金辰
中国医学科学院阜外医院 冠心病诊治黄宗羲
At least 12 months of dual antiplatelet therapy (DAPT) is 1 of the standards of care following percutaneous coronary intervention in patients with acute coronary syndrome. However, study on prolonged DAPT for patients with acute myocardial infarction (AMI) without revascularization is limited. We studied 1,744 patients with AMI without revascularization from the China Acute Myocardial Infarction registry between January 2013 and September 2014. These patients were on DAPT and did not experience AMI, stroke, or bleeding events at the 12-month follow-up. We divided them into 2 groups: 12-month DAPT group (DAPT for at least 12 months but <18 months) and 18-month DAPT group (DAPT for at least 18 months). The primary outcome was 24-month all-cause death. Overall, 1,221 patients (70.0%) took DAPT for ≥12 months but <18 months, whereas 523 patients (30.0%) took DAPT for ≥18 months. The proportion of patients at high ischemic risk and the proportion of patients at high bleeding risk were similar in the 2 groups. At 24 months, the all-cause mortality rate of the 18-month DAPT group was significantly lower than that for the 12-month DAPT group (3.7% vs 5.9%, p = 0.0471). The adjusted hazard ratio for all-cause death also showed statistical significance (0.59, 95% confidence interval 0.35 to 0.99, p = 0.0444). In conclusion, DAPT for at least 18 months appears to be associated with lower 24-month mortality for non-revascularization AMI patients without events within 12 months after onset.
The American journal of cardiology 2024
BACKGROUND:Extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (MSCs) pretreated with atorvastatin (ATV) (MSCATV-EV) have a superior cardiac repair effect on acute myocardial infarction (AMI). The mechanisms, however, have not been fully elucidated. This study aims to explore whether inflammation alleviation of infarct region via macrophage polarization plays a key role in the efficacy of MSCATV-EV.METHODS:MSCATV-EV or MSC-EV were intramyocardially injected 30 min after coronary ligation in AMI rats. Macrophage infiltration and polarization (day 3), cardiac function (days 0, 3, 7, 28), and infarct size (day 28) were measured. EV small RNA sequencing and bioinformatics analysis were conducted for differentially expressed miRNAs between MSCATV-EV and MSC-EV. Macrophages were isolated from rat bone marrow for molecular mechanism analysis. miRNA mimics or inhibitors were transfected into EVs or macrophages to analyze its effects on macrophage polarization and cardiac repair in vitro and in vivo.RESULTS:MSCATV-EV significantly reduced the amount of CD68+ total macrophages and increased CD206+ M2 macrophages of infarct zone on day 3 after AMI compared with MSC-EV group (P < 0.01-0.0001). On day 28, MSCATV-EV much more significantly improved the cardiac function than MSC-EV with the infarct size markedly reduced (P < 0.05-0.0001). In vitro, MSCATV-EV also significantly reduced the protein and mRNA expressions of M1 markers but increased those of M2 markers in lipopolysaccharide-treated macrophages (P < 0.05-0.0001). EV miR-139-3p was identified as a potential cardiac repair factor mediating macrophage polarization. Knockdown of miR-139-3p in MSCATV-EV significantly attenuated while overexpression of it in MSC-EV enhanced the effect on promoting M2 polarization by suppressing downstream signal transducer and activator of transcription 1 (Stat1). Furthermore, MSCATV-EV loaded with miR-139-3p inhibitors decreased while MSC-EV loaded with miR-139-3p mimics increased the expressions of M2 markers and cardioprotective efficacy.CONCLUSIONS:We uncovered a novel mechanism that MSCATV-EV remarkably facilitate cardiac repair in AMI by promoting macrophage polarization via miR-139-3p/Stat1 pathway, which has the great potential for clinical translation.
BMC medicine 2023
Objective:To evaluate the long-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) treated with different reperfusion strategies in Chinese county-level hospitals.Methods:A total of 2,514 patients with STEMI from 32 hospitals participated in the China Acute Myocardial Infarction registry between January 2013 and September 2014. The success of fibrinolysis was assessed according to indirect measures of vascular recanalization. The primary outcome was 2-year mortality.Results:Reperfusion therapy was used in 1,080 patients (42.9%): fibrinolysis ( n= 664, 61.5%) and primary percutaneous coronary intervention (PCI) ( n= 416, 38.5%). The most common reason for missing reperfusion therapy was a prehospital delay > 12 h (43%). Fibrinolysis [14.5%, hazard ratio ( HR): 0.59, 95% confidence interval ( CI) 0.44-0.80] and primary PCI (6.8%, HR= 0.32, 95% CI: 0.22-0.48) were associated with lower 2-year mortality than those with no reperfusion (28.5%). Among fibrinolysis-treated patients, 510 (76.8%) achieved successful clinical reperfusion; only 17.0% of those with failed fibrinolysis underwent rescue PCI. There was no difference in 2-year mortality between successful fibrinolysis and primary PCI (8.8% vs. 6.8%, HR = 1.53, 95% CI: 0.85-2.73). Failed fibrinolysis predicted a similar mortality (33.1%) to no reperfusion (33.1% vs. 28.5%, HR= 1.30, 95% CI: 0.93-1.81).Conclusion:In Chinese county-level hospitals, only approximately 2/5 of patients with STEMI underwent reperfusion therapy, largely due to prehospital delay. Approximately 30% of patients with failed fibrinolysis and no reperfusion therapy did not survive at 2 years. Quality improvement initiativesare warranted, especially in public health education and fast referral for mechanical revascularization in cases of failed fibrinolysis.
Biomedical and environmental sciences : BES 2023
BACKGROUND:Data on fibrinolytic therapy use for ST-segment elevation myocardial infarction (STEMI) and long-term clinical outcomes in developing countries are limited. We aimed to investigate the management and 2-year mortality of fibrinolytic-treated patients in China.METHODS:A total of 19,112 patients with STEMI from 108 hospitals participated in the China Acute Myocardial Infarction registry between January 2013 and September 2014. We investigated the 2-year all-cause mortality among patients treated with fibrinolysis. Non-invasive clinical indexes were used to diagnose successful fibrinolysis or not.RESULTS:Only 1823 patients (9.5%) enrolled in the registry underwent fibrinolysis and 679 (37.2%) could be treated within 3 h after symptom onset. The overall use of rescue percutaneous coronary intervention was 8.9%. Successful fibrinolysis, which could be achieved in 1428 patients (78.3%), was related to types of fibrinolytic agents, symptom to needle time, infarction site, and Killip class. Follow-up data were available for 1745 patients (95.7%). After multivariate adjustment, successful fibrinolysis was strongly associated with a decreased risk of death compared with failed fibrinolysis at 2 years (8.5% vs. 29.0%, hazard ratio: 0.27, 95% confidence interval: 0.20-0.35).CONCLUSION:Within a minority of STEMI patients in the CAMI registry underwent fibrinolysis, most of them could achieve successful clinical reperfusion, presenting a much benign 2-year survival outcome than those with failed fibrinolysis. Quality improvement initiatives focusing on fibrinolysis are warranted to achieve its promise fully.TRIAL REGISTRATION:URL: https// www.CLINICALTRIALS:gov . Unique identifier: NCT01874691. Registered 11/06/2013.
BMC cardiovascular disorders 2023
Background To evaluate the role of ST-segment resolution (STR) alone and in combination with Thrombolysis in Myocardial Infarction (TIMI) flow in reperfusion evaluation after primary percutaneous coronary intervention (PPCI) for ST-segment-elevation myocardial infarction by investigating the long-term prognostic impact. Methods and Results From January 2013 through September 2014, we studied 5966 patients with ST-segment-elevation myocardial infarction enrolled in the CAMI (China Acute Myocardial Infarction) registry with available data of STR evaluated at 120 minutes after PPCI. Successful STR included STR ≥50% and complete STR (ST-segment back to the equipotential line). After PPCI, the TIMI flow was assessed. The primary outcome was 2-year all-cause mortality. STR < 50%, STR ≥50%, and complete STR occurred in 20.6%, 64.3%, and 15.1% of patients, respectively. By multivariable analysis, STR ≥50% (5.6%; adjusted hazard ratio [HR], 0.45 [95% CI, 0.36-0.56]) and complete STR (5.1%; adjusted HR, 0.48 [95% CI, 0.34-0.67]) were significantly associated with lower 2-year mortality than STR <50% (11.7%). Successful STR was an independent predictor of 2-year mortality across the spectrum of clinical variables. After combining TIMI flow with STR, different 2-year mortality was observed in subgroups, with the lowest in successful STR and TIMI 3 flow, intermediate when either of these measures was reduced, and highest when both were abnormal. Conclusions Post-PPCI STR is a robust long-term prognosticator for ST-segment-elevation myocardial infarction, whereas the integrated analysis of STR plus TIMI flow yields incremental prognostic information beyond either measure alone, supporting it as a convenient and reliable surrogate end point for defining successful PPCI. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01874691.
Journal of the American Heart Association 2023
To determine whether late percutaneous coronary intervention (PCI) of an infarct-related artery >12 h after ST-segment elevation myocardial infarction onset is beneficial, patients were included from the prospective, nationwide, multicenter China Acute Myocardial Infarction registry. The number of patients who underwent PCI or received drug therapy alone was 4791 and 1149, respectively. Hazard ratio (HR) and associated 95% confidence interval (CI) were calculated. Compared with drug therapy, PCI was associated with lower incidences of 2-year major adverse cardiac and cerebrovascular events (MACCE; 6.43 vs 20.19%; HR, .27; 95% CI, .23-.32; P < .001), all-cause death (4.13 vs 15.74%; HR, .24; 95% CI, .20-.30; P < .001), myocardial infarction (1.73 vs 3.31%; HR, .49; 95% CI, .33-.72; P = .0003), stroke (1.02 vs 2.00%; HR, .47; 95% CI, .28-.77; P = .0026), and revascularization (10.96 vs 27.56%; HR, .32; 95% CI, .26-.39; P < .001). Subgroup analysis consistently indicated that PCI was superior to drug therapy. Moreover, the left ventricular ejection fraction in the PCI group was increased after 2-year follow-up, whereas there was no significant increase in the drug therapy group. In conclusion, late PCI is common in Chinese clinical practice, and it is associated with significant improvements in cardiac function and survival compared with drug therapy alone.
Angiology 2023
OBJECTIVE:To evaluate the prognostic influence of the presence of right ventricular myocardial infarction (RVMI) on patients with inferior ST-segment elevation myocardial infarction (STEMI) in the contemporary reperfusion era.METHODS:9308 patients with inferior STEMI were included from the prospective, nationwide, multicenter China Acute Myocardial Infarction Registry, including 1745 (18.75%) patients with RVMI and 7563 (81.25%) patients without RVMI. The primary outcome was two-year all-cause mortality. The secondary outcome was major adverse cardiac and cerebrovascular event (MACCE) defined as a composite of all-cause mortality, recurrent MI, revascularization, stroke, and major bleeding.RESULTS:After two-year follow up, there were no significant differences between inferior STEMI patients with or without RVMI in all-cause mortality (12.0% vs 11.3%; adjusted HR: 1.05; 95% CI: 0.90 to 1.24; P = 0.5103). Inferior STEMI with RVMI was associated with higher risk of MACCE (25.6% vs 22.0%; adjusted HR: 1.17; 95% CI: 1.05 to 1.31; P = 0.0038), revascularization (10.3% vs 8.1%; adjusted HR: 1.23; 95% CI: 1.03 to 1.48; P = 0.0218), and major bleeding (4.6% vs 2.7%; adjusted HR: 1.56; 95% CI: 1.18 to 2.07; P = 0.0019). Primary percutaneous coronary intervention (PCI) and thrombolysis were independent predictors to decrease all-cause mortality. For patients who received timely reperfusion, RVMI involvement did not increase all-cause mortality, whereas for those who did not undergo reperfusion, RVMI increased all-cause mortality (20.3% vs 15.7%; HR: 1.34; 95% CI: 1.10 to 1.63).CONCLUSION:RVMI did not increase all-cause mortality for inferior STEMI patients in contemporary reperfusion era, whereas the risk was increased for patients with no reperfusion treatment.
International journal of cardiology 2022
PURPOSE:We sought to investigate the short- and long-term outcomes in patients with right ventricular infarction in China.METHODS:Data from China Acute Myocardial Infarction (CAMI) Registry for patients with right ventricular infarction between January 2013 and September 2014 were analyzed.RESULTS:Of the 1,988 patients with right ventricular infarction, 733 patients did not receive reperfusion therapy, 281 patients received thrombolysis therapy, and 974 patients underwent primary PCI. Primary PCI and thrombolysis were all associated with lower risks of in-hospital (3.1 vs. 12.6%; adjusted OR: 0.48; 95% CI: 0.27-0.87; P = 0.0151 and 5.7 vs. 12.6%; adjusted OR: 0.43; 95% CI: 0.22-0.85; P = 0.0155, respectively), and 2-year all-cause mortality (6.3 vs. 20.9%; adjusted HR: 0.50; 95% CI: 0.34-0.73; P = 0.0003 and 11.0 vs. 20.9%; adjusted HR: 0.59; 95% CI: 0.38-0.92; P = 0.0189, respectively), compared with no reperfusion therapy. Meanwhile, primary PCI was superior to thrombolysis in reducing the risks of in-hospital atrial-ventricular block (4.2 vs. 8.9%; adjusted OR: 0.46; 95% CI: 0.23-0.91; P = 0.0257), cardiogenic shock (5.3 vs. 13.9%; adjusted OR: 0.43; 95% CI: 0.23-0.83; P = 0.0115), and heart failure (8.5 vs. 23.5%; adjusted OR: 0.35; 95% CI: 0.22-0.56; P < 0.0001). Primary PCI could reduce the risk of 2-year major adverse cardiac and cerebrovascular event (19.1 vs. 33.3%; adjusted HR: 0.72; 95% CI: 0.56-0.92; P = 0.0092) relative to no reperfusion therapy, whereas thrombolysis may increase the risk of 2-year revascularization (15.5 vs. 8.7%; adjusted HR: 1.90; 95% CI: 1.15-3.16; P = 0.0124) compared with no reperfusion therapy.CONCLUSIONS:Timely reperfusion therapy is essential for patients with right ventricular infarction. Primary PCI may be considered as the default treatment strategy for patients with right ventricular infarction in the contemporary primary PCI era.
Frontiers in cardiovascular medicine 2022
BACKGROUND:Recent publications reported a paradoxical finding that there was an inverse association between the number of standard modifiable risk factors (SMuRFs; smoking, hypertension, diabetes, and hyperlipidemia) and mortality in patients with myocardial infarction. However, the current evidence is only limited to those highly developed countries with advanced medical management systems.METHODS:The China Acute Myocardial Infarction registry is a prospective observational study including patients with acute myocardial infarction from three-level hospitals across 31 administrative regions throughout mainland China. A total of 16,228 patients with first-presentation ST-elevation myocardial infarction (STEMI) admitted to hospitals from January 2013 to September 2014 were enrolled in the current analysis. Cox proportional hazard models adjusting for baseline characteristics, clinical profiles at presentation, and in-hospital treatments were used to assess the association of the number of SMuRFs with all-cause mortality at 30 days after STEMI presentation.RESULTS:A total of 1918 (11.8%), 11,503 (70.9%), and 2807 (17.3%) patients had 0, 1-2, and 3-4 SMuRFs at presentation, respectively. Patients with fewer SMuRFs were older and more likely to be females, experienced longer pre-hospital delays, and were less likely to receive primary percutaneous coronary intervention and evidence-based medications. Compared with those without any SMuRF, patients with 1-2 SMuRFs and 3-4 SMuRFs were associated with an HR of 0.74 (95% CI, 0.63-0.87) and 0.63 (0.51-0.77) for all-cause mortality up to 30 days in the unadjusted model (Ptrend < 0.0001). However, after multivariate adjustment, the number of SMuRFs was positively associated with increased mortality risk (HR for 1-2 SMuRFs, 1.15 [0.95-1.39]; HR for 3-4 SMuRFs, 1.31 [1.02-1.68]; Ptrend = 0.03), and the association was only significant among patients admitted to hospitals beyond 12 h from onset (HR for 1-2 SMuRFs, 1.39 [1.03-1.87]; HR for 3-4 SMuRFs, 2.06 [1.41-3.01]) but not their counterparts (Pinteraction = 0.01).CONCLUSIONS:The increased crude mortality risk among patients without SMuRFs is explained by confounding factors related to their poor risk profiles (old age, longer pre-hospital delays, and poor clinical management). After multivariate adjustment, a higher risk-factor burden was associated with poor prognosis among patients with STEMI.
BMC medicine 2022
BACKGROUND:Bone marrow cells (BMCs), especially mesenchymal stem cells (MSCs), have shown attractive application prospects in acute myocardial infarction (AMI). However, the weak efficacy becomes their main limitation in clinical translation. Based on the anti-inflammation and anti-apoptosis effects of a Chinese medicine-Tongxinluo (TXL), we aimed to explore the effects of TXL-pretreated MSCs (MSCsTXL) in enhancing cardiac repair and further investigated the underlying mechanism.METHODS:MSCsTXL or MSCs and the derived exosomes (MSCsTXL-exo or MSCs-exo) were collected and injected into the infarct zone of rat hearts. In vivo, the anti-apoptotic and anti-inflammation effects, and cardiac functional and histological recovery were evaluated. In vitro, the apoptosis was evaluated by western blotting and flow cytometry. miRNA sequencing was utilized to identify the significant differentially expressed miRNAs between MSCsTXL-exo and MSCs-exo, and the miRNA mimics and inhibitors were applied to explore the specific mechanism.RESULTS:Compared to MSCs, MSCsTXL enhanced cardiac repair with reduced cardiomyocytes apoptosis and inflammation at the early stage of AMI and significantly improved left ventricular ejection fraction (LVEF) with reduced infarct size in an exosome-dependent way. Similarly, MSCsTXL-exo exerted superior therapeutic effects in anti-apoptosis and anti-inflammation, as well as improving LVEF and reducing infarct size compared to MSCs-exo. Further exosomal miRNA analysis demonstrated that miR-146a-5p was the candidate effector of the superior effects of MSCsTXL-exo. Besides, miR-146a-5p targeted and decreased IRAK1, which inhibited the nuclear translocation of NF-κB p65 thus protecting H9C2 cells from hypoxia injury.CONCLUSIONS:This study suggested that MSCsTXL markedly facilitated cardiac repair via a new mechanism of the exosomal transfer of miR-146a-5p targeting IRAK1/NF-κB p65 pathway, which has great potential for clinical translation.
Stem cell research & therapy 2022
