Publications by authors named "Junbo Ge"

799 Publications

Integrated Analysis of Angiogenesis Related lncRNA-miRNA-mRNA in Patients With Coronary Chronic Total Occlusion Disease.

Front Genet 2022 25;13:855549. Epub 2022 Apr 25.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.

Coronary chronic total occlusion (CTO) disease is common and its specific characteristic is collateral formation. The Integrated analysis of angiogenesis related lncRNA-miRNA-mRNA network remains unclear and might provide target for future studies. A total of five coronary artery disease (control group) and five CTO (CTO group) patients were selected for deep RNA and miRNA sequencing. The expression profiles of lncRNAs, mRNAs circRNA and miRNAs were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were then performed. The expression of a 14q32 miRNA gene cluster, including miRNA-494, miRNA-495 and miRNA-329, were selected to be determined in another larger patient cohort. Analysis of the lncRNA-miRNA495-mRNA network was constructed to find potential targets for future studies. A total of 871 lncRNAs, 1,080 mRNAs, 138 circRNAs and 56 miRNAs were determined as differentially expressed (DE) in CTO patients compared with control patients. GO and KEGG analyses revealed that the top terms included MAPK signaling pathway, HIF-1 signaling pathway, EGFR tyrosine kinase inhibitor resistance, embryonic organ development, wound healing, MAPK signaling pathway and JAK-STAT signaling pathway, which are related to angiogenesis. The expression of miRNA-494, miRNA-495 and miRNA-329 were all significantly down-regulated in CTO patients and they were confirmed to be down-regulated in another cohort of 68 patients. Then we divided the CTO patients into two groups according to CC grade (poor CC group, CC = 0 or one; good CC group, CC = 2). MiRNA-494, miRNA-495 and miRNA-329 were found to be down-regulated in good CC group compared with poor CC group. Analysis of the lncRNA-miRNA495-mRNA network showed 3 DE lncRNA sponges (NONHSAG008675, NONHSAG020957 and NONHSAG010989), 4 DE lncRNA targets (NONHSAT079547.2, NONHSAT081776.2, NONHSAT148555.1 and NONHSAT150928.1) and 2 DE mRNA targets (RAD54L2 and ZC3H4) of miRNA495. This study revealed that the lncRNA-miRNA-mRNA network might play a critical role in angiogenesis in CTO patients.
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http://dx.doi.org/10.3389/fgene.2022.855549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081538PMC
April 2022

Targeted neutrophil-mimetic liposomes promote cardiac repair by adsorbing proinflammatory cytokines and regulating the immune microenvironment.

J Nanobiotechnology 2022 May 7;20(1):218. Epub 2022 May 7.

Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.

Acute myocardial infarction (MI) induces a sterile inflammatory response that may result in poor cardiac remodeling and dysfunction. Despite the progress in anti-cytokine biologics, anti-inflammation therapy of MI remains unsatisfactory, due largely to the lack of targeting and the complexity of cytokine interactions. Based on the nature of inflammatory chemotaxis and the cytokine-binding properties of neutrophils, we fabricated biomimetic nanoparticles for targeted and broad-spectrum anti-inflammation therapy of MI. By fusing neutrophil membranes with conventional liposomes, we fabricated biomimetic liposomes (Neu-LPs) that inherited the surface antigens of the source cells, making them ideal decoys of neutrophil-targeted biological molecules. Based on their abundant chemokine and cytokine membrane receptors, Neu-LPs targeted infarcted hearts, neutralized proinflammatory cytokines, and thus suppressed intense inflammation and regulated the immune microenvironment. Consequently, Neu-LPs showed significant therapeutic efficacy by providing cardiac protection and promoting angiogenesis in a mouse model of myocardial ischemia-reperfusion. Therefore, Neu-LPs have high clinical translation potential and could be developed as an anti-inflammatory agent to remove broad-spectrum inflammatory cytokines during MI and other neutrophil-involved diseases.
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http://dx.doi.org/10.1186/s12951-022-01433-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9077972PMC
May 2022

A Randomized Multicenter Trial to Evaluate Early Invasive Strategy for Patients with Acute ST-segment Elevation Myocardial Infarction Presenting 24-48 Hours from Symptom Onset: protocol of the RESCUE-MI study.

Am Heart J 2022 May 4. Epub 2022 May 4.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, Shanghai, China. Electronic address:

Background: For ST-segment elevation myocardial infarction (STEMI) patients presenting 24-48 hours from symptom onset, whether early invasive strategy should be performed still remains controversial.

Methods: This is a prospective, open-label, multicenter, investigator initiated, randomised controlled trial (NCT04962178) to evaluate the efficacy of early invasive strategy for STEMI patients within 24-48h of symptom onset. A total of 366 patients will be included from 10 hospitals in mainland China. They will be randomly (1:1) divided into 2 groups: the early invasive strategy group (primary percutaneous coronary intervention, PPCI) and conservative strategy group (optimal medical therapy with primary PCI not performed).All patients will be followed for 1 month. The primary endpoint is myocardial infarction size on cardiac magnetic resonance (CMR). The secondary endpoints are as follows: 1, major adverse cardiovascular events (MACE), which is defined as a composite of cardiac death, recurrent myocardial infarction, ischemic driven target vessel revascularization and stroke; 2, other CMR endpoints, including microvascular obstruction, intramyocardial hemorrhage, myocardial area at risk, left ventricular ejection fraction, left ventricular end diastolic volume and left ventricular end systolic volume.

Discussion: This study is designed to evaluate the efficacy of early invasive strategy for STEMI patients within 24-48h of symptom onset and will add more evidence for clinical practice.

Trial Registration: ClinicalTrials.gov Identifier: NCT04962178. Registered on 14July 2021.
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http://dx.doi.org/10.1016/j.ahj.2022.05.002DOI Listing
May 2022

Twin peaks of in-hospital mortality among patients with STEMI across five phases of COVID-19 outbreak in China: a nation-wide study.

Sci China Life Sci 2022 May 5. Epub 2022 May 5.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 518038, China.

Lockdown and re-opening may become cyclical due to the recurrent waves of the COVID-19 epidemic. Few studies have examined temporal trends and determinants of in-hospital mortality among patients with ST-segment elevation myocardial infarction (STEMI), a life-threatening condition that requires emergency medical care. Using nation-wide data before, during and after the Wuhan lockdown, we aimed to depict temporal patterns and major determinants of STEMI in-hospital mortality in China across five time periods of the COVID-19 epidemic. We analyzed the data of 283,661 STEMI patients who were admitted to 4,487 chest-pain-centers across China, from January 1, 2019 to May 31, 2020. Compared with the period before the lockdown, STEMI in-hospital mortality increased by 25% (OR 1.25, 95%CI 1.16-1.34) during Early Lockdown, by 12% (OR 1.12, 95%CI 1.03-1.22) during Later Lockdown, by 35% (OR 1.35, 95%CI 1.21-1.50) during Early Lift, and returned to pre-COVID risk (OR 1.04, 95%CI 0.95-1.14) during Later Lift. For each time-period, we observed a clear mortality gradient by timing and types of revascularization procedure. In conclusion, the COVID-19 epidemic had a significant adverse impact on STEMI in-hospital mortality, with bimodal peaks during early lockdown and early lift periods and clear mortality gradients by timing and types of revascularization procedure, independent of the time periods.
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http://dx.doi.org/10.1007/s11427-021-2046-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9077341PMC
May 2022

Heart failure with preserved ejection fraction (HFpEF) in type 2 diabetes mellitus: from pathophysiology to therapeutics.

J Mol Cell Biol 2022 May 3. Epub 2022 May 3.

Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Type 2 diabetes mellitus (T2D) is a devastating metabolic abnormality featured by insulin resistance, hyperglycemia, and hyperlipidemia. T2D provokes unique metabolic changes and compromises cardiovascular geometry and function. Meanwhile, T2D increases the overall risk for heart failure (HF) and acts independent of classical risk factors including coronary artery disease, hypertension, and valvular heart diseases. The incidence of HF is extremely high in patients with T2D and is manifested as heart failure with preserved, reduced, and midrange ejection fraction (HFpEF, HFrEF, and HFmrEF, respectively), all of which significantly worsen the prognosis for T2D. HFpEF is seen in approximately half of HF cases and is defined as a heterogenous syndrome with discrete phenotypes, in particularly in close association with metabolic syndrome. Nonetheless, management of HFpEF in T2D remains unclear, largely due to the poorly defined pathophysiology behind HFpEF. Here, in this review, we will summarize findings from multiple preclinical and clinical studies as well as recent clinical trials, mainly focusing on the pathophysiology, potential mechanisms, and therapies of HFpEF in T2D.
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http://dx.doi.org/10.1093/jmcb/mjac028DOI Listing
May 2022

Evaluation of electrophysiological characteristics and ventricular synchrony: An intrapatient-controlled study during His-Purkinje conduction system pacing versus right ventricular pacing.

Clin Cardiol 2022 May 3. Epub 2022 May 3.

Department of Cardiology, National Clinical Research Center for Interventional Medicine, Shanghai Clinical Research Center for Interventional Medicine, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital of Fudan University, Shanghai, China.

Objectives To Background: To compare electromechanical ventricular synchrony when pacing from different sites, including right ventricular apex pacing (RVAP), right ventricular septum pacing (RVSP), His bundle pacing (HBP), left bundle branch pacing (LBBP), and RVSP during unipolar pacing from the ring electrode of LBBP lead (RVSP ) in each patient and evaluate the correlations between electrophysiological characteristics and ventricular synchrony.

Methods: Twenty patients with complete atrioventricular block indicated for dual-chamber pacemaker implantation were included in the study. Unipolar pacing at different sites, including RVAP, RVSP, HBP, LBBP, and RVSP , was successively performed in each patient. The pacing characteristics and echocardiogram parameters were collected and compared among intrinsic rhythm and pacing at different sites.

Results: Similar to HBP (114.84 ± 18.67 ms), narrower paced QRSd was found in LBBP (116.15 ± 11.60 ms) as compared to RVSP (135.11 ± 13.68 ms), RVSP (141.65 ± 14.26 ms), and RVAP (160.15 ± 19.35 ms) (p < .001). LBBP showed comparable pacing parameters to RVAP or RVSP and was significantly better than HBP, with maintained cardiac function. TS-12-SD was significantly improved in LBBP (41.80 ± 20.97 ms) than RVAP (69.70 ± 32.42 ms, p = .003) and RVSP (63.30.56 ± 32.53 ms, p = .018) but similar to HBP (51.50 ± 25.67 ms, p = .283) or RVSP (57.80 ± 25.65 ms, p = .198). Among these pacing strategies, negative values of interventricular mechanical delay (IVMD) were only identified in LBBP (-19.25 ± 18.43 ms), significantly different from RVAP (35.00 ± 30.72 ms), RVSP (22.85 ± 22.05 ms), HBP (5.20 ± 18.64 ms), and RVSP (16.00 ± 26.76 ms (all p < .05). Using Pearson's analysis, Sti-LVAT was positively correlated with QRS duration, IVMD, TS-12-SD, LVEDV, and LVESV, while a negative relationship could be observed for left ventricular ejection fraction.

Conclusions: His-Purkinje conduction system pacing (HPCSP) achieved better electrical and mechanical synchrony than conventional RV pacing. For interventricular synchrony, only LBBP initiated earlier LV activation than RV, in accordance with the right bundle branch block (RBBB) pattern of paced QRS during LBBP. Sti-LVAT might be a good parameter correlating with LV systolic function and mechanical synchrony.
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http://dx.doi.org/10.1002/clc.23837DOI Listing
May 2022

Current of Injury is an Indicator of Lead Depth and Performance during Left Bundle Branch Pacing Lead Implantation.

Heart Rhythm 2022 Apr 29. Epub 2022 Apr 29.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, Shanghai, China.

Background: Monitoring of lead depth is crucial to achieve left bundle branch pacing (LBBP) with a low capture threshold and avoid septal perforation, but lacks informative approach.

Objective: We aimed to prospectively assess the predictive value of current of injury on the occurrence of inadequate LBB capture threshold and acute septal perforation.

Methods: Consecutive patients who received LBBP were enrolled. ST-segment elevation ≥ 25% of intrinsic R wave amplitude on the unipolar intracardiac electrogram was defined as a sign of distinct current of injury. A LBB capture threshold < 1.5 V / 0.5 ms was considered acceptable.

Results: LBBP was attempted 513 times in 212 patients. LBB capture threshold was more likely to improve to an acceptable level after 10min in cases with initial (33/47 vs. 0/8, with vs. without) and residual (29/33 vs. 4/14, with vs. without) current of injury on the tip electrode (p < 0.0001). Lead perforation during the procedure has occurred in 11 cases who had no current of injury on the tip electrode. The ratio of current of injury on the tip electrode to that on the ring electrode was correlated to the lead depth determined by sheath angiography (Spearman's Correlation Coefficient = -0.624, p < 0.0001), and microperforation is highly possible when the ratio is decreased to <1 (sensitivity: 100% and specificity: 96.6%).

Conclusions: Current of injury is a useful tool in forecasting LBBP lead depth and septal perforation, and it could facilitate the decision-making process when the initial LBB capture threshold is undesirable.
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http://dx.doi.org/10.1016/j.hrthm.2022.04.027DOI Listing
April 2022

Association Between Early Oral β-Blocker Therapy and In-Hospital Outcomes in Patients With ST-Elevation Myocardial Infarction With Mild-Moderate Heart Failure: Findings From the CCC-ACS Project.

Front Cardiovasc Med 2022 15;9:828614. Epub 2022 Apr 15.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.

Background: There are limited data available on the impact of early (within 24 h of admission) β-blocker therapy on in-hospital outcomes of patients with ST-elevation myocardial infarction (STEMI) and mild-moderate acute heart failure. This study aimed to explore the association between early oral β-blocker therapy and in-hospital outcomes.

Methods: Inpatients with STEMI and Killip class II or III heart failure from the Improving Care for Cardiovascular Disease in China project ( = 10,239) were enrolled. The primary outcome was a combined endpoint composed of in-hospital all-cause mortality, successful cardiopulmonary resuscitation after cardiac arrest, and cardiogenic shock. Inverse-probability-of-treatment weighting, multivariate Cox regression, and propensity score matching were performed.

Results: Early oral β-blocker therapy was administered to 56.5% of patients. The incidence of the combined endpoint events was significantly lower in patients with early therapy than in those without (2.7 vs. 5.1%, < 0.001). Inverse-probability-of-treatment weighting analysis demonstrated that early β-blocker therapy was associated with a low risk of combined endpoint events (HR = 0.641, 95% CI: 0.486-0.844, = 0.002). Similar results were shown in multivariate Cox regression (HR = 0.665, 95% CI: 0.496-0.894, = 0.007) and propensity score matching (HR = 0.633, 95% CI: 0.453-0.884, = 0.007) analyses. A dose-response trend between the first-day β-blocker dosages and adverse outcomes was observed in a subset of participants with available data. No factor could modify the association of early treatment and the primary outcomes among the subgroups analyses.

Conclusion: Based on nationwide Chinese data, early oral β-blocker therapy is independently associated with a lower risk of poor in-hospital outcome in patients with STEMI and Killip class II or III heart failure.
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http://dx.doi.org/10.3389/fcvm.2022.828614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9051227PMC
April 2022

Different approaches for ablation of RVOT-type arrhythmia: comparison between the choice of RVOT and pulmonary sinus cusp region for the first ablation attempt.

J Interv Card Electrophysiol 2022 Apr 28. Epub 2022 Apr 28.

Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, No. 180, Feng-Lin Road, Shanghai, People's Republic of China, 200032.

Background: This study aimed (1) to explore the electrophysiological characteristics of the bipolar and unipolar electrograms of ablation targets for RVOT arrhythmias with different ablation methods and to access the clinical outcome with different ablation strategies.

Methods: A consecutive series of 106 patients with RVOT arrhythmias who underwent radiofrequency catheter ablation (RFCA) were studied. Conventional ablation method for RVOT targets and reverse U-curve technique for PSC targets were respectively used with different mapping outcomes. The electrophysiological characteristics of the bipolar and unipolar electrograms for ablation targets and clinical ablation outcome with different ablation strategies were evaluated.

Results: When there was an obvious difference (≥ 3 ms) of earliest targets (ETs) between the PSC and RVOT regions, conventional ablation technique in the RVOT region can achieve the same and high success rate compared with the reverse-U ablation technique in the PSC region as we choose the region with a better ET for first ablation attempt. When similar (< 3 ms) ETs were observed in the PSC and RVOT regions, ablation in the PSC region can achieve an apparently higher success rate compared with ablation in the RVOT region. ETs in the PSC region had a different pattern of bipolar potential compared with those in the RVOT region, as a discrete sharp near-field potential or a fractionated potential with low voltage was more frequently observed in the PSC region.

Conclusions: Different mapping outcomes led to different success rate with two ablation strategies. When similar ETs were observed in the PSC and RVOT regions, ablation in the PSC region could achieve an apparently higher success rate. A discrete sharp or fractionated potential could help to identify the sites of PVCs' origination.
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http://dx.doi.org/10.1007/s10840-022-01237-6DOI Listing
April 2022

HMGB1 in macrophage nucleus protects against pressure overload induced cardiac remodeling via regulation of macrophage differentiation and inflammatory response.

Biochem Biophys Res Commun 2022 Apr 15;611:91-98. Epub 2022 Apr 15.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.

Pressure overload induced cardiac remodeling is associated with a complex spectrum of pathophysiological mechanisms. As inflammatory cells, macrophages maintain a critical position in mechanical stress-induced myocardial remodeling. HMGB1 is a highly conserved, ubiquitous protein in various types of cells whose biological roles are closely dependent on subcellular sites. However, whether HMGB1 expressed in macrophages performs the protective or pathological responses in cardiac remodeling is unknown. In this study, we generated the myeloid-specific HMGB1 knockout mice and detected the effects of macrophage HMGB1 in response to pathophysiological stress. Our data showed HMGB1 in macrophages played a protective role against the pressure overload induced cardiac pathophysiology. The deletion of HMGB1 in macrophages gains more differentiation of M1-type pro-inflammatory macrophage during the mechanical stress-induced myocardial remodeling, thereby aggravating the inflammatory response in whole heart, resulting in accelerated deterioration of cardiac function. Moreover, in vitro data also validated HMGB1 got involved in the process of macrophage polarization. Macrophages without HMGB1 are more inclined to differentiate into M1 during the stretch process. In summary, the present results indicated that loss of HMGB1 in macrophages can exacerbate heart failure through increased differentiation of pro-inflammatory macrophages and enhanced inflammatory response.
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http://dx.doi.org/10.1016/j.bbrc.2022.04.053DOI Listing
April 2022

Risk factors of pacing dependence and cardiac dysfunction in patients with permanent pacemaker implantation.

ESC Heart Fail 2022 Apr 26. Epub 2022 Apr 26.

Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.

Aims: Right ventricular pacing (RVP) dependence could impair left ventricular ejection fraction (LVEF). This study aimed to illuminate the relationship between RVP proportion and LVEF, as well as disclosing independent predictors of RVP dependence.

Methods And Results: Patients indicated for permanent pacemaker implantation were included (2016-2020). The ventricular pacing lead was placed in right ventricular apex or septum. Pacing mode programming followed universal standard. Electrocardiographic, echocardiographic, and serological parameters were collected. RVP dependence was defined according to its influence on LVEF. This study was of case-control design. Included patients were matched by potentially confounding factors through propensity score matching. A total of 1183 patients were included, and the mean duration of follow-up was 24 months. Percentage of RVP < 80% hardly influenced LVEF; however, LVEF tended to decrease with higher RVP proportion. High degree/complete atrioventricular block (AVB) [odds ratio (OR) = 5.71, 95% confidence interval (CI): 3.66-8.85], atrial fibrillation (AF) (OR = 2.04, 95% CI: 1.47-2.82), percutaneous coronary intervention (PCI) (OR = 2.89, 95% CI: 1.24-6.76), maximum heart rate (HR ) < 110 b.p.m. (OR = 2.74, 95% CI: 1.58-4.76), QRS duration > 120 ms (OR = 2.46, 95% CI: 1.42-4.27), QTc interval > 470 ms (OR = 2.01, 95% CI: 1.33-3.05), and pulmonary artery systolic pressure (PASP) > 40 mmHg (OR = 1.93, 95% CI: 1.46-2.56) were proved to predict RVP dependence.

Conclusions: High RVP percentage (>80%) indicating RVP dependence significantly correlates with poor prognosis of cardiac function. High degree/complete AVB, AF, ischaemic aetiology, PCI history, HR  < 110 b.p.m., QRS duration > 120 ms, QTc interval > 470 ms, and PASP > 40 mmHg were verified as independent risk factors of RVP dependence.
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http://dx.doi.org/10.1002/ehf2.13918DOI Listing
April 2022

Highly Purified Eicosapentaenoic Acid Alleviates the Inflammatory Response and Oxidative Stress in Macrophages during Atherosclerosis via the miR-1a-3p/sFRP1/Wnt/PCP-JNK Pathway.

Oxid Med Cell Longev 2022 13;2022:9451058. Epub 2022 Apr 13.

Department of Cardiology, Zhongshan Hospital, Fudan University, Research Unit of Cardiovascular Techniques and Devices, Chinese Academy of Medical Sciences, Shanghai, China.

Highly purified eicosapentaenoic acid (EPA) has shown great effects in the prevention of atherosclerosis. In a murine model, it significantly reduced plaque accumulation, lowered plasma lipid levels, and decreased inflammation levels, which was also observed . Using microRNA sequencing, we identified differentially expressed microRNAs, among which miR-1a-3p was selected for further validation. Overexpression of miR-1a-3p in RAW264.7 cells worsened lipid accumulation, increased oxidative stress, and exacerbated inflammatory responses whereas its downregulation produced the opposite results. Potential targets of miR-1a-3p were analyzed by prediction tools. Then, secreted frizzled-related protein 1 (sFRP1), an antagonist of the Wnt pathway, was confirmed as the target gene of miR-1a-3p by a dual-luciferase reporter assay. Further research showed that in macrophages, EPA influenced the activation of the Wnt/planar cell polarity-c-Jun N-terminal kinase (Wnt/PCP-JNK) axis, which is consistent with the phenomenon that miR-1a-3p has an impact on this same axis. Collectively, our findings suggest that EPA mitigates inflammatory responses and oxidative responses both and by targeting the miR-1a-3p/sFRP1/Wnt/PCP-JNK axis in macrophages, which may explain the cardioprotective role of EPA and promote the application of EPA in clinical practice.
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http://dx.doi.org/10.1155/2022/9451058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021996PMC
April 2022

Hourly Air Pollutants and Acute Coronary Syndrome Onset In 1.29 Million Patients.

Circulation 2022 Apr 22. Epub 2022 Apr 22.

School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China; Children's Hospital of Fudan University, National Center for Children's Health, Shanghai, China.

Short-term exposure to ambient air pollution has been linked with daily hospitalization and mortality of acute coronary syndrome (ACS); however, the associations of sub-daily (hourly) levels of criteria air pollutants with the onset of ACS and its subtypes have rarely been evaluated. We conducted a time-stratified case-crossover study among 1,292,880 ACS patients from 2,239 hospitals in 318 Chinese cities between January 1, 2015, and September 30, 2020. Hourly concentrations of fine particulate matter (PM), coarse particulate matter (PM), nitrogen dioxide (NO), sulfur dioxide (SO), carbon monoxide (CO), and ozone (O) were collected. Hourly onset data of ACS and its subtypes, including ST-segment-elevation myocardial infarction, non-ST-segment-elevation myocardial infarction, and unstable angina, were also obtained. Conditional logistic regressions combined with polynomial distributed lag models were applied. Acute exposures to PM, NO, SO, and CO were each associated with the onset of ACS and its subtype. These associations were strongest in the concurrent hour of exposure and were attenuated thereafter, with the weakest effects observed after 15-29 hours. There were no apparent thresholds in the concentration-response curves. An interquartile range increase in concentrations of PM (36.0 μg/m), NO (29.0 μg/m), SO (9.0 μg/m), and CO (0.6 mg/m) over the 0-24 hours preceding onset was significantly associated with 1.32%, 3.89%, 0.67%, and 1.55% higher risks of ACS onset, respectively. For a given pollutant, the associations were comparable in magnitude across different subtypes of ACS. Generally, NO showed the strongest associations with all three subtypes, followed by PM, CO, and SO. Greater magnitude of associations was observed among patients older than 65, without a history of smoking or chronic cardiorespiratory diseases, and in the cold season. Null associations of exposure to either PM or O with ACS onset were observed. The results suggest that transient exposure to the air pollutants of PM, NO, SO, CO, but not PM or O, may trigger the onset of ACS, even at concentrations below the World Health Organization air-quality guidelines.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.057179DOI Listing
April 2022

Targeted immunomodulation therapy for cardiac repair by platelet membrane engineering extracellular vesicles via hitching peripheral monocytes.

Biomaterials 2022 May 16;284:121529. Epub 2022 Apr 16.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Feng Lin Road, Shanghai, 200032, China; National Clinical Research Center for Interventional Medicine& Shanghai Clinical Research Center for Interventional Medicine, 180 Feng Lin Road, Shanghai, 200032, China; Institute of Biomedical Science, Fudan University, 180 Feng Lin Road, Shanghai, 200032, China.

Immune regulation therapies have been considered promising in the treatment of myocardial ischemia reperfusion (MI/R) injury. Mesenchymal stem cells derived extracellular vesicles (MSC-EVs) are of great potential for immune modulation by reprogramming macrophages but their therapeutic efficacy is hindered by insufficient targeting ability in vivo. Herein, we introduced the platelet membrane modified EVs (P-EVs) based on membrane fusion method to mimic the binding ability of platelets to monocytes. In the mouse model of MI/R injury, the intravenously injected P-EVs were mainly carried by circulating monocytes into the ischemic myocardium. In the inflammatory microenvironment, those monocytes subsequently differentiated into macrophages with enhanced phagocytosis, which probably promoted in-situ endocytosis of the superficial P-EVs by monocytes differentiated macrophages in large quantities. Then, the P-EVs successfully escaped from the macrophage lysosome and released the functional microRNAs (miRNAs) into the cytosol which facilitated the inflammatory macrophages (M1 phenotype) reprogramming to reparative macrophages (M2 phenotype). Finally, the immune microenvironment was regulated to realize cardiac repair. Thus, we supposed that the most likely delivery method was that monocytes mediated P-EVs migration into ischemic myocardium where P-EVs were mainly in-situ endocytosed by monocytes derived macrophages, which holds potential for immunoregulation on MI/R and other immune-related diseases in the future.
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http://dx.doi.org/10.1016/j.biomaterials.2022.121529DOI Listing
May 2022

Geographic Variation in Cardiovascular Health as Analyzed from the China Cardiovascular Health Index Study - 31 PLADs, China, 2017-2021.

China CDC Wkly 2022 Apr;4(13):265-270

National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

What Is Already Known About This Topic?: The prevalence of cardiovascular disease (CVD) in China is high, while effective prevention and proper management is lacking. No available indicators were found before 2016 that could comprehensively evaluate different aspects of CVD prevention and treatment.

What Is Added By This Report?: Constructed by combining data from multiple dimensions, China cardiovascular health index (CHI) has provided a practical indicator for each provincial-level administrative division (PLAD) to comprehensively understand its overall level and rankings of the specific dimensions of cardiovascular health.

What Are The Implications For Public Health Practice?: The CHI will be beneficial for each PLAD to identify weak aspects in CVD control and prevention and redistribute resources to the most needed areas.
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http://dx.doi.org/10.46234/ccdcw2022.067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005480PMC
April 2022

Cardiac Resident Macrophage-Derived Legumain Improves Cardiac Repair by Promoting Clearance and Degradation of Apoptotic Cardiomyocytes After Myocardial Infarction.

Circulation 2022 May 18;145(20):1542-1556. Epub 2022 Apr 18.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, China (D.J., P.B., J.L., A.S., J.G.).

Background: Cardiac resident macrophages are self-maintaining and originate from embryonic hematopoiesis. After myocardial infarction, cardiac resident macrophages are responsible for the efficient clearance and degradation of apoptotic cardiomyocytes (efferocytosis). This process is required for inflammation resolution and tissue repair; however, the underlying molecular mechanisms remain unknown. Therefore, we aimed to identify the mechanisms of the continued clearance and degradation of phagolysosomal cargo by cardiac resident macrophages during myocardial infarction.

Methods: Multiple transgenic mice such as Lgmn, Lgmn; LysM, Lgmn; Cx3cr1, Lgmn; Lyve, and cardiac macrophage Lgmn overexpression by adenovirus gene transfer were used to determine the functional significance of Lgmn in myocardial infarction. Immune cell filtration and inflammation were examined by flow cytometry and quantitative real-time polymerase chain reaction. Moreover, legumain (Lgmn) expression was analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction in the cardiac tissues of patients with ischemic cardiomyopathy and healthy control subjects.

Results: We identified as a gene specifically expressed by cardiac resident macrophages. Lgmn deficiency resulted in a considerable exacerbation in cardiac function, accompanied by the accumulation of apoptotic cardiomyocytes and a reduced index of in vivo efferocytosis in the border area. It also led to decreased cytosolic calcium attributable to defective intracellular calcium mobilization. Furthermore, the formation of LC3-II-dependent phagosome around secondary-encountered apoptotic cardiomyocytes was disabled. In addition, Lgmn deficiency increased infiltration of MHC-II CCR2 macrophages and the enhanced recruitment of MHC-II CCR2 monocytes with downregulation of the anti-inflammatory mediators, interleukin-10, and transforming growth factor-β and upregulationof the proinflammatory mediators interleukin-1β, tumor necrosis factor-α, interleukin-6, and interferon-γ.

Conclusions: Our results directly link efferocytosis to wound healing in the heart and identify Lgmn as a significant link between acute inflammation resolution and organ function.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.057549DOI Listing
May 2022

Percutaneous balloon mitral valvuloplasty using veno-arterial loop and neuro-embolic protection for mitral stenosis with thrombus.

Catheter Cardiovasc Interv 2022 Apr 14. Epub 2022 Apr 14.

Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Disease, Fudan University, Shanghai, China.

Percutaneous balloon mitral valvuloplasty (PBMV) is not traditionally suitable for patients with mitral stenosis (MS) and left atrium (LA) thrombus. Moreover, PBMV cannot be performed in patients with LA thrombus not resolving after anti-coagulation treatment. Here we present a case of PBMV using a novel technique employing both a veno-arterial loop and neuro-embolic protection, in a patient with MS and LA thrombus resistant to warfarin therapy. The patient successfully underwent PBMV without any complications.
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http://dx.doi.org/10.1002/ccd.30203DOI Listing
April 2022

Development and Validation of a Novel Tool for the Prediction of Clopidogrel Response in Chinese Acute Coronary Syndrome Patients: The GeneFA Score.

Front Pharmacol 2022 21;13:854867. Epub 2022 Mar 21.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.

Growing evidence indicated that CYP2C19 genotypes could only explain a fraction of the pharmacodynamic response to clopidogrel, while a number of clinical factors also have contributing roles. Our objective was to develop a new risk score to improve prognostication of ischemic events in Chinese patients treated with clopidogrel. A new risk score was developed and internally validated in 445 patients with acute coronary syndrome (ACS) undergoing coronary stenting. The final score was named the GeneFA score based on the inclusion of CYP2C19 genotype, fibrinogen, and age. External validation of the GeneFA score and comparison with the ABCD-GENE score were performed in an independent ACS cohort. Based on the observed frequencies of high platelet reactivity (HRPR) in relation to the GeneFA risk score, a relatively higher clinical HRPR was observed in the upper quintile with a representative score of 3 (52.90%) and 4 (59.10%), whereas it was found less frequently in groups with scores 0 (6.70%), 1 (15.10%), and 2 (16.70%). Participants with a GeneFA score >2 had an increased risk of HRPR (54.3 14.7%, < 0.001) and ischemic recurrence (20.7 5.4%, < 0.001). The GeneFA score exhibited a better prediction for high HRPR patients as compared to the ABCD-GENE score ( < 0.001). In the validation population, GeneFA illustrated a similarly high prognostic value for HRPR incidence (C-statistic: 0.855 for GeneFA and 0.843 for ABCD-GENE) and ischemic recurrence (C-statistic: 0.726 for GeneFA and 0.724 for ABCD-GENE) on clopidogrel as compared to ABCD-GENE. The GeneFA risk score had a moderate predictive ability for HRPR on clopidogrel for CAD patients in Chinese populations. The predictive value of the GeneFA score was consistent with the ABCD-GENE score for HRPR identification.
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http://dx.doi.org/10.3389/fphar.2022.854867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8977638PMC
March 2022

Fine particulate matter air pollution and subclinical cardiovascular outcomes: A longitudinal study in 15 Chinese cities.

Environ Int 2022 May 28;163:107218. Epub 2022 Mar 28.

School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Laboratory of Health Technology Assessment, Fudan University, Shanghai, China. Electronic address:

Aims: Although previous studies have linked short-term exposure to fine particulate matter (PM) air pollution with various molecular biomarkers of cardiovascular system, limited evidence is available for indicators at clinical or subclinical levels. We examined the associations between short-term PM exposure and a range of clinical or subclinical indicators of cardiovascular health in general population.

Methods And Results: A longitudinal repeated-measure study was conducted among 247,640 participants who repeatedly visited health examination centers in 15 typical cities across China from 2013 to 2020. A total of 19 well-established indicators of cardiovascular risk or injury were evaluated and air quality data at nearest fixed-site monitors were collected. Linear mixed-effects models with distributed lag models were used to analyze the potentially lagged effects of PM. The average daily PM concentration was 48 μg/m during the study period. PM exposure was associated with significant changes of 16 indicators with the effects generally peaked on lag 0 to 3 day. For an interquartile range (IQR) elevation (37 μg/m) in PM concentrations over lag 0-7 day, the cumulative percentage changes were 0.50% to 1.27% in heart rates and blood pressure, 0.10% to 5.04% in inflammatory markers, -0.29% to 1.39% in blood viscosity parameters, -0.67% to 3.45% in blood lipids, 0.89% in blood homocysteine, 0.13% to 0.78% in myocardial enzymes, and 3.03% in pulse wave velocity. These associations were not substantially changed after adjusting concomitant exposures to gaseous pollutants.

Conclusion: Short-term exposure to PM may induce early cardiovascular effects in general population, including acute inflammation, myocardial injury, increased blood viscosity, vascular stiffness and hyperlipidemia.
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http://dx.doi.org/10.1016/j.envint.2022.107218DOI Listing
May 2022

Valosin Containing Protein as a Specific Biomarker for Predicting the Development of Acute Coronary Syndrome and Its Complication.

Front Cardiovasc Med 2022 18;9:803532. Epub 2022 Mar 18.

Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Background: Acute coronary syndrome (ACS) consists of a range of acute myocardial ischemia-related manifestations. The adverse events of ACS are usually associated with ventricular dysfunction (VD), which could finally develop to heart failure. Currently, there is no satisfactory indicator that could specifically predict the development of ACS and its prognosis. Valosin-containing protein (VCP) has recently been proposed to protect against cardiac diseases. Hence, we aimed to assess whether VCP in serum can serve as a valuable biomarker for predicting ACS and its complication.

Methods: Human serum samples from 291 participants were collected and classified into four groups based on their clinical diagnosis, namely healthy control ( = 64), ACS ( = 40), chronic coronary syndrome (CCS, = 99), and nonischemic heart disease (non-IHD, = 88). Clinical characteristics of these participants were recorded and their serum VCP levels were detected by enzyme-linked immunosorbent assay (ELISA). Association of serum VCP with the development of ACS and its complication VD was statistically studied. Subsequently, GWAS and eQTL analyses were performed to explore the association between polymorphism and monocyte count. A stability test was also performed to investigate whether VCP is a stable biomarker.

Results: Serum VCP levels were significantly higher in the ACS group compared with the rest groups. Besides, the VCP levels of patients with ACS with VD were significantly lower compared to those without VD. Multivariate logistic regression analysis revealed that VCP was associated with both the risk of ACS ( = 0.042, OR = 1.222) and the risk of developing VD in patients with ACS ( = 0.035, OR = 0.513) independently. The GWAS analysis also identified an association between polymorphism (rs684562) and monocyte count, whereas the influence of rs684562 on mRNA expression level was further verified by eQTL analysis. Moreover, a high stability of serum VCP content was observed under different preservation circumstances.

Conclusion: Valosin-containing protein could act as a stable biomarker in predicting the development of ACS and its complication VD.
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http://dx.doi.org/10.3389/fcvm.2022.803532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971847PMC
March 2022

The proteasome activator REGγ promotes diabetic endothelial impairment by inhibiting HMGA2-GLUT1 pathway.

Transl Res 2022 Mar 31. Epub 2022 Mar 31.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Cardiovascular Diseases, Shanghai, China; Institutes of Biomedical Science, Fudan University, Shanghai, China. Electronic address:

Diabetic vascular endothelial impairment is one of the main causes of death in patients with diabetes lacking adequately defined mechanisms or effective treatments. REGγ, the 11S proteasome activator known to promote the degradation of cellular proteins in a ubiquitin- and ATP-independent manner, emerges as a new regulator in the cardiovascular system. Here, we found that REGγ was upregulated in streptozocin (STZ)-induced diabetic mouse aortic endothelium in vivo and high glucose (HG)-treated vascular endothelial cells (ECs) in vitro. REGγ deficiency ameliorated endothelial impairment in STZ-induced diabetic mice by protecting against a decline in cellular glucose uptake and associated vascular ECs dysfunction by suppressing high mobility group AT-hook 2 (HMGA2) decay. Mechanically, REGγ interacted with and degraded the transcription factor HMGA2 directly, leading to decreased HMGA2 transcriptional activity, subsequently lowered expression of glucose transporter type 1 (GLUT1), and reduced cellular glucose uptake, vascular endothelial dysfunction, and impaired diabetic endothelium. Ablation of endogenous GLUT1 or HMGA2 or overexpressing exogenous HMGA2 in vascular ECs significantly blocked or reestablished the REGγ-dependent action on cellular glucose uptake and vascular endothelial functions of HG stimulation in vitro. Furthermore, exogenously introducing HMGA2 improved diabetic mice endothelial impairment features caused by REGγ in vivo, thereby substantiating a REGγ-HMGA2-GLUT1 pathway in diabetic endothelial impairment. Our findings indicate that modulating REGγ-proteasome activity may be a potential therapeutic approach for diabetic disorders with endothelial impairment.
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http://dx.doi.org/10.1016/j.trsl.2022.03.007DOI Listing
March 2022

Impact and potential mechanism of effects of chronic moderate alcohol consumption on cardiac function in aldehyde dehydrogenase 2 gene heterozygous mice.

Alcohol Clin Exp Res 2022 May 20;46(5):707-723. Epub 2022 Apr 20.

Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

Background: Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in alcohol metabolism. The ALDH2*2 mutations are found in approximately 45% of East Asians, with 40% being heterozygous (HE) ALDH2*1/*2 and 5% homozygous (HO) ALDH2*2/*2. Studies have shown that HO mice lack cardioprotective effects induced by moderate alcohol consumption. However, the impact of moderate alcohol consumption on cardiac function in HE mice is unknown.

Methods: In this study, HO, HE, and wild-type (WT) mice were subjected to a 6-week moderate alcohol drinking protocol, following which myocardial tissue and cardiomyocytes of the mice were extracted.

Results: We found that moderate alcohol exposure did not increase mortality, myocardial fibrosis, apoptosis, or inflammation in HE mice, which differs from the effects observed in HO mice. After exposure to the 6-week alcohol drinking protocol, there was impaired cardiac function, cardiomyocyte contractility, and intracellular Ca homeostasis and mitochondrial function in both HE and HO mice as compared to WT mice. Moreover, these animals showed overt oxidative stress production and increased levels of the activated forms of calmodulin-dependent protein kinase II (CaMKII) and ryanodine receptor type 2 (RYR2) phosphorylation protein.

Conclusion: We found that moderate alcohol exposure impaired cardiac function in HE mice, possibly by increasing reactive oxygen species (ROS)/CaMKII/RYR2-mediated Ca handling abnormalities. Hence, we advocate that people with ALDH2*1/*2 genotypes rigorously avoid alcohol consumption to prevent potential cardiovascular harm induced by moderate alcohol consumption.
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http://dx.doi.org/10.1111/acer.14811DOI Listing
May 2022

Minimizing Guidewire Unwilling Passage and Related Perforation During Transradial Procedures: Prevention Is Better Than Cure.

Front Cardiovasc Med 2022 1;9:730648. Epub 2022 Mar 1.

Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Current guidewires for transradial coronary angiography had defects of passage difficulty or branch injury. This study sought to investigate the safety and efficiency of a novel method of active knuckle-angle 0.035-inch hydrophilic guidewire in transradial coronary angiography.

Methods: Patients undergoing a transradial coronary procedure in our team from August 2015 to June 2020 were retrospectively investigated. We compared the demographic and interventional characteristics of 1,457 patients receiving advancement of unmodified guidewires (Traditional group) and 1,322 patients receiving advancement of the knuckle guidewire (Knuckle group). Afterwards we included 239 patients and randomized them according to a random number table to either the unmodified or the knuckle guidewire to further confirm the efficiency and safety of knuckle guidewire advancement.

Results: In the retrospective analysis, unwilling passage of guidewire into branches occurred more in the Traditional group than in the Knuckle group (9.5 vs. 0.08%, < 0.001). Two patients in the Traditional group experienced guidewire-associated perforation. One patient was treated with covered stent for internal mammarian artery perforation, while the other was managed with compression for brachial branch perforation. In the randomized controlled study, unwilling passage of guidewire also occurred more in the Traditional group (10.8 vs. 1%, < 0.001). Median duration of guidewire advancement from the sheath to aortic root significantly decreased from 33 seconds in the Traditional group to 21 seconds in the Knuckle group.

Conclusion: Active knuckle angle guidewire represented a novel method to prevent unwilling passage and associated perforation with efficiency improvement and a reduction in radiation exposure.
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http://dx.doi.org/10.3389/fcvm.2022.730648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918946PMC
March 2022

Performance of Management Strategies With Class I Recommendations Among Patients Hospitalized With ST-Segment Elevation Myocardial Infarction in China.

JAMA Cardiol 2022 May;7(5):484-491

Division of Cardiology, University of North Carolina, Chapel Hill.

Importance: Despite advances in the treatment of ST-segment elevation myocardial infarction (STEMI), little is known about how this evolving knowledge is applied in current clinical practice in China.

Objective: To evaluate hospital performance and temporal trends in the management of STEMI.

Design, Setting, And Participants: This study used data from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome Project, a nationwide quality improvement registry, in collaboration with the American Heart Association and the Chinese Society of Cardiology. Participants included patients with STEMI admitted to 143 tertiary hospitals across China from November 2014 to July 2019, and data were analyzed from November 2020 to December 2021.

Main Outcomes And Measures: Levels, hospital-level variations, and trends for utilization rates of the 9 management strategies with Class I recommendations in Chinese and US guidelines.

Results: A total of 57 560 hospitalizations with STEMI were included. Overall, 20.0% of patients received all the care according to the 9 guideline-recommended strategies. The performance rate of quality measures was low for reperfusion therapy (61.0%, 35 115/57 560 patients), β-blocker at discharge (68.3%, 37 750/55 285 patients), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker at discharge (55.1%, 2524/4578 patients), and smoking cessation counseling (36.5%, 9586/26 265 patients) among those who were eligible. Of 25 563 patients who underwent primary percutaneous coronary intervention (PCI), 66.8% underwent this procedure within 90 minutes of hospital arrival. Of 1128 patients who underwent fibrinolysis therapy, 253 (22.4%) underwent this treatment within 30 minutes of hospital arrival. Measures with high performance rates included receipt of dual antiplatelet therapy within 24 hours (95.5%, 54 263/56 848 patients) and at discharge (91.8%, 51 452/56 019 patients) and receipt of statin at discharge (93.0%, 52 214/56 141 patients) for those eligible. There was significant variation between hospitals in all-or-none score (ranging from 0 to 61.9%) and performance of individual measures. The quality of care improved during the study period, especially for reperfusion therapy, primary PCI within the first 90 minutes of hospital arrival, and smoking cessation counseling.

Conclusions And Relevance: The quality of care for patients hospitalized with STEMI does not meet guideline-recommended strategies in China, with only 1 in 5 patients receiving all the care according to the 9 guideline-recommended strategies. Large disparities in the quality of care exist across hospitals.
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http://dx.doi.org/10.1001/jamacardio.2022.0117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8928093PMC
May 2022

Genetic variants in Chinese patients with sporadic dilated cardiomyopathy: a cross-sectional study.

Ann Transl Med 2022 Feb;10(3):129

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China.

Background: Multiple genes have been associated with familial dilated cardiomyopathy (DCM). However, the role of genetic factors in sporadic DCM (SDCM) remains unclear. Therefore, we studied the genetic variations in Chinese patients with SDCM.

Methods: Sixty-six unrelated Chinese patients (mean age 49.1±17.0 years; 71% male) diagnosed with SDCM were enrolled. The clinical history and genomic DNA of the cohort were collected and examined. The exons of 24 genes closely associated with familial DCM (, and ) were sequenced using targeted next-generation sequencing method. All called nonsynonymous variants and their occurrence frequencies were compared against population data from public databases. And the nonsynonymous variants were also evaluated for pathogenicity by PolyPhen 2 (PP2) and Sorts Intolerant From Tolerant (SIFT) algorithms.

Results: Eighty-five nonsynonymous variants were detected in 17 genes. The variants and their occurrence frequencies in the patients were compared against population data from the 1000 Genomes and NHLBI (National Heart, Lung, and Blood Institute) Go Exome Sequencing Project. Forty-nine nonsynonymous variants had occurrence frequencies that were significantly higher in the study patients than in the general population, indicating that they have the potential to increase the risk of DCM. The risk variants were distributed in 40 (61%) patients, among whom 25 carried a single variant, while the remaining patients carried multiple (2 to 4) variants. Risk variants occurred more frequently in (14% of the patients), (14%), (12%), (9%), and (8%), as verified by Poisson distribution analysis, which were considered "the five risky genes".

Conclusions: We found that genetic variants with potential risk for DCM were commonly present in SDCM patients, indicating that genetic factors contribute to the pathogenesis, and (probably) the onset, of DCM in these patients.
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http://dx.doi.org/10.21037/atm-21-6774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8904992PMC
February 2022

Efficacy of interatrial shunt devices: an opening window to acute pulmonary hypertensive crisis and chronic pulmonary arterial hypertension.

J Thromb Thrombolysis 2022 Mar 13. Epub 2022 Mar 13.

Division of Cardiology, Department of Cardiology, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital Affiliated to Fudan University, No 180, Fenglin Road, Shanghai, 200032, China.

The current study aimed to elucidate the efficacy of interatrial shunt device (IASD) for the treatment of acute pulmonary hypertensive crisis (PHC) and chronic pulmonary arterial hypertension (PAH). After establishing chronic PAH models using dehydrogenized monocrotaline (DHMCT), PAH dogs were implanted with IASDs (group A) or received no intervention (group B). One month later, DHMCT was injected again to establish an acute PHC. The prognosis, hemodynamics, ultrasound cardiography, electrocardiogram, and lung pathology of the dogs were observed. The baseline mean pulmonary arterial pressure increased from 12.70 ± 1.03 to 19.95 ± 1.75 mmHg and established a chronic PAH model 2 months after DHMCT injection (1.50 mg/kg). After an additional injection of DHMCT (1.50 mg/kg) in the chronic PAH model, acute PHC occurred. Mean PAP, sPAP, and pulmonary vascular resistance increased to 22.67 ± 1.80 mmHg, 35.70 ± 1.66 mmHg, and 12.50 ± 3.50 WOOD U, respectively. Cardiac output (CO) decreased to 1.31 ± 0.26 L/min, and the right-to-left shunt caused hypoxemia. The survival rates of the dogs with and those without IASD were 70.0% and 22.2% (P = 0.037), respectively. Six months after PHC, the CO between the dogs with and those without IASD were 1.44 ± 0.11 L/min and 1.18 ± 0.04 L/min (P = 0.028). The long-term survival rates were 50.0% and 22.2%, respectively (P = 0.21). IASD might be efficacious and beneficial for treating acute PHC and chronic PAH, as well as improving prognosis.
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http://dx.doi.org/10.1007/s11239-022-02635-3DOI Listing
March 2022

The selective STING inhibitor H-151 preserves myocardial function and ameliorates cardiac fibrosis in murine myocardial infarction.

Int Immunopharmacol 2022 Jun 9;107:108658. Epub 2022 Mar 9.

Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address:

Background: During myocardial infarction (MI), the stimulation of the cGAS-STING-IRF3 pathway in infiltrated macrophages can induce the apoptosis of cardiomyocytes and the fibrosis of cardiac fibroblasts, while H-151 is reported as a selective STING inhibitor. We intended to use H-151 to alleviate MI injury.

Methods: Male C57BL/6J mice were subjected to induce MI, while H-151 (750 nmol) were used for treatment. Myocardial function was assessed through echocardiology and cardiac fibrosis was evaluated by Masson's Trichrome-staining. The stimulation of the STING pathway and the aggravation of inflammation was assessed by levels of protein and mRNA. BMDMs were stimulated by dsDNA extracted from the murine heart, while H-151 was used as treatment. After co-culturing adult cardiomyocytes and cardiac fibroblasts with supernatant of BMDMs, the apoptosis of adult cardiomyocytes and the fibrosis of cardiac fibroblasts was assessed.

Results: H-151 treatment showed significant function in preserving myocardial function and decreasing cardiac fibrosis 28 days after MI. H-151 treatment showed significant function in inhibiting the cGAS-STING-IRF3 pathway and inflammation, especially type I interferon response. H-151 could alleviate the type I interferon response in BMDMs elicited by cardiac dsDNA, and thus H-151 could attenuate the apoptosis of adult cardiomyocytes and fibrosis of cardiac fibroblasts after co-culturing them with the supernatant of BMDMs.

Conclusions: H-151, a selective inhibitor of the cGAS-STING-IRF3 pathway, can preserve myocardial function and alleviate cardiac fibrosis after MI by inhibiting the type I interferon response in infiltrated macrophages triggered by cardiac dsDNA which increase the apoptosis of adult cardiomyocytes and fibrosis of cardiac fibroblasts.
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http://dx.doi.org/10.1016/j.intimp.2022.108658DOI Listing
June 2022

Validation of a Novel Renal Denervation System With Cryoablation: A Preclinical Study and Case Series.

JACC Basic Transl Sci 2022 Feb 2;7(2):101-112. Epub 2022 Feb 2.

Department of Cardiology, Zhongshan Hospital, Fudan University, Research Unit of Cardiovascular Techniques and Devices, Chinese Academy of Medical Sciences, Shanghai, China.

Recently, we designed a renal denervation with cryoablation (Cryo-RDN) system using liquid nitrogen and proved its short-term safety and effectiveness. In this study, we first conducted a 6-month follow-up in a swine model. Renal sympathetic nerve activity remained at a significantly lower level than that of the control group after 6 months. In patients with resistant hypertension, Cryo-RDN demonstrated preliminary safety. Renal function fluctuations and vascular-related complications were not detected. In addition, the average 24-hour systolic and diastolic blood pressure decreased by 12.17 ± 8.35 mm Hg and 8.50 ± 3.83 mm Hg at the 6-month follow-up, respectively, compared with their baseline values.
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http://dx.doi.org/10.1016/j.jacbts.2021.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8897167PMC
February 2022

Device-based antegrade dissection re-entry versus parallel wire techniques for the percutaneous revascularization of coronary chronic total occlusions.

Cardiol J 2022 Mar 4. Epub 2022 Mar 4.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai, China.

Background: Device-based antegrade dissection re-entry (ADR) and parallel wire technique (PWT) are two important techniques in the antegrade approach in percutaneous coronary intervention (PCI) of chronic total occlusion (CTO). The study is aimed to compare the procedural and mid-term outcomes between device-based ADR using the CrossBoss/Stingray system and PWT in CTO PCI.

Methods: Data was retrospectively collected from consecutive patients who underwent CTO PCI using device-based ADR or PWT. CTO due to in-stent restenosis were excluded.

Results: A total of 273 patients were included in the study (n = 55 in device-based ADR group, n = 218 in PWT group). Baseline characteristics were similar across groups except for higher prevalence of prior PCI and lower level of lipid profile in the ADR group. Moreover, although patients in the ADR group showed higher contrast volume (441.6 ± 162.4 mL vs. 361.5 ± 142.1 mL, p < 0.001), more intravascular ultrasound guidance (50.9% vs. 22.9%, p < 0.001), more guidewires used (4.6 ± 1.4 vs. 3.4 ± 1.2, p < 0.001) and higher troponin T level after PCI (0.167 vs. 0.087, p = 0.004), the technical success, procedural success and in-hospital complications were similar between the two groups. During a median follow-up of 1 year, the ADR group showed no difference in major adverse cardiac events (MACE, including all cause death, nonfatal myocardial infarction, and ischemia driven target vessel revascularization) (7.3% vs. 14.7%, p = 0.150) as compared with the PWT group.

Conclusions: In the documented center, the use of device-based ADR for CTO PCI showed no difference in in-hospital complications and mid-term MACE as compared with PWT, despite higher procedure complexity in ADR group.
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http://dx.doi.org/10.5603/CJ.a2022.0008DOI Listing
March 2022
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