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BACKGROUND: Following percutaneous coronary intervention with stent placement to treat acute coronary syndromes, international clinical guidelines generally recommend dual antiplatelet therapy with aspirin plus a P2Y12 receptor inhibitor for 12 months to prevent myocardial infarction and stent thrombosis. However, data on single antiplatelet therapy with a potent P2Y12 inhibitor earlier than 12 months after percutaneous coronary intervention for patients with an acute coronary syndrome are scarce. The aim of this trial was to assess whether the use of ticagrelor alone, compared with ticagrelor plus aspirin, could reduce the incidence of clinically relevant bleeding events without an accompanying increase in major adverse cardiovascular or cerebrovascular events (MACCE). METHODS: In this randomised, placebo-controlled, double-blind clinical trial, patients aged 18 years or older with an acute coronary syndrome who completed the IVUS-ACS study and who had no major ischaemic or bleeding events after 1-month treatment with dual antiplatelet therapy were randomly assigned to receive oral ticagrelor (90 mg twice daily) plus oral aspirin (100 mg once daily) or oral ticagrelor (90 mg twice daily) plus a matching oral placebo, beginning 1 month and ending at 12 months after percutaneous coronary intervention (11 months in total). Recruitment took place at 58 centres in China, Italy, Pakistan, and the UK. Patients were required to remain event-free for 1 month on dual antiplatelet therapy following percutaneous coronary intervention with contemporary drug-eluting stents. Randomisation was done using a web-based system, stratified by acute coronary syndrome type, diabetes, IVUS-ACS randomisation, and site, using dynamic minimisation. The primary superiority endpoint was clinically relevant bleeding (Bleeding Academic Research Consortium [known as BARC] types 2, 3, or 5). The primary non-inferiority endpoint was MACCE (defined as the composite of cardiac death, myocardial infarction, ischaemic stroke, definite stent thrombosis, or clinically driven target vessel revascularisation), with an expected event rate of 6·2% in the ticagrelor plus aspirin group and an absolute non-inferiority margin of 2·5 percentage points between 1 month and 12 months after percutaneous coronary intervention. The two co-primary endpoints were tested sequentially; the primary superiority endpoint had to be met for hypothesis testing of the MACCE outcome to proceed. All principal analyses were assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Sept 21, 2019, and Oct 27, 2022, 3400 (97·0%) of the 3505 participants in the IVUS-ACS study were randomly assigned (1700 patients to ticagrelor plus aspirin and 1700 patients to ticagrelor plus placebo). 12-month follow-up was completed by 3399 (>99·9%) patients. Between month 1 and month 12 after percutaneous coronary intervention, clinically relevant bleeding occurred in 35 patients (2·1%) in the ticagrelor plus placebo group and in 78 patients (4·6%) in the ticagrelor plus aspirin group (hazard ratio [HR] 0·45 [95% CI 0·30 to 0·66]; p<0·0001). MACCE occurred in 61 patients (3·6%) in the ticagrelor plus placebo group and in 63 patients (3·7%) in the ticagrelor plus aspirin group (absolute difference -0·1% [95% CI -1·4% to 1·2%]; HR 0·98 [95% CI 0·69 to 1·39]; pnon-inferiority<0·0001, psuperiority=0·89). INTERPRETATION: In patients with an acute coronary syndrome who had percutaneous coronary intervention with contemporary drug-eluting stents and remained event-free for 1 month on dual antiplatelet therapy, treatment with ticagrelor alone between month 1 and month 12 after the intervention resulted in a lower rate of clinically relevant bleeding and a similar rate of MACCE compared with ticagrelor plus aspirin. Along with the results from previous studies, these findings show that most patients in this population can benefit from superior clinical outcomes with aspirin discontinuation and maintenance on ticagrelor monotherapy after 1 month of dual antiplatelet therapy. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and the Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.
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Síndrome Coronariana Aguda , Aspirina , Quimioterapia Combinada , Hemorragia , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Ticagrelor , Humanos , Ticagrelor/uso terapêutico , Aspirina/uso terapêutico , Aspirina/administração & dosagem , Intervenção Coronária Percutânea/métodos , Síndrome Coronariana Aguda/terapia , Método Duplo-Cego , Masculino , Feminino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Idoso , Hemorragia/induzido quimicamente , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Terapia Antiplaquetária Dupla/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Intravascular ultrasound-guided percutaneous coronary intervention has been shown to result in superior clinical outcomes compared with angiography-guided percutaneous coronary intervention. However, insufficient data are available concerning the advantages of intravascular ultrasound guidance for patients with an acute coronary syndrome. This trial aimed to investigate whether the use of intravascular ultrasound guidance, as compared with angiography guidance, improves the outcomes of percutaneous coronary intervention with contemporary drug-eluting stents in patients presenting with an acute coronary syndrome. METHODS: In this two-stage, multicentre, randomised trial, patients aged 18 years or older and presenting with an acute coronary syndrome at 58 centres in China, Italy, Pakistan, and the UK were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention or angiography-guided percutaneous coronary intervention. Patients, follow-up health-care providers, and assessors were masked to random assignment; however, staff in the catheterisation laboratory were not. The primary endpoint was target vessel failure, a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularisation at 1 year after randomisation. This trial is registered at ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Aug 20, 2019 and Oct 27, 2022, 3505 patients with an acute coronary syndrome were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention (n=1753) or angiography-guided percutaneous coronary intervention (n=1752). 1-year follow-up was completed in 3504 (>99·9%) patients. The primary endpoint occurred in 70 patients in the intravascular ultrasound group and 128 patients in the angiography group (Kaplan-Meier rate 4·0% vs 7·3%; hazard ratio 0·55 [95% CI 0·41-0·74]; p=0·0001), driven by reductions in target vessel myocardial infarction or target vessel revascularisation. There were no significant differences in all-cause death or stent thrombosis between groups. Safety endpoints were also similar in the two groups. INTERPRETATION: In patients with an acute coronary syndrome, intravascular ultrasound-guided implantation of contemporary drug-eluting stents resulted in a lower 1-year rate of the composite outcome of cardiac death, target vessel myocardial infarction, or clinically driven revascularisation compared with angiography guidance alone. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.
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Síndrome Coronariana Aguda , Angiografia Coronária , Stents Farmacológicos , Intervenção Coronária Percutânea , Ultrassonografia de Intervenção , Humanos , Síndrome Coronariana Aguda/terapia , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/cirurgia , Intervenção Coronária Percutânea/métodos , Ultrassonografia de Intervenção/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Angiografia Coronária/métodos , Idoso , Resultado do Tratamento , ChinaRESUMO
BACKGROUND: Previous studies primarily demonstrated that transfemoral transcatheter aortic valve replacement (TAVR) with self-expanding valve appeared to be a safe and feasible treatment for patients with pure native aortic regurgitation (AR). However, the routine application of transfemoral TAVR for pure AR patients lacks support from randomized trials. TRIAL DESIGN: SEASON-AR trial is a prospective, multicenter, randomized, controlled, parallel-group, open-label trial, involving at least 20 sites in China, aiming to enroll 210 patients with pure native severe AR and high surgical risk. All enrolled patients are randomly assigned in a 1:1 fashion to undergo transfemoral TAVR with VitaFlowTM valve and receive guideline-directed medical therapy (GDMT) or to receive GDMT alone. The primary endpoint is the rate of major adverse cardiac events (MACE) at 12 months after the procedure, defined by the composite of all-cause mortality, disabling stroke, and rehospitalization for heart failure. The major secondary endpoints encompass various measures, including procedure-related complications, device success, 6-minute walk distance, and the occurrence of each individual component of the primary endpoint. After hospital discharge, follow-up was conducted through clinical visits or telephone contact at 1, 6, and 12 months. The follow-up will continue annually until 5 years after the index procedure to assess the long-term outcomes. CONCLUSION: SEASON-AR trial is the first study designed to investigate the clinical efficacy and safety of transfemoral TAVR with a self-expanding valve in patients with pure native severe AR with inoperable or high-risk, as compared to medical treatment only.
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Insuficiência da Valva Aórtica , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/métodos , Insuficiência da Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/epidemiologia , Estudos Prospectivos , Masculino , Feminino , Idoso , Artéria Femoral , Valva Aórtica/cirurgia , Desenho de Prótese , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/epidemiologia , China/epidemiologia , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controleRESUMO
BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1,212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at 1-year follow-up between 2 groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.
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AIMS: To evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) for the treatment of aortic regurgitation (AR). METHODS: From September 2019 to February 2022, 62 patients who underwent transfemoral TAVI procedure for pure, symptomatic severe AR with the VitaFlow system were enrolled in the current study. The outcomes were assessed according to the Valve Academic Research Consortium 3 criteria. Procedural results and clinical outcomes for 1 year were analyzed. RESULTS: The mean age was 71.56 ± 7.34 years and 58.1% were male. The mean Society of Thoracic Surgeons score was 5.44 ± 3.22%. The device success rate was 79.0%. Only one patient was converted to open surgery. The in-hospital mortality rate was 1.6%. The 1-year all-cause mortality rate was 6.5%. The new permanent pacemaker implantation rate was 29.0% in-hospital and 30.7% at 1-year follow-up. The second valve implantation rate was 14.5%. No patient developed more than moderate paravalvular leakage during follow-up. The mean ejection fraction improved from 54.05 ± 10.83% at baseline to 59.32 ± 8.70% (p < 0.001 compared with baseline) at 12 months. Left ventricular end-diastolic diameter decreased from 61.62 ± 5.58 mm at baseline to 55.20 ± 4.51 mm (p < 0.001 compared with the baseline) at 12 months. CONCLUSIONS: Transfemoral TAVI procedure shows efficacy in treating patients with severe pure native AR. The safety is improved with the development of the VitaFlow system.
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BACKGROUND: This study aimed to investigate the association between estimated pulse wave velocity (ePWV) and mortality outcomes among individuals with hypertension. METHODSâANDâRESULTS: Based on the National Health and Nutrition Examination Survey (NHANES) 1999-2018, a total of 14,396 eligible participants with hypertension were enrolled. The ePWV was calculated using the equation based on blood pressure and age. The mortality outcomes of included participants were directly acquired from the National Death Index database. The multivariable Cox regression analysis was used to examine the relationship between ePWV and mortality outcomes. Moreover, the restricted cubic spline (RCS) was also used to explore this relationship. Receiver operating characteristics curves (ROC) were adopted to evaluate the prognostic ability of ePWV for predicting mortality outcomes of patients with hypertension. The median follow-up duration was 10.8 years; individuals with higher an ePWV had higher risks of mortality from both all causes (HR: 2.79, 95% CI: 2.43-3.20) and cardiovascular diseases (HR: 3.41, 95% CI: 2.50-4.64). After adjusting for confounding factors, each 1 m/s increase in ePWV was associated with a 43% increase in all-cause mortality risk (HR: 1.43, 95% CI: 1.37-1.48) and a 54% increase in cardiovascular mortality risk (HR: 1.54, 95% CI: 1.43-1.66). CONCLUSIONS: This study indicates that ePWV is a novel prognostic indicator for predicting the risks of mortality among patients with hypertension.
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Doenças Cardiovasculares , Sistema Cardiovascular , Hipertensão , Humanos , Inquéritos Nutricionais , Análise de Onda de PulsoRESUMO
Epicardial adipose tissue (EAT) is a metabolically active organ which generates inflammatory cytokines. Thickness of EAT is associated with onset and development of heart failure with preserved ejection fraction (HFpEF). However, it is still unclear the specific mechanisms and pharmacological targets on EAT induced inflammation in HFpEF. A two-hit protocol with western diet and Nω-nitrol-arginine methyl ester (L-NAME) was used to establish HFpEF mouse model. In HFpEF mice, inflammatory biomarkers, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and von willebrand factor (vWF) elevated in myocardium compared to control. Inflammatory cell infiltration in myocardium was increased. In HFpEF mice, inflammasome-mediated pyroptosis pathway was activated in the EAT. Suppression of pyroptosis-related protein gasdermin D (GSDMD) in cultured EAT could lower cardiomyocyte inflammation and autophagy. Furthermore, spironolactone and rosuvastatin, the two-hit anti-inflammatory agents, reduced NLR family pyrin domain containing 3 (NLRP3)/GSDMD pyroptosis in EAT and autophagy in myocardium of HFpEF mouse. The combination treatment also enhanced exercise tolerance and appeased inflammatory injuries in HFpEF mice. CONCLUSION: Pyroptosis signaling is involved in EAT-myocardium axis in mouse model of HFpEF. Targeting adipocyte-derived inflammation in EAT bears potential to treatment HFpEF.
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Insuficiência Cardíaca , Piroptose , Camundongos , Animais , Insuficiência Cardíaca/metabolismo , Volume Sistólico , Inflamassomos/metabolismo , Miocárdio/metabolismo , Tecido Adiposo/metabolismo , Inflamação/patologia , Modelos Animais de Doenças , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismoRESUMO
BACKGROUND: Five definitions of peri-procedural myocardial infarction (PMI) following percutaneous coronary intervention (PCI) are used in clinical trials; their clinical relevance in coronary bifurcation stenting remains unclear. OBJECTIVES: To understand the correlation between PMI and mortality in bifurcation lesions from the DKCRUSH studies. METHODS: PMI was defined using serum creatine kinase-myocardial band (CK-MB) values within 48 h of PCI according to the SYNTAX, Fourth Universal Definition of MI (4th UDMI), ISCHEMIA, SCAI, and EXCEL definitions. Overall, 1300 patients with both CK and CK-MB measurements pre- and post-stenting were evaluated. The association of each PMI type and all-cause death or cardiac death at a median of 5.58 years of follow-up was analyzed using Cox regression. RESULTS: In total, 56 (4.3%) patients had PMI. According to SYNTAX, 4th UDMI or ISCHEMIA, SCAI, and EXCEL definitions, PMI occurred in 21 (1.6%), 56 (4.3%), 29 (2.2%), and 32 (2.5%) patients, respectively. All definitions were significantly correlated with unadjusted mortality at the end of follow-up but not at 30 days or 1-year after stenting. PMI using SYNTAX, SCAI, and EXCEL definitions rather than 4th UDMI definition was strongly associated with adjusted all-cause death. By adjusted analysis, PMI according to 4th UDMI, SCAI, and EXCEL definitions but not SYNTAX definition was positively correlated with cardiac death at a median of 5.58 years of follow-up. CK-MB ≥ 5 x UNL strongly enhanced the correlation of CK-MB values with mortality. CONCLUSIONS: PMI rate varies with the definition following stenting for bifurcation lesions. PMI defined by SCAI and EXCEL definitions is strongly correlates with adjusted all-cause and cardiac death.
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Doença da Artéria Coronariana , Infarto do Miocárdio , Intervenção Coronária Percutânea , Biomarcadores , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Análise de Dados , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do TratamentoRESUMO
Endothelial dysfunction is an early step in the development of atherosclerotic cardiovascular disease. Iron overload can lead to excessive mitochondrial reactive oxygen species (mtROS) production, resulting in mitochondrial dysfunction and vascular endothelial cell (EC) damage. Mitoferrin 2 (Mfrn2) is an iron transporter in the inner mitochondrial membrane. This study aimed to assess whether Mfrn2 and mitochondrial iron overload were involved in atherosclerosis progression and to explore the potential mechanism. We observed significant upregulation of Mfrn2 in the arteries of high-fat diet (HFD)-fed Apolipoprotein E-/- (ApoE-/-) mice and in TNF-α-induced mouse aortic endothelial cells (MAECs). Mfrn2 gene silencing inhibited mitochondrial iron overload, stabilized mitochondrial membrane potential and improved mitochondrial function in TNF-α-induced MAECs. Vascular EC-specific knockdown of Mfrn2 in ApoE-/- mice markedly decreased atherosclerotic lesion formation and the levels of ICAM-1 in aortas and reduced monocyte infiltration into the vascular wall. Furthermore, TNF-α increased the binding of 14-3-3 epsilon (ε) and Mfrn2, preventing Mfrn2 degradation and leading to mitochondrial iron overload in ECs, while 14-3-3ε overexpression increased Mfrn2 stability by inhibiting its ubiquitination. Together, our results reveal that Mfrn2 deficiency attenuates endothelial dysfunction by decreasing iron levels within the mitochondria and mitochondrial dysfunction. These findings may provide new insights into preventive and therapeutic strategies against vascular endothelial dysfunction in atherosclerotic disease.
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Apolipoproteínas E/genética , Aterosclerose/genética , Proteínas de Transporte de Cátions/genética , Sobrecarga de Ferro/genética , Mitocôndrias/metabolismo , Proteínas 14-3-3/genética , Animais , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Endotélio/lesões , Endotélio/metabolismo , Endotélio/patologia , Humanos , Molécula 1 de Adesão Intercelular/genética , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/metabolismo , Camundongos Knockout , Mitocôndrias/patologia , Fator de Necrose Tumoral alfa/genéticaRESUMO
BACKGROUND: Current guidelines recommend administering dual antiplatelet therapy (DAPT) for 12 months to patients with acute coronary syndromes (ACS) and without contraindications after drug-eluting stent (DES) implantation. A recent study reported that 3 months of DAPT followed by ticagrelor monotherapy is effective and safe in ACS patients undergoing DES implantation compared with the standard duration of DAPT. However, it is unclear whether antiplatelet monotherapy with ticagrelor alone versus ticagrelor plus aspirin reduces the incidence of clinically relevant bleeding without increasing the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in ACS patients undergoing percutaneous coronary intervention (PCI) with DES implantation guided by either intravascular ultrasound (IVUS) or angiography who have completed a 1-month course of DAPT with aspirin plus ticagrelor. METHODS: The IVUS-ACS and ULTIMATE-DAPT is a prospective, multicenter, randomized, controlled trial designed to determine (1) whether IVUS-guided versus angiography-guided DES implantation in patients with ACS reduces the risk of target vessel failure (TVF) at 12 months and (2) whether ticagrelor alone versus ticagrelor plus aspirin reduces the risk of clinically relevant bleeding without increasing the risk of MACCE 1-12 months after the index PCI in ACS patients undergoing DES implantation guided by either IVUS or angiography. This study will enroll 3486 ACS patients eligible for DES implantation, as confirmed by angiographic studies. The patients who meet the inclusion criteria and none of the exclusion criteria will be randomly assigned in a 1:1 fashion to the IVUS- or angiography-guided group (first randomization). All enrolled patients will complete a 1-month course of DAPT with aspirin plus ticagrelor after the index PCI. Patients with no MACCEs or major bleeding (≥Bleeding Academic Research Consortium (BARC) 3b) within 30 days will be randomized in a 1:1 fashion to either the ticagrelor plus matching placebo (SAPT)group or ticagrelor plus aspirin (DAPT)group for an additional 11 months (second randomization). The primary endpoint of the IVUS-ACS trial is TVF at 12 months, including cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target vessel revascularization (CD-TVR). The primary superiority endpoint of the ULTIMATE-DAPT trial is clinically relevant bleeding, defined as BARC Types 2, 3, or 5 bleeding, and the primary non-inferiority endpoint of the ULTIMATE-DAPT trial is MACCE, defined as cardiac death, myocardial infarction, ischemic stroke, CD-TVR, or definite stent thrombosis occurring 1-12 months in the second randomized population. CONCLUSION: The IVUS-ACS and ULTIMATE-DAPT trial is designed to test the efficacy and safety of 2 different antiplatelet strategies in ACS patients undergoing PCI with DES implantation guided by either IVUS or angiography. This study will provide novel insights into the optimal DAPT duration in ACS patients undergoing PCI and provide evidence on the clinical benefits of IVUS-guided PCI in ACS patients.
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Síndrome Coronariana Aguda/terapia , Aspirina , Duração da Terapia , Hemorragia , Intervenção Coronária Percutânea , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ticlopidina , Adulto , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Angiografia Coronária/métodos , Stents Farmacológicos , Terapia Antiplaquetária Dupla/métodos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Masculino , Estudos Multicêntricos como Assunto/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Complicações Pós-Operatórias/etiologia , Risco Ajustado/métodos , Cirurgia Assistida por Computador/métodos , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Ultrassonografia de Intervenção/métodosRESUMO
BACKGROUND: Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion. TRIAL DESIGN: DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure. CONCLUSIONS: DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.
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Angiografia Coronária/métodos , Doença das Coronárias/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/métodos , Ultrassonografia de Intervenção/métodos , Causas de Morte , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/mortalidade , Doença das Coronárias/patologia , Reestenose Coronária/etiologia , Trombose Coronária/etiologia , Stents Farmacológicos/efeitos adversos , Humanos , Infarto do Miocárdio/etiologia , Revascularização Miocárdica , Estudos ProspectivosRESUMO
BACKGROUND: Provisional side branch (SB) stenting is correlated with target vessel myocardial infarction (TVMI) in patients with coronary bifurcation lesions. However, the mechanisms underlying this association remain unknown. OBJECTIVES: To determine the correlation between SB lesion length with vulnerable plaques and TVMI using optical coherence tomography (OCT). BACKGROUND: The correlation between SB lesion length with vulnerable plaques and TVMI is unknown. METHODS: A total of 405 patients with 405 bifurcation lesions who underwent preprocedure OCT imaging of both the main vessel (MV) and the SB were enrolled. Patients were divided into long SB lesion (SB lesion length ≥10 mm) and short SB lesion (SB lesion length <10 mm) groups according to quantitative coronary analysis; they were also stratified by the presence of vulnerable plaques identified by OCT. The primary endpoint was the occurrence of TVMI after provisional stenting at 1-year follow-up. RESULTS: In total, 178 (43.9%) patients had long SB lesions. Vulnerable plaques were predominantly localized in the MV and were more frequently in the long SB lesion group (42.7%) than in the short SB lesion group (24.2%, p < .001). At 1-year follow-up after provisional stenting, there were 31 (7.7%) TVMIs, with 21 (11.8%) in the long SB lesion group and 10 (4.4%) in the short SB lesion group (p = .009). Multivariate regression analysis showed that long SB lesion length (p = .011), absence of vulnerable plaques in the polygon of confluence (p = .001), and true coronary bifurcation lesions (p = .004) were the three independent factors of TVMI. CONCLUSIONS: The presence of long SB lesion with MV vulnerable plaques predicts the increased risk of TVMI after provisional stenting in patients with true coronary bifurcation lesions. Further studies are warranted to identify the best stenting techniques for coronary bifurcation lesions with long SB lesions.
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Doença da Artéria Coronariana , Estenose Coronária , Infarto do Miocárdio , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Humanos , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/etiologia , Fatores de Risco , Stents , Tomografia de Coerência Óptica , Resultado do TratamentoRESUMO
ABSTRACT: Percutaneous coronary intervention has become the main revascularization strategy for coronary artery disease. Compared with early percutaneous coronary angioplasty and the extensive clinical application of bare metal stents, drug-eluting stents can significantly reduce the stenosis caused by the elastic retraction of plaque and neoatherosclerosis (NA), but there is still a high incidence of in-stent restenosis (ISR), which restricts the clinical efficacy of stent implantation. In-stent neoatherosclerosis (ISNA), defined as atherosclerotic lesions in the neointima, is one of the main causes of late stent failure. ISNA plays an important role in stent thrombosis and ISR. The rate of target lesion revascularization and in-stent thrombosis is high when NA arises. Therefore, it is of great clinical significance to explore the occurrence of NA and its development mechanism after stent implantation to prevent ISR and improve stent implantation efficacy and associated clinical prognosis. In this article, we systematically reviewed the existing clinical research on ISNA and the role of optical coherence tomography in its evaluation.
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Doença da Artéria Coronariana/terapia , Reestenose Coronária/etiologia , Trombose Coronária/etiologia , Vasos Coronários/patologia , Neointima , Intervenção Coronária Percutânea/instrumentação , Placa Aterosclerótica , Stents , Animais , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/patologia , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/patologia , Vasos Coronários/diagnóstico por imagem , Stents Farmacológicos , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Valor Preditivo dos Testes , Fatores de Risco , Tomografia de Coerência Óptica , Resultado do TratamentoRESUMO
PURPOSE: This study was to analyze the incidence of definite stent thrombosis (ST) after the implantation of drug-eluting stents (DESs) and cutoff value of overlapping length for predicting definite ST. An overlapping stent is associated with a high rate of clinical events after DES implantation compared with a non-overlapping stent. However, the rates of definite ST and clinical outcomes from a large patient population remain underreported. METHODS: A total of 15,561 patients with 24,183 lesions who underwent DES implantation from January 2005 to February 2017 were retrospectively included in 5 tertiary hospitals in China. The main endpoint was the incidence of definite ST after procedures. RESULTS: With a median of 1932 (IQR = 1194-2929) days, clinical follow-up was available in 7484 patients in the overlap group and in 8077 patients in the non-overlap group. The rates of definite ST were 3.1% in the overlap group and 1.2% in the non-overlap group (HR: 2.67 (95% CI: 2.11-3.38), p < 0.001). Of the 24,183 treated lesions, the incidences of definite ST were 2.4% in the overlap group and 0.9% in the non-overlap group (HR: 2.96 (95% CI: 2.38-3.69), p < 0.001). Stent overlap was associated with a higher rate of target lesion revascularization (TLR) (9.4%) compared with stent non-overlap (6.4%, p < 0.001). The length of overlapping stent ≥ 2.93 mm strongly correlated with definite ST. CONCLUSION: The present study shows that overlapping DES increases definite ST and revascularization in patients during long-term follow-up. In addition, the longer overlapping zone was associated with worse clinical outcomes.
Assuntos
Trombose Coronária/epidemiologia , Stents Farmacológicos/estatística & dados numéricos , Revascularização Miocárdica/estatística & dados numéricos , Intervenção Coronária Percutânea/métodos , Fatores Etários , Idoso , Fármacos Cardiovasculares/uso terapêutico , China/epidemiologia , Comorbidade , Terapia Antiplaquetária Dupla/métodos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Estudos Retrospectivos , Fatores de Risco , Fatores SexuaisRESUMO
Vascular dysfunction resulting from diabetes is an important factor in arteriosclerosis. Previous studies have shown that during hyperglycaemia and diabetes, AKAP150 promotes vascular tone enhancement by intensifying the remodelling of the BK channel. However, the interaction between AKAP150 and the BK channel remains open to discussion. In this study, we investigated the regulation of impaired BK channel-mediated vascular dysfunction in diabetes mellitus. Using AKAP150 null mice (AKAP150-/- ) and wild-type (WT) control mice (C57BL/6J), diabetes was induced by intraperitoneal injection of streptozotocin. We found that knockout of AKAP150 reversed vascular remodelling and fibrosis in mice with diabetes and in AKAP150-/- diabetic mice. Impaired Akt/GSK3ß signalling contributed to decreased BK-ß1 expression in aortas from diabetic mice, and the silencing of AKAP150 increased Akt phosphorylation and BK-ß1 expression in MOVAS cells treated with HG medium. The inhibition of Akt activity caused a decrease in BK-ß1 expression, and treatment with AKAP150 siRNA suppressed GSK3ß expression in the nuclei of MOVAS cells treated with HG. Knockout of AKAP150 reverses impaired BK channel-mediated vascular dysfunction through the Akt/GSK3ß signalling pathway in diabetes mellitus.
Assuntos
Proteínas de Ancoragem à Quinase A/genética , Complicações do Diabetes/genética , Diabetes Mellitus Experimental/genética , Glicogênio Sintase Quinase 3 beta/genética , Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Animais , Arteriosclerose/complicações , Arteriosclerose/genética , Arteriosclerose/patologia , Arteriosclerose/terapia , Complicações do Diabetes/patologia , Complicações do Diabetes/terapia , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/terapia , Modelos Animais de Doenças , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Humanos , Hiperglicemia/complicações , Hiperglicemia/genética , Hiperglicemia/patologia , Hiperglicemia/terapia , Canais de Potássio Ativados por Cálcio de Condutância Alta/genética , Camundongos , Camundongos Knockout , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologiaRESUMO
BACKGROUND: Reports showed no change of 7-day mortality after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) between 2001 and 2011 in China. National rolling one-year interventional standardized training programme began in September 2009. However, the improvement in clinical outcome following STEMI PCI after 2011 remains unclear. METHODS AND RESULTS: This multicentre MOODY registry study aimed to analyse the clinical improvement after STEMI PCI. Of a total of 9265 acute MI patients registered from 24 centres, 3142 STEMIs having a first medical contact time ≤12 hours and undergoing primary PCI were assigned to the Pre Group (n = 1014, between March 1999 and October 2010) or the Post Group (n = 2128, between 2010 November and 2016 October). The primary endpoint was in-hospital cardiac death. Study endpoints were also compared between trained and untrained operators and between experienced (≥50 primary PCIs/year) and inexperienced personnel. In-hospital death after PCI was 3.0% in the Pre Group, significantly higher than 1.6% in the Post Group (P = .035). The improvements in clinical outcome after PCI between the 2016 and Pre Groups were stably sustained through one-year follow-up. The significant reduction for in-hospital death was noted when primary PCI was performed by trained (1.4% vs 5.4%, P < .001) or experienced (2.7% vs 4.8%, P = .001) operators, compared to untrained or inexperienced operators, respectively. Inclusion of the untrained operator into the conventional risk model strongly enhanced the prediction for endpoints. Age, Killip Class 3, diabetes, trans-radial approach and system delay were five predictors of in-hospital death after primary PCI. CONCLUSION: PCI for STEMI by a trained and experienced operator was associated with significant reduction of in-hospital death. Our results strongly warrant the need for promoting the current system response and patient education.
Assuntos
Mortalidade Hospitalar , Intervenção Coronária Percutânea/educação , Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Fatores Etários , Idoso , China/epidemiologia , Comorbidade , Diabetes Mellitus/epidemiologia , Feminino , Artéria Femoral , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Revascularização Miocárdica/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Artéria Radial , Sistema de Registros , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Stents , Trombose/epidemiologia , Tempo para o Tratamento/estatística & dados numéricos , Resultado do TratamentoRESUMO
BACKGROUND: Main vessel (MV) stent deformation and overstretch caused by classical kissing balloon inflation (C-KBI) using two balloons with a longer overlapping in the MV for bifurcation lesions has caused a widespread concern. PURPOSE: This bench study tested our hypothesis that mini-KBI (M-KBI) with a shorter protrusion of side branch (SB) balloon would ascertain a better result after Culotte stenting. METHODS: Twenty-four coronary stents were deployed using Culotte approach in twelve bifurcation models with a bifurcation angle of 45°, 3.5 mm in MV diameter, and 3.0 mm in SB diameter. After stent implantation, the final KBI were assigned to C-KBI (two kissing balloons juxtaposed within the MV stent, at least overlap for 3 mm; n = 6) and M-KBI (the proximal marker of SB balloon just sited at the level of upper edge of SB ostium; n = 6). Proximal optimization technique (POT) was performed after KBI. Stent geometry was visually evaluated based on bench photos, microscopy, videoscopy, micro-CT, and scanning electron microscopy. Stent deformation index, minimal lumen diameter, and cross-sectional area at either carina level of MV and ostium of SB were measured from optical coherence tomography (OCT). RESULTS: In Culotte technique, C-KBI was associated with visually significant stent deformation, overexpansion and the "bottleneck" effect of the MV stent, which could not be effectively rectified by POT, while M-KBI could keep the circle shape of MV stent with good stent apposition in both MV and SB stent. By quantitative measurements, deformation index of MV was 0.06 ± 0.01 after M-KBI, significantly lower than 0.25 ± 0.02 if C-KBI was performed. In the line in carina, compared to C-KBI, M-KBI has smaller CSA-stent/CSA-reference, which indicated a less overstretch of MV stent. However, minimal lumen diameter and cross-sectional area of SB ostium was not different in the mini-KBI group (3.0958 ± 0.0285 mm and 7.9667 ± 0.1741 mm), when compared those after C-KBI (3.1217 ± 0.0772 mm and 7.9083 ± 0.3115 mm, p > .05). CONCLUSIONS: Followed by POT, M-KBI is preferable than C-KBI in preventing stent deformation, overexpansion in MV stent and could get well apposed of MV stent and well-opened SB stent as expected in a Culotte technique.
Assuntos
Angioplastia Coronária com Balão/instrumentação , Doença da Artéria Coronariana/terapia , Vasos Coronários , Stents , Angioplastia Coronária com Balão/efeitos adversos , Vasos Coronários/diagnóstico por imagem , Análise de Falha de Equipamento , Humanos , Teste de Materiais , Modelos Anatômicos , Modelos Cardiovasculares , Falha de PróteseRESUMO
BACKGROUND: Defining the optimal conduction of percutaneous-coronary-intervention (PCI) to treat bifurcation lesions has been the subject of many clinical studies showing that the applied stenting technique may influence clinical outcome. Accordingly, bifurcation stenting classifications and technical sequences should be standardized to allow proper reporting and comparison. METHODS: The European Bifurcation Club (EBC) is a multidisciplinary group dedicated to optimize the treatment of bifurcations and previously created a classification of bifurcation stenting techniques that is based on the first stent implantation site. Since some techniques have been abandoned, others have been refined and dedicated devices became available, EBC promoted an international task force aimed at updating the classification of bifurcation stenting techniques as well as at highlighting the best practices for most popular techniques. Original descriptive images obtained by drawings, bench tests and micro-computed-tomographic reconstructions have been created in order to serve as tutorials in both procedure reporting and clinical practice. RESULTS: An updated Main-Across-Distal-Side (MADS)-2, classification of bifurcation stenting techniques has been realized and is reported in the present article allowing standardized procedure reporting in both clinical practice and scientific studies. The EBC-promoted task force deeply discussed, agreed on and described (using original drawings and bench tests) the optimal steps for the following major bifurcation stenting techniques: (a) 1-stent techniques ("provisional" and "inverted provisional") and (b) 2-stent techniques ("T/TAP," "culotte," and "DK-crush"). CONCLUSIONS: The present EBC-promoted paper is intended to facilitate technique selection, reporting and performance for PCI on bifurcated lesions during daily clinical practice.
Assuntos
Angioplastia Coronária com Balão/instrumentação , Doença da Artéria Coronariana/terapia , Stents , Angioplastia Coronária com Balão/efeitos adversos , Tomada de Decisão Clínica , Doença da Artéria Coronariana/diagnóstico por imagem , Humanos , Resultado do TratamentoRESUMO
Uncoupled endothelial nitric oxide synthase (eNOS) produces O2- instead of nitric oxide (NO). Earlier, we reported rapamycin, an autophagy inducer and inhibitor of cellular proliferation, attenuated low shear stress (SS) induced O2- production. Nevertheless, it is unclear whether autophagy plays a critical role in the regulation of eNOS uncoupling. Therefore, this study aimed to investigate the modulation of autophagy on eNOS uncoupling induced by low SS exposure. We found that low SS induced endothelial O2- burst, which was accompanied by reduced NO release. Furthermore, inhibition of eNOS by L-NAME conspicuously attenuated low SS-induced O2- releasing, indicating eNOS uncoupling. Autophagy markers such as LC3 II/I ratio, amount of Beclin1, as well as ULK1/Atg1 were increased during low SS exposure, whereas autophagic degradation of p62/SQSTM1 was markedly reduced, implying impaired autophagic flux. Interestingly, low SS-induced NO reduction could be reversed by rapamycin, WYE-354 or ATG5 overexpression vector via restoration of autophagic flux, but not by N-acetylcysteine or apocynin. eNOS uncoupling might be ascribed to autophagic flux blockade because phosphorylation of eNOS Thr495 by low SS or PMA stimulation was also regulated by autophagy. In contrast, eNOS acetylation was not found to be regulated by low SS and autophagy. Notably, although low SS had no influence on eNOS Ser1177 phosphorylation, whereas boosted eNOS Ser1177 phosphorylation by rapamycin were in favor of the eNOS recoupling through restoration of autophagic flux. Taken together, we reported a novel mechanism for regulation of eNOS uncoupling by low SS via autophagy-mediated eNOS phosphorylation, which is implicated in geometrical nature of atherogenesis.
Assuntos
Aterosclerose/genética , Autofagia/genética , Óxido Nítrico Sintase Tipo III/genética , Estresse Mecânico , Animais , Autofagia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Células Endoteliais/metabolismo , Humanos , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/biossíntese , Óxido Nítrico/química , Óxido Nítrico Sintase Tipo III/química , Oxigênio/metabolismo , Fosforilação , Transdução de SinaisRESUMO
Hyperglycemia-induced apoptosis plays a critical role in the pathogenesis of diabetic cardiomyopathy (DCM). Our previous study demonstrated that ivabradine, a selective If current antagonist, significantly attenuated myocardial apoptosis in diabetic mice, but the underlying mechanisms remained unknown. This study investigated the underlying mechanisms by which ivabradine exerts anti-apoptotic effects in experimental DCM. Pretreatment with ivabradine, but not ZD7288 (an established If current blocker), profoundly inhibited high glucose-induced apoptosis via inactivation of nuclear factor (NF)-κB signaling in neonatal rat cardiomyocytes. The effect was abolished by transfection of an siRNA targeting protein phosphatase 2A catalytic subunit (PP2Ac). In streptozotocin-induced diabetic mice, ivabradine treatment significantly inhibited left ventricular hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) and HCN4 (major components of the If current), activated PP2Ac, and attenuated NF-κB signaling activation and apoptosis, in line with improved histological abnormalities, fibrosis, and cardiac dysfunction without affecting hyperglycemia. These effects were not observed in diabetic mice with virus-mediated knockdown of HCN2 or HCN4 after myocardial injection, but were alleviated by knockdown of PP2Acα. Molecular docking and phosphatase activity assay confirmed direct binding of ivabradine to, and activation of, PP2Ac. In conclusion, ivabradine may directly activate PP2Ac, leading to inhibition of NF-κB signaling activation, myocardial apoptosis, and fibrosis, and eventually improving cardiac function in experimental DCM. Taken together, the present findings suggest that ivabradine may be a promising drug for treatment of DCM.