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Background: Postprocedural anticoagulation (PPA) is frequently administered after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction, although no conclusive data support this practice., Methods: The RIGHT trial (Comparison of Anticoagulation Prolongation vs no Anticoagulation in STEMI Patients After Primary PCI) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled, superiority trial conducted at 53 centers in China. Patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention were randomly assigned by center to receive low-dose PPA or matching placebo for at least 48 hours. Before trial initiation, each center selected 1 of 3 PPA regimens (40 mg of enoxaparin once daily subcutaneously; 10 U·kg·h of unfractionated heparin intravenously, adjusted to maintain activated clotting time between 150 and 220 seconds; or 0.2 mg·kg·h of bivalirudin intravenously). The primary efficacy objective was to demonstrate superiority of PPA to reduce the primary efficacy end point of all-cause death, nonfatal myocardial infarction, nonfatal stroke, stent thrombosis (definite), or urgent revascularization (any vessel) within 30 days. The key secondary objective was to evaluate the effect of each specific anticoagulation regimen (enoxaparin, unfractionated heparin, or bivalirudin) on the primary efficacy end point. The primary safety end point was Bleeding Academic Research Consortium 3 to 5 bleeding at 30 days., Results: Between January 10, 2019, and September 18, 2021, a total of 2989 patients were randomized. The primary efficacy end point occurred in 37 patients (2.5%) in both the PPA and placebo groups (hazard ratio, 1.00 [95% CI, 0.63 to 1.57]). The incidence of Bleeding Academic Research Consortium 3 to 5 bleeding did not differ between the PPA and placebo groups (8 [0.5%] vs 11 [0.7%] patients; hazard ratio, 0.74 [95% CI, 0.30 to 1.83])., Conclusions: Routine PPA after primary percutaneous coronary intervention was safe but did not reduce 30-day ischemic events., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03664180., Competing Interests: Disclosures Dr Yan was funded by grants from the National Natural Science Foundation of China (82100260) and Beijing Hospitals Authority Youth Program (QML20210605). Dr X. Wang was funded by grants from National Key Research & Development Program of China (2022YFC2505600), Beijing Nova Program (Z201100006820087), Interdisciplinary Cooperation Project of Beijing Nova Program (Z211100002121165), and Natural Science Foundation of Beijing, China (7222046). Dr Ma reports honoraria from Bristol-Myers Squibb, Pfizer, Johnson & Johnson, Boehringer-Ingelheim, Bayer, and AstraZeneca for giving lectures. Dr Vicaut reports consulting fees from Abbott and Bristol-Myers Squibb. Dr Montalescot reports research grants to the institution or consulting or lecture fees from Abbott, Amgen, AstraZeneca, Ascendia, Bayer, Bristol-Myers Squibb, Boehringer-Ingelheim, Boston-Scientific, Celecor, CSL Behring, Idorsia, Lilly, Novartis, Novo, Opalia, Pfizer, Quantum Genomics, Sanofi, and Terumo. Dr Nie was funded by Beijing Hospitals Authority Clinical Medicine Development of Special Funding support (grant ZLRK202318), National Natural Science Foundation of China (grant 82270258), and Beijing Municipal Science & Technology Commission, China (grant Z221100003522027), and reports research grants to the institution from Boston Scientific, Abbott, Jiangsu Hengrui Pharmaceuticals, China Resources Sanjiu Medical & Pharmaceuticals, and East China Pharmaceuticals. The other authors have no conflicts of interest to declare.

Background and Aims: The association of comorbidities on the prognosis of patients with acute coronary syndrome (ACS) was well documented. However, the impact of obstructive sleep apnea (OSA) on this association has been less studied., Methods and Results: Between June 2015 to Jan 2020, we included consecutively eligible patients with ACS who underwent cardiorespiratory polygraphy. The definition of OSA was apnea-hypopnea index (AHI) ≥15 events/hour. Charlson Comorbidity Index (CCI) was used to evaluate the comorbidities. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, and hospitalization for unstable angina or heart failure. In the 1927 ACS patients, 1014 (52.6%) had OSA. The prevalence of the mild (CCI = 0), moderate (CCI = 1-2), and severe (CCI≥3) comorbidity were 23.6%, 65.9%, and 10.5%, respectively. During a median follow-up of 2.9 (1.5, 3.6) years, compared with patients without OSA, the presence of OSA increased the risk of MACCE in the moderate comorbidity group (22.6% vs. 17.5%; adjusted HR: 1.327; 95% CI: 1.019-1.728, p = 0.036) and severe comorbidity group (36.2% vs. 18.6%; adjusted HR: 2.194; 95% CI: 1.170-4.117, p = 0.014). There was no significant difference between OSA and non-OSA patients in the mild comorbidity group., Conclusion: Among ACS patients, OSA was associated with an increased risk of subsequent events in the moderate and severe comorbidity groups but not in the mild comorbidity group. ACS patients with comorbidities should not be overlooked for OSA screening., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest. Siyi Li and Wen Zheng equally contributed to this work., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objective: The prognostic significance of obstructive sleep apnea (OSA) in patients with acute coronary syndrome (ACS) according to prior myocardial infarction (MI) remains unclear. We aimed to investigate the association between OSA and long-term cardiovascular outcomes in ACS patients with or without prior MI., Methods: We prospectively recruited eligible 2160 ACS patients with portable sleep monitoring in Beijing Anzhen Hospital between June 2015 and January 2020. OSA was defined as an apnea hypopnea index (AHI) ≥15 events/hour. The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure., Results: Among 1927 patients enrolled, 1014 (52.6%) had OSA and 316 (16.4%) had prior MI. During 2.9 (1.5, 3.6) years of follow-up, multivariate analysis showed that OSA was associated with 1.7 times the risk of MACCE in patients with prior MI (50 events [28.2%] vs 24 events [17.3%]; adjusted HR = 1.74, 95%CI 1.04-2.90, P = 0.034), but not in patients without prior MI group (177 events [21.1%] vs 138 events [17.8%]; adjusted HR = 1.19, 95%CI 0.94-1.51, P = 0.15). There was no significant interaction between prior MI and OSA for MACCE (interaction P = 0.14)., Conclusions: OSA was independently associated with an increased risk of MACCE among ACS patients, particularly among ACS patients with prior MI. Further trials exploring the efficacy of OSA treatment in high-risk patients with ACS characterized by prior MI are warranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Standard modifiable risk factors (SMuRFs) increase the risk of cardiovascular events in patients with acute coronary syndrome (ACS) and are also strongly associated with obstructive sleep apnea (OSA) in a bidirectional relationship. However, the association of OSA with recurrent cardiovascular events in ACS patients based on the number of SMuRFs remains unclear. Hence, we aimed to elucidate the prognostic implication of OSA in ACS patients stratified by the number of SMuRFs., Methods: This was a post hoc analysis of the OSA-ACS study (NCT03362385), including 1927 patients admitted for ACS and undergoing portable sleep monitoring. OSA was defined as an apnea hypopnea index ≥ 15 events/h. The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE) including cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina or heart failure, and ischemia-driven revascularization. Cox proportional hazards model and Kaplan-Meier analysis were used to investigated the relationship between OSA and subsequent cardiovascular events after patients were stratified by the number of SMuRFs., Results: Among 1927 patients enrolled, 130 (6.7%) had no SMuRF, 1264 (65.6%) exhibited 1-2 SMuRFs and 533 (27.7%) presented 3-4 SMuRFs. With the increase of the number of SMuRFs, the proportion of OSA in ACS patients tended to increase (47.7% vs. 51.5% vs. 56.6%), but there was no significant difference between them (P = 0.08). After the stratification of ACS patients via SMuRF numbers and adjustment for confounding factors, fully adjusted Cox regression indicated that OSA increased the risk of MACCE (adjusted HR, 1.65; 95%CI, 1.06-2.57; P = 0.026) and ischemia-driven revascularization (adjusted HR, 2.18; 95%CI, 1.03-4.65; P = 0.042) in ACS patients with 3-4 SMuRFs., Conclusions: In hospitalized ACS patients, OSA is associated with an increased risk of MACCE and ischemia-driven revascularization among patients with 3-4 SMuRFs. Therefore, screening for OSA should be emphasized in ACS patients with 3-4 SMuRFs, and intervention trials should be prioritized in these high-risk patients., (© 2023. The Author(s).)

Background: Obstructive sleep apnea (OSA) and metabolic syndrome (MetS) are each increasingly common in patients with acute coronary syndrome (ACS). Whether OSA increases cardiovascular consequences in ACS patients with MetS has not been investigated., Hypothesis: OSA increases cardiovascular risk in ACS patients with MetS. We aimed to examine the association between OSA and cardiovascular consequences in ACS patients with MetS., Methods: In this prospective cohort study, we consecutive recruited 2160 ACS patients who underwent portable sleep breathing monitoring. OSA is defined as an apnea-hypopnea index (AHI) ≥ 15 events/h. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure., Results: A total of 1927 patients with ACS were enrolled. Among them, 1486 (77.1%) had MetS and 1014 (52.6%) had OSA. During 2.9 years of follow-up, the cumulative incidence of MACCE was similar between OSA and non-OSA groups in patients with MetS (21.9% vs. 17.9%, adjusted hazard ratio [HR] = 1.29 95% confidence interval [CI]: 0.99-1.67, p = .06) and patients without MetS (24.4% vs. 17.3%, adjusted HR = 1.21 95% CI: 0.73-2.03, p = .46). Patients with MetS and OSA had a significantly higher risk of MACCE than patients with MetS and without OSA in women (27.8% vs. 18.1%, adjusted HR = 1.70, 95% CI: 1.01-3.09, p = .04) but not in men (21.0% vs. 17.9%, adjusted HR = 1.19, 95% CI: 0.91-1.59, p = .21)., Conclusions: In hospitalized ACS patients with MetS, comorbid OSA was associated with increased risk of cardiovascular consequences among women., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: To study the impact of de-escalation antiplatelet therapy retaining P2Y12 inhibition on major bleeding and ischemic outcomes after percutaneous coronary intervention (PCI) among East Asians and non-East Asians was unclear., Methods: We systematically searched PubMed, Embase, and the Cochrane Library for randomized controlled trials through September 2020. Eight trials were included, which studied de-escalation of DAPT (D-DAPT, switching to P2Y12 inhibitor monotherapy, or switching to clopidogrel or dose reduction of the P2Y12 inhibitor after 1 to 3 months) versus 12 months standard DAPT (S-DAPT). The primary outcomes data was conducted using random effects models., Results: Among the 8 included trials consisting of 37,775 patients, 62.6% presented with acute coronary syndrome. The median follow-up duration ranged from 12 to 24 months. Compared with S-DAPT, D-DAPT was associated with a lower risk of major bleeding (RR = 0.67, 95% CI 0.48-0.93, p = 0.02); however, this was only observed among East-Asians (RR = 0.61, 95% CI 0.37-0.99, p = 0.048). Among non-East Asians, the rate of major bleeding was similar between the two groups (RR = 0.73, 95% CI 0.46-1.14, p = 0.17, p for interaction = 0.59). There were no significant differences in the major adverse cardiovascular events (MACE) between D-DAPT and S-DAPT treatment among both East Asians (RR = 0.84, 95% CI 0.66-1.08, p = 0.18) and non-East Asians (RR = 0.89, 95% CI 0.79-1.00, p = 0.059, p for interaction = 0.71)., Conclusions: The De-escalation strategy that retains P2Y12 inhibition after a PCI was associated with reduced risk of bleeding events, which was only demonstrated in East Asians patients, and not in non-East Asian patients., (© 2022. The Author(s).)

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., (© 2021 Wiley Periodicals LLC.)

Cardiac rupture is a fatal complication of acute myocardial infarction (MI), associated with increased inflammation and damaged extracellular matrix. C57BL/6 J wild type (WT) and Pde5a knockout (Pde5a -/- ) mice were selected to establish MI model. The rupture rate of Pde5a -/- mice was significantly reduced (P < 0.01) within 7 days post MI. The cardiac function of Pde5a -/- mice was better than WT mice both at day 3 and 7 post MI. Immunohistochemical staining and flow cytometry showed neutrophils and macrophages were decreased in Pde5a -/- mouse hearts. Inflammatory factors expression such as IL-1β, IL-6, IL-8, Mcp-1, TNF-α significantly decreased in Pde5a -/- mice post MI. Moreover, western blot showed the inhibition of inflammatory response was accompanied by down-regulation of intercellular adhesion molecule-1(ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) in Pde5a -/- mice. Knockout of Pde5a reduced inflammatory cells infiltration by down-regulating the expression of ICAM-1 and VCAM-1, and prevented early cardiac rupture after MI. All authors declare that they have no conflicts of interest. This article does not contain any studies with human participants performed by any of the authors. All applicable international, national, and institutional guidelines for the care and use of animals were followed., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Purpose: Free wall rupture (FWR) is a lethal complication after acute myocardial infarction; however, the un-derlying mechanisms of FWR are unclear. This study analyzes the relationship between neutrophil counts and FWR following ST-elevation myocardial infarction (STEMI)., Methods: The case group was STEMI patients with FWR and the control group was STEMI patients without FWR (case-control ratio was 1:4). The demographic data, clinical manifestation and laboratory test results were retrospectively collected and analyzed., Results: Of a total of 6,712 consecutive STEMI patients, 78 patients (1.2%) had FWR. Compared with STEMI patients, patients with FWR were older and more likely to be female with an anterior infarct. White blood cell (WBC) counts were significantly higher in the FWR group. Moreover, we found that the elevated neutrophil counts mainly accounted for the elevated WBC counts. There was also a correlation between the age and neu-trophil counts (P=0.0109); as patient age increased, neutrophil counts decreased (P=0.0387). We also found no correlation between neutrophil counts and the time between myocardial infarction attack and FWR; however, when dividing these patients into FWR ≤48 h after admission to hospital for STEMI and FWR >48 h, there was a significant difference in neutrophil counts (P=0.0196). Furthermore, the results of logistic regression analy-sis showed that increased neutrophil was an independent risk factor for FWR (odds ratio: 2.404, confidence interval: 1.055-5.477)., Conclusion: Elevated neutrophil counts were found to be the main cause of differences in WBC counts be-tween FWR and STEMI. Elevated neutrophil was an independent risk factor for FWR. This study provided clues for further research and development of therapeutics for the prevention of FWR.

Background: Acute myocardial infarction (AMI) recurrence is still high despite great progress in secondary prevention. Patients with recurrent AMI suffer worse prognosis compared to those with first AMI. The objective was to evaluate the effect of optimal medical therapy (OMT) on these patients with recurrent AMI., Methods and Results: Sub-analysis was performed including 13,343 patients with AMI from the international multicenter Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome (BleeMACS) registry. OMT was defined as the combination of aspirin, any P2Y12 inhibitor, statin, angiotensin converting enzyme inhibitor/angiotensin receptor blocker, and beta-blocker. Among 1285 patients with prior AMI, 56.8% received OMT prescription. Patients receiving OMT suffered from less congestive heart failure, peripheral artery disease, malignancy, and bleeding history. Kaplan-Meier survival estimates revealed that OMT was strongly related to decreased in all-cause death (4.2% vs. 10.1%, p < .001) and the composite endpoint of death/re-AMI (11.1% vs. 16.9%, p = .005) at 1-year follow-up. OMT was the independent protect factor of primary endpoint even after adjusting for multiple possible confounders (HR, 0.46; 95% CI, 0.27-0.78; p = .004). However, no significant difference was observed regarding re-AMI between OMT and non-OMT groups. OMT also reduced all-cause death in patients with recurrent AMI after propensity score matching., Conclusions: The prescription of OMT was seriously insufficient in patients with recurrent AMI, especially high-risk patients, even though OMT was associated with improved prognosis. Further improvements in pharmacological therapy are needed to reduce subsequent recurrent events., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Rationale: Obstructive sleep apnea-hypopnea syndrome, a sleep breathing disorder in which chronic intermittent hypoxia (CIH) is the primary pathology, is associated with multiple cardiovascular diseases. However, whether and how CIH may affect cardiac remodeling following myocardial infarction (MI) remains unknown., Objective: To determine whether CIH exposure at different periods of MI may exacerbate post-MI heart failure and to identify the mechanisms underlying CIH-exacerbated post-MI remodeling., Methods and Results: Adult male mice were subjected to MI (4 weeks) with and without CIH (4 or 8 weeks). CIH before MI (CIH+MI) had no significant effect on post-MI remodeling. However, double CIH exposure (CIH+MI+CIH) or CIH only during the MI period (MI+CIH) significantly exacerbated pathological remodeling and reduced survival rate. Mechanistically, CIH activated TGF-β (tumor growth factor-β)/Smad (homologs of both the Drosophila protein MAD and the C. elegans protein SMA) signaling and enhanced cardiac epithelial to mesenchymal transition, markedly increasing post-MI cardiac fibrosis. Transcriptome analysis revealed that, among 15 genes significantly downregulated (MI+CIH versus MI), Ctrp9 (a novel cardioprotective cardiokine) was one of the most significantly inhibited genes. Real-time polymerase chain reaction/Western analysis confirmed that cardiomyocyte CTRP9 expression was significantly reduced in MI+CIH mice. RNA-sequencing, real-time polymerase chain reaction, and dual-luciferase reporter assays identified that microRNA-214-3p is a novel Ctrp9 targeting miRNA. Its upregulation is responsible for Ctrp9 gene suppression in MI+CIH. Finally, AAV9 (adeno-associated virus 9)-mediated cardiac-specific CTRP9 overexpression or rCTRP9 (recombinated CTRP9) administration inhibited TGF-β/Smad and Wnt/β-catenin pathways, attenuated interstitial fibrosis, improved cardiac function, and enhanced survival rate in MI+CIH animals., Conclusions: This study provides the first evidence that MI+CIH upregulates miR-214-3p, suppresses cardiac CTRP9 (C1q tumor necrosis factor-related protein-9) expression, and exacerbates cardiac remodeling, suggesting that CTRP9 may be a novel therapeutic target against pathological remodeling in MI patients with obstructive sleep apnea-hypopnea syndrome.

Cardiac rupture (CR) is a complication of acute myocardial infarction (AMI) that is associated with a high mortality rate. This study aimed to identify the risk factors for CR in patients with AMI. Medline, Cochrane, EMBASE, and Google Scholar databases were searched for relevant literature published through September 16, 2018. Eligible studies included patients with AMI and compared factors between patients with and without CR. Sixteen studies were identified and included in the meta-analysis. Results revealed that female gender (pooled OR=2.72, 95% CI 2.04 to 3.63, p<0.001), older age (pooled difference in means=6.91, 95% CI 4.20 to 9.62, p<0.001), infarction at left anterior descending coronary artery (LAD) (pooled OR=1.85, 95% CI 1.03 to 3.32, p=0.039), and anterior wall infarction (pooled OR=1.87, 95% CI 1.30 to 2.68, p=0.001) were associated with increased risk of CR, whereas history of MI, smoking, and multivessel disease were associated with reduced risk of CR. Patients treated with primary percutaneous coronary intervention (PCI) had reduced risk of CR, while patients who had received any thrombolysis had increased risk of CR. In conclusion, results of systematic review and meta-analysis of existing literature suggest that risk factors for CR in patients with AMI include female gender, older age, new-onset MI, non-smoking status, LAD infarction, anterior wall infarction, and single-vessel disease. Furthermore, treatment with primary PCI may help reduce the risk for CR, while thrombolysis might increase the risk for CR., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: Cardiac rupture (CR) is a catastrophic complication of acute myocardial infarction (MI). At present, there are no effective pharmacological strategies for preventing post-MI rupture. Here we investigated the effect of trimetazidine (TMZ) on post-MI CR., Methods: MI models were induced by left coronary artery ligation in male C57BL/6 mice. Animals allocated to the rupture incidence were closely monitored for 7 days; autopsy was performed once animals were found dead to determine the reason of death. Heart function was detected by echocardiography. Oxidative stress markers and matrix metalloproteinases (MMPs) were analyzed by Western Blotting., Results: TMZ markedly reduced the post-MI CR incidence of mice. We found that the expression of metalloproteinase (MMP) -2 and MMP-9 in the TMZ-treated group was significantly lower than the saline-treated group. Further, TMZ markedly attenuated MI-induced oxidative stress. To investigate the mechanism of the effect of TMZ on CR, we pretreated H9c2 cells with H 2 O 2 and found that TMZ treatment markedly decreased H 2 O 2 -induced MMP-2 and MMP-9 expression. TMZ prevents CR through inhibition of oxidative stress, which is attributable to the down-regulation of MMP-2, MMP-9 expression., Conclusions: Our findings indicate that TMZ suppresses oxidative stress, inhibits MMP-2 and MMP-9 expression, and prevents CR in mice with MI., (© 2018 John Wiley & Sons Ltd.)

Background: Cell senescence is involved in the process of organ damage and repair; however, the underlying molecular mechanism needs to be further explored., Methods and Results: Senescence-related genes (ie, p21, p53, and ataxia telangiectasia mutated [ATM]) were shown to be elevated after myocardial infarction (MI) in both mouse and human hearts. Ten- to 12-week-old male wild-type littermates (ATM +/+ ) and ATM heterozygous mice (ATM +/- ) were subjected to MI. Cardiac echography showed that ATM haplodeficiency did not affect the survival rate but aggravated heart failure at day 28 post MI. Histologic analysis showed increased fibrosis in the noninfarct area of ATM +/- mice compared with that in ATM +/+ mice. Senescence-associated β-galactosidase staining showed that the number of senescent fibroblasts was decreased when ATM was haplodeficient both in vivo and in vitro. Costaining of α-smooth muscle actin with p53 or p19 showed fewer senescent myofibroblasts in ATM +/- mouse hearts. Moreover, angiogenesis was also examined using the endothelial markers CD31 both at early (day 7) and late stages (day 28) after MI, and ATM haplodeficiency reduced angiogenesis after MI. Finally, cardiac fibroblasts were isolated from infarcted mouse heart and the medium were tested for its capacity of endothelial tubing formation, revealing that ATM haplodeficiency led to lower vascular endothelial growth factor production from cardiac fibroblast and reduced capacity of endothelial tube formation in vitro., Conclusions: The present study shows that ATM haplodeficiency decreases fibroblast senescence and vascular endothelial growth factor production and impaired angiogenesis in response to MI, leading to accelerated heart failure., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Aim: Basic fibroblast growth factor (bFGF) increases the migration and viability of bone marrow mesenchymal stem cells (MSCs) in vitro. Retrograde coronary venous infusion can provide both increased regional bFGF concentrations and homogeneous cell dissemination. We determined whether retrograde delivery of bFGF enhances the potency of transplanted MSCs for cardiac repair in a canine infarct model., Methods and Results: Under hypoxic conditions, cellular migration was significantly increased in MSCs co-cultured with bFGF compared to vascular endothelial growth factor or insulin-like growth factor, and bFGF promoted MSCs differentiation into a cardiomyocyte phenotype. A canine infarct model was employed by coronary ligation. One week later, animals were subjected to retrograde infusion of combination bFGF (200ng/mL) and MSCs (1×10(8) cells) (n=5), MSCs (1×10(8) cells, n=5), bFGF (200ng/mL, n=5), or placebo (phosphate-buffered saline, n=3). Four weeks after infusion, only the bFGF+MSCs therapy exhibited significantly increased left ventricular ejection fraction (LVEF) by echocardiography (p<0.01 vs pre-infusion), and the treatment effect (delta LVEF) was greater in the bFGF+MSCs group compared to saline (7.43±1.51% versus -10.07±2.94%; p<0.001). Morphologic analysis revealed an increased infarct wall thickness in the bFGF+MSCs group compared to all others (p<0.05), accompanied by increased vascular density and reduced apoptosis. Immunofluorescence demonstrated increased cell engraftment and enhanced vascular differentiation in the bFGF+MSCs group compared to MSCs alone (p<0.05)., Conclusions: Retrograde coronary venous bFGF infusion augments engraftment and differentiation capacity of transplanted MSCs, recovering cardiac function and preventing adverse remodeling. This novel combined treatment and delivery method is a promising strategy for cardiac repair after ischemic injury.

Background: Mesenchymal stem cells (MSCs) have been recently demonstrated as a promising stem cell type to rescue damaged myocardium after acute infarction. One of the most important mechanisms underlying their therapeutic effects is the secretion of paracrine factors. However, the expression profile of paracrine factors of MSCs in infarcted hearts, especially at single cell level, is poorly defined., Methods and Results: We aimed to depict the transcriptional profile of paracrine factors secreted by MSCs in vivo, with particular interest in the comparison between normal and infarcted hearts. Bone marrow mesenchymal stem cells were isolated and injected into mice hearts immediately after infarction surgery. Bioluminescence imaging (BLI) indicated a proportion of cells still alive even up to 10 days post surgery. Paralleled with survived cells, cardiac function was significantly improved after MSC injection compared to that in PBS-injected mice, indicated by MRI and histology. Despite increased number of vessels in MSC-injected hearts, endothelial cells and cardiomyocytes transdifferentiation were not observed in infarcted hearts 5 days after infarction. Furthermore, laser capture microdissection (LCM) followed by high through-put real time PCR was employed in our study, uncovering that the injected MSCs, compared to local cardiomyocytes, displayed elevated levels of secreted factors. To further investigate the regulation of those factors, we performed single cell analysis to dissect the gene expression profile of MSCs at single cell level in infarcted and normal hearts, respectively. Consistent with the in vivo observation, a similar regulation pattern of those factors was detected in cultured MSCs under hypoxia., Conclusions: Our study, for the first time, elucidated gene expression profiles, as well as regulation of paracrine factors, of MSCs at single cell level in vivo, indicating that paracrine factors from MSCs account for the improvement of cardiac function after infarction.

Aims This study sought to evaluate the association of coronary angiography-derived index of microcirculatory resistance (angio-IMR) measured after primary percutaneous coronary intervention (PPCI) with the evolution of infarct pathology during 3-month follow-up after ST-segment-elevation myocardial infarction (STEMI). Methods and Results Patients with STEMI undergoing PPCI were prospectively enrolled between October 2019 and August 2021. Angio-IMR was calculated using computational flow and pressure simulation immediately after PPCI. Cardiac magnetic resonance (CMR) imaging was performed at a median of 3.6 days and 3 months. A total of 286 STEMI patients (mean age 57.8 years, 84.3% men) with both angio-IMR and CMR at baseline were included. High angio-IMR (>40 U) occurred in 84 patients (29.4%) patients. Patients with angio-IMR >40 U had a higher prevalence and extent of MVO. An angio-IMR >40 U was a multivariable predictor of infarct size with a three-fold higher risk of final infarct size >25% (adjusted OR 3.00, 95% CI 1.23–7.32, P = 0.016). Post-procedure angio-IMR >40 U significantly predicted presence (adjusted OR 5.52, 95% CI 1.65–18.51, P = 0.006) and extent (beta coefficient 0.27, 95% CI 0.01–0.53, P = 0.041) of myocardial iron at follow-up. Compared with patients with angio-IMR ≤40 U, those with angio-IMR >40 U had less regression of infarct size and less resolution of myocardial iron at follow-up. Conclusions Angio-IMR immediately post-PPCI showed a significant association with the extent and evolution of infarct pathology. An angio-IMR >40 U indicated extensive microvascular damage with less regression of infarct size and more persistent iron at follow-up. [ABSTRACT FROM AUTHOR]

Background and objective: The impact of obstructive sleep apnoea (OSA) in the setting of acute ST‐segment elevation myocardial infarction (STEMI) is complex and divergent. This study aimed to investigate the association between OSA and coronary collateral vessel (CCV) development in patients with STEMI. Methods: The present study prospectively screened 282 STEMI patients with an overnight sleep study. OSA was defined as apnoea–hypopnoea index (AHI) ≥15 events/h. The coronary angiograms were used for the assessment of Rentrop grades representing CCVs. Results: Among 119 patients enrolled, 60 patients had OSA (50.4%). The prevalence of CCV development (Rentrop grade ≥ 2) was significantly higher in OSA group than in the non‐OSA group (43.3% vs. 5.1%, p < 0.001). There was a parallel increase in the Rentrop grades associated with OSA severity and worsening of hypoxaemia indicators (minimum arterial oxygen saturation [SaO2], mean SaO2 and time with SaO2 below 90%). After adjustment for clinical and angiographic characteristics, and pre‐procedure medications that might interact with OSA, AHI as a continuous variable (OR 1.11, 95% CI 1.08–1.21, p < 0.001) and the presence of OSA (OR 11.41, 95% CI 2.70–48.15, p = 0.001) were both associated with dramatically higher incidence of CCV development. Conclusion: Our study demonstrated that the presence of OSA might augment CCV development in STEMI patients. The potential protective effects and mechanisms of OSA in the acute setting of STEMI should be further investigated in larger studies. [ABSTRACT FROM AUTHOR]

Chronic intermittent hypoxia (CIH) is the main feature of obstructive sleep apnea (OSA) and is known to exaggerate cardiac remodeling after myocardial infarction (MI). However, the specific contribution of CIH to overall OSA-induced pathological complications and the transcriptomic mechanisms underlying CIH-exaggerated post-MI remodeling remains unclear. In this study, we used RNA-sequencing to construct the expression profiles of cardiac mRNAs, microRNAs, and long non-coding RNAs (lncRNA) in four groups of C57BL/6J mice (Sham, CIH, MI, MI + CIH) to evaluate how CIH regulates cardiac remodeling after MI. Compared with the other three groups, the MI + CIH group exhibited 345 lncRNAs, 35 microRNAs, and 5,220 differentially expressed mRNAs. Further analysis showed that CIH led to significant changes in Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the differentially expressed mRNAs. Co-expression network analysis identified two core lncRNAs (Mirt1 and AC125351.1) and two core microRNAs (miR-466i-5p and miR-574-5p) during the development of CIH-exaggerated post-MI remodeling, and they were verified by quantitative real-time PCR (qRT-PCR). LncRNA-mRNA correlation analysis further showed that lncRNA Mirt1 was positively correlated with Apbb1ip and Lcp2. In addition, microRNA-mRNA correlation analysis showed that microRNA miR-466i-5p was positively correlated with Snai2, Cdc27, and Ngfr. Furthermore, combining with lncRNA-mRNA and miRNA-mRNA networks, 44 RNAs were identified in the competitive endogenous RNA (ceRNA) network. Mirt1 acts as a ceRNA to bind to miR-466i-5p to further regulate the expression levels of the target gene, thereby aggravating cardiac remodeling after MI. In conclusion, our study provides a systematic perspective on the potential functions of mRNAs, microRNAs, and lncRNAs in CIH-exaggerated post-MI cardiac remodeling. Our data suggest that lncRNA Mirt1 may be the most critical regulator of MI aggravated by CIH. [ABSTRACT FROM AUTHOR]

Eicosanoids play important roles in the cardiovascular system. The metabolic disorders involving some eicosanoids in the pathophysiologic process include myocardial infarction and myocardial ischaemia–reperfusion injury. Percutaneous coronary intervention (PCI) is often the first‐choice strategy for acute ST‐segment elevation myocardial infarction (STEMI) according to current guidelines. This study aimed to investigate the dynamic eicosanoid metabolic profile in STEMI patients after PCI. The eicosanoid profiles in plasma of 20 patients at seven times (30 minutes before surgery; 6, 12, 24, and 72 hours after surgery; 1 day before discharge; and 28 days after surgery) were studied by using metabolomics. Levels of PGE2, PGD2, and TXA2 were decreased significantly and EETs contents were increased significantly at 6 hours after PCI. EETs were hydrolysed to DHETs within a short time after surgery (12–72 hours). 20‐HETE content was significantly increased. In samples taken at the time of discharge and at follow‐up after discharge, LTB4 level continued to increase. This work suggests that change in content of some functional eicosanoids may be involved in cardiac injury and repair after PCI in a synergistic manner. [ABSTRACT FROM AUTHOR]

Ventricular free wall rupture (FWR) is a catastrophic complication after acute myocardial infarction (AMI). However, patients with FWR die of cardiac tamponade secondary to intrapericardial hemorrhage that can be treated if properly diagnosed. Unfortunately, FWR was still not diagnosed and classified quickly and accurately. The aim of this study was to present a new clinical classification for FWR. Seventy-eight patients with FWR after STEMI were enrolled in the study. We classified FWR, according to clinical situations after onset, into the cardiac arrest type, unstable type, and stable type. The cardiac arrest type was the most common type, accounting for about 83.3%. 90.8% of patients of this type were complicated with electromechanical dissociation at the time of FWR onset, and 100% of patients of this type died in the hospital. The unstable type was characterized by sudden clinical condition changes with moderate/massive pericardial effusion. In this study, 9.0% of patients were diagnosed as the unstable type. The average time from onset to death was 4.5 hours. This period was the "golden time" to rescue such patients. The stable types usually have stable hemodynamics, but may worsen, requiring rigorous detection of pericardial effusion and vital signs. In this study, 7.7% of patients were diagnosed as the stable type, and 83.5% of them survived in the hospital. The new clinical classification provides a basis for clinical diagnosis and treatment of FWR. The clinical application of the new classification is expected to improve the prognosis of FWR patients. [ABSTRACT FROM AUTHOR]

Background. Obstructive sleep apnea (OSA) is closely related to the incidence and progression of coronary artery disease (CAD), and the mechanisms linking OSA and CAD are multifactorial. C1q/TNF-related protein-9 (CTRP9) is a novel adipokine that protects the heart against ischemic injury and ameliorates cardiac remodeling. We aimed to ascertain the clinical relevance of CTRP9 with OSA prevalence in patients with CAD. Methods. From August 2016 to March 2019, consecutive eligible patients with CAD (n = 154 ; angina pectoris, n = 88 ; acute myocardial infarction [AMI], n = 66) underwent cardiorespiratory polygraphy. OSA was defined as an apnea-hypopnea index (AHI) ≥15 events·h−1. Plasma CTRP9 concentrations were measured by ELISA method. Results. Moderate/severe OSA was present in 89 patients (57.8%). CTRP9 levels were significantly decreased in the moderate/severe OSA group than in the no/mild OSA group (4.7 [4.1-5.2] ng/mL vs. 4.9 [4.4-6.0] ng/mL, P = 0.003). The difference between groups was only observed in patients with AMI (3.0 [2.3-4.9] vs. 4.5 [3.2-7.9], P = 0.009). Correlation analysis showed that CTRP9 levels were negatively correlated with AHI (r = − 0.238 , P = 0.003) and oxygen desaturation index (r = − 0.234 , P = 0.004) and positively correlated with left ventricular ejection fraction (r = 0.251 , P = 0.004) in all subjects. Multivariate analysis showed that male gender (OR 3.099, 95% CI 1.029-9.330, P = 0.044), BMI (OR 1.148, 95% CI 1.040-1.268, P = 0.006), and CTRP9 levels (OR 0.726, 95% CI 0.592-0.890, P = 0.002) were independently associated with the prevalence of moderate/severe OSA. Conclusions. Plasma CTRP9 levels were independently related to the prevalence of moderate/severe OSA in patients with CAD, suggesting that CTRP9 might play a role in the pathogenesis of CAD exacerbated by OSA. [ABSTRACT FROM AUTHOR]

In patients with acute coronary syndrome (ACS), treatment using ticagrelor demonstrated significant ischemic benefits over clopidogrel; however, it was associated with increased bleeding complications leading to frequent de-escalation to clopidogrel. The objective of the present study was to investigate the efficacy and safety of de-escalation in early and late phase after percutaneous coronary intervention (PCI). We performed a retrospective study of 4678 ACS patients from March 2016 to April 2017 who initially received ticagrelor then de-escalated to clopidogrel and categorized them into Group 1: early phase (1–30 days) and Group 2: late phase (>30 days–1 year) switching groups. The primary efficacy endpoints included cardiovascular death, definite/probable stent thrombosis, myocardial infarction, unplanned revascularization, and stroke. The safety endpoint was Bleeding Academic Research Consortium classification 3 or 5 bleeding events within 1 year after PCI. The incidence of switching occurred in 1019 patients; 380 (37.3%) in Group 1 (median 14 days, interquartile range 4–30 days) versus 639 (62.7%) in Group 2 (median 180 days, interquartile range 90–270 days). The ischemic endpoints occurred in 53 (13.9%) patients in Group 1 versus 35 (5.4%) in Group 2 (HR 1.93,95%CI 1.22–3.08, p <.0001). There were no significant differences of major bleeding events (HR 0.91; 95%CI, 0.58–1.43, p =.90) seen between the groups. The main cause for switching between the two groups was due to BARC 1 or 2 bleeding types. Early de-escalation from ticagrelor to clopidogrel during the initial 30 days after ACS was associated with higher risk of ischemic events when compared with switching beyond 30 days. [ABSTRACT FROM AUTHOR]

Background. The present study aimed to evaluate the prevalence and prognosis of residual lipid abnormalities in statin-treated acute coronary syndrome (ACS) patients after percutaneous coronary intervention (PCI). Subjects and Methods. A total of 3,047 ACS patients who underwent PCI and received statin therapy were included. Plasma concentrations of LDL-C, HDL-C, and TG were measured. For the follow-up study, major adverse cardiovascular cerebrovascular events (MACCE; including total death, cardiovascular death, myocardial infarction, and revascularization) were documented. Results. A total of 93.14% of all individuals were followed up for 18.1 months (range, 0–29.3 months). Of all 3,047 patients, those with a suboptimal goal were 67.75%, 85.85%, and 33.64% for LDL-C, HDL-C, and TG levels, respectively. Multiple Cox regression analysis revealed there were significant increases in cumulative MACCE of 41% (HR = 1.41, 95% CI [1.09–1.82], p=0.008), and revascularization of 48% (HR = 1.48, 95% CI [1.10–1.99], p=0.01) in low HDL-C patients with ACS after PCI, but not the high TG group at the end of study. Conclusions. Our results showed there is high rate of dyslipidemia in Chinese ACS patients after PCI. Importantly, low HDL-C but not high TG levels are associated with higher MACCE and revascularization rates in ACS patients after PCI. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of data from large prospective study evaluating the prognostic significance of the residual Synergy between percutaneous intervention with Taxus drug-eluting stents and cardiac surgery (SYNTAX) Score (rSS) in patients with obstructive sleep apnea (OSA) and Acute Coronary Syndrome (ACS).Methods: ACS patients who undergoing percutaneous coronary angiography and completing a sleep study during hospitalization were prospectively enrolled. The baseline SYNTAX Score (bSS) and the rSS after revascularization were assessed. Complete revascularization (CR, rSS = 0) and incomplete revascularization (ICR, rSS > 0) were categorized. OSA (apnea hypopnea index, AHI ≥ 15) and non-OSA (AHI < 15) were grouped according to AHI. The primary endpoint of the study was major adverse cardiovascular and cerebrovascular events (MACCEs), defined as a composite of cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for UAP or heart failure.Results: Overall, 752 patients were prospectively enrolled. At a median follow-up of 1 year, the incidence of MACCEs was significantly higher in the OSA than in the non-OSA group (hazard ratio [HR]:1.68; 95% confidence interval [CI]:1.04-2.72; P = .034). ICR was associated with a higher risk of MACCEs in the non-OSA group (HR:3.34;95% CI:1.0-11.12; P = .05). The OSA patients with ICR had a 5.1 higher risk of MACCEs compared with the non-OSA with CR group, P = .007. The OSA patients with CR had a similar 1-year MACCEs as all the non-OSA patients (HR:1.10; 95% CI:0.515-2.349; P = 0.806).Conclusions: ACS patients with OSA and ICR have a high rate of MACCEs at 1 year. In contrast, the prognosis of ACS patients with OSA but CR is favorable and similar to patients without OSA. Adequate level of revascularization is recommended to optimize clinical outcomes in ACS patients with OSA.Trial Registration: Clinicaltrials.gov identifier NCT03362385. [ABSTRACT FROM AUTHOR]

Background: In-hospital cardiac arrest (IHCA) is one of the most deleterious complications of ST-segment elevation myocardial infarction (STEMI).Objectives: We systematically analyzed the clinical characteristics of STEMI patients with IHCA, as well as predictors and treatments associated with risk of IHCA, using a nationwide database.Methods: In the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project (2014-2019), we stratified patients presenting with STEMI within 24 hours after symptom onset according to IHCA or no IHCA during the index hospitalization. We analyzed patients' clinical characteristics, mortality, and independent correlates of IHCA.Results: Of 40,670 STEMI patients, 2.2% (95% CI: 2.1%-2.4%) experienced IHCA. Among IHCA patients, the in-hospital mortality was 53.0% (95% CI: 49.7%-56.3%). IHCA represents 55.0% (95% CI: 51.6%-58.4%) of inpatient deaths. Age ≥75 years, female, nonsmoker, prior diabetes mellitus, prior renal failure, out-of-hospital cardiac arrest, heart rate >100 beats/min, systolic blood pressure <90 mm Hg, and Killip IV were identified as predictors of IHCA. IHCA patients were less likely to receive β-blockers and ticagrelor during the first 24 hours after first medical contact and were less likely to undergo primary percutaneous coronary intervention. After adjustment, primary percutaneous coronary intervention (adjusted HR: 0.82; 95% CI: 0.71-0.95), β-blockers (adjusted HR: 0.63; 95% CI: 0.47-0.86), and ticagrelor (adjusted HR: 0.57; 95% CI: 0.42-0.76) were associated with a reduced risk of IHCA.Conclusions: IHCA is rare in STEMI but is associated with high mortality. Multiple modifiable and unmodifiable factors are associated with its occurrence, suggesting that early intervention and rational drug treatment may improve its prognosis. (CCC Project- Acute Coronary Syndrome; NCT02306616). [ABSTRACT FROM AUTHOR]

Purpose: Free wall rupture (FWR) is a lethal complication after acute myocardial infarction; however, the un-derlying mechanisms of FWR are unclear. This study analyzes the relationship between neutrophil counts and FWR following ST-elevation myocardial infarction (STEMI).Methods: The case group was STEMI patients with FWR and the control group was STEMI patients without FWR (case-control ratio was 1:4). The demographic data, clinical manifestation and laboratory test results were retrospectively collected and analyzed.Results: Of a total of 6,712 consecutive STEMI patients, 78 patients (1.2%) had FWR. Compared with STEMI patients, patients with FWR were older and more likely to be female with an anterior infarct. White blood cell (WBC) counts were significantly higher in the FWR group. Moreover, we found that the elevated neutrophil counts mainly accounted for the elevated WBC counts. There was also a correlation between the age and neu-trophil counts (P=0.0109); as patient age increased, neutrophil counts decreased (P=0.0387). We also found no correlation between neutrophil counts and the time between myocardial infarction attack and FWR; however, when dividing these patients into FWR ≤48 h after admission to hospital for STEMI and FWR >48 h, there was a significant difference in neutrophil counts (P=0.0196). Furthermore, the results of logistic regression analy-sis showed that increased neutrophil was an independent risk factor for FWR (odds ratio: 2.404, confidence interval: 1.055-5.477).Conclusion: Elevated neutrophil counts were found to be the main cause of differences in WBC counts be-tween FWR and STEMI. Elevated neutrophil was an independent risk factor for FWR. This study provided clues for further research and development of therapeutics for the prevention of FWR. [ABSTRACT FROM AUTHOR]

We aimed to explored the association between the use of optimal medical therapy (OMT) in patients with myocardial infarction (AMI) and diabetes mellitus (DM) and clinical outcomes. Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome (BleeMACS) is an international registry that enrolled participants with acute coronary syndrome followed up for at least 1 year across 15 centers from 2003 to 2014. Baseline characteristics and endpoints were analyzed. Among 3095 (23.2%) patients with AMI and DM, 1898 (61.3%) received OMT at hospital discharge. OMT was associated with significantly reduced mortality (4.3% vs. 10.8%, p < 0.001), re-AMI (4.4% vs. 8.1%, p < 0.001), and composite endpoint of death/re-AMI (8.0% vs. 17.6%, p < 0.001). No difference was observed among regions. Propensity score matching confirmed that OMT significantly associated with lower mortality. After adjusting for confounding variables, OMT, drug-eluting stents, and complete revascularization were independent protective factors of 1-year mortality, whereas left ventricular ejection fraction and age were risk factors. Guideline-recommended OMT was prescribed at suboptimal frequencies with geographic variations in this worldwide cohort. OMT can improve long-term clinical outcomes in patients with DM and AMI. Clinical Trial Registration: NCT02466854 June 9, 2015. [ABSTRACT FROM AUTHOR]

Background: Whether the rate of drug elution and polymer absorption affects clinical outcomes of biodegradable polymer-based drug-eluting stents (DES) is unknown. The widely used polylactide polymer-based Excel stent (JW Medical, Weihai, China) elutes sirolimus within 180 days, and the polylactide polymer is completely absorbed within 6 to 9 months. In contrast, the poly-lactide-co-glycolide polymer-based BuMA stent (Sino Medical, Tianjin, China) elutes sirolimus within 30 days, and the poly-lactide-co-glycolide polymer is completely absorbed within 3 months. Thus, both metallic DES elute sirolimus, isolating major differences to the polymer and elution kinetics.Objectives: The goal of this study was to compare the safety and effectiveness between the BuMA sirolimus-eluting stent (SES) and Excel SES in an "all-comers" population.Methods: PANDA III was a multicenter trial with few exclusion criteria, powered for sequential noninferiority and superiority testing. The primary endpoint was 1-year target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization.Results: Between December 2013 and August 2014, 2,348 patients were randomly assigned to treatment with BuMA (n = 1,174) or Excel SES (n = 1,174). The 1-year primary endpoint of TLF occurred in 6.4% of patients in each group (difference: 0.06%; 95% confidence interval: 1.93% to 2.04%; pnoninferiority = 0.0003; psuperiority = 0.95). There were no significant between-group differences in any of the secondary endpoints other than the incidence of definite/probable stent thrombosis, which occurred less frequently with the BuMA stent (0.5% vs. 1.3%; log-rank p = 0.048).Conclusions: The BuMA SES was demonstrated to be noninferior to the Excel SES for 1-year TLF, with a lower incidence of stent thrombosis. (Comparison of BuMA eG Based BioDegradable Polymer Stent With EXCEL Biodegradable Polymer Sirolimus-eluting Stent in "Real-World" Practice [PANDA-III]; NCT02017275). [ABSTRACT FROM AUTHOR]