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Background: Patients with coronary artery disease (CAD) often experience pulmonary ventilation dysfunction following their initial event. However, there is insufficient research exploring the relationship between this dysfunction and CAD prognosis. Methods: To address this gap, a retrospective observational study was conducted involving 3800 CAD patients without prior pulmonary ventilation disease who underwent cardiopulmonary exercise testing (CPET) during hospitalization between November 2015 and September 2021. The primary endpoint was a composite of major adverse cardiovascular events (MACE), such as death, myocardial infarction (MI), repeat revascularization, and stroke. Propensity score matching (PSM) was used to minimize selection bias between the two groups, with a subgroup analysis stratified by smoking status. Results: The results showed that patients were divided into normal (n = 2159) and abnormal (n = 1641) groups based on their pulmonary ventilation function detected by CPET, with 1469 smokers and 2331 non-smokers. The median follow-up duration was 1237 (25-75% interquartile range 695-1596) days. The primary endpoint occurred in 390 patients (10.26%). 1472 patients in each of the two groups were enrolled in the current analysis after PSM, respectively. However, pulmonary function was not associated with MACE before (hazard ratio (HR) 1.20, 95% confidence interval (95% CI) 0.99-1.47; Log-rank p = 0.069) or after PSM (HR 1.07, 95% CI 0.86-1.34; Log-rank p = 0.545) among the entire population. Nonetheless, pulmonary ventilation dysfunction was significantly associated with an increased risk of MACE in smoking patients (HR 1.65, 95% CI 1.25-2.18; p < 0.001) but not in non-smoking patients (HR 0.81, 95% CI 0.60-1.09; p = 0.159). In addition, there was a significant interaction between current smoking status and pulmonary ventilation dysfunction on MACE (p for interaction < 0.001). Conclusions: Pulmonary ventilation dysfunction identified through CPET was independently associated with long-term poor prognosis in smoking patients with CAD but not in the overall population.
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OBJECTIVES: To investigate the effect of moderate-intensity continuous training (MICT) on the improvement of cardiopulmonary function for patients undergoing transcatheter aortic valve replacement (TAVR). DESIGN: Randomized controlled study. SETTING AND PARTICIPANTS: Between August 20, 2021, and February 28, 2022, a total of 66 patients after TAVR were screened for inclusion and randomly divided into the MICT and control groups at a ratio of 1:1. MICT was scheduled 3 times per week for 3 months in the intervention group. Patients in the control group received one-time advice on physical activity according to the current guideline. METHODS: The primary endpoint was the 3-month change in peak oxygen consumption (peak VO2) assessed by cardiopulmonary exercise testing. The secondary endpoints included the 3-month change in 6-minute walk test (6MWT), the 12-Item Short Form Health Survey (SF-12), New York Heart Association (NYHA) class, echocardiographic parameters, and laboratory parameters. RESULTS: After 3 months, the change in peak VO2 was higher in the MICT group than that in the control group (1.63 mL/kg/min, 95% CI 0.58-2.67, P = .003). Change in 6MWT (21.55 m, 95% CI 0.38-42.71, P = .046) was higher in the MICT group compared with the control group. A significant change in favor of MICT was also observed for low-density lipoprotein cholesterol (-0.62 mmol/L, 95% CI -1.00 to -0.23, P = .002). However, there were no significant changes in other echocardiographic indices, laboratory parameters, and SF-12 between the 2 groups (all P > .05). CONCLUSIONS AND IMPLICATIONS: MICT had a positive effect on the cardiopulmonary function and physical capacity of patients after TAVR.
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Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Humanos , Exercício Físico , Terapia por Exercício , Caminhada , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Resultado do TratamentoRESUMO
Objective: To demonstrate the effect of daily exercise on the incidence of major adverse cardiovascular events (MACE) for patients with acute coronary syndrome (ACS). Methods: A cohort of 9,636 patients with ACS were consecutively enrolled in our retrospective study between November 2015 and September 2017, which were used for model development. 6,745 patients were assigned as the derivation cohort and 2,891 patients were assigned as the validation cohort. The least absolute shrinkage and selection operator (LASSO) regression and COX regression were used to screen out significant variables for the construction of the nomogram. Multivariable COX regression analysis was employed for the development of a model represented by a nomogram. The nomogram was then evaluated for performance traits such as discrimination, calibration, and clinical efficacy. Results: Among 9,636 patients with ACS (mean [SD] age, 60.3 [10.4] years; 7,235 men [75.1%]), the 5-year incidence for MACE was 0.19 at a median follow-up of 1,747 (1,160-1,825) days. Derived from the LASSO regression and COX regression, the nomogram has included 15 factors in total including age, previous myocardial infarction (MI), previous percutaneous coronary intervention (PCI), systolic pressure, N-terminal Pro-B-type natriuretic peptide (NT-proBNP), high-density lipoprotein cholesterol (HDL), serum creatinine, left ventricular end-diastolic diameter (LVEDD), Killip class, the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score, left anterior descending (LAD) stenosis (≥50%), circumflex (LCX) stenosis (≥50%), right coronary artery (RCA) stenosis (≥50%), exercise intensity, cumulative time. The 5-year area under the ROC curve (AUC) of derivation and validation cohorts were 0.659 (0.643-0.676) and 0.653 (0.629-0.677), respectively. The calibration plots showed the strong concordance performance of the nomogram model in both two cohorts. Moreover, decision curve analysis (DCA) also showed the usefulness of nomogram in clinical practice. Conclusion: The present work provided a prediction nomogram predicting MACE for patients with ACS after incorporating the already known factors and the daily exercise, which demonstrated the effectiveness of daily exercise on the improvement of prognosis for patients with ACS.
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Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Masculino , Humanos , Pessoa de Meia-Idade , Síndrome Coronariana Aguda/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Constrição Patológica/etiologia , PrognósticoRESUMO
BACKGROUND: This study aimed to investigate the efficiency of nicotinamide-based supportive therapy for lymphopenia in patients with coronavirus disease-2019 (COVID-19). METHODS: Twenty four patients diagnosed with COVID-19 were randomly divided into 2 groups (n = 12) during hospitalization in a ratio of 1:1. Based on conventional treatment, the treatment group was administered 100 mg nicotinamide 5 times a day for 2 days. The control group received routine treatment only. The primary endpoint was the change in the absolute lymphocyte count. The secondary endpoints included both in-hospital death and the composite endpoint of aggravation, according to upgraded oxygen therapy, improved nursing level, and ward rounds of superior physicians for changes in conditions. RESULTS: Full blood counts before and after nicotinamide administration were comparable in each group (all P > .05). Before and after receiving nicotinamide, mean absolute lymphocyte counts were similar between the two groups ([0.94 ± 0.26] × 109/L vs [0.89 ± 0.19] × 109/L, P = .565; [1.15 ± 0.48] × 109/L vs [1.02 ± 0.28] × 109/L, P = .445, respectively). Therefore, there was no statistically significant difference in the lymphocyte improvement rate between the two groups (23.08 ± 46.10 vs 16.52 ± 24.10, P = .67). There was also no statistically significant difference in the secondary endpoints between the two groups. CONCLUSION: Among patients with COVID-19, there was no statistically significant difference in the change of whole blood counts and absolute lymphocyte counts before and after intervention in both groups. Therefore, no new evidence has been found regarding the effect of niacinamide on lymphopenia in COVID-19 patients.
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COVID-19 , Linfopenia , Humanos , COVID-19/complicações , SARS-CoV-2 , Niacinamida/uso terapêutico , Mortalidade Hospitalar , Linfopenia/etiologiaRESUMO
Background: In clinical practice, some cases indicated that the loading dose of bivalirudin increased the bleeding risk, particularly in patients with renal insufficiency. Therefore, this study aimed to assess the efficacy and safety of the low-dose (80%) bolus injection of bivalirudin in patients undergoing cardiac catheterization stratified by renal function. Methods: A total of 204 individuals in the REDUCE BOLUS trial were stratified 1:1 to the estimated glomerular filtration rate (eGFR) ≥ 60 ml/min cohort or eGFR < 60 ml/min cohort, then randomized 1:1 to the reduced bolus bivalirudin group (i.e., the experimental group) or normal bolus bivalirudin group (i.e., the control group), respectively. The primary end point was to compare the differences of the area under the curve of activated clotting time (ACT) between the two groups. The secondary end points were the postoperative net adverse clinical events (NACEs) before discharge, defined as the all-cause mortality, recurrent myocardial infarction, ischemia-driven target vessel revascularization, stroke, and bleeding events. Results: Between January 3, 2020, and March 26, 2021, 204 patients undergoing coronary angiography were randomly assigned, including 102 (i.e., 51 in the control group and 51 in the experimental group) with normal eGFR and 102 (i.e., 51 control and 51 experimental) with abnormal eGFR. No difference was observed in the curve of ACT between the control group and the experimental group (0.55 ± 0.09 vs. 0.56 ± 0.08, P = 0.542 and 0.55 ± 0.06 vs. 0.57 ± 0.05, P = 0.075, respectively, for normal eGFR cohort and abnormal eGFR cohort). The one-sided 97.5% lower confidence bound for the difference in the area under the ACT curve was -0.017 and 0.0015 in eGFR ≥ 60 ml/min and eGFR<60 ml/min cohort, respectively, both above the preset non-inferiority criterion of -0.07, establishing the non-inferiority. There was no incidence of NACE and stent thrombosis before discharge in each group. Conclusion: In patients undergoing cardiac catheterization, the efficacy and safety of the reduced bolus of bivalirudin were non-inferior to the normal one, even in patients without chronic kidney disease. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03588611].
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INTRODUCTION: There are scarce real-world data on the long-term efficacy and safety of cardiopulmonary exercise testing (CPET) combined with the systematic education of cardiac rehabilitation (CR) approach for patients post-coronary stenting, which is, therefore, the subject of this study. METHODS: Data collected between 1 April 2015 and 20 May 2017 from 11,345 patients in the rehabilitation center database at our hospital were retrospectively analyzed. Five hundred thirty-six patients with incomplete information, or unable to cooperate with telephone follow-up, were excluded; 4001 patients received the combined CR approach; and 6808 patients received only routine post-procedure education (controls). Of these, 2805 CR participants (CR group) were matched 1:1 to controls (control group) using propensity scores. The main outcome was quality of life in Seattle Angina Questionnaire (SAQ) scores. SAQ was measured in hospital and at follow-up; meanwhile, volume/type of habitual exercise, major adverse cardiovascular event (MACE), and its components of target vessel revascularization, myocardial infarction, and cardiac death were recorded and analyzed. RESULTS: At median 583 (range 184-963) day follow-up, compared with controls, the CR group showed fewer patients not engaging in physical exercise (22 vs. 956, p < 0.05); more cumulative exercise time (h/week) (8.22 ± 6.17 h vs. 3.00 ± 1.65 h, p < 0.05); higher SAQ scores (physical limitation, 69.59 ± 10.96 vs. 57.49 ± 7.19; anginal stability, 80.50 ± 18.21 vs. 58.82 ± 11.95; anginal frequency, 78.58 ± 11.07 vs. 67.14 ± 22.41; treatment satisfaction, 82.33 ± 13.21 vs. 56.84 ± 21.61; quality of life, 68.69 ± 18.33 vs. 60.26 ± 17.13, all p < 0.01), but a similar MACE rate (log-rank p = 0.621). CONCLUSION: Compared with only routine post-procedure education, CR combining at least one-time CPET with a systematic cardiac education program before discharge improved engagement in physical activity and quality of life for patients after percutaneous coronary intervention (PCI) without increasing clinical adverse events.
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Reabilitação Cardíaca , Intervenção Coronária Percutânea , Teste de Esforço , Humanos , Qualidade de Vida , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Background Acute penetrating aortic ulcers (PAUs) are reported to dynamically evolve into different clinical outcomes ranging from regression to aortic rupture, but no practice guidelines are available in China. Methods and Results All 109 patients with acute PAUs were monitored clinically. At 30 days follow-up, 31 patients (28.44%) suffered from aortic-related adverse events, a composite of aortic-related mortality, aortic dissection, or an enlarged ulcer. In addition, 7 (6.42%) patients had clinically related adverse events, including all-cause mortality, cerebral stroke, nonfatal myocardial infarction, acute heart failure alone or acute exacerbation of chronic heart failure, acute renal failure, arrhythmia, and bleeding events. In the present study, the intervention criteria for the Chinese PAU population included a PAU diameter of 12.5 mm and depth of 9.5 mm. The multivariate analysis showed that an ulcer diameter >12.5 mm (hazard ratio [HR], 3.846; 95% CI, 1.561-9.476; P=0.003) and an ulcer depth >9.5 mm (HR, 3.359; 95% CI, 1.505-7.494; P=0.003) were each independent predictors of aortic-related events. Conclusions Patients with acute PAUs were at high risk for aortic-related adverse events and clinically related adverse events within 30 days after onset. Patients with an ulcer diameter >12.5 mm or an ulcer depth >9.5 mm have a higher risk for disease progression, and early intervention may be recommended.
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Doenças da Aorta/diagnóstico por imagem , Úlcera/diagnóstico por imagem , Doença Aguda , Idoso , Doenças da Aorta/diagnóstico , Doenças da Aorta/patologia , Ruptura Aórtica/etiologia , Angiografia por Tomografia Computadorizada , Progressão da Doença , Feminino , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Úlcera/complicações , Úlcera/diagnóstico , Úlcera/patologiaRESUMO
Prolyl aminopeptidase (PAP) is an important exopeptidase which might be a biomarker for pathogen infection and a potential therapeutic target. However, very few fluorescent probes have been developed for detecting PAP activity. Here we report the development of the first near infrared (NIR) turn-on fluorescent probe (NIR-PAP) for detecting and imaging PAP in living cells. The probe is prepared by reacting a cysteine-proline dipeptide with an acryloylated NIR fluorophore via a facile thiol-Michael addition reaction. NIR-PAP exhibits a dynamic response toward PAP in the range of 0.02-2.5 U mL-1 with an estimated limit of detection of 0.013 U mL-1. In vitro studies also reveal that the probe displays high specificity and robust responses toward PAP under physiological pH and temperature conditions. Moreover, NIR-PAP is successfully introduced to detect and differentiate PAP activity in four different cell lines via both confocal fluorescence imaging and flow cytometry. Therefore, our probe may hold great promise in diagnosing infectious diseases caused by pathogens and screening therapeutic drugs in vivo.
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Aminopeptidases/metabolismo , Corantes Fluorescentes/química , Raios Infravermelhos , Imagem Óptica/métodos , Células HeLa , Células Hep G2 , Humanos , Limite de Detecção , Células MCF-7RESUMO
BACKGROUND: Intramural hematomas (IMHs) are reported to dynamically evolve into different clinical outcomes ranging from regression to aortic rupture, but no practice guidelines are available in China. OBJECTIVE: To determine the evolution of IMHs after long-term follow-up and to identify the predictive factors of IMH outcomes in the Chinese population. METHODS: A total of 123 IMH patients with clinical and imaging follow-up data were retrospectively studied. The primary endpoints were aortic disease-related death, aortic dissection, penetrating aortic ulcer (PAU), thickening of the aortic hematoma and aortic complications requiring surgical or endovascular treatment. RESULTS: All 123 IMH patients were monitored clinically. The follow-up duration ranged from 1.4 to 107â¯months (median, 20â¯months). Thirty-nine patients had type A IMH, and 84 had type B. The multivariate analysis showed that a baseline MADâ¯≥â¯44.75â¯mm (2.9% vs 61.4%, Pâ¯<â¯0.001) and acute PAUs (2.9% vs 34.1%, Pâ¯=â¯0.008) were independent predictors of aorta-related events. CONCLUSIONS: Medication and short-term imaging are recommended for Chinese IMH patients with a hematoma thicknessâ¯<â¯10.45â¯mm and a baseline MADâ¯<â¯44.75â¯mm. Rigorous medical observation should also be performed during the acute phase of IMH.
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Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/epidemiologia , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/epidemiologia , Hematoma/diagnóstico por imagem , Hematoma/epidemiologia , Idoso , China/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Splenic artery embolization (SAE) has been an effective adjunct to the Non-operative management (NOM) for blunt splenic injury (BSI). However, the optimal embolization techniques are still inconclusive. To further understand the roles of different embolization locations and embolic materials in SAE, we conducted this system review and meta-analyses. METHODS: Clinical studies related to SAE for adult patients were researched in electronic databases, included PubMed, Embase, ScienceDirect and Google Scholar Search (between October 1991 and March 2013), and relevant information was extracted. To eliminate the heterogeneity, a sensitivity analysis was conducted on two reduced study sets. Then, the pooled outcomes were compared and the quality assessments were performed using Newcastle-Ottawa Scale (NOS). The SAE success rate, incidences of life-threatening complications of different embolization techniques were compared by χ2 test in 1st study set. Associations between different embolization techniques and clinical outcomes were evaluated by fixed-effects model in 2nd study set. RESULTS: Twenty-three studies were included in 1st study set. And then, 13 of them were excluded, because lack of the necessary details of SAE. The remaining 10 studies comprised 2nd study set, and quality assessments were performed using NOS. In 1st set, the primary success rate is 90.1% and the incidence of life-threatening complications is 20.4%, though the cases which required surgical intervention are very few (6.4%). For different embolization locations, there was no obvious association between primary success rate and embolization location in both 1st and 2nd study sets (P > 0.05). But in 2nd study set, it indicated that proximal embolization reduced severe complications and complications needed surgical management. As for the embolic materials, the success rate between coil and gelfoam is not significant. However, coil is associated with a lower risk of life-threatening complications, as well as less complications requiring surgical management. CONCLUSIONS: Different embolization techniques affect the clinical outcomes of SAE. The proximal embolization is the best option due to the less life-threatening complications. For commonly embolic material, coil is superior to gelfoam for fewer severe complications and less further surgery management.
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Embolização Terapêutica/normas , Baço/lesões , Artéria Esplênica/efeitos dos fármacos , Ferimentos não Penetrantes/complicações , Embolização Terapêutica/métodos , Humanos , Baço/efeitos dos fármacos , Baço/fisiopatologia , Artéria Esplênica/cirurgia , Ferimentos não Penetrantes/tratamento farmacológicoRESUMO
Transcatheter arterial embolization (TAE) is the best non-laparotomy choice for solid visceral organs rupture and bleeding nowadays. In our previous study, a new biodegradable macromolecule material thrombin-loaded alginate-calcium microsphere (TACM) was prepared and its characteristics were investigated preliminarily. In this study, we further investigated the biocompatibility of TACMs, as well as physical characteristic, application method and effect of TACMs with thrombus (embolic agent). The in vivo results attested that TACMs were non-irritating and non-genotoxic with desired biocompatibility, although brought about a slight and temporary inflammation. Application research showed that the function of thrombin was inhibited by common contrast agents, and it was impracticable to add contrast agents in TACMs with thrombus for tracing under X-rays in TAE. Then, a novel delivery method was developed. In addition, stress resistance test indicated that the TACMs with thrombus was significantly stronger than single autologous thrombus, the optimized ratio of TACMs to whole blood was 2:3 for forming mixed thrombus. Finally, large animal experiment revealed that the novel embolic agent - TACMs mixed thrombus was effective and safe in treating hemorrhage of solid abdominal viscera by TAE.
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Alginatos/química , Cálcio/química , Catéteres , Embolização Terapêutica/instrumentação , Microesferas , Trombina/química , Trombina/farmacologia , Animais , Citocinas/biossíntese , Ácido Glucurônico/química , Hemostáticos/efeitos adversos , Hemostáticos/química , Hemostáticos/farmacologia , Ácidos Hexurônicos/química , Masculino , Camundongos , Coelhos , Pele/efeitos dos fármacos , Trombina/efeitos adversosRESUMO
Cellular repressor of E1A-stimulated genes (CREG), a novel cellular glycoprotein, has been identified as a suppressor of various cardiovascular diseases because of its capacity to reduce hyperplasia, maintain vascular homeostasis, and promote endothelial restoration. However, the effects and mechanism of CREG in metabolic disorder and hepatic steatosis remain unknown. Here, we report that hepatocyte-specific CREG deletion dramatically exacerbates high-fat diet and leptin deficiency-induced (ob/ob) adverse effects such as obesity, hepatic steatosis, and metabolic disorders, whereas a beneficial effect is conferred by CREG overexpression. Additional experiments demonstrated that c-Jun N-terminal kinase 1 (JNK1) but not JNK2 is largely responsible for the protective effect of CREG on the aforementioned pathologies. Notably, JNK1 inhibition strongly prevents the adverse effects of CREG deletion on steatosis and related metabolic disorders. Mechanistically, CREG interacts directly with apoptosis signal-regulating kinase 1 (ASK1) and inhibits its phosphorylation, thereby blocking the downstream MKK4/7-JNK1 signaling pathway and leading to significantly alleviated obesity, insulin resistance, and hepatic steatosis. Importantly, dramatically reduced CREG expression and hyperactivated JNK1 signaling was observed in the livers of nonalcoholic fatty liver disease (NAFLD) patients, suggesting that CREG might be a promising therapeutic target for NAFLD and related metabolic diseases. CONCLUSION: The results of our study provides evidence that CREG is a robust suppressor of hepatic steatosis and metabolic disorders through its direct interaction with ASK1 and the resultant inactivation of ASK1-JNK1 signaling. This study offers insights into NAFLD pathogenesis and its complicated pathologies, such as obesity and insulin resistance, and paves the way for disease treatment through targeting CREG. (Hepatology 2017;66:834-854).
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Dieta Hiperlipídica , Regulação da Expressão Gênica , Resistência à Insulina/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Proteínas Repressoras/genética , Animais , Biópsia por Agulha , Modelos Animais de Doenças , Humanos , Imuno-Histoquímica , Metabolismo dos Lipídeos/genética , MAP Quinase Quinase Quinase 5/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Distribuição Aleatória , Valores de Referência , Transdução de Sinais , Estatísticas não ParamétricasRESUMO
To date, transcatheter arterial embolization (TAE) has become a standard treatment to control intracavitary bleeding as an alternative to surgery. Due to excellent biocompatibility and no residual in vivo, biodegradable materials are preferred in TAE. However, gelfoam is the only commercially available biodegradable embolic material used to treat blunt trauma of solid abdominal viscera until now, and controversial on its stability and reliability never stopped in the past five decades. In this study, a new biodegradable macromolecule material (thrombin-loaded alginate-calcium microspheres, TACMs) was prepared using electrostatic droplet techniques and a special method was developed for hemostatic embolization. Thrombin was successfully loaded into microspheres with high encapsulation efficiency and drug loading capacity. A burst release of TACMs was observed at early stage and sustained release later on, with the activity of thrombin preserved well. The strength of TACMs mixed thrombus, which was used as embolic agent, increased in a dose-dependent manner after TACMs were added. In addition, the TACMs were verified to be of no cytotoxicity and systemic toxicity, and biodegradable in vivo. Finally, the results of preliminary applications revealed that the TACMs could serve as an effective and promising embolic material for blunt trauma and hemorrhage of solid abdominal viscera.
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Alginatos/química , Materiais Biocompatíveis/farmacologia , Cálcio/química , Embolização Terapêutica , Hemostáticos/farmacologia , Microesferas , Trombina/farmacologia , Animais , Coagulação Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Varredura , Especificidade de Órgãos/efeitos dos fármacos , Tamanho da Partícula , Coelhos , Ratos Sprague-Dawley , Artéria Renal/efeitos dos fármacos , Artéria Renal/patologia , Tela Subcutânea/efeitos dos fármacos , Testes de ToxicidadeRESUMO
BACKGROUND: The gender difference on long-term outcome in unselected patients after percutaneous coronary intervention (PCI) has not yet been fully investigated. This study aimed to evaluate the gender difference on five-year outcomes following EXCEL biodegradable polymer-coated sirolimus-eluting stenting in patients with coronary disease. METHODS: A total of 2077 "all comers", consisting of 1528 (73.6%) men and 549 (26.4%) women, who were exclusively treated with EXCEL coronary stents were enrolled in the prospective CREATE study at 59 centers from four countries. After propensity score matching, the baseline characteristics of the two groups were well matched. Recommended antiplatelet regimen was clopidogrel and aspirin for six months followed by chronic aspirin therapy. The primary outcome that was the rate of major adverse cardiac events (MACE), defined as a composite of cardiac mortality, non-fatal myocardial infarction (MI) and target lesion revascularization (TLR), and stent thrombosis (ST) at five years were compared between the two gender groups. RESULTS: In the two groups, women had higher proportions of clinical risk factors, such as being elderly, diabetes mellitus, hypertension and hyperlipidemia, compared to men. Besides, the mean target vessel number per patient was higher and the mean reference vessel diameter smaller for women. Men had higher risks of cardiac death (3.7% vs. 1.6%, P = 0.021) and MACE (8.4% vs. 4.7%, P = 0.004) at five years compared with women. However, the cumulative hazards of non-fatal MI and TLR were similar between men and women. The incidence of Academic Research Consortium (ARC) definite or probable stent thrombosis was similar between the two groups (1.3% vs. 1.0%, P = 0.639). Prolonged clopidogrel therapy (>6 months) did not reduce the cumulative hazards of ST from six months to five years in both men (χ(2) = 0.098, log rank P = 0.754) and women (χ(2) = 2.043, log rank P = 0.153) patients. CONCLUSIONS: Women had a lower MACE and cardiac death rate than men after biodegradable polymer-coated sirolimus-eluting stenting in long term follow-up. Effects of prolonged dual antiplatelet therapy (DAPT) in preventing stent thrombosis was similar with six-month DAPT after EXCEL stent implantation in both men and women groups.
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Angioplastia Coronária com Balão/métodos , Stents Farmacológicos , Polímeros/química , Sirolimo/uso terapêutico , Idoso , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Sexuais , Resultado do TratamentoRESUMO
κ-opioid receptor (κ-OR) activation with U50,488H, a selective κ-OR agonist, has been previously demonstrated to prevent against cardiac arrhythmias via stabilizing the synthesis and degradation of an integral membrane protein, Cx43, in gap junctions. However, the exact prevention mechanism remains unclear. The present study tested the hypothesis that the kappa OR agonist U50,488H mediates the prevention of arrhythmia through the regulation of intracellular calcium leading to the preservation of Cx43 protein. By performing electrocardiogram monitoring and immunoblotting in isolated Langendorff-perfused rat hearts, high concentrations of calcium-perfused rat hearts exhibited increased cardiac arrhythmias. Diminished expression of Cx43 protein was observed. The utilization of a whole-cell patch clamp technique revealed that U50,488H inhibited L-type calcium current in single ventricular myocytes in a dose-dependent manner. These effects were blocked by nor-binaltorphimine, potent and selective κ-OR antagonists. Administration of U50,488H before myocardial ischemia resulted in an attenuated of total arrhythmia scores. The attenuation effect was blocked by nor-binaltorphimine. The attenuation effect was antagonized both by Bay K8644, a L-type calcium channel agonist, and also by the Cx43 uncoupler heptanol. Finally, immunoblotting data demonstrated that the preservation of Cx43 protein conferred by U50,488H was reversed in the presence of Bay K8644. In summary, the present study demonstrates κ-OR activation with U50,488H may confer antiarrhythmic effects via modulation of the calcium-Cx43 pathway.
Assuntos
(trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , Anti-Hipertensivos/farmacologia , Arritmias Cardíacas/prevenção & controle , Conexina 43/metabolismo , Receptores Opioides kappa/agonistas , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Animais , Cálcio/metabolismo , Agonistas dos Canais de Cálcio/farmacologia , Relação Dose-Resposta a Droga , Masculino , Miócitos Cardíacos/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Opioides kappa/antagonistas & inibidoresRESUMO
BACKGROUND: Until now there has been scarce evidence regarding an optimal antiplatelet strategy and clinical outcomes for patients who had suffered from stent thrombosis (ST). METHODS AND RESULTS: 140 patients who suffered from stent thrombosis were prospectively registered. Patients received dual (aspirin and 150 mg clopidogrel, N = 66) or triple (additional cilostazol, N = 74) antiplatelet therapy at the physician's discretion. Thereafter platelet reactivity and one year clinical outcomes were analyzed. The primary outcome included the composite of cardiac death, non-fatal myocardial infarction (MI) or stroke at one year,which developed in 41 (29.3%) patients, consisting of 31 (22.1%) cardiac death, 9 (6.4%) non-fatal MI and 1 (1.4%) stroke. Recurrent definite and probable ST according to ARC definition was observed in 8 (5.7%) and 14 (10.0%) patients, respectively. Triple therapy was associated with significantly lower platelet reactivities (50.2 ± 17.8, % vs. 59.6 ± 17.2, %, P = 0.002) compared to high dose dual antiplatelet therapy. However, the incidence of primary events (24.3% vs. 34.8%, P = 0.172) did not differ between triple and dual antiplatelet therapies. High on-treatment platelet reactivity (HR: 8.35, 95% CI: 2.234â¼30.867, P = 0.002) and diabetes (HR: 3.732, 95% CI: 1.353â¼10.298, P = 0.011) were independent predictors of primary events. CONCLUSIONS: Patients who suffered from stent thrombosis have a poor prognosis even after revascularization with intensive antiplatelet therapy. Triple antiplatelet therapy was more effective in reducing on-treatment platelet reactivity, compared to high dose dual antiplatelet therapy.
Assuntos
Trombose Coronária/diagnóstico , Trombose Coronária/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Stents/efeitos adversos , Idoso , Angiografia Coronária , Trombose Coronária/etiologia , Trombose Coronária/mortalidade , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Plaquetária , Prognóstico , Curva ROC , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
AIMS: The aim of the present study was to evaluate the five-year safety and efficacy of a biodegradable polymer-coated sirolimus-eluting stent with six months dual antiplatelet therapy in daily practice. METHODS AND RESULTS: Two thousand and seventy-seven daily practice patients, exclusively treated with biodegradable polymer-coated sirolimus-eluting stents (EXCEL; JW Medical Systems, Weihai, China), were prospectively enrolled in the multicentre CREATE study. Clinical follow-up was completed in 1,982 patients (95.4%) at five-year follow-up. The rates of cardiac death, non-fatal myocardial infarction (MI), target lesion revascularisation and overall major adverse cardiac events (MACE) at five-year follow-up were 3.0%, 1.5%, 3.7% and 7.4%, respectively. The rates of definite or probable stent thrombosis (ST) at five years and definite ST from one to five years were 1.1% and 0.3%, respectively. Heart failure (hazard ratio [HR]: 3.324, 95% confidence interval [CI]: 1.729-6.391, p<0.001) and prior MI (HR: 2.664, 95% CI: 1.358-5.227, p=0.004) were independent predictors of ST. Landmark analysis of a propensity score matched patient cohort showed that patients with or without clopidogrel treatment after six months had similar clinical outcomes. CONCLUSIONS: The present study demonstrates satisfactory and sustained five-year clinical safety and efficacy profiles as evidenced by the low rates of MACE and ST for the EXCEL, a biodegradable polymer-based sirolimus-eluting stent, when patients were treated with six months dual antiplatelet therapy in daily practice.
Assuntos
Implantes Absorvíveis , Fármacos Cardiovasculares/administração & dosagem , Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/instrumentação , Polímeros , Sirolimo/administração & dosagem , Idoso , Aspirina/uso terapêutico , China , Clopidogrel , Doença da Artéria Coronariana/mortalidade , Trombose Coronária/etiologia , Intervalo Livre de Doença , Quimioterapia Combinada , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação Plaquetária/uso terapêutico , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Desenho de Prótese , Sistema de Registros , Medição de Risco , Fatores de Risco , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Coronary stents are widely used in percutaneous coronary intervention (PCI) procedures. We aimed to explore the incidence, predictors and characteristics of stent thrombosis (ST) after coronary stent implantation in routine clinical practice. METHODS: From data of 18 063 consecutive patients who underwent successful stent implantation in Shenyang Northern Hospital from 2004 to 2010, we identified patients with definite ST (n = 140) and control patients (n = 280) matched on age, diagnosis, sex, current antiplatelet medication and stent type. The incidence, predictors and characteristics of ST after coronary stent implantation were investigated. RESULTS: The incidence of angiographically confirmed ST was 0.78% (140/18 063). The time distribution of ST was acute in 43 (30.7%), subacute in 50 (35.7%), and late in 47 (33.6%) patients. Binary Logistic regression analysis identied the angiotensin-converting enzyme inhibitor (ACEI) (odds ratio (OR) = 0.472, 95%CI: 0.276 - 0.807, P = 0.006) and heparin (OR = 0.477, 95%CI: 0.278 - 0.819, P = 0.007) were associated with an reduced risk of cumulative ST. Stent length (OR = 1.042, 95%CI: 1.026 - 1.058, P < 0.001), serum creatinine total (OR = 1.020, 95%CI: 1.004 - 1.035, P = 0.04), cholesterol (OR = 1.267, 95%CI: 1.021 - 1.573, P = 0.032), glucose (OR = 1.086, 95%CI: 1.002 - 1.176, P = 0.044), and platelet aggregation (OR = 1.113, 95%CI: 1.075 - 1.154, P < 0.001) were associated with an increased risk of cumulative ST. CONCLUSION: ST is associated with longer stent length and higher level of total cholesterol, glucose and platelet aggregation.
Assuntos
Trombose Coronária/epidemiologia , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Angiografia Coronária , Trombose Coronária/etiologia , Trombose Coronária/metabolismo , Stents Farmacológicos/efeitos adversos , Feminino , Heparina/metabolismo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/terapiaRESUMO
BACKGROUND: Some larger scale, randomized studies have demonstrated the superiority of drug-eluting stents (DES) over bare metal stents (BMS) for the treatment of acute myocardial infarction (AMI). This study aimed to investigate the impact of DES, in comparison with BMS, on the 2-year clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). METHODS: From January 2002 to December 2008, a total of 1301 consecutive STEMI patients treated with coronary stenting in Shenyang Northern Hospital were prospectively registered. Patients received BMS (n = 868) or DES (n = 435) implantation in the infarction related artery according to physician's discretion. A propensity score analysis was performed and two well matched subgroups were selected (BMS, n = 288; DES, n = 288) to evaluate the 2-year clinical outcomes. The primary outcome was the occurrence of major adverse cardiac events (MACE), which was defined as a composite of all-cause death, myocardial infarction (MI), or target vessel revascularization (TVR). RESULTS: Survival salvage analysis showed that 2-year cumulative hazards were not significantly different between the two groups with respect to TVR (2.8% vs. 3.1%, log-rank P = 0.780), stent thrombosis (1.7% vs. 4.2%, log-rank P = 0.079) and MACE (8% vs. 10.8%, log-rank P = 0.236). Multivariate analysis showed that DES was an independent protective factor of MI (HR: 0.211, 95%CI: 0.049 to 0.908) and stent thrombosis (HR: 0.327, 95%CI: 0.107 to 0.994). CONCLUSION: DES was associated with similar 2-year clinical outcomes to those of BMS for the treatment of STEMI in daily practice.
Assuntos
Angioplastia Coronária com Balão/métodos , Stents Farmacológicos/efeitos adversos , Infarto do Miocárdio/terapia , Stents/efeitos adversos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Estudos Prospectivos , Trombose/etiologia , Resultado do TratamentoRESUMO
OBJECTIVE: Acute myocardial ischemia induces electrical and chemical uncoupling of gap junctions, which contributes to conduction abnormalities and re-entrant arrhythmias. We tested the hypothesis that structure and function of Connexin43 may vibrate during acute myocardial ischemia and reperfusion and κ-opioid receptor stimulation may stabilize the alteration of Connexin43. DESIGN: An animal intervention study was conducted with comparison to a control group. SETTING: University preclinical research laboratory. SUBJECTS: Age-, weight-, and sex-matched Sprague-Dawley rats. INTERVENTIONS: Adult rat hearts were subjected to ischemia or ischemia/reperfusion, which was induced by temporary occlusion of the left main coronary artery. U50488H was given 10 mins before tissue specimens were taken or before ischemia (1.5 mg/kg, intravenous) and nor-BNI was given 15 mins before tissue specimens were taken or before ischemia (2 mg/kg, intravenous). Tissue samples came from left ventricular myocardium of the rat hearts. MEASUREMENTS AND MAIN RESULTS: Electrocardiogram, immunohistochemistry, immunoblotting, and reverse transcription-polymerase chain reaction were used to measure changes of arrhythmias, protein, and gene expression of Connexin43, respectively. κ-opioid receptor activation with U50 decreased arrhythmia in a model of myocardial ischemia and reperfusion. In normal hearts, immunohistochemical data showed reduced amount and lateralization of Connexin43 induced by κ-opioid receptor activation, whereas immunoblotting data demonstrated no significant changes between control and U50 group. During ischemia, however, Connexin43 protein underwent dephosphorylation and degradation, and Connexin43 mRNA was upregulated. These alterations were significantly attenuated on κ-opioid receptor stimulation. During ischemia and reperfusion, Connexin43 protein underwent dephosphorylation and degradation and recovered slowly during reperfusion. Activation of κ-opioid receptor accelerated recovery of phosphorylated and total Connexin43. CONCLUSIONS: In normal rat hearts, Connexin43 translocates from intercellular junctions to intracellular locations on κ-opioid receptor activation. In rat hearts experiencing acute myocardial ischemia and reperfusion, protein and gene expression of Connexin43 undergo vibration. This phenomenon is stabilized when κ-opioid receptor is activated and by the fact that κ-opioid receptor produces antiarrhythmic effects.