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1.
J Nanobiotechnology ; 20(1): 218, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35525963

RESUMO

Acute myocardial infarction (MI) induces a sterile inflammatory response that may result in poor cardiac remodeling and dysfunction. Despite the progress in anti-cytokine biologics, anti-inflammation therapy of MI remains unsatisfactory, due largely to the lack of targeting and the complexity of cytokine interactions. Based on the nature of inflammatory chemotaxis and the cytokine-binding properties of neutrophils, we fabricated biomimetic nanoparticles for targeted and broad-spectrum anti-inflammation therapy of MI. By fusing neutrophil membranes with conventional liposomes, we fabricated biomimetic liposomes (Neu-LPs) that inherited the surface antigens of the source cells, making them ideal decoys of neutrophil-targeted biological molecules. Based on their abundant chemokine and cytokine membrane receptors, Neu-LPs targeted infarcted hearts, neutralized proinflammatory cytokines, and thus suppressed intense inflammation and regulated the immune microenvironment. Consequently, Neu-LPs showed significant therapeutic efficacy by providing cardiac protection and promoting angiogenesis in a mouse model of myocardial ischemia-reperfusion. Therefore, Neu-LPs have high clinical translation potential and could be developed as an anti-inflammatory agent to remove broad-spectrum inflammatory cytokines during MI and other neutrophil-involved diseases.


Assuntos
Citocinas , Neutrófilos , Animais , Anti-Inflamatórios , Biomimética , Modelos Animais de Doenças , Lipopolissacarídeos , Lipossomos , Camundongos
3.
Am Heart J ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35525262

RESUMO

BACKGROUND: For ST-segment elevation myocardial infarction (STEMI) patients presenting 24-48 hours from symptom onset, whether early invasive strategy should be performed still remains controversial. METHODS: This is a prospective, open-label, multicenter, investigator initiated, randomised controlled trial (NCT04962178) to evaluate the efficacy of early invasive strategy for STEMI patients within 24-48h of symptom onset. A total of 366 patients will be included from 10 hospitals in mainland China. They will be randomly (1:1) divided into 2 groups: the early invasive strategy group (primary percutaneous coronary intervention, PPCI) and conservative strategy group (optimal medical therapy with primary PCI not performed).All patients will be followed for 1 month. The primary endpoint is myocardial infarction size on cardiac magnetic resonance (CMR). The secondary endpoints are as follows: 1, major adverse cardiovascular events (MACE), which is defined as a composite of cardiac death, recurrent myocardial infarction, ischemic driven target vessel revascularization and stroke; 2, other CMR endpoints, including microvascular obstruction, intramyocardial hemorrhage, myocardial area at risk, left ventricular ejection fraction, left ventricular end diastolic volume and left ventricular end systolic volume. DISCUSSION: This study is designed to evaluate the efficacy of early invasive strategy for STEMI patients within 24-48h of symptom onset and will add more evidence for clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04962178. Registered on 14July 2021.

4.
Front Pharmacol ; 13: 854867, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35387342

RESUMO

Aim: Growing evidence indicated that CYP2C19 genotypes could only explain a fraction of the pharmacodynamic response to clopidogrel, while a number of clinical factors also have contributing roles. Our objective was to develop a new risk score to improve prognostication of ischemic events in Chinese patients treated with clopidogrel. Methods: A new risk score was developed and internally validated in 445 patients with acute coronary syndrome (ACS) undergoing coronary stenting. The final score was named the GeneFA score based on the inclusion of CYP2C19 genotype, fibrinogen, and age. External validation of the GeneFA score and comparison with the ABCD-GENE score were performed in an independent ACS cohort. Results: Based on the observed frequencies of high platelet reactivity (HRPR) in relation to the GeneFA risk score, a relatively higher clinical HRPR was observed in the upper quintile with a representative score of 3 (52.90%) and 4 (59.10%), whereas it was found less frequently in groups with scores 0 (6.70%), 1 (15.10%), and 2 (16.70%). Participants with a GeneFA score >2 had an increased risk of HRPR (54.3 vs. 14.7%, p < 0.001) and ischemic recurrence (20.7 vs. 5.4%, p < 0.001). The GeneFA score exhibited a better prediction for high HRPR patients as compared to the ABCD-GENE score (p < 0.001). In the validation population, GeneFA illustrated a similarly high prognostic value for HRPR incidence (C-statistic: 0.855 for GeneFA and 0.843 for ABCD-GENE) and ischemic recurrence (C-statistic: 0.726 for GeneFA and 0.724 for ABCD-GENE) on clopidogrel as compared to ABCD-GENE. Conclusion: The GeneFA risk score had a moderate predictive ability for HRPR on clopidogrel for CAD patients in Chinese populations. The predictive value of the GeneFA score was consistent with the ABCD-GENE score for HRPR identification.

5.
Biomaterials ; 284: 121529, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35447403

RESUMO

Immune regulation therapies have been considered promising in the treatment of myocardial ischemia reperfusion (MI/R) injury. Mesenchymal stem cells derived extracellular vesicles (MSC-EVs) are of great potential for immune modulation by reprogramming macrophages but their therapeutic efficacy is hindered by insufficient targeting ability in vivo. Herein, we introduced the platelet membrane modified EVs (P-EVs) based on membrane fusion method to mimic the binding ability of platelets to monocytes. In the mouse model of MI/R injury, the intravenously injected P-EVs were mainly carried by circulating monocytes into the ischemic myocardium. In the inflammatory microenvironment, those monocytes subsequently differentiated into macrophages with enhanced phagocytosis, which probably promoted in-situ endocytosis of the superficial P-EVs by monocytes differentiated macrophages in large quantities. Then, the P-EVs successfully escaped from the macrophage lysosome and released the functional microRNAs (miRNAs) into the cytosol which facilitated the inflammatory macrophages (M1 phenotype) reprogramming to reparative macrophages (M2 phenotype). Finally, the immune microenvironment was regulated to realize cardiac repair. Thus, we supposed that the most likely delivery method was that monocytes mediated P-EVs migration into ischemic myocardium where P-EVs were mainly in-situ endocytosed by monocytes derived macrophages, which holds potential for immunoregulation on MI/R and other immune-related diseases in the future.


Assuntos
Vesículas Extracelulares , MicroRNAs , Traumatismo por Reperfusão Miocárdica , Animais , Plaquetas/metabolismo , Vesículas Extracelulares/metabolismo , Imunomodulação , Macrófagos/metabolismo , Camundongos , MicroRNAs/genética , Monócitos/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo
6.
Front Cardiovasc Med ; 9: 730648, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295252

RESUMO

Background: Current guidewires for transradial coronary angiography had defects of passage difficulty or branch injury. This study sought to investigate the safety and efficiency of a novel method of active knuckle-angle 0.035-inch hydrophilic guidewire in transradial coronary angiography. Methods: Patients undergoing a transradial coronary procedure in our team from August 2015 to June 2020 were retrospectively investigated. We compared the demographic and interventional characteristics of 1,457 patients receiving advancement of unmodified guidewires (Traditional group) and 1,322 patients receiving advancement of the knuckle guidewire (Knuckle group). Afterwards we included 239 patients and randomized them according to a random number table to either the unmodified or the knuckle guidewire to further confirm the efficiency and safety of knuckle guidewire advancement. Results: In the retrospective analysis, unwilling passage of guidewire into branches occurred more in the Traditional group than in the Knuckle group (9.5 vs. 0.08%, p < 0.001). Two patients in the Traditional group experienced guidewire-associated perforation. One patient was treated with covered stent for internal mammarian artery perforation, while the other was managed with compression for brachial branch perforation. In the randomized controlled study, unwilling passage of guidewire also occurred more in the Traditional group (10.8 vs. 1%, p < 0.001). Median duration of guidewire advancement from the sheath to aortic root significantly decreased from 33 seconds in the Traditional group to 21 seconds in the Knuckle group. Conclusion: Active knuckle angle guidewire represented a novel method to prevent unwilling passage and associated perforation with efficiency improvement and a reduction in radiation exposure.

7.
Cardiol J ; 2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35244198

RESUMO

BACKGROUND: Device-based antegrade dissection re-entry (ADR) and parallel wire technique (PWT) are two important techniques in the antegrade approach in percutaneous coronary intervention (PCI) of chronic total occlusion (CTO). The study is aimed to compare the procedural and mid-term outcomes between device-based ADR using the CrossBoss/Stingray system and PWT in CTO PCI. METHODS: Data was retrospectively collected from consecutive patients who underwent CTO PCI using device-based ADR or PWT. CTO due to in-stent restenosis were excluded. RESULTS: A total of 273 patients were included in the study (n = 55 in device-based ADR group, n = 218 in PWT group). Baseline characteristics were similar across groups except for higher prevalence of prior PCI and lower level of lipid profile in the ADR group. Moreover, although patients in the ADR group showed higher contrast volume (441.6 ± 162.4 mL vs. 361.5 ± 142.1 mL, p < 0.001), more intravascular ultrasound guidance (50.9% vs. 22.9%, p < 0.001), more guidewires used (4.6 ± 1.4 vs. 3.4 ± 1.2, p < 0.001) and higher troponin T level after PCI (0.167 vs. 0.087, p = 0.004), the technical success, procedural success and in-hospital complications were similar between the two groups. During a median follow-up of 1 year, the ADR group showed no difference in major adverse cardiac events (MACE, including all cause death, nonfatal myocardial infarction, and ischemia driven target vessel revascularization) (7.3% vs. 14.7%, p = 0.150) as compared with the PWT group. CONCLUSIONS: In the documented center, the use of device-based ADR for CTO PCI showed no difference in in-hospital complications and mid-term MACE as compared with PWT, despite higher procedure complexity in ADR group.

8.
Clin Cardiol ; 45(1): 136-144, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34989416

RESUMO

BACKGROUND: Chronic total occlusion (CTO) in a noninfarct-related artery (IRA) is one of the risk factors for mortality after acute myocardial infarction (AMI). However, there are limited data comparing the long-term outcomes of patients undergoing percutaneous coronary intervention (PCI) with patients having medical therapy (MT) in CTO lesion after AMI PCI. METHODS: We retrospectively enrolled 330 patients (successful CTO PCI in 166 patients, failed CTO PCI in 32 patients, MT in 132 patients) with non-IRA CTO from a total of 4372 patients who underwent PCI after AMI in our center. Propensity score matching (PSM) was used to adjust for baseline differences. RESULTS: The primary analysis is based on the intention-to-treat population. During a median follow-up period of 946 days, patients in the PCI group (n = 198) had significantly higher cardiac death-free survival (96.6% vs. 82.8%, p = .004) compared with patients in MT group (n = 132). However, no significant difference in the occurrence of cardiac death was observed after PSM. The analysis based on the per-protocol population demonstrated significantly higher cardiac death-free survival in the successful CTO PCI group (n = 166) compared with the occluded CTO group (n = 164) both before and after PSM. In subgroup analysis, successful CTO PCI was associated with less cardiac death in patients over 65 years old, with LVEF < 50%, left anterior descending (LAD) IRA, and non-LAD CTO lesion compared with occluded CTO group. CONCLUSIONS: Patients undergoing successful revascularization of non-IRA CTO after AMI might have a better long-term prognosis. Moreover, patients with LVEF < 50% may benefit from successful non-IRA CTO PCI after AMI.


Assuntos
Oclusão Coronária , Infarto do Miocárdio , Intervenção Coronária Percutânea , Idoso , Artérias , Doença Crônica , Oclusão Coronária/diagnóstico , Oclusão Coronária/cirurgia , Humanos , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
9.
Cardiovasc Toxicol ; 22(4): 341-351, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34997458

RESUMO

To explore the mechanism by which rosuvastatin prevents coronary microembolism (CME)-induced cardiac injury and cardiomyocyte apoptosis. Animal and cell models of CME were established and treated with different doses of rosuvastatin. Echocardiography and histological staining were applied to assess left ventricular function and cardiac injury. Masson trichrome staining was used to evaluate fibrin deposition in the myocardium. The activity of lactate dehydrogenase (LDH) in serum and cell culture supernatant was detected. TUNEL staining and flow cytometry were used to evaluate apoptosis in myocardium and cardiomyocytes, respectively. The activity of ROS was revealed by DHE staining. The expression levels of Nox2, cleaved caspase-3, cytochrome C, p53, Bax and Bcl-2 were also detected. Rosuvastatin pretreatment improved the left ventricular function of CME mice and reduced inflammatory cell infiltration and fibrin deposition in the myocardium. Rosuvastatin reduced the production of ROS by inhibiting the expression of Nox2. Rosuvastatin also downregulated pro-apoptotic proteins cleaved caspase-3, cytochrome C, p53 and Bax, and upregulated anti-apoptotic Bcl-2. Rosuvastatin mitigates CME-induced cardiac injury by inhibiting Nox2-induced ROS overproduction and alleviating p53/Bax/Bcl-2-dependent cardiomyocyte apoptosis.


Assuntos
Citocromos c , Proteína Supressora de Tumor p53 , Animais , Apoptose , Caspase 3/metabolismo , Citocromos c/metabolismo , Fibrina/metabolismo , Camundongos , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Rosuvastatina Cálcica/metabolismo , Rosuvastatina Cálcica/farmacologia , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo
10.
Eur J Clin Invest ; 52(2): e13686, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34596236

RESUMO

BACKGROUND: Angiographic no-reflow is associated with poor outcomes in patients with ST-segment elevation myocardial infarction (STEMI). We sought to develop and validate a score system to predict angiographic no-reflow in primary percutaneous coronary intervention (PCI). METHODS: ST-segment elevation myocardial infarction patients undergoing primary PCI were consecutively enrolled and were randomly divided into the training and validation set. Angiographic no-reflow was defined as thrombolysis in myocardial infarction (TIMI) flow grade 0 to 2 after PCI. In the training set, independent predictors were identified by logistic regression analysis, and a score system (PredIction of Angiographic NO-reflow, the PIANO score) was constructed based on the ß-coefficient of each variable. The established model was evaluated for discrimination and calibration. RESULTS: Angiographic no-reflow occurred in 362 (17.8%) of 2036 patients. Age ≥70 years, absence of pre-infarction angina, total ischaemic time ≥4 h, left anterior descending as culprit artery, pre-PCI TIMI flow grade ≤1 and pre-PCI TIMI thrombus score ≥4 were independent predictors of angiographic no-reflow. The PIANO score ranged from 0 to 14 points, yielding a concordance index of 0.857 (95% confidence interval: 0.833 to 0.880), with good calibration. In the high-risk (≥8 points) group, the probability of angiographic no-reflow phenomenon was 38.7%, while it was only 4.8% in the low-risk (<8 points) group. The score system performed well in the validation set. CONCLUSIONS: We establish and validate a score system based on six clinical variables to predict angiographic no-reflow in STEMI patients undergoing primary PCI, which may help choose the optimal individual treatment strategy.


Assuntos
Angiografia Coronária , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Falha de Tratamento , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos
11.
Am Heart J ; 244: 86-93, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34785173

RESUMO

BACKGROUND: The efficacy and safety of intravenous infusion of nicorandil during primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) remain uncertain. OBJECTIVES: The primary objective of the CLinical Efficacy and sAfety of intravenous Nicorandil (CLEAN) trial is to evaluate the long-term efficacy and safety of intravenous administration of nicorandil as adjuncts to reperfusion therapy in patients with STEMI undergoing primary PCI. DESIGN: The CLEAN trial is a multicenter, randomized, double-blind, placebo-controlled trial that will enroll 1,500 patients from 40 centers across china. patients were randomly (1:1) assigned to receive intravenous nicorandil (6 mg as a bolus before reperfusion, followed by 48 hours of continuous infusion at a dose of 6 mg/h after coronary intervention) or the same dose of placebo according to randomization. The primary efficacy outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, target vessel revascularization, and unplanned hospitalization for heart failure within 12 months. The secondary efficacy outcomes included the individual components of the combined efficacy endpoint, incidence of slow coronary flow after PCI, and incidence of complete ST-segment resolution at 2 hours after PCI. the safety outcomes included the incidence of hypotension after drug infusion and other adverse events during medication. SUMMARY: CLEAN will determine whether the addition of intravenous nicorandil as adjuncts to reperfusion therapy reduces the major adverse cardiovascular events in STEMI patients undergoing primary PCI. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04665648.


Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Administração Intravenosa , Humanos , Nicorandil/uso terapêutico , Intervenção Coronária Percutânea/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Resultado do Tratamento
12.
Catheter Cardiovasc Interv ; 99(2): 226-233, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34787375

RESUMO

BACKGROUND: Chronic total occlusion (CTO) lesions remain technically challenging for percutaneous coronary intervention (PCI). The introduction of a retrograde approach has allowed marked improvement in the success rate of CTO recanalization. Reverse controlled anterograde and retrograde sub-intimal tracking (reverse CART) is the predominant retrograde wire crossing technique and can be broadly classified into three categories: (1) conventional (2) contemporary and (3) extended. The present study aimed to compare the safety and efficacy of conventional and contemporary reverse CART techniques. METHODS: From March 2015 to May 2020, 303 patients achieving successful retrograde guidewire crossing with conventional or contemporary reverse CART during CTO PCI were included in the study. The patient characteristics, procedural outcomes and in-hospital and 1-year clinical events were compared between the conventional and contemporary groups. RESULTS: The distributions of the baseline and angiographic characteristics were similar in both study arms, except the CTO lesions of the conventional group were more complex, as reflected by borderline significantly higher mean J-CTO scores (3.4 ± 0.7 vs. 3.3 ± 0.8; p = 0.059). Recanalization using contemporary reverse CART was associated with a short procedure time (189.8 ± 44.4 vs. 181.7 ± 37.3 min; p = 0.044) and decreased procedural complications, particularly target vessel perforation (3.6% vs. 0.6%; p = 0.063) and major side-branch occlusion (36.7% vs. 28.0%; p = 0.051). Technical and procedural success and the in-hospital and 1-year outcomes were not significantly different between the groups. CONCLUSIONS: Contemporary reverse CART is associated with favorably high efficiency and low-complication rates and carries a comparable success rate and 1-year clinical outcomes as conventional reverse CART.


Assuntos
Oclusão Coronária , Intervenção Coronária Percutânea , Doença Crônica , Angiografia Coronária/métodos , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/terapia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Resultado do Tratamento
13.
Cardiol J ; 29(2): 284-292, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32207842

RESUMO

BACKGROUND: Periprocedural myocardial injury (PMI) is a frequent complication of percutaneous coronary intervention (PCI) associated with poor prognosis. However, no effective method has been found to identify patients at risk of PMI before the procedure. MicroRNA-133a (miR-133a) has been reported as a novel biomarker in various cardiovascular diseases. Herein, it was sought to determine whether circulating miR-133a could predict PMI before the procedure. METHODS: Eighty patients with negative preoperative values of cardiac troponin T (cTnT) receiving elective PCI for stable coronary artery disease (CAD) were recruited. Venous serum samples were collected on admission and within 16-24 hours post-PCI for miRNA measurements. PMI was defined as a cTnT value above the 99% upper reference limit after the procedure. The association between miR-133a and PMI was further assessed. RESULTS: Periprocedural myocardial injury occurred in 48 patients. The circulating level of miR-133a was significantly higher in patients with PMI before and after the procedure (both p < 0.001). Receiver operating characteristic curve analysis of the preoperative miR-133a level revealed an area under the curve of 0.891, with a sensitivity of 93.8% and a specificity of 71.9% to predict PMI. Additionally, a decrease was found in fibroblast growth factor receptor 1 (FGFR1) in parallel with an increase in miR-133a levels in patients with PMI. CONCLUSIONS: This study demonstrates for the first time that serum miR-133a can be used as a novel biomarker for early identification of stable CAD patients at risk of PMI undergoing elective PCI. The miR-133a-FGFR1 axis may be involved in the pathogenesis of PMI.


Assuntos
Doença da Artéria Coronariana , Traumatismos Cardíacos , MicroRNAs , Intervenção Coronária Percutânea , Biomarcadores , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Traumatismos Cardíacos/diagnóstico , Traumatismos Cardíacos/etiologia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Fatores de Risco , Troponina T
14.
Angiology ; 73(4): 374-379, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34344170

RESUMO

Spontaneous coronary intramural hematoma (SCIH) was one type of spontaneous coronary artery dissection without obvious intimal tear, which is easy to misdiagnose. We aimed to study the characteristics, management, and prognosis of SCIH in our center. All the SCIH patients (n = 30) diagnosed by coronary angiography from January 1, 2012 to December 31, 2018 were enrolled. The demographic characteristics, history, therapy, and follow-up were collected. The mean age of the patients was 51.8 ± 9.5 years. Most of the patients were females (66.7%) with hypertension. Patients with diffuse lesion, focal lesion, and multiple vessels were 70%, 13.3%, and 16.7%, respectively. Conservative treatment was the first choice (76.7%). The mean follow-up time was 29.3 ± 13.5 months. None of the patients had unplanned readmission due to worsening symptoms. Nine patients underwent coronary artery computed tomography reexamination after 10.3 ± 7.5 months, which showed complete recovery of SCIH. Eight patients were hospitalized for coronary angiography 6.4 ± 4.7 months later, which did not show any sign of SCIH. Spontaneous coronary intramural hematoma was most common in post-menopausal women with hypertension. Possibly, antiplatelet drugs should be avoided in SCIH. Waiting for the hematoma to heal was preferable and had a good prognosis.


Assuntos
Anomalias dos Vasos Coronários , Hematoma , Adulto , Angiografia Coronária , Feminino , Hematoma/diagnóstico por imagem , Hematoma/etiologia , Hematoma/terapia , Humanos , Pessoa de Meia-Idade , Prognóstico
15.
J Nucl Cardiol ; 29(2): 622-629, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32770319

RESUMO

BACKGROUND: The aim of this study was to investigate the correlation of coronary flow reserve (CFR) assessed by rest/stress myocardial perfusion imaging with dynamic single-photon emission computed tomography (SPECT) with intracoronary pressure-derived fractional flow reserve (FFR) in patients with single-vessel coronary artery disease (CAD). METHODS: Patients with suspected or known stable CAD who were referred for invasive coronary angiography were prospectively enrolled. Both invasive FFR and SPECT were performed in subjects with single-vessel intermediate coronary stenosis. A cutoff value of < 0.8 was used to define abnormal FFR. RESULTS: A total of 34 patients were enrolled. The mean age of the subjects was 62.1 ± 6.7 years, and 79.4% were male. SPECT-derived CFR showed a significantly moderate correlation with FFR (r = 0.505, P = .003). The diagnostic performance for the identification of abnormal FFR in terms of sensitivity, specificity, and accuracy was 88.9%, 83.3%, and 87.9%, respectively, for CFR, with an optimized cutoff value of 1.73. CONCLUSION: In patients with single-vessel CAD, SPECT CFR was useful for the detection of functionally significant stenosis. Our data support the use of this technique as an optional method for hemodynamic assessment, especially when FFR results are in normal range.


Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Imagem de Perfusão do Miocárdio , Idoso , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Tomografia Computadorizada de Emissão de Fóton Único/métodos
16.
Artigo em Inglês | MEDLINE | ID: mdl-34962992

RESUMO

AIMS: This study aimed to investigate the prognostic implications of increased postprocedural cardiac troponin levels in patients undergoing elective percutaneous coronary intervention (PCI) and to define the threshold of prognostically relevant periprocedural myocardial injury (PMI). METHODS AND REASULTS: A total of 3,249 patients with normal baseline troponin levels referred for elective PCI were enrolled and followed up for a median period of 20 months. The primary endpoint was major adverse cardiovascular events (MACEs) comprising all-cause death, myocardial injury (MI) and ischemic stroke. Post-PCI high-sensitivity cardiac troponin T (hs-cTnT) > 99% upper reference limit (URL) occurred in 78.3% of patients and did not increase the risk of MACEs (adjusted hazard ratio (adHR), 1.00, 95% confidence interval (CI), 0.58-1.74, p = 0.990). Nor did 'major PMI' defined as post-PCI hs-cTnT above 5 × URL (adHR, 1.30, 95% CI, 0.76-2.23, p = 0.340). Post-PCI troponin > 8 × URL, with an incidence of 15.2%, started to show an association with a higher risk of MACEs (adHR, 1.89, 95% CI, 1.06-3.37, p = 0.032), mainly driven by myocardial infarction (adHR, 2.38, 95% CI, 1.05-5.38, p = 0.037) and ischemic stroke (adHR 3.35, 95% CI, 1.17-9.64, p = 0.025). CONCLUSIONS: In patients with normal baseline troponin values undergoing elective PCI, PMI defined as hs-cTnT > 8 × URL after PCI was more appropriate for identifying patients with an increased risk of MACEs, which may help guide clinical practice in this population.

17.
Basic Res Cardiol ; 116(1): 65, 2021 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-34914018

RESUMO

Current evidence indicates that coronary microcirculation is a key target for protecting against cardiac ischemia-reperfusion (I/R) injury. Mitochondrial calcium uniporter (MCU) complex activation and mitochondrial calcium ([Ca2+]m) overload are underlying mechanisms involved in cardiovascular disease. Histidine triad nucleotide-binding 2 (HINT2) has been reported to modulate [Ca2+]m via the MCU complex, and our previous work demonstrated that HINT2 improved cardiomyocyte survival and preserved heart function in mice with cardiac ischemia. This study aimed to explore the benefits of HINT2 on cardiac microcirculation in I/R injury with a focus on mitochondria, the MCU complex, and [Ca2+]m overload in endothelial cells. The present work demonstrated that HINT2 overexpression significantly reduced the no-reflow area and improved microvascular perfusion in I/R-injured mouse hearts, potentially by promoting endothelial nitric oxide synthase (eNOS) expression and phosphorylation. Microvascular barrier function was compromised by reperfusion injury, but was repaired by HINT2 overexpression via inhibiting VE-Cadherin phosphorylation at Tyr731 and enhancing the VE-Cadherin/ß-Catenin interaction. In addition, HINT2 overexpression inhibited the inflammatory response by suppressing vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Mitochondrial fission occurred in cardiac microvascular endothelial cells (CMECs) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury and resulted in mitochondrial dysfunction and mitochondrion-dependent apoptosis, the effects of which were largely relieved by HINT2 overexpression. Additional experiments confirmed that [Ca2+]m overload was an initiating factor for mitochondrial fission and that HINT2 suppressed [Ca2+]m overload via modulation of the MCU complex through directly interacting with MCU in CMECs. Regaining [Ca2+]m overload by spermine, an MCU agonist, abolished all the protective effects of HINT2 on OGD/R-injured CMECs and I/R-injured cardiac microcirculation. In conclusion, the present report demonstrated that HINT2 overexpression inhibited MCU complex-mitochondrial calcium overload-mitochondrial fission and apoptosis pathway, and thereby attenuated cardiac microvascular ischemia-reperfusion injury.


Assuntos
Canais de Cálcio/metabolismo , Cálcio , Hidrolases/metabolismo , Proteínas Mitocondriais/metabolismo , Traumatismo por Reperfusão , Animais , Cálcio/metabolismo , Células Endoteliais/metabolismo , Camundongos , Mitocôndrias , Miócitos Cardíacos/metabolismo , Traumatismo por Reperfusão/metabolismo
18.
Angiology ; : 33197211052133, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34791903

RESUMO

Repeat revascularization is still common in the era of drug-eluting stents (DES), especially for non-target lesions. However, few validated models exist to predict the need for revascularization. We aimed to develop and validate an easy-to-use predictive model for repeat revascularization after DES implantation in patients with stable coronary artery disease (CAD). A total of 1,653 stable CAD patients with angiographic follow-up after DES implantation were consecutively enrolled. Split-sample testing was adopted to develop and validate the model. In the training set, male, diabetes, number of target lesions, occlusion lesion, number of non-target lesions, recurrent angina, suboptimal low density lipoprotein-cholesterol level, and high lipoprotein (a) level were independent predictors of repeat revascularization using logistic regression analyses. The established model (Model 1) yielded a bias-corrected concordance index of 0.700 (95% confidence interval: 0.667 to 0.735), with good calibration. It also performed well in the validation set. Compared with the traditional empirical model only including recurrent angina (Model 2), Model 1 had better discriminative ability and clinical usefulness. In conclusion, we established and validated a simple model including 8 easily accessible variables to predict repeat revascularization after DES implantation in stable CAD patients, contributing to better risk stratification, decision making, and patient consultation.

19.
Cell Death Dis ; 12(10): 877, 2021 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-34564708

RESUMO

Progressive cardiac fibrosis accelerates the development of heart failure. Here, we aimed to explore serum Wnt5a and Wnt11 levels in hypertension patients, the roles of Wnt5a and Wnt11 in cardiac fibrosis and potential mechanisms under pressure overload. The pressure overload mouse model was built by transverse aortic constriction (TAC). Cardiac fibrosis was analyzed by Masson's staining. Serum Wnt5a or Wnt11 was elevated and associated with diastolic dysfunction in hypertension patients. TAC enhanced the expression and secretion of Wnt5a or Wnt11 from cardiomyocytes (CMs), cardiac fibroblasts (CFs), and cardiac microvascular endothelial cells (CMECs). Knockdown of Wnt5a and Wnt11 greatly improved cardiac fibrosis and function at 4 weeks after TAC. In vitro, shWnt5a or shWnt11 lentivirus transfection inhibited pro-fibrotic effects in CFs under mechanical stretch (MS). Similarly, conditional medium from stretched-CMs transfected with shWnt5a or shWnt11 lentivirus significantly suppressed the pro-fibrotic effects induced by conditional medium from stretched-CMs. These data suggested that CMs- or CFs-derived Wnt5a or Wnt11 showed a pro-fibrotic effect under pressure overload. In vitro, exogenous Wnt5a or Wnt11 activated ERK and p38 (fibrotic-related signaling) pathway, promoted the phosphorylation of EGFR, and increased the expression of Frizzled 5 (FZD5) in CFs. Inhibition or knockdown of EGFR greatly attenuated the increased FZD5, p-p38, and p-ERK levels, and the pro-fibrotic effect induced by Wnt5a or Wnt11 in CFs. Si-FZD5 transfection suppressed the increased p-EGFR level, and the fibrotic-related effects in CFs treated with Wnt5a or Wnt11. In conclusion, pressure overload enhances the secretion of Wnt5a or Wnt11 from CMs and CFs which promotes cardiac fibrosis by activation the crosstalk of FZD5 and EGFR. Thus, Wnt5a or Wnt11 may be a novel therapeutic target for the prevention of cardiac fibrosis under pressure overload.


Assuntos
Receptores ErbB/metabolismo , Receptores Frizzled/metabolismo , Miocárdio/metabolismo , Transdução de Sinais , Proteínas Wnt/metabolismo , Proteína Wnt-5a/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Animais Recém-Nascidos , Cardiomiopatias/metabolismo , Fibroblastos/metabolismo , Fibrose , Humanos , Hipertensão/sangue , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Miocárdio/patologia , Pressão , Ratos Sprague-Dawley , Estresse Mecânico , Proteínas Wnt/sangue , Proteína Wnt-5a/sangue
20.
Front Cardiovasc Med ; 8: 708200, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368259

RESUMO

Objective: We aimed to assess the association of erectile dysfunction (ED) with the extent of coronary atherosclerosis, and to examine whether revascularization and medication use have an impact on ED status in patients with early onset of coronary artery disease (EOCAD). Methods: International Index of Erectile Function (IIEF-5) was used to evaluate sexual function in 296 male patients with EOCAD (age, 39.9 ± 4.8 years), and 354 male controls (age, 40.6 ± 4.4 years). The extent of coronary atherosclerosis was measured by Gensini score. Endothelial function was evaluated by two vasomotor indexes including endothelin-1 (ET-1) and nitric oxide (NO) by ELISA. Results: ED was more frequent (57.8 vs. 31.1%, P < 0.001) and serious (IIEF-5 score:17.7 ± 6.0 vs. 21.6 ± 5.0, P < 0.001) among EOCAD patients than that among controls. IIEF-5 score was negatively correlated with Gensini score (r = -0.383, P < 0.001). The adjusted odds ratio (OR) for the presence of ED (EOCAD vs. controls) was 1.88 [95% confidential interval (CI), 1.12-3.18]. However, ET-1 and NO attenuated the association between ED and EOCAD (adjusted OR: 1.54, 95% CI: 0.84-2.80). IIEF-5 score increased after coronary revascularization in patients not on beta-blockers (18.71 ± 4.84 vs. 17.59 ± 6.05, P < 0.001) as compared with baseline, while stayed unchanged in the subgroup using beta-blockers (17.82 ± 5.12 vs. 17.70 ± 5.98, P = 0.09). Conclusions: ED was common in patients with EOCAD, and associated with the severity of coronary atherosclerosis. Endothelial dysfunction may be a pathophysiologic mechanism underlying both ED and EOCAD. Coronary revascularization confers a benefit in ED amelioration, while this effect did not appear in patients using beta-blocker.

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