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Background: Chronic total occlusion (CTO) is the most challenging subset in percutaneous coronary intervention (PCI), but the optimal selection of patients and indication for such procedures remain a subject of debate. We sought to investigate the role of physiological function in treatment decisions of CTO PCI by measuring fractional flow reserve (FFR) and Dynamic SPECT imaging in this study. Methods: All the FFR of CTO vessel were measured before and immediately after CTO revascularization, and Dynamic SPECT imaging were detected before PCI in patients with an identified CTO. Results: A total of 53 patients with single-vessel CTO lesions were included in this cohort study. The mean FFR value was 0.34 ± 0.09 at baseline. Immediately after successful CTO PCI, the FFR value significantly increased to 0.79 ± 0.11. The regional coronary flow reserve (CFR) of CTO vessels was 1.62 ± 0.64, which was significantly and positively correlated with the baseline FFR value (r = 0.607, p = 0.005). The area under the ROC curve of the baseline FFR for the detection of ischemia was 0.923 (p

Abstract Background Indobufen is widely used in patients with aspirin intolerance in East Asia. The OPTION trial launched by our cardiac center examined the performance of indobufen based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, the vast majority of patients with acute coronary syndrome (ACS) and aspirin intolerance were excluded. We aimed to explore this question in a real-world population. Methods Patients enrolled in the ASPIRATION registry were grouped according to the DAPT strategy that they received after PCI. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. Propensity score matching (PSM) was adopted for confounder adjustment. Results A total of 7135 patients were reviewed. After one-year follow-up, the indobufen group was associated with the same risk of MACCE versus the aspirin group after PSM (6.5% vs. 6.5%, hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.65 to 1.52, P = 0.978). However, BARC type 2, 3, or 5 bleeding was significantly reduced (3.0% vs. 11.9%, HR = 0.24, 95% CI = 0.15 to 0.40, P

Abstract CD47‐SIRPα axis is an immunotherapeutic target in tumor therapy. However, current monoclonal antibody targeting CD47‐SIRPα axis is associated with on‐target off‐tumor and antigen sink effects, which significantly limit its potential clinical application. Herein, a biomimetic nano‐degrader is developed to inhibit CD47‐SIRPα axis in a site‐specific manner through SIRPα degradation, and its efficacy in acute myocardial infarction (AMI) is evaluated. The nano‐degrader is constructed by hybridizing liposome with red blood cell (RBC) membrane (RLP), which mimics the CD47 density of senescent RBCs and possesses a natural high‐affinity binding capability to SIRPα on macrophages without signaling capacity. RLP would bind with SIRPα and induce its lysosomal degradation through receptor‐mediated endocytosis. To enhance its tissue specificity, Ly6G antibody conjugation (aRLP) is applied, enabling its attachment to neutrophils and accumulation within inflammatory sites. In the myocardial infarction model, aRLP accumulated in the infarcted myocardium blocks CD47‐SIRPα axis and subsequently promoted the efferocytosis of apoptotic cardiomyocytes by macrophage, improved heart repair. This nano‐degrader efficiently degraded SIRPα in lysosomes, providing a new strategy for immunotherapy with great clinical transformation potential.

The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.

Background The presence of mental health conditions is pervasive in patients who experienced acute myocardial infarction (AMI), significantly disrupting their recovery. Providing timely and easily accessible psychological interventions using virtual reality-based cognitive–behavioural therapy (VR-CBT) could potentially improve both acute and long-term symptoms affecting their mental health.Aims We aim to examine the effectiveness of VR-CBT on anxiety symptoms in patients with AMI who were admitted to the intensive care unit (ICU) during the acute stage of their illness.Methods In this single-blind randomised clinical trial, participants with anxiety symptoms who were admitted to the ICU due to AMI were continuously recruited from December 2022 to February 2023. Patients who were Han Chinese aged 18–75 years were randomly assigned (1:1) via block randomisation to either the VR-CBT group to receive VR-CBT in addition to standard mental health support, or the control group to receive standard mental health support only. VR-CBT consisted of four modules and was delivered at the bedside over a 1-week period. Assessments were done at baseline, immediately after treatment and at 3-month follow-up. The intention-to-treat analysis began in June 2023. The primary outcome measure was the changes in anxiety symptoms as assessed by the Hamilton Anxiety Rating Scale (HAM-A).Results Among 148 randomised participants, 70 were assigned to the VR-CBT group and 78 to the control group. The 1-week VR-CBT intervention plus standard mental health support significantly reduced the anxiety symptoms compared with standard mental health support alone in terms of HAM-A scores at both post intervention (Cohen’s d=−1.27 (95% confidence interval (CI): −1.64 to −0.90, p

Abstract Background Early diagnosis and treatment effectiveness of early-onset coronary artery disease (EOCAD) are crucial, and non-invasive predictive biomarkers are needed for young adults. We aimed to evaluate the usefulness of the triglyceride-glucose (TyG) index, a novel marker of insulin resistance, in identifying young CAD patients and predicting their risk of developing target lesion failure (TLF). Methods We recruited EOCAD patients (luminal narrowing ≥ 70%) and controls free from CAD (luminal narrowing

Mitochondria-associated ferroptosis exacerbates cardiac microvascular dysfunction in diabetic cardiomyopathy (DCM). Nicorandil, an ATP-sensitive K+ channel opener, protects against endothelial dysfunction, mitochondrial dysfunction, and DCM; however, its effects on ferroptosis and mitophagy remain unexplored. The present study aimed to assess the beneficial effects of nicorandil against endothelial ferroptosis in DCM and the underlying mechanisms. Cardiac microvascular perfusion was assessed using a lectin perfusion assay, while mitophagy was assessed via mt-Keima transfection and transmission electron microscopy. Ferroptosis was examined using mRNA sequencing, fluorescence staining, and western blotting. The mitochondrial localization of Parkin, ACSL4, and AMPK was determined via immunofluorescence staining. Following long-term diabetes, nicorandil treatment improved cardiac function and remodeling by alleviating cardiac microvascular injuries, as evidenced by the improved microvascular perfusion and structural integrity. mRNA-sequencing and biochemical analyses showed that ferroptosis occurred and Pink1/Parkin-dependent mitophagy was suppressed in cardiac microvascular endothelial cells after diabetes. Nicorandil treatment suppressed mitochondria-associated ferroptosis by promoting the Pink1/Parkin-dependent mitophagy. Moreover, nicorandil treatment increased the phosphorylation level of AMPKα1 and promoted its mitochondrial translocation, which further inhibited the mitochondrial translocation of ACSL4 via mitophagy and ultimately suppressed mitochondria-associated ferroptosis. Importantly, overexpression of mitochondria-localized AMPKα1 (mitoAα1) shared similar benefits with nicorandil on mitophagy, ferroptosis and cardiovascular protection against diabetic injury. In conclusion, the present study demonstrated the therapeutic effects of nicorandil against cardiac microvascular ferroptosis in DCM and revealed that the mitochondria-localized AMPK-Parkin-ACSL4 signaling pathway mediates mitochondria-associated ferroptosis and the development of cardiac microvascular dysfunction.

Abstract Background Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the standard of care after coronary stenting, including coronary stenting involving bioresorbable scaffolds (BRSs). Current clinical guidelines recommend at least 12 months of DAPT after BRS implantation. However, the correlation between prolonged DAPT and net clinical benefits remains unknown. Methods The SPARTA trial is designed to be a prospective, randomized, parallel-group, clinical trial. It aims to compare the benefits and risks of DAPT applied for either 12 or 36 months after XINSORB BRS implantation. The primary endpoints are the incidence of the composite endpoint of major adverse cardiac events (MACEs), including all-cause death, any myocardial infarction (MI), and all revascularizations, as well as Bleeding Academic Research Consortium Definition (BARC) type 3 or 5 bleeding events. The secondary endpoints of the study include the device-oriented composite endpoint of target lesion failure (defined as cardiac death, target vessel-related MI, or ischemia-driven target lesion revascularization), target vessel failure (defined as cardiac death, MI, or ischemia-driven target vessel revascularization), scaffold thrombosis, and minor bleeding events. This trial will enroll 2106 subjects treated with the XINSORB BRS only. All subjects will receive DAPT after the index procedure for 12 (± 1) months. Subjects without MACEs or major bleeding will be randomized to receive either 24 additional months of DAPT or aspirin alone. Discussion This trial is designed to investigate the impact of extending the duration of DAPT up to 3 years after XINSORB BRS implantation by investigating the balance of risks and benefits in a broad population of treated patients. Trial registration ClinicalTrials.gov NCT04501900 . Registered on 6 August 2020.

Abstract Resolvin D1 (RvD1) has been shown to provide effective protection against ischemia–reperfusion injury in multiple vital organs such as the heart, brain, kidney. However, the clinical translational potential of systemic administration of RvD1 in the treatment of ischemia–reperfusion injury is greatly limited due to biological instability and lack of targeting ability. Combining the natural inflammatory response and reactive oxygen species (ROS) overproduction after reperfusion injury, we developed a platelet-bionic, ROS-responsive RvD1 delivery platform. The resulting formulation enables targeted delivery of RvD1 to the injury site by hijacking circulating chemotactic monocytes, while achieving locally controlled release. In a mouse model of myocardial ischemia repefusuin (MI/R) injury, intravenous injection of our formula resulted in the enrichment of RvD1 in the injured area, which in turn promotes clearance of dead cells, production of specialized proresolving mediators (SPMs), and angiogenesis during injury repair, effectively improving cardiac function. This delivery system integrates drug bio-protection, targeted delivery and controlled release, which endow it with great clinical translational value.

Background: Periprocedural myocardial injury (PMI) is a common complication of percutaneous coronary intervention (PCI) associated with poor prognosis. Inflammation has been demonstrated to exert a crucial role in PMI. However, how the inflammation is initiated or sustained in PMI remains elusive. Methods: RNA-seq in peripheral blood mononuclear cells (PBMCs) from 3 Non-PMI and 6 PMI patients was performed with subsequent bioinformatics analysis. RNA-seq results were verified in a patient cohort. We also established the coronary microembolization (CME) mice model to mimic PMI. The activity of caspase-1 in PBMCs was detected by flow cytometry. The levels of interleukin (IL)-1β, IL-18 and cardiac troponin in plasma were measured by enzyme-linked immunosorbent assay. Results: We identified a total of 901 differentially expressed genes (DEGs) between Non-PMI and PMI patients. These DEGs participated in several inflammation-related processes. NOD-like receptor signaling pathway was significantly enriched in pathway analysis. All the key genes composed in the NLRP3 inflammasome, including NLRP3, PYCARD, CASP1 and IL1B, were upregulated in PMI patients. The activation of NLRP3 inflammasome was then verified by increased activity of caspase-1 in PBMCs, and elevated levels of IL-1β and IL-18 in plasma in PMI patients. Spearman analysis confirmed tight correlations between caspase-1 activity, IL-1β, IL-18 levels and troponin T level. In addition, caspase-1 activity, IL-1β and IL-18 levels were also enhanced in CME mice. Conclusions: We discovered that NLRP3 inflammasome was involved in PMI, thus providing evidence supporting the therapeutic value of NLRP3 inflammasome-targeted strategies in PMI.

A 79-year-old female patient was admitted to the hospital due to intense chest pain. Emergency percutaneous coronary intervention (PCI) revealed an occlusion in the distal portion of the left circumflex artery (LCx). The patient suffered from cardiac rupture, an uncommon yet extremely perilous condition, within 30 minutes following the procedure. This was verified through a computed tomography angiography (CTA) scan and bedside echocardiography. The etiology of cardiac rupture remains elusive, yet potential factors such as the patient's age, gender, initial acute myocardial infarction (AMI), and single-vessel disease without collateral circulation may be linked to this occurrence. This case report emphasizes that occluded tiny distal coronary arteries can also induce cardiac rupture and that a sufficient level of suspicion for the diagnosis of cardiac rupture should be raised when adequate fluid resuscitation fails to alleviate hypotension. Additionally, contrast-enhanced spiral computed tomography (CESCT) is highly effective in revealing certain pathological features associated with cardiac rupture.

BackgroundAtherosclerosis (AS) risk is elevated in diabetic patients, but the underlying mechanism such as involvement of epigenetic control of foam macrophages remains unclear. We have previously shown the importance of immune regulation on endothelial cells to AS development in diabetes. In this study, we examined the hypothesis that diabetes may promote AS through modification of the epigenetic status of macrophages.MethodsWe employed the Laser Capture Microdissection (LCM) method to evaluate the expression levels of key epigenetic regulators in both endothelial cells and macrophages at the AS lesions of patients. We then assessed the correlation between the significantly altered epigenetic regulator and serum levels of low-density Lipoprotein (LDL), triglycerides (TRIG) and high-density Lipoprotein (HDL) in patients. In vitro, the effects of high glucose on glucose utilization, lactate production, succinate levels, oxygen consumption and polarization in either undifferentiated or differentiated bone marrow-derived macrophages (BMDMs) were analyzed. The effects of depleting this significantly altered epigenetic regulator in macrophages on AS development were assessed in AS-prone diabetic mice.ResultsHistone deacetylase 3 (HDAC3) was identified as the most significantly altered epigenetic regulator in macrophages from the AS lesions in human diabetic patients. The levels of HDAC3 positively correlated with high serum LDL and TRIG, as well as low serum HDL. High glucose significantly increased glucose utilization, lactate production, succinate levels and oxygen consumption in cultured macrophages, and induced proinflammatory M1-like polarization. Macrophage depletion of HDAC3 significantly attenuated AS severity in AS-prone diabetic mice.ConclusionEpigenetically altered macrophages promote development of diabetes-associated AS, which could be prevented through HDAC3 depletion.

Aims: Altered lipid, energy metabolism and sleep disorders had been linked with coronary heart disease (CHD), however, the metabolic signatures and sleep rhythm in non-obstructive coronary atherosclerosis-CHD remain unclear. This pilot study aims to investigate the lipidome and central carbon metabolites profiles and associated sleep characteristics among CHD patients without traditional risk factors. Methods: From January to July 2021, 15 CHD patients and 15 healthy controls were randomly selected from the cardiology unit of Zhongshan Hospital, Shanghai. A total of 464 lipids and 45 central carbon metabolites (CCM) were quantified in blood plasma. Metabolic signatures were selected through orthogonal projections to latent structures discriminant analysis (OPLS-DA) and principal component analysis (PCA) was conducted to link the profiles of identified metabolites with CHD risk, sleep patterns, cardiometabolic traits and cardiac electrophysiologic parameters. Results: Using OPLS-DA, we identified 40 metabolites (variable influence on projection >1) that were altered in CHD patients, with 38 lipids, including 25 triacylglycerols (TAGs), 8 diacylglycerols (DAGs), being elevated and two CCM metabolites (i.e., succinic acid and glycolic acid) being reduced. Using PCA, four principal components (PCs) were identified and associated with increased risk of CHD. Specifically, one standard unit increasement in the PC that was characterized by high levels of DAG (18:1) and low succinic acid and the PC that was characterized by high levels of two sphingomyelins [SM (26:0) and SM (24:0)] was associated with 21% [odds ratio (OR) = 1.21, 95% CI: 1.02,1.43] and 14% (OR = 1.14,1.02,1.29) increased risk of CHD, respectively. Further regression analyses confirmed that the identified metabolites and the four PCs were positively associated with TG and ALT. Interestingly, glycolic acid was negatively associated with sleep quality and PSQI. Participants with night sleep mode tended to have a high level of the identified lipids, especially FFA (20:4). Conclusion: In the present pilot study, our findings provide clues on alterations of lipid and energy metabolism in CHD patients without traditional risk factors, with multiple triacylglycerols and diacylglycerols metabolites seemingly elevated and certain nonlipids metabolites (e.g., succinic acid and glycolic acid) decreased in cases. Considering the limit sample size, further studies are warranted to confirm our results.

Abstract 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. Graphical Abstract

Abstract Dilated cardiomyopathy (DCM), as characterized by the left ventricular dilatation and contractile dysfunction, is one of the molecular mechanisms of which are largely unexplored. Here, we profiled the region‐resolved transcriptome and proteome of healthy and DCM human myocardial tissue and obtained the deep‐coverage dataset consisting 7,605 proteins and 19,880 transcripts in four chambers of the human heart. On the basis of the core proteome and transcriptome characters of the healthy hearts, chamber‐specific proteome alterations were further revealed in end‐stage DCM, among which extracellular matrix (ECM), mitochondrial function, and muscle contraction were the most dysregulated biological processes. Protein–protein interaction network demonstrated divergent functional networks of DCM atrium and ventricle. Additionally, a 4‐biomarker panel (CTSB, vWF, C9, and MFGE8) was established with promising diagnostic potential for the DCM. Collectively, our data provide a global proteomic basis of the chamber‐specific cardiac tissue, and establish a protein catalog that holds promise for better definition and diagnosis of DCM.

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

Background: The perturbation of fatty acid metabolism in heart failure (HF) has been a critical issue. It is unclear whether the amounts of circulating carnitines will benefit primary etiology diagnosis and prognostic prediction in HF. This study was designed to assess the diagnostic and prognostic values of serum carnitine profiles between ischemic and non-ischemic derived heart failure. Methods: HF patients (non-ischemic dilated cardiomyopathy: DCM-HF, n = 98; ischemic heart disease: IHD-HF, n = 63) and control individuals (n = 48) were enrolled consecutively. The serum carnitines were quantitatively measured using the UHPLC-MS/MS method. All patients underwent a median follow-up of 28.3 months. Multivariate Cox regression analysis was performed during the prognosis evaluation. Results: Amongst 25 carnitines measured, all of them were increased in HF patients, and 20 acylcarnitines were associated with HF diagnosis independently. Seven acylcarnitines were confirmed to increase the probability of DCM diagnosis independently. The addition of isobutyryl-L-carnitine and stearoyl-L-carnitine to conventional clinical factors significantly improved the area under the receiver operating characteristic curve (ROC) from 0.771 to 0.832 (p = 0.023) for DCM-HF diagnosis (calibration test for the composite model: Hosmer-Lemeshow χ2 = 7.376, p = 0.497 > 0.05). Using a multivariate COX survival analysis adjusted with clinical factors simultaneously, oleoyl L-carnitine >300 nmol/L (HR = 2.364, 95% CI = 1.122–4.976, p = 0.024) and isovaleryl-L-carnitine p = 0.026) increased the prediction of all-cause mortality independently, while linoleoyl-L-carnitine >420 nmol/L, succinyl carnitine >60 nmol/L and isovaleryl-L-carnitine

Doxorubicin (DOX) as a chemotherapeutic agent can cause mitochondrial dysfunction and heart failure. COX5A has been described as an important regulator of mitochondrial energy metabolism. We investigate the roles of COX5A in DOX-induced cardiomyopathy and explore the underlying mechanisms. C57BL/6J mice and H9c2 cardiomyoblasts were treated with DOX, and the COX5A expression was assessed. An adeno-associated virus serum type 9 (AAV9) and lenti-virus system were used to upregulate COX5A expression. Echocardiographic parameters, morphological and histological analyses, transmission electron microscope and immunofluorescence assays were used to assess cardiac and mitochondrial function. In a human study, we found that cardiac COX5A expression was dramatically decreased in patients with end-stage dilated cardiomyopathy (DCM) compared to the control group. COX5A was significantly downregulated following DOX stimulation in the heart of mice and H9c2 cells. Reduced cardiac function, decreased myocardium glucose uptake, mitochondrial morphology disturbance, reduced activity of mitochondrial cytochrome c oxidase (COX) and lowered ATP content were detected after DOX stimulation in mice, which could be significantly improved by overexpression of COX5A. Overexpression of COX5A effectively protected against DOX-induced oxidative stress, mitochondrial dysfunction and cardiomyocyte apoptosis in vivo and in vitro. Mechanistically, the phosphorylation of Akt (Thr308) and Akt (Ser473) were also decreased following DOX treatment, which could be reserved by the upregulation of COX5A. Furthermore, PI3K inhibitors abrogated the protection effects of COX5A against DOX-induced cardiotoxicity in H9c2 cells. Thus, we identified that PI3K/Akt signaling was responsible for the COX5A-mediated protective role in DOX-induced cardiomyopathy. These results demonstrated the protective effect of COX5A in mitochondrial dysfunction, oxidative stress, and cardiomyocyte apoptosis, providing a potential therapeutic target in DOX-induced cardiomyopathy.

Abstract Background The jailed balloon technique is widely used for coronary bifurcation lesions, but a residual risk of SB occlusion remains, necessitating SB rewiring and further interventions, including balloon inflation or stenting, which may result in failure and SB loss. This study introduced a novel modified technique of small side branch (SB) protection, namely, double kissing inflation outside the stent (DKo) technique, for coronary bifurcations without the need for SB rewiring. Methods We performed the DKo technique in consecutive patients in our center from 1/2019 to 12/2019. The procedure was as follows. We inserted a guide wire into both branches followed by proper preparation. The SB balloon was simultaneously inflated with main vessel (MV) stenting. The SB balloon remained in situ until it was kissing inflated with postdilation of the bifurcation core, which is different from traditional strategies. The proximal optimization technique was performed with a short noncompliant balloon strictly not exceeding the bifurcation. Rates of SB loss and in-hospital outcomes were evaluated. Results The technique was successfully performed in all 117 enrolled patients without any rewiring or SB loss. The mean lesion lengths of the MV and SB were 38.3 ± 19.9 mm and 11.7 ± 7.1 mm, respectively. On average, 1.5 ± 0.6 stents were used per patient, while the mean pressure of the SB balloon was 7.4 ± 3.1 atm. DKo achieved excellent procedural success in the proximal and distal MVs: increased minimal lumen diameter (0.64 ± 0.58 mm to 3.05 ± 0.38 mm, p

Abstract Background Due to the technical limitations of coronary artery angiography (CAG), ramus intermedius (RI) is sometimes difficult to distinguish from a high-origin obtuse marginal branch or a high-origin diagonal branch. This study sought to investigate the role of intravascular ultrasonography (IVUS) in the rectification of angiographically judged RI. Methods This study retrospectively analyzed 165 patients who were reported to have an RI based on CAG and underwent IVUS implementation from 02/01/2009 to 31/12/2019 in Zhongshan Hospital, Fudan University. Taking IVUS as the gold standard, we calculated the accuracy of RI identification by CAG and evaluated the impact of RI on revascularization strategy. Results Among the 165 patients, 89 patients (54%) were demonstrated to have an RI on IVUS (IVUS-RI), 32 patients (19%) were identified to have a high-origin diagonal branch on IVUS (IVUS-h-D), and 44 patients (27%) had an actual high-origin obtuse marginal artery on IVUS (IVUS-h-OM). Among 84 patients who underwent one-stent crossover stenting because of left main furcation lesions (48 patients in the IVUS-RI group, 12 patients in the IVUS-h-D group, and 24 in the IVUS-h-OM group), 14.6% of patients in the IVUS-RI group, 33.3% in the IVUS-h-D group and 0% in the IVUS-h-OM group had CAG-RI compromise (P = 0.02), which was defined as severe stenosis of the RI ostium (> 75%) or significant RI flow impairment (TIMI

Abstract Coronary microembolization (CME), a common reason for periprocedural myocardial infarction (PMI), bears very important prognostic implications. However, the molecular mechanisms related to CME remain largely elusive. Statins have been shown to prevent PMI, but the underlying mechanism has not been identified. Here, we examine whether the NLRP3 inflammasome contributes to CME-induced cardiac injury and investigate the effects of statin therapy on CME. In vivo study, mice with CME were treated with 40 mg/kg/d rosuvastatin (RVS) orally or a selective NLRP3 inflammasome inhibitor MCC950 intraperitoneally (20 mg/kg/d). Mice treated with MCC950 and RVS showed improved cardiac contractile function and morphological changes, diminished fibrosis and microinfarct size, and reduced serum lactate dehydrogenase (LDH) level. Mechanistically, RVS decreased the expression of NLRP3, caspase-1, interleukin-1β, and Gasdermin D N-terminal domains. Proteomics analysis revealed that RVS restored the energy metabolism and oxidative phosphorylation in CME. Furthermore, reduced reactive oxygen species (ROS) level and alleviated mitochondrial damage were observed in RVS-treated mice. In vitro study, RVS inhibited the activation of NLRP3 inflammasome induced by tumor necrosis factor α plus hypoxia in H9c2 cells. Meanwhile, the pyroptosis was also suppressed by RVS, indicated by the increased cell viability, decreased LDH and propidium iodide uptake in H9c2 cells. RVS also reduced the level of mitochondrial ROS generation in vitro. Our results indicate the NLRP3 inflammasome-dependent cardiac pyroptosis plays an important role in CME-induced cardiac injury and its inhibitor exerts cardioprotective effect following CME. We also uncover the anti-pyroptosis role of RVS in CME, which is associated with regulating mitochondrial ROS.

BackgroundCurrent 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.MethodsPatients 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.ResultsIn the retrospective analysis, unwilling passage of guidewire into branches occurred more in the Traditional group than in the Knuckle group (9.5 vs. 0.08%, p < 0.001). Two patients in the Traditional group experienced guidewire-associated perforation. One patient was treated with covered stent for internal mammarian artery perforation, while the other was managed with compression for brachial branch perforation. In the randomized controlled study, unwilling passage of guidewire also occurred more in the Traditional group (10.8 vs. 1%, p < 0.001). Median duration of guidewire advancement from the sheath to aortic root significantly decreased from 33 seconds in the Traditional group to 21 seconds in the Knuckle group.ConclusionActive knuckle angle guidewire represented a novel method to prevent unwilling passage and associated perforation with efficiency improvement and a reduction in radiation exposure.

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

Abstract Background Provisional 1-stent technique is currently regarded as the default approach for the majority of bifurcation lesions. Nonetheless, 2-stent techniques may be required for complex bifurcations with high compromise risk or fatal consequences of side branch (SB) occlusion. Limitations exist in current approaches, as stents gap, multiple metal layers and stent malapposition caused by imprecise placement with fluoroscopic guide and intrinsic technical defects. This study was designed to investigate the effectiveness of the novel Szabo 2-stent technique for coronary bifurcation lesions. Methods In the Szabo 2-stent technique, one stent is precisely implanted at the SB ostium with Szabo technique resulting in a single strut protruding into the main vessel (MV). After MV rewiring and SB guidewire withdrawal, another stent is implanted in MV followed by proximal optimization technique, SB rewiring, and final kissing inflation (FKI). Results The technique tested successfully in silicone tubes (n = 9) with: procedure duration, 31.2 ± 6.8 min; MV and SB rewiring time, 26.8 ± 11.2 s and 33.3 ± 15 s; easy FKI; and 2.3 ± 0.5 balloons/procedure. Bifurcation lesions (n = 22) were treated with angiographic success in MV and SB, respectively: increased minimal lumen diameter (0.63 ± 0.32 mm to 3.20 ± 0.35 mm; 0.49 ± 0.37 mm to 2.67 ± 0.25 mm); low residual stenosis (12.4 ± 2.4%; 12.4 ± 2.3%); and intravascular ultrasound confirmed (n = 19) full coverage; minimal overlap and malapposition; minimal lumen area (2.4 ± 1.2 mm2; 2.1 ± 1.0 mm2); plaque burden (78.1 ± 11.3%; 71.6 ± 15.5%); and minimal stent area (9.1 ± 1.6 mm2; 6.1 ± 1.3 mm2). Periprocedural cardiac troponin increased in 1 asymptomatic patient without electrocardiographic change. There was no target lesion failure (cardiac death, myocardial infarction, target lesion revascularization) at 6-month follow-up. Conclusions The Szabo 2-stent technique for bifurcation lesions provided acceptable safety and efficacy at short-term follow-up.

Abstract Background Myocardial infarction (MI) is a major cause of death worldwide. Although percutaneous coronary intervention and coronary artery bypass grafting can prolong life, cardiac damage persists. In particular, cardiomyocytes have no regenerative capacity. Mesenchymal stem cells (MSCs) are attractive candidates for the treatment of MI. The manner by which MSCs exert a beneficial effect upon injured cells is a source of continued study. Methods After the isolation and identification of exosomes from MSCs, the expression of miR-210 was determined by microarray chip. Subsequently, gain- and loss-function approaches were conducted to detect the role of exosomes and exosomal-miR-210 in cell proliferation and apoptosis of cardiomyocytes, as well as the MI in vivo. Dual-Luciferase Report Gene System was used to demonstrate the target gene of miR-210. Results We tested the hypothesis that MSC-derived exosomes transfer specific miRNA to protect cardiomyocytes from apoptotic cell death. Interestingly, direct cardiac injection of MSC exosomes reduced infarct size and improved heart function after coronary ligation. In vitro, the MSC exosomes enhanced cardiomyocyte survival to hypoxia. Confirmation of exosome uptake in myocytes was confirmed. Dual-luciferase reporter assay implicated miR-210 as a mediator of the therapeutic effect and AIFM3 as a downstream target. Treatment with miR-210 overexpressing MSC exosomes improved myocyte protection to both in vitro and in vivo stress. Furthermore, the endogenous and exogenous miR-210 had the same therapeutic effects. Conclusion These results demonstrated that the beneficial effects offered by MSC-exosomes transplantation after MI are at least partially because of excreted exosome containing mainly miR-210. Graphical abstract

Abstract Background The management of diagonal branch (D) occlusion is still controversary. The association between the flow loss of D and the prognosis remains unclear. We aim to detect the impact of D flow on cardiac function and clinical outcomes in patients with anterior ST-segment elevation myocardial infarction (STEMI). Methods Patients with anterior STEMI undergoing primary percutaneous coronary intervention (PCI) at our clinic between October 2015 and October 2018were reviewed. Anterior STEMI due to left anterior descending artery (LAD) occlusion with or without loss of the main D flow (TIMI grade 0–1 or 2–3) was enrolled in the analysis. The short- and long-term incidence of major adverse cardiac events (MACEs, a composite of all-cause death, target vessel revascularization and reinfarction) and left ventricular ejection fraction (LVEF) were analyzed. Results A total of 392 patients (mean age of 63.9 years) with anterior STEMI treated with primary PCI was enrolled in the study. They were divided into two groups, loss (TIMI grade 0–1, n = 69) and no loss (TIMI grade2–3, n = 323) of D flow, before primary PCI. Compared with the group without loss of D flow, the group with loss of D flow showed a lower LVEF post PCI (41.0% vs. 48.8%, p = 0.003). Meanwhile, loss of D flow resulted in the higher in-hospital, one-month, and 18-month incidence of MACEs, especially in all-cause mortality (all p

Background: To determine whether intracoronary pro-urokinase or tirofiban improves myocardial reperfusion during primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI).Methods: The study included patients with acute STEMI presenting within 12 h of symptoms at 11 hospitals in China between November 2015 and July 2017. Patients were randomized to receive selective intracoronary infusion of recombinant pro-urokinase (20 mg), tirofiban (10 μg/kg), or saline (20 mL) proximal to the infarct-related lesion over a 3-min period before stent implantation during primary PCI. The primary outcome was final corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) after PCI.Results: This study included 345 patients. Initial angiography identified a high-grade thrombus (TIMI 4–5) in 80% of patients. Final CTFC after PCI was significantly lower in the pro-urokinase (P < 0.001) and tirofiban (P < 0.001) groups than in the saline group and similar between the pro-urokinase and tirofiban groups (P > 0.05). The pro-urokinase (P = 0.008) and tirofiban groups (P = 0.022) had more complete ST-segment resolution at 2 h and lower peak creatine kinase-MB levels after PCI than the saline group (P = 0.006 and P = 0.023). The 30-day incidence of major adverse cardiac events was 4.5% in the pro-urokinase group, 3.4% in the tirofiban group, and 2.6% in the saline group. The incidence of in-hospital TIMI major bleeding events was low and comparable between groups.Conclusions: Adjunctive intracoronary pro-urokinase or tirofiban given before stent implantation during primary PCI improves myocardial reperfusion without increasing the incidence of major bleeding events.

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

Abstract Background Heart failure (HF) is the end stage of most heart disease. Mesenchymal stem cells (MSCs), with their specific biological effects, have been applied in several clinical trials to evaluate the efficacy in HF therapy. We performed this meta-analysis to review the clinical evidence of their therapeutic effect on HF. Methods Three databases were searched. The outcomes of interest were death, readmission, the 6-min walk test (6MWT), New York Heart Association (NYHA) class and left ventricular ejection fraction (LVEF). The relative risk (RR) and weighted mean difference (WMD) were calculated to evaluate the effects of MSCs on HF compared to placebo. Results A total of nine studies were included, involving 612 patients who underwent MSCs or placebo treatment. The overall rate of death showed a trend of reduction of 36% (RR [CI] = 0.64 [0.35, 1.16], p = 0.143) in the MSC treatment group. The incidence of readmission was reduced by 34% (RR [CI] = 0.66 [0.51, 0.85], p = 0.001). The patients in the MSC treatment group realised an average of 40.44 m (WMD [95% CI] = 40.44 m [19.07, 61.82], p

Abstract Background Primary percutaneous coronary intervention (PCI) for patients presenting with acute myocardial infarction (AMI) caused by left main coronary artery occlusion is associated with significantly higher mortality and risks of major adverse cardiovascular events. Deferred stent implantation may improve prognosis of primary PCI by reducing distal embolization and no-reflow phenomenon. There is no randomized clinical trial focusing on the effect and outcome of deferred stent implantation on primary PCI for left main coronary artery occlusion in contrast with conventional strategy. Methods The Optimal Strategy of Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction due to Unprotected Left Main Coronary Artery Occlusion (OPTIMAL) study (ClinicalTrials.gov Identifier: NCT03282773) is an open-label, randomized, multicenter clinical trial in which 480 patients presenting with AMI caused by left main coronary artery occlusion recruited from 30 hospitals in mainland China will be randomly assigned 1:1 to immediate stenting or deferred stenting (scheduled 4–10 days after primary angioplasty) groups. The primary endpoint is a composite of all-cause mortality or recurrent myocardial infarction at 30 days after randomization. The secondary outcomes include all-cause mortality, cardiac death, recurrent myocardial infarction, and unplanned target vessel revascularization at 30 days, 6 months, and 12 months. Discussion The OPTIMAL study is designed to compare the clinical performance of deferred stenting with that of immediate stenting for AMI caused by left main coronary artery occlusion. Trial registration ClinicalTrials.gov Identifier: NCT03282773. Registered on 10 September 2017.

Objective: The aim of the study is to assess the predictors of failure of percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) lesions using a retrograde approach. Methods: The present study retrospectively enrolled all 211 patients who underwent retrograde CTO PCI from January 2009 to December 2015 at Shanghai Institute of Cardiovascular Disease. Multivariate Cox regression analysis was used to assess potential predictors of retrograde CTO PCI failure including sex, vascular access site, sheath size, prior PCI, prior coronary artery bypass grafting, history of myocardial infarction, target vessel of CTO, J-CTO score, retrograde wire crossing collaterals, and reverse controlled antegrade and retrograde subintimal tracking (CART) use. Results: Of the 211 patients studied, retrograde CTO PCI was successful in 115 (54.5%) patients, and in an additional 46 (21.8%) with an antegrade approach after retrograde failure. For the 50 (23.7%) patients who failed both retrograde and antegrade approaches, the most common (50% [25/50]) reason was inability to cross collaterals with the retrograde wire. This group of patients had fewer instances of a prior PCI (P < 0.05). Retrograde CTO PCI failure rate was lower with increasing sheath size and with either radial-only or one radial and one femoral access versus femoral-only access (P < 0.05). A multivariate Cox regression analysis showed that the inability to cross collaterals with the retrograde wire (hazard ratio, 5.52 [95% confidence interval, 2.08–12.81];P < 0.001), no prior PCI (3.27 [1.24–8.58];P = 0.01), and no reverse CART use (4.19 [1.33–13.19];P = 0.03) were an independent predictors of retrograde CTO PCI failure. Conclusion: Independent predictors of retrograde CTO PCI failure were the inability to cross collaterals with the retrograde wire, no prior PCI, and no reverse CART use. Vascular access site and sheath size do not have effect on the success of the retrograde approach.

Inflammation is a crucial mediator of atherosclerosis, and several therapeutic methods that focus on inflammatory cytokines, including interleukin-1β (IL-1β), have proven effective in preventing atherogenesis. Circular RNAs (circRNAs) are a subclass of non-coding RNAs (ncRNAs) that can exert critical functions in the regulation of atherosclerosis. Here, using circRNA sequencing, we revealed that circRNA circDENND1B (mmu_circ_0000081) is a promising novel mediator of atherosclerosis in mouse. The expression of circDENND1B is negatively related to the progression of atherosclerosis and foam cell formation, and the upregulation of circDENND1B significantly alleviates foam cell formation induced by ox-LDL by promoting cholesterol efflux. Moreover, circDENND1B participates in the anti-atherosclerotic effect of IL-1β monoclonal antibody (IL-1β mAb), both in vivo and in vitro. With bioinformatic prediction and RNA pull-down assays, we determined that circDENND1B sponges mmu-miR-17-5p to promote Abca1 expression in cells treated with IL-1β mAb. Our study revealed that circDENND1B, a novel regulator of cholesterol efflux, is a potential therapeutic target in atherosclerosis and provides new insights into the interaction between inflammation and cholesterol transport.

Objectives. The present study aimed to investigate the short- and long-term clinical outcomes of self-made polyurethane-covered stents (PU-CS) in patients for the management of coronary artery perforation (CAP) during percutaneous coronary intervention (PCI). Background. Coronary artery perforation is reckoned as a serious complication in PCI and associated with considerable morbidity and mortality. Covered stents have been used for treating the life-threatening CAP during PCI. But in some catheterization laboratories, no commercial CS is immediately available when there is an urgent need for CS to rescue the coronary rupture site. Methods. We retrospectively identified 24 patients who underwent 31 self-made PU-CS implantations due to CAP in Zhongshan Hospital, Fudan University, from June 2015 to January 2020. Results. The total procedural success rate of CS to seal the perforation was 79.2%. Nine patients (37.5%) developed cardiac tamponade, of which 8 patients (33.3%) underwent pericardiocentesis and 4 patients (16.7%) underwent cardiac surgeries. Except for 4 cardiac death cases (16.7%), none of myocardial infarction (MI), target lesion revascularization (TLR), and stent thrombosis (ST) was reported during hospital stay. Data from 22 patients (91.7%) were available at 610.4 ± 420.9 days of follow-up. Major adverse cardiac events (MACE) occurred in 6 patients (27.3%), including 5 cases of cardiac death and one TLR case. Conclusions. Self-made PU-CS demonstrates high rates of successful delivery and sealing of severe CAP during PCI. Although the in-hospital mortality remains high after PU-CS implantation, the long-term follow-up shows favorable clinical outcomes, indicating the feasibility of PU-CS in treating CAP.

Objective. The initial recanalization rate of coronary chronic total occlusions (CTOs) is >85% when performed by experienced operators, but only 10% of prior failed CTO patients receive reattempted recanalization. This retrospective study analyzed the success rate and strategies used in reattempt percutaneous coronary intervention (PCI) of CTOs after prior failures. Methods. Overall, 206 patients with 212 CTOs were enrolled. All patients with prior recanalization failures received reattempt PCIs from January 2015 to March 2019 at Zhongshan Hospital, Fudan University. Data on clinical factors (age, sex, comorbidities, left ventricular ejection fraction, history of cigarette usage, and revascularization), angiographic characteristics of CTOs (target lesion, Japanese Chronic Total Occlusion (J-CTO) score, the morphology of CTO lesions, and collateral channel scale), strategies (procedural approach and use of devices), and major adverse events were obtained and analyzed. Results. The mean age of enrolled patients was 60.96 ± 12.36 years, with a male predominance of 90.3%. Of the patients, 47.1% had a prior myocardial infarction and 70.4% underwent stent implantation previously, while the in-stent occlusion rate was 6.6%. CTOs were primarily localized in the left anterior descending artery (43.9%) and the right coronary artery (43.9%). 80.7% of lesions were classified as very difficult (J-CTO score ≥3), and the overall success rate was 81.1%. In multivariable regression analysis, J-CTO score, collateral channel scale, application of coronary multispiral computed tomography angiography, dual injection, intravascular ultrasound, active greeting technique, parallel wiring, and CTO morphology were predictors of recanalization success. There were no significant differences in rates of procedural complications between the final recanalization success and failure groups. Conclusions. Recanalization of complex CTOs is associated with high success rate and low complication rates when performed by high-volume CTO operators and after multiple reattempts.

Background. Periprocedural myocardial injury (PMI) is a most common complication of percutaneous coronary intervention (PCI). Microembolization and inflammation underlying PMI could lead to coronary microvascular dysfunction (CMD) and vice versa. Reactive hyperemia index (RHI) assessed by peripheral artery tonometry (PAT) has been considered as a noninvasive method to assess endothelial function and CMD, which could be useful to predict PMI. Methods. 268 patients suspected with stable coronary artery disease (CAD) and scheduled for elective coronary angiography were enrolled. RHI was measured by using the Endo-PAT2000™ device before angiography. The association among RHI, PMI, and cardiovascular events was further assessed. Results. In this cohort, 189 patients (70.5%) were diagnosed with CAD and 119 patients (44.4%) underwent drug-eluting stent (DES) implantation. Compared with patients without CAD, CAD patients had lower RHI (1.88 ± 0.55 vs. 2.02 ± 0.58, P

Aims: This study investigated the application of the domestic Argus Insight-100 optical coherence tomography (OCT) system in porcine arteries and to evaluate the efficiency and safety of Insight-100°CT immediately after implantation and at 4-week follow-up. Subjects and Methods: Eight porcine arteries were implanted with HELIOS drug-eluting stents. Scans were performed with Insight-100 and C7-XR OCT immediately after implantation and at 4-week follow-up, respectively, to obtain lumen images and measured data. Statistical Analysis Used: SPSS v22 software was used for statistical analysis. Results: Both the Insight-100 and C7-XR scans were successfully performed during the implantation and follow-up. Parameters at 4-week postoperatively showed no significant difference between these two groups. No differences were observed in the reference vessel minimal lumen diameters between Insight-100 and C7-XR in the same frame (2.59 ± 0.18 mm vs. 2.60 ± 0.23 mm, respectively, P = 0.91 and 2.83 ± 0.27 mm vs. 2.98 ± 0.27 mm, respectively, P = 0.19). Moreover, the values of mean lumen diameter in the stent segment are comparable between Insight-100 and C7-XR (2.91 ± 0.11 mm vs. 2.97 ± 0.16 mm, P = 0.50). At 4-week follow-up, the mean lumen diameter of Insight-100 was 2.54 ± 0.28 mm, while that of C7-XR was 2.55 ± 0.32 mm, without difference between two groups (P = 0.92). Conclusions: The Argus OCT system appears to be safe during implantation and follow-up. The efficacy and measurement accuracy of Argus OCT is equivalent to that of the C7-XR.

Abstract Background The stiffness of the myocardial extracellular matrix (ECM) and the transplanted cell type are vitally important in promoting angiogenesis. However, the combined effect of the two factors remains uncertain. The purpose of this study is to investigate in vitro the combined effect of myocardial ECM stiffness postinfarction with a bone marrow-derived cell subset expressing or not expressing CD34 on endothelial lineage commitment. Methods Myocardial stiffness of the infarct zone was determined in mice at 1 h, 24 h, 7 days, 14 days, and 28 days after coronary artery ligation. Polyacrylamide (PA) gel substrates of different stiffnesses were prepared to mechanically mimic the myocardial ECM after infarction. Mouse bone marrow-derived CD34+ and CD34– cells were seeded on the flexible PA gels. The double-positive expression for DiI-acetylated low-density lipoprotein (acLDL) uptake and fluorescein isothiocyanate-Ulex europaeus agglutinin-1 (FITC-UEA-1) binding, the endothelial lineage antigens CD31, von Willebrand factor (vWF), Flk-1, and VE-cadherin, as well as cytoskeleton were measured by immunofluorescent staining on day 7. Cell apoptosis was evaluated by both immunofluorescent staining and flow cytometry at 24 h after culture. Results We found that the numbers of the CD34+ cell subset adherent to the flexible substrates (4–72 kPa) was much larger than that of the CD34– subset. More double-positive cells for DiI-acLDL uptake/FITC-UEA-1 binding were seen on the 42-kPa (moderately stiff) substrate, corresponding to the stiffness of myocardial ECM at 7–14 days postinfarction, compared with those on substrates of other stiffnesses. Similarly, the moderately stiff substrate showed benefits in promoting the positive expressions of the endothelial lineage markers CD31, vWF, Flk-1, and VE-cadherin. In addition, the cytoskeleton F-actin network within CD34+ cells was organized more significantly at the leading edge of the adherent cells on the moderately stiff (42 kPa) or stiff (72 kPa) substrates as compared with those on the soft (4 kPa and 15 kPa) substrates. Moreover, the moderately stiff or stiff substrates showed a lower percentage of cell apoptosis than the soft substrates. Conclusions Infarcted myocardium-like ECM of moderate stiffness (42 kPa) more beneficially regulated the endothelial lineage commitment of a bone marrow-derived CD34+ subset. Thus, the combination of a CD34+ subset with a “suitable” ECM stiffness might be an optimized strategy for cell-based cardiac repair.

Objective: The main objective is to investigate the value of the treadmill exercise test (TET) for guiding the clinical therapy of myocardial bridging (MB) patients. Subjects and Methods: We retrospectively analyzed the TET results of 70 patients with MB and their electrocardiography (ECG) characteristics then evaluated the relationship between the TET results and the patients' clinical characteristics, including sex, age, bridge length, and the degree of bridge compression. Results: There were 27 patients (38.6%) with a positive TET, 31 (44.3%) negative, and 12 (17.1%) probably positive. For positive and probably positive patients, 31 patients had ECGs that shared similar ST segments depression in II, III, and avF leads with or without V4–V6 segments depression. Male patients had a higher TET positive rate than female patients. No relationships were found between the bridge length, bridge compression, and TET results. In addition, no relationships were identified between hypertension, diabetes, hyperlipemia, smoking, age, and TET results. Conclusions: The main ECG characteristics of patients with MB whose TET results were positive were II, III, and avF ST-T segment depression with or without V4–V6 segment depression. Male patients had higher TET positive rates than female patients. No relationships were identified between the bridge length, bridge compression, and the TET results.

Heart failure (HF) is a worldwide pandemic with an unacceptable high level of morbidity and mortality. Understanding the different pathophysiological mechanisms will contribute to prevention and individualized therapy of HF. We established mouse models for ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) by inducing myocardial infarction (MI) and Coxsackievirus B3 infection, respectively. Isobaric tags for relative and absolute quantitation and liquid chromatography coupled with tandem mass spectrometry technology was used to identify the protein expression profiles in control and failing hearts. A total of 1,638 proteins were identified and compared in this proteomics analysis. Among them, 286 proteins were differently expressed. Gene ontology, KEGG pathway and ingenuity pathway analysis was performed to systematically assess the potential connections of the differentially expressed proteins to biological functions. Compared with control group, the differentially expressed proteins derived from the hearts of ICM and DCM mice were partially similar and mainly modulated in oxidative phosphorylation, metabolism and protein folding pathways. Moreover, difference still existed, the differentially expressed proteins between DCM and ICM hearts were significantly modulated in oxidative phosphorylation, metabolic and AMPK signaling pathways. Confirmatory western bolt analysis demonstrated that SDHB was down-regulated in both ICM and DCM hearts, while UQCRQ, GLUT4 and adiponectin were up-regulated in ICM hearts. Adenosine triphosphate (ATP) concentration significantly decreased in both DCM and ICM hearts. The protein expression of phospho-AMPKα decreased significantly in DCM hearts, but increased in ICM. In summary, oxidative phosphorylation, cardiac metabolism, and protein folding play critical roles in the pathogenesis of HF. The diverse changes in protein expression profiles between failing hearts induced by either MI or CVB3 infection demonstrated the heterogeneity of HF. Understanding the differences in proteome profiles could offer more precise therapeutic options for HF.

Background. Recent reports about radiation risk gradually raised the safety concerns for interventional therapy. However, limited data exist on the optimized radiation strategy in primary percutaneous coronary intervention (P-PCI) for patients with ST-segment-elevation myocardial infarction (STEMI). Methods. A total of 214 STEMI patients undergoing P-PCI were retrospectively analyzed. Patients were divided into the optimized radiation strategy (ORS) group (N = 151) and normal radiation strategy (NRS) group (N = 63) according to the radiation protocol utilized. The primary endpoint was the relative dose reduction of total air kerma. The secondary endpoint was 30-day major adverse cardiac and cerebrovascular events (MACCE), as a composite of all-cause death, reinfarction, ischemia-driven target vessel revascularization, and stroke. Results. Patient groups were well matched for baseline characteristics. There were no differences in terms of age, body mass index, radial artery access, nonculprit vessel PCI, and fluoroscopy time between 2 groups. With optimized radiation strategy, a 40.9% radiation dose reduction (901.2 ± 628.7 mGy versus 1524.0 ± 866.6 mGy, p

Introduction. Although coronary artery disease (CAD) presentations and clinical outcomes differ by sex, little is known about premature CAD (PCAD). The present analysis aimed to evaluate the gender-related differences of PCAD in an Asian population from the FOCUS registry. Methods. A total of 1397 Asian young patients with angiographically confirmed CAD undergoing drug-eluting stent implantation were included in this analysis and divided into two groups according to the genders. Patients were followed up for three years and clinical outcomes were compared between groups. Results. Young women were older and more likely to have hypertension and diabetes than men (all p0.05). Conclusion. Despite remarkable differences in clinical characteristics between Asian males and females with PCAD, the two groups did not differ significantly in clinical outcomes.

Background: Background: Delayed platelet inhibition by ticagrelor has been initially documented in STEMI subjects. To the best of our knowledge, no data exists about the direct description of early onset of platelet inhibition after ticagrelor loading dose (LD) in different clinical forms of ACS, especially in Chinese patients. The ST-ON-SET study is designed to address this unmet need. Method/Design: The ST-ON-SET study is a single center, prospective, observational, open-label, investigator-initiated study. Platelet inhibition assessed by Light transmittance aggregometry (LTA) and plasma concentrations of ticagrelor and its metabolites would be investigated serially. The primary outcome is the inhibition of platelet aggregation measured by LTA at 2 hours after ticagrelor LD. Moreover, baseline inflammatory and thrombotic biomarkers would be measured to investigate the potential underlying influences of platelet inhibition. Conclusion: The study is designed to characterize pharmacokinetic and pharmacodynatic profiles of ticagrelor LD in Chinese STEMI and NSTEMI patients. Furthermore, preliminary investigation of the underlying mechanism of initial delayed platelet inhibition by ticagrelor would be conducted.

Coronary microembolization (CME) is an important clinical problem, and it is related to poor outcome. The specific molecular mechanisms of CME are not fully understood. In the present study, we established a mice model of CME. Isobaric tags for relative and absolute quantitation (iTRAQ) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) technologies identified 249 differentially expressed proteins in the myocardial tissues of CME mice as compared with sham-operated mice. Bioinformatics analysis demonstrated that these differentially expressed proteins were enriched in several energy metabolism or cytoskeleton organization related processes or pathways. Quantitative PCR and Western blotting validation experiments revealed that succinate dehydrogenase (SDHA and SDHB) were upregulated, Rho GDP dissociation inhibitor α (RhoGDIα) and Filamin-A (FLNA) were downregulated significantly in CME mice. These findings indicated that the alternations of the cytoskeleton and energy metabolism pathways play important roles in the pathogenesis of CME, future studies are warranted to verify if targeting these molecules might be useful to alleviate CME injury or not.

The original article [1] displayed a co-author, Junbo Ge who has since stated that he should not have been a co-author in the article; the article has now been amended to remove Junbo Ge accordingly. All authors agreed to this amendment.

The therapeutic effect of transplantation of mesenchymal stem cells (MSCs) in myocardial infarction (MI) appears to be limited by poor cell viability in the injured tissue, which is a consequence of oxidative stress and pro-apoptotic factors. High density lipoprotein (HDL) reverses cholesterol transport and has anti-oxidative and anti-apoptotic properties. We, therefore, investigated whether HDL could protect MSCs from oxidative stress-induced apoptosis. MSCs derived from the bone marrow of rats were pre-incubated with or without HDL, and then were exposed to hydrogen peroxide (H2O2) in vitro, or were transplanted into experimentally infarcted hearts of rats in vivo. Pre-incubation of MSCs with HDL increased cell viability, reduced apoptotic indices and resulted in parallel decreases in reactive oxygen species (ROS) in comparison with control MSCs. Each of the beneficial effects of HDL on MSCs was attenuated by inhibiting the PI3K/Akt pathway. Preconditioning with HDL resulted in higher MSC survival rates, improved cardiac remodeling and better myocardial function than in the MSC control group. Collectively, these results suggest that HDL may protect against H2O2-induced apoptosis in MSCs through activation of a PI3K/Akt pathway, and by suppressing the production of ROS.

Magnetic targeting has the potential to enhance the therapeutic effects of stem cells through increasing retention of transplanted cells. To investigate the effects of magnetic targeting intensities on cell transplantation, we performed different magnetic intensities for mesenchymal stem cell (MSC)-targeting therapy in a rat model of ischemia/reperfusion. Rat MSCs labeled with superparamagnetic oxide nanoparticles (SPIOs) were injected into the left ventricular (LV) cavity of rats during a brief aorta and pulmonary artery occlusion. The 0.15 Tesla (T), 0.3 T, and 0.6 T magnets were placed 0~1 mm above the injured myocardium during and after the injection of 1 × 10 6 MSCs. Fluorescence imaging and quantitative PCR revealed that magnetic targeting enhanced cell retention in the heart at 24 h in a magnetic field strength-dependent manner. Compared with the 0 T group, three magnetic targeting groups enhanced varying cell engraftment at 3 weeks, at which time LV remodeling was maximally attenuated, and the therapeutic benefit (LV ejection fraction) was also highest in the 0.3 T groups. Interestingly, due to the low MSC engraftment resulting from microvascular embolisms, the 0.6 T group failed to translate into additional therapeutic outcomes, though it had the highest cell retention. Magnetic targeting enhances cell retention in a magnetic field strength-dependent manner. However, too high of a magnetic intensity may result in microembolization and consequently undermine the functional benefits of cell transplantation.

Coronary collateral circulation plays a protective role in patients with coronary artery disease (CAD). We investigated whether thrombospondin-1(TSP-1) has an inhibitory effect on angiogenesis potential in endothelial progenitor cells(EPCs) and tested whether TSP-1 are altered in plasma of patients who had chronic total occlusion (CTO) in at least one coronary artery and with different collateral stages(according to Rentrop grading system).We isolated early and late EPCs from human cord blood and investigated a dose-dependent effect of TSP-1 on their angiogenesis potential by Matrigel angiogenesis assay. We found that TSP-1 (5 µg/ml) inhibited early EPCs incorporation into tubules after pretreatment for 1, 6 and 12 hours, respectively (83.3±11.9 versus 50.0±10.1 per field for 1 hour,161.7±12.6 versus 124.0±14.4 for 6 hours, 118.3±12.6 versus 68.0±20.1 for 12 hours, p