Zhu T, et al. Day-night pattern of acute ST-segment elevation myocardial infarction onset in patients with obstructive sleep apnea. J Clin Sleep Med. 2024;20(5):765-775.
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Infarto do Miocárdio com Supradesnível do Segmento ST , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Estudos Prospectivos , Fatores de Risco , Idoso , Fatores de Tempo , Ritmo Circadiano/fisiologiaRESUMO
The progression of NTLs after PCI accounts for a significant portion of future adverse cardiac events. The reduction in LDL-C reduces cardiovascular events. This has, however, not yet been shown in a real-world setting. We aimed to investigate the association between LDL-C changes with progression in NTLs. A total of 847 patients with successful PCI were enrolled. Patients with follow-up LDL-C ≥ 1.4 mmol/L or percent reduction <50% compared to baseline were Non-optimal group (n = 793); patients with follow-up LDL-C < 1.4 mmol/L and percent reduction ≥50% compared to baseline were Optimal group (n = 54). Compared to Non-optimal group, Optimal group presented a lower rate of NTL plaque progression (11.11% vs. 23.96%; p = 0.007) and a lower follow-up TC (2.77 ± 0.59 vs. 3.66 ± 0.97; p < 0.001) and LDL-C (1.09 ± 0.26 vs. 2.03 ± 0.71; p < 0.001). The univariate logistic regression analysis revealed that follow-up LDL-C < 1.4 mmol/L and a percent reduction ≥50% from baseline was a protective factor for NTL plaque progression (OR: 0.397; 95%CI: 0.167-0.941; p = 0.036). The multivariate logistic regression model revealed that follow-up LDL-C < 1.4 mmol/L and percent reduction ≥50% was indeed an independent factor associated with a lower rate of plaque progression of NTLs (OR: 0.398; 95% CI: 0.167-0.945; p = 0.037). Therefore, achieving guideline-recommended LDL-C level was associated with a significantly reduced risk of NTL plaque progression.
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BACKGROUND: Investigating the prognostic value of the Murray law-based quantitative flow ratio (µQFR) on the clinical outcome after treatment of in-stent restenosis (ISR) with a drug-coated balloon (DCB). METHODS: Patients participating in a previous randomized clinical trial for DCB-ISR were post-hoc analyzed. The primary endpoint was vessel-oriented composite endpoint (VOCE), defined as cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization. µQFRs at baseline and after DCB angioplasty was calculated, and its prognostic value as a predictor of VOCE was explored in Cox regression. RESULTS: A total of 169 lesions in 169 patients were analyzed. At 1-year follow-up, 20 VOCEs occurred in 20 patients. Receiver-operating characteristic curve analysis identified a post-procedural µQFR of ≤ 0.89 as the best cut-off to predict VOCE (area under curve [AUC]: 0.74; 95% confidence interval [CI]: 0.67-0.80; p < 0.001), superior to post-procedural in-stent percent diameter stenosis, which reported an AUC of 0.61 (95% CI: 0.53-0.68; p = 0.18). Post-procedural µQFR was significantly lower in patients with VOCE compared with those without (0.88 [interquartile range: 0.79-0.94] vs. 0.96 [interquartile range: 0.91-0.98], respectively; p < 0.001). After correction for potential confounders, post-procedural µQFR ≤ 0.89 was associated with a 6-fold higher risk of VOCE than lesions with µQFR > 0.89 (hazard ratio: 5.94; 95% CI: 2.33-15.09; p < 0.001). CONCLUSIONS: Post-procedural µQFR may become a promising predictor of clinical outcome after treatment of DES-ISR lesions by DCB angioplasty.
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Reestenose Coronária , Stents Farmacológicos , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Prognóstico , Constrição Patológica , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Resultado do Tratamento , Fatores de Risco , Materiais Revestidos BiocompatíveisRESUMO
Motion estimation is a fundamental step in dynamic medical image processing for the assessment of target organ anatomy and function. However, existing image-based motion estimation methods, which optimize the motion field by evaluating the local image similarity, are prone to produce implausible estimation, especially in the presence of large motion. In addition, the correct anatomical topology is difficult to be preserved as the image global context is not well incorporated into motion estimation. In this study, we provide a novel motion estimation framework of dense-sparse-dense (DSD), which comprises two stages. In the first stage, we process the raw dense image to extract sparse landmarks to represent the target organ's anatomical topology, and discard the redundant information that is unnecessary for motion estimation. For this purpose, we introduce an unsupervised 3-D landmark detection network to extract spatially sparse but representative landmarks for the target organ's motion estimation. In the second stage, we derive the sparse motion displacement from the extracted sparse landmarks of two images of different time points. Then, we present a motion reconstruction network to construct the motion field by projecting the sparse landmarks' displacement back into the dense image domain. Furthermore, we employ the estimated motion field from our two-stage DSD framework as initialization and boost the motion estimation quality in light-weight yet effective iterative optimization. We evaluate our method on two dynamic medical imaging tasks to model cardiac motion and lung respiratory motion, respectively. Our method has produced superior motion estimation accuracy compared to the existing comparative methods. Besides, the extensive experimental results demonstrate that our solution can extract well-representative anatomical landmarks without any requirement of manual annotation. Our code is publicly available online: https://github.com/yyguo-sjtu/DSD-3D-Unsupervised-Landmark-Detection-Based-Motion-Estimation.
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Processamento de Imagem Assistida por Computador , Processamento de Imagem Assistida por Computador/métodos , Movimento (Física)RESUMO
OBJECTIVES: The B cell activating factor (BAFF) is a B cell survival factor involved in atherosclerosis and ischemia-reperfusion (IR) injury. This study sought to investigate whether BAFF is a potential predictor of poor outcomes in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: We prospectively enrolled 299 patients with STEMI, and serum levels of BAFF were measured. All subjects were followed for three years. The primary endpoint was major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal reinfarction, hospitalization for heart failure (HF), and stroke. Multivariable Cox proportional hazards models were constructed to analyze the predictive value of BAFF for MACEs. RESULTS: In multivariate analysis, BAFF was independently associated with risk of MACEs (adjusted HR 1.525, 95% CI 1.085-2.145; p = 0.015) and cardiovascular death (adjusted hazard ratio [HR] 3.632, 95% confidence interval [CI] 1.132-11.650, p = 0.030) after adjustment for traditional risk factors. Kaplan-Meier survival curves demonstrated that patients with BAFF levels above the cut-off value (1.46 ng/mL) were more likely to have MACEs (log-rank p < 0.0001) and cardiovascular death (log-rank p < 0.0001). In subgroup analysis, the impact of high BAFF on MACEs development was stronger in patients without dyslipidemia. Furthermore, the C-statistic and Integrated Discrimination Improvement (IDI) values for MACEs were improved with BAFF as an independent risk factor or when combined with cardiac troponin I. CONCLUSIONS: This study suggests that higher BAFF levels in the acute phase are an independent predictor of the incidence of MACEs in patients with STEMI.
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BACKGROUD: Left ventricular remodeling (LVR) is a major predictor of adverse outcomes in patients with acute ST-elevation myocardial infarction (STEMI). This study aimed to prospectively evaluate LVR in patients with STEMI who were successfully treated with primary percutaneous coronary intervention (PCI) and examine the relationship between early left ventricular dilation and late LVR. METHODS: Overall 301 consecutive patients with STEMI who underwent primary PCI were included. Serial echocardiography was performed on the first day after PCI, on the day of discharge, at 1 month, and 6 months after discharge. RESULTS: Left ventricular remodeling occurred in 57 (18.9%) patients during follow-up. Left ventricular end-diastolic volume (LVEDV) reduced from day 1 postoperative to discharge in the LVR group compared with that in the non-LVR (n-LVR) group. The rates of change in LVEDV (ΔLVEDV%) were -5.24 ± 16.02% and 5.05 ± 16.92%, respectively (p < 0.001). LVEDV increased in patients with LVR compared with n-LVR at 1-month and 6-month follow-ups (ΔLVEDV% 13.05 ± 14.89% vs. -1.9 ± 12.03%; 26.46 ± 14.05% vs. -3.42 ± 10.77%, p < 0.001). Receiver operating characteristic analysis showed that early changes in LVEDV, including ΔLVEDV% at discharge and 1-month postoperative, predicted late LVR with an area under the curve value of 0.80 (95% confidence interval 0.74-0.87, p < 0.0001). CONCLUSIONS: Decreased LVEDV at discharge and increased LVEDV at 1-month follow-up were both associated with late LVR at 6-month. Comprehensive and early monitoring of LVEDV changes may help to predict LVR.
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Earlier studies have demonstrated that aldose reductase (AR) plays a key role in mediating ischemia-reperfusion (I/R) injury. Our objective was to investigate if AR mediates I/R injury by influencing phosphorylation of glycogen synthase kinase-3ß (p-GSK3ß). To investigate this issue, we used three separate models to study the effects of stress injury on the heart. Hearts isolated from wild-type (WT), human expressing AR transgenic (ARTg), and AR knockout (ARKO) mice were perfused with/without GSK3ß inhibitors (SB-216763 and LiCl) and subjected to I/R. Ad-human AR (Ad-hAR)-expressing HL-1 cardiac cells were exposed to hypoxia (0.5% O(2)) and reoxygenation (20.9% O(2)) conditions. I/R in a murine model of transient occlusion and reperfusion of the left anterior descending coronary artery (LAD) was used to study if p-GSK3ß was affected through increased AR flux. Lactate dehydrogenase (LDH) release and left ventricular developed pressure (LVDP) were measured. LVDP was decreased in hearts from ARTg mice compared with WT and ARKO after I/R, whereas LDH release and apoptotic markers were increased (P < 0.05). p-GSK3ß was decreased in ARTg hearts compared with WT and ARKO (P < 0.05). In ARKO, p-GSK3ß and apoptotic markers were decreased compared with WT (P < 0.05). WT and ARTg hearts perfused with GSK3ß inhibitors improved p-GSK3ß expression and LVDP and exhibited decreased LDH release, apoptosis, and mitochondrial pore opening (P < 0.05). Ad-hAR-expressing HL-1 cardiac cells, exposed to hypoxia (0.5% O(2)) and reoxygenation (20.9% O(2)), had greater LDH release compared with control HL-1 cells (P < 0.05). p-GSK3ß was decreased and correlated with increased apoptotic markers in Ad-hAR HL-1 cells (P < 0.05). Treatment with phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) inhibitor increased injury demonstrated by increased LDH release in ARTg, WT, and ARKO hearts and in Ad-hAR-expressing HL-1 cells. Cells treated with protein kinase C (PKC) α/ß inhibitor displayed significant increases in p-Akt and p-GSK3ß expression, and resulted in decreased LDH release. In summary, AR mediates changes in p-GSK3ß, in part, via PKCα/ß and Akt during I/R.
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Aldeído Redutase/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Traumatismo por Reperfusão Miocárdica/enzimologia , Miócitos Cardíacos/enzimologia , Aldeído Redutase/deficiência , Aldeído Redutase/genética , Animais , Apoptose , Linhagem Celular , Modelos Animais de Doenças , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Fosfatidilinositol 3-Quinase/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , Proteína Quinase C beta , Proteína Quinase C-alfa/antagonistas & inibidores , Proteína Quinase C-alfa/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , Recuperação de Função Fisiológica , Transfecção , Função Ventricular Esquerda , Pressão VentricularRESUMO
Chronic kidney disease (CKD) accelerates atherosclerosis. The mechanism of CKD-related atherosclerosis is complex, and CKD-specific risk factors may contribute to this process in addition to traditional risk factors such as hypertension, diabetes, and hypercholesterolemia. In the present study, to discover CKD-specific atherosclerosis risk factors, a total of 62 patients with different stages of kidney function were enrolled. All patients underwent coronary angiographies and the severity of coronary atherosclerosis was defined by the SYNTAX score. Patients were divided into different groups according to their kidney function levels and coronary atherosclerosis severity. Data-independent acquisition mass spectrometry was used to identify differentially expressed proteins (DEPs) in the plasma samples, and weighted correlation network analysis (WGCNA) was employed to identify significant protein modules and hub proteins related to CKD-specific atherosclerosis. The results showed that 10 DEPs associated with atherosclerosis were found in the comparative groups with modest and severe CKD. Through WGCNA, 1768 proteins were identified and 8 protein modules were established. Enrichment analyses of protein modules revealed functional clusters mainly associated with inflammation and the complement and coagulation cascade as atherosclerosis developed under CKD conditions. The results may help to better understand the mechanisms of CKD-related atherosclerosis and guide future research on developing treatments for CKD-related atherosclerosis.
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Aterosclerose , Doença da Artéria Coronariana , Insuficiência Renal Crônica , Humanos , Proteômica , Fatores de Risco , Espectrometria de MassasRESUMO
Automated segmentation of left ventricular cavity (LVC) in temporal cardiac image sequences (consisting of multiple time-points) is a fundamental requirement for quantitative analysis of cardiac structural and functional changes. Deep learning methods for segmentation are the state-of-the-art in performance; however, these methods are generally formulated to work on a single time-point, and thus disregard the complementary information available from the temporal image sequences that can aid in segmentation accuracy and consistency across the time-points. In particular, single time-point segmentation methods perform poorly in segmenting the end-systole (ES) phase image in the cardiac sequence, where the left ventricle deforms to the smallest irregular shape, and the boundary between the blood chamber and the myocardium becomes inconspicuous and ambiguous. To overcome these limitations in automatically segmenting temporal LVCs, we present a spatial sequential network (SS-Net) to learn the deformation and motion characteristics of the LVCs in an unsupervised manner; these characteristics are then integrated with sequential context information derived from bi-directional learning (BL) where both chronological and reverse-chronological directions of the image sequence are used. Our experimental results on a cardiac computed tomography (CT) dataset demonstrate that our spatial-sequential network with bi-directional learning (SS-BL-Net) outperforms existing methods for spatiotemporal LVC segmentation.