Dynamic perfusion SPECT for functional evaluation in symptomatic patients with myocardial bridging.

BACKGROUND: The aim of this study was to investigate the feasibility and diagnostic value of myocardial flow reserve (MFR) assessed by rest/stress myocardial perfusion imaging with dynamic single-photon emission computed tomography (SPECT) in the functional evaluation of myocardial bridge (MB). METHODS: From May 2017 to July 2021, patients with angiographically confirmed isolated MB on the left anterior descending artery (LAD) who underwent dynamic SPECT myocardial perfusion imaging were retrospectively included. The assessment of semiquantitative indices of myocardial perfusion (summed stress scores, SSS) and quantitative parameters (MFR) was performed. RESULTS: A total of 49 patients were enrolled. The mean age of the subjects was 61.0 ± 9.0 years. All of the patients were symptomatic, and 16 cases (32.7%) presented with typical angina. SPECT-derived MFR showed a borderline significantly negative correlation with SSS (r = 0.261, P = .070). There was a trend of higher prevalence of impaired myocardial perfusion defined as MFR < 2 than as SSS ≥ 4 (42.9% vs 26.5%; P = .090). CONCLUSION: Our data support that SPECT MFR may be a useful parameter for the functional assessment of MB. In patients with MB, the use of dynamic SPECT could be a potential method for hemodynamic assessment.

Outcomes of contemporary versus conventional reverse controlled and antegrade and retrograde subintimal tracking in chronic total occlusion revascularization.

BACKGROUND: Chronic total occlusion (CTO) lesions remain technically challenging for percutaneous coronary intervention (PCI). The introduction of a retrograde approach has allowed marked improvement in the success rate of CTO recanalization. Reverse controlled anterograde and retrograde sub-intimal tracking (reverse CART) is the predominant retrograde wire crossing technique and can be broadly classified into three categories: (1) conventional (2) contemporary and (3) extended. The present study aimed to compare the safety and efficacy of conventional and contemporary reverse CART techniques. METHODS: From March 2015 to May 2020, 303 patients achieving successful retrograde guidewire crossing with conventional or contemporary reverse CART during CTO PCI were included in the study. The patient characteristics, procedural outcomes and in-hospital and 1-year clinical events were compared between the conventional and contemporary groups. RESULTS: The distributions of the baseline and angiographic characteristics were similar in both study arms, except the CTO lesions of the conventional group were more complex, as reflected by borderline significantly higher mean J-CTO scores (3.4 ± 0.7 vs. 3.3 ± 0.8; p = 0.059). Recanalization using contemporary reverse CART was associated with a short procedure time (189.8 ± 44.4 vs. 181.7 ± 37.3 min; p = 0.044) and decreased procedural complications, particularly target vessel perforation (3.6% vs. 0.6%; p = 0.063) and major side-branch occlusion (36.7% vs. 28.0%; p = 0.051). Technical and procedural success and the in-hospital and 1-year outcomes were not significantly different between the groups. CONCLUSIONS: Contemporary reverse CART is associated with favorably high efficiency and low-complication rates and carries a comparable success rate and 1-year clinical outcomes as conventional reverse CART.

Functional significance of intermediate coronary stenosis in patients with single-vessel coronary artery disease: A comparison of dynamic SPECT coronary flow reserve with intracoronary pressure-derived fractional flow reserve (FFR).

BACKGROUND: The aim of this study was to investigate the correlation of coronary flow reserve (CFR) assessed by rest/stress myocardial perfusion imaging with dynamic single-photon emission computed tomography (SPECT) with intracoronary pressure-derived fractional flow reserve (FFR) in patients with single-vessel coronary artery disease (CAD). METHODS: Patients with suspected or known stable CAD who were referred for invasive coronary angiography were prospectively enrolled. Both invasive FFR and SPECT were performed in subjects with single-vessel intermediate coronary stenosis. A cutoff value of < 0.8 was used to define abnormal FFR. RESULTS: A total of 34 patients were enrolled. The mean age of the subjects was 62.1 ± 6.7 years, and 79.4% were male. SPECT-derived CFR showed a significantly moderate correlation with FFR (r = 0.505, P = .003). The diagnostic performance for the identification of abnormal FFR in terms of sensitivity, specificity, and accuracy was 88.9%, 83.3%, and 87.9%, respectively, for CFR, with an optimized cutoff value of 1.73. CONCLUSION: In patients with single-vessel CAD, SPECT CFR was useful for the detection of functionally significant stenosis. Our data support the use of this technique as an optional method for hemodynamic assessment, especially when FFR results are in normal range.

Clinical Outcomes of Self-Made Polyurethane-Covered Stent Implantation for the Treatment of Coronary Artery Perforations.

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.

Bivalirudin in percutaneous coronary intervention for chronic total occlusion: A single-center pilot study.

BACKGROUND: Bivalirudin has been reported to be an alternative to unfractionated heparin (UFH) for anticoagulation during percutaneous coronary intervention (PCI) and associated with less bleeding risk. However, the feasibility of bivalirudin during PCI of chronic total occlusion lesions (CTO) remains unknown. OBJECTIVE: To evaluate the efficacy and safety of bivalirudin versus UFH in CTO PCI. METHODS: In this prospective and randomized controlled trial in single center, CTO patients with high bleeding risk were randomized to treatment with bivalirudin (bolus 0.75 mg/kg followed by infusion of 1.75, extra bolus 0.3 mg/kg before stenting) or UFH (100 IU/kg). The primary efficacy end point was the incidence of major adverse cardiac events (MACEs, composite of all-cause mortality, cardiac death, stent thrombosis, periprocedural myocardial infarction, or additional unplanned target lesion revascularization, or any other post-PCI ischemic event) in-hospital, and at 1-year follow-up. The primary safety end point was the occurrence of any bleeding or entry-site complications after PCI. RESULTS: A total of 84 high bleeding risk patients undergoing PCI for CTO lesions were enrolled. The baseline characteristics were similar in both treatment arms. In hospital MACEs rates were 21.4% in the bivalirudin group and 14.3% in the UFH group (P = 0.393). During 1-year's follow-up, end points did not significantly differ between the groups either. Occurrence of the major bleeding events were 4.8% in the bivalirudin group and 9.5% in the UFH group (P = 0.676). No entry-site complication was observed. CONCLUSION: In CTO patients at high risk for bleeding undergoing PCI, our data indicates that bivalirudin appears to be at least comparable in efficacy and safety to UFH. A larger clinical trial should be designed to further elucidate its efficacy and safety.

Role of KCa3.1 Channels in Macrophage Polarization and Its Relevance in Atherosclerotic Plaque Instability.

OBJECTIVE: Emerging evidence indicates that proinflammatory macrophage polarization imbalance plays a key role in atherosclerotic plaque progression and instability. The calcium-activated potassium channel KCa3.1 is critically involved in macrophage activation and function. However, the role of KCa3.1 in macrophage polarization is unknown. This study investigates the potential role of KCa3.1 in transcriptional regulation in macrophage polarization and its relationship to plaque instability. APPROACH AND RESULTS: Human monocytes were differentiated into macrophages using macrophage colony-stimulating factor. Macrophages were then polarized into proinflammatory M1 cells by interferon-γ and lipopolysaccharide and into alternative M2 macrophages by interleukin-4. A model for plaque instability was induced by combined partial ligation of the left renal artery and left common carotid artery in apolipoprotein E knockout mice. Significant upregulation of KCa3.1 expression was observed during the differentiation of human monocytes into macrophages. Blocking KCa3.1 significantly reduced the expression of proinflammatory genes during macrophages polarization. Further mechanistic studies indicated that blocking KCa3.1 inhibited macrophage differentiation toward the M1 phenotype by downregulating signal transducer and activator of transcription-1 phosphorylation. In animal models, KCa3.1 blockade therapy strikingly reduced the incidence of plaque rupture and luminal thrombus in carotid arteries, decreased the expression of markers associated with M1 macrophage polarization, and enhanced the expression of M2 markers within atherosclerotic lesions. CONCLUSIONS: These results suggest that blocking KCa3.1 suppresses plaque instability in advanced stages of atherosclerosis by inhibiting macrophage polarization toward an M1 phenotype.

Exploration of Bivalirudin Use during Percutaneous Coronary Intervention for High Bleeding Risk Patients with Chronic Total Occlusion.

The safety and efficacy of bivalirudin during percutaneous coronary intervention (PCI) in high bleeding risk patients with chronic total occlusion lesions (CTO) has not been studied till date. The use of bivalirudin may increase the thrombotic events during CTO-PCI.Between May 2013 and April 2014, a total of 117 high bleeding risk patients with CTOs underwent PCI. Bivalirudin was used in 89 cases with different strategies, including standard usage, combination of heparin, and additional bolus of bivalirudin on the basis of standard usage. The clinical characteristics, procedural details and antithrombotic strategies were assessed, and the bleeding and ischemic events were evaluated. The first 7 of 9 patients with standard application of bivalirudin exhibited acute thrombogenesis in the procedure. Heparin was then added in decreasing amounts in the next 8 patients wherein no thrombosis occurred; however, 2 patients had bleeding complications. The subsequent 72 patients were randomly assigned to the heparin bolus or additional bivalirudin bolus groups before the percutaneous transluminal coronary angioplasty (PTCA) was performed. The baseline clinical characteristics and procedure information were identical in both the groups. There were no ischemic and bleeding events in both the groups during the 6-month follow-up.Monotherapy with bivalirudin in CTO-PCI should be treated with caution, as the potential risk of thrombogenesis may be due to the long procedure time, the frequent change of equipment and temporary blood flow convection. Combination of heparin or an additional bolus of bivalirudin before PTCA was observed to be likely to decrease the incidence of thrombogenesis.

Multiple systemic embolism in infective endocarditis underlying in Barlow's disease.

BACKGROUND: Systemic embolism, especially septic embolism, is a severe complication of infective endocarditis (IE). However, concurrent embolism to the brain, coronary arteries, and spleen is very rare. Because of the risk of hemorrhage or visceral rupture, anticoagulants are recommended only if an indication is present, e.g. prosthetic valve. Antiplatelet therapy in IE is controversial, but theoretically, this therapy has the potential to prevent and treat thrombosis and embolism in IE. Unfortunately, clinical trial results have been inconclusive. CASE PRESENTATION: We describe a previously healthy 50-year-old man who presented with dysarthria secondary to bacterial endocarditis with multiple cerebral, coronary, splenic, and peripheral emboli; antibiotic therapy contributed to the multiple emboli. Emergency splenectomy was performed, with subsequent mitral valve repair. Pathological examination confirmed mucoid degeneration and mitral valve prolapse (Barlow's disease) as the underlying etiology of the endocardial lesion. Continuous antibiotics were prescribed, postoperatively. Transthoracic echocardiography at 1.5, 3, and 6 months after the onset of his illness showed no severe regurgitation, and there was no respiratory distress, fever, or lethargy during follow-up. CONCLUSIONS: Although antibiotic use in IE carries a risk of septic embolism, these drugs have bactericidal and antithrombotic benefits. It is important to consider that negative blood culture and symptom resolution do not confirm complete elimination of bacteria. However, vegetation size and Staphylococcus aureus infection accurately predict embolization. It is also important to consider that bacteria can be segregated from the microbicide when embedded in platelets and fibrin. Therefore, antimicrobial therapy with concurrent antiplatelet therapy should be considered carefully.

Effect of the Kv1.3 voltage-gated potassium channel blocker PAP-1 on the initiation and progress of atherosclerosis in a rat model.

Acute coronary syndrome is a serious medical emergency. It occurs when an atherosclerotic plaque ruptures, leading to thrombus formation within a coronary artery. Previous studies have shown that T cells are involved in the initiation and progression of acute coronary syndrome. CD4(+)CD28(null) T lymphocytes increase in atherosclerotic plaque, and voltage-gated potassium channel Kv1.3 blockers can suppress the function of these cells in vitro by preventing exocytosis of their cytoplasmic granules. The purpose of this study was to investigate the effect of PAP-1, a small molecule voltage-gated potassium channel Kv1.3 blocker, on the development of atherosclerosis (AS) in a rat model and the potential mechanism for this effect. Plasma lipids, interferonγ, CRP, CD4(+)CD28(null) T cells, and perforin were increased and unstable atherosclerotic plaques developed in the rat model of AS. Blockade of the Kv1.3 potassium channel via PAP-1 administration decreased perforin levels and prevented plaque formation but had no effect on the other changes seen in this AS model. These findings suggest that the small molecule, voltage-gated potassium channel Kv1.3 blocker PAP-1 can suppress the development of AS in a rat model, most likely by inhibiting the exocytosis of cytoplasmic granules from CD4(+)CD28(null) T cells.

Early resolution of ST-segment elevation after reperfusion therapy for acute myocardial infarction: Its relation to echocardiography-determined left ventricular global and regional function and deformation.

AIMS: To evaluate the relationships between ST-segment resolution (STR) and echocardiography-determined left ventricular (LV) global and regional function and deformation in the sub-acute phase of STEMI. METHODS AND RESULTS: STR, defined as either complete (≥70%) or incomplete (<70%), was evaluated 60minutes after primary percutaneous coronary intervention (PCI) of 84 STEMI patients. Conventional two-dimensional (2D) echocardiography and 2D speckle-tracking echocardiography (STE) were performed at 3-7days after reperfusion. LV deformation [including the infarction-related regional longitudinal (RLS), circumferential (RCS), and radial (RRS) strains, and global longitudinal (GLS), circumferential (GCS), and radial (GRS) strains] was measured by 2D STE. LV segmental function was assessed by wall motion score index (WMSI). Patients in incomplete vs. complete STR groups had higher WMSI (p<0.001); decreased peak amplitude of RLS (p<0.001), RCS (p=0.008), RRS (p=0.002); and decreased peak amplitude of GLS (p<0.001), GCS (p<0.001), GRS (p=0.003). RLS (r=0.27, p=0.015) and GLS (r=0.33, p=0.003) were best correlates of STR at the regional and global level, respectively. CONCLUSIONS: STR correlated with global and regional LV function and deformation in patients with sub-acute phase of STEMI after PCI. RLS and GLS were the strongest correlates of STR at the regional and global levels, respectively.

Validation of a new non-hyperemic physiological index: the constant-resistance ratio (cRR).

OBJECTIVES: The instantaneous wave-free ratio (iwFR) has limited availability. A new resting index called the constant-resistance ratio (cRR), which dynamically identifies cardiac intervals with constant and minimum resistance, has been developed; however, its diagnostic performance is unknown. The aim of this study was to validate the cRR by retrospectively calculating the cRR values from raw pressure waveforms of 2 publicly available datasets and compare them with those of the iwFR. METHODS: Waveform data from the CONTRAST and VERIFY 2 studies were used. The primary endpoint was Bland-Altman bias between cRR and iwFR. Secondary endpoints included diagnostic agreement, correlation, receiver operating characteristic (ROC) analysis, and success rates of cRR and iwFR. RESULTS: Among the 1036 waveforms, 871 were successful in determining paired cRR and iwFR values, while cRR was 6% more successful than iwFR (P less than .0001). The mean bias between cRR and iwFR was 0.003, with 95% limits of agreement [-0.021,0.028]. These 2 indices were highly correlated (r = 0.991; P less than .0001). Using an iwFR of 0.89 or less as the reference standard, the optimal cRR cutoff was 0.89, with an area under the ROC curve of 0.991 (P less than .001) and a diagnostic accuracy of 96.9% (95% CI [96%, 98%]). CONCLUSIONS: The cRR, a new resting index for identifying dynamic cardiac intervals with constant and minimum resistance, demonstrated high numerical agreement, diagnostic consistency, and a higher success rate than the iwFR based on the 2 publicly available datasets.

Polycystic kidneys have decreased vascular density: a micro-CT study.

OBJECTIVE: Polycystic kidney disease (PKD) is a common cause of end-stage renal failure and many of these patients suffer vascular dysfunction and hypertension. It remains unclear whether PKD is associated with abnormal microvascular structure. Thus, this study examined the renovascular structure in PKD. METHODS: PKD rats (PCK model) and controls were studied at 10 weeks of age, and mean arterial pressure (MAP), renal blood flow, and creatinine clearance were measured. Microvascular architecture and cyst number and volume were assessed using micro-computed tomography, and angiogenic pathways evaluated. RESULTS: Compared with controls, PKD animals had an increase in MAP (126.4 ± 4.0 vs. 126.2 ± 2.7 mmHg) and decreased clearance of creatinine (0.39 ± 0.09 vs. 0.30 ± 0.05 mL/min), associated with a decrease in microvascular density, both in the cortex (256 ± 22 vs. 136 ± 20 vessels per cm2) and medullar (114 ± 14 vs. 50 ± 9 vessels/cm2) and an increase in the average diameter of glomeruli (104.14 ± 2.94 vs. 125.76 ± 9.06 mm). PKD animals had increased fibrosis (2.2 ± 0.2 fold vs. control) and a decrease in the cortical expression in hypoxia inducible factor 1-α and vascular endothelial growth factor. CONCLUSIONS: PKD animals have impaired renal vascular architecture, which can have significant functional consequences. The PKD microvasculature could represent a therapeutic target to decrease the impact of this disease.

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

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.

Soluble interleukin-2 receptor predicts acute kidney injury and in-hospital mortality in patients with acute myocardial infarction.

BACKGROUND: Acute kidney injury (AKI) is the most common and critical complication in patients with acute myocardial infarction (AMI). This study aims to evaluate the significance of elevated soluble interleukin 2 receptor (sIL-2R) levels in predicting AKI and mortality. METHODS: A total of 446 patients with AMI were enrolled between January 2020 and July 2022, including 58 patients with AKI and 388 without AKI. The sIL-2R levels were measured using a commercially available chemiluminescence enzyme immunoassay. Logistic regression analysis was used to examine the risk factors for AKI. Discrimination was assessed based on the area under the receiver operating characteristic curve. The model was internally validated using 10-fold cross-validation. RESULTS: During hospitalization, 13% of patients developed AKI following AMI, with higher sIL-2R levels (0.61 ± 0.27 U/L vs. 0.42 ± 0.19 U/L, p = 0.003) and in-hospital all-cause mortality (12.1% vs. 2.6%, P < 0.001). The sIL-2R levels emerged as an independent risk factor for both AKI (OR = 5.08, 95% CI (1.04-24.84, p < 0.045) and in-hospital all-cause mortality (OR = 73.57,95% CI 10.24-528.41, p < 0.001) in AMI patients. The sIL-2R levels were found to be useful biomarkers in prediction of AKI and in-hospital all-cause mortality in patients with AMI (AUC: 0.771 and 0.894, respectively). The respective cutoff values for sIL-2R levels in predicting AKI and in-hospital all-cause mortality were determined to be 0.423 U/L and 0.615 U/L. CONCLUSIONS: The level of sIL-2R was an independent risk factor and predictor for both AKI and in-hospital all-cause mortality in patients with AMI. These findings highlight the potential of sIL-2R as a valuable tool for identifying high-risk patients regarding AKI and in-hospital mortality.

The Association Between Angiographically Derived Radial Wall Strain and the Risk of Acute Myocardial Infarction.

BACKGROUND: The radial wall strain (RWS) is a novel angiography-based method to assess the biomechanical property of the coronary artery and whether it can predict future acute myocardial infarction (AMI) events remains to be elucidated. OBJECTIVES: This study aimed to investigate the association between angiography-derived RWS and future AMI events in mild to intermediate lesions. METHODS: We performed a matched case-control analysis nested in a retrospective cohort of patients who had received prior angiography (the index procedure) at least 1 month before and were hospitalized again for repeat angiography. Patients with at least 1 de novo mild to intermediate lesion identified at the index procedure and eligible for RWS analysis were enrolled. The study identified cases with target lesion-related AMI diagnosed at the repeat angiography, matching each case to 3 control subjects without AMI. RESULTS: Altogether 44 patients with lesion-related AMI and 132 matched controls were enrolled. The median diameter stenosis of the overall interrogated lesions was 34.0%. The baseline maximum RWS (RWSmax), which was defined as the highest RWS in the stenotic segment, was significantly higher in lesions responsible for AMI than those that remained quiescent (median 13% vs 10%; P < 0.001). RWSmax was predictive of lesion-related AMI, with an area under the curve of 0.83 (95% CI: 0.76-0.90; P < 0.001) and an optimal cutoff >12%. RWSmax >12% was found to be independently associated with subsequent AMI events with a risk ratio of 7.25 (95% CI: 3.94-13.37; P < 0.001). CONCLUSIONS: Among angiographically mild to intermediate lesions, a high-strain pattern identified by angiography-derived RWS was associated with an increased risk of AMI events.

A TEMPOL and rapamycin loaded nanofiber-covered stent favors endothelialization and mitigates neointimal hyperplasia and local inflammation.

An increased level of reactive oxygen species (ROS) plays a major role in endothelial dysfunction and vascular smooth muscle cell (VSMC) proliferation during in-stent thrombosis and restenosis after coronary artery stenting. Herein, we report an electrospun core-shell nanofiber coloaded with 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL) and rapamycin (RAPA) that correspondingly serves as an ROS scavenger and VSMC inhibitor. This system has the potential to improve the biocompatibility of current drug-eluting stent (DES) coatings with the long-term and continuous release of TEMPOL and rapamycin. Moreover, the RAPA/TEMPOL-loaded membrane selectively inhibited the proliferation of VSMCs while sparing endothelial cells (ECs). This membrane demonstrated superior ROS-scavenging, anti-inflammatory and antithrombogenic effects in ECs. In addition, the membrane could maintain the contractile phenotype and mitigate platelet-derived growth factor BB (PDGF-BB)-induced proliferation of VSMCs. In vivo results further revealed that the RAPA/TEMPOL-loaded covered stents promoted rapid restoration of vascular endothelium compared with DES and persistently impeded inflammation and neointimal hyperplasia in porcine models.

Kv1.3 channels as a potential target for immunomodulation of CD4+ CD28null T cells in patients with acute coronary syndrome.

Modulation of CD4(+)CD28null T cells through K+ channels could provide potential novel targets for the treatment acute coronary syndrome (ACS). However, the surface phenotype and K+ channel expression of CD4(+)CD28null T cells in patients with ACS is unclear. The aim of this study was to investigate the surface phenotype and K+ channel expression of CD4(+)CD28null T cells in patients with ACS. We found that more than 80% of CD4(+)CD28null T cells in patients with ACS showed a CD45RA(-)CD45RO(+)CCR7- surface phenotype. CD4(+)CD28(null) T expressed small numbers of the voltage-gated Kv1.3 and intermediate-conductance Ca2+-activated K+ channel KCa3.1 when quiescent, but increased Kv1.3 expression 4-fold with little change in KCa3.1 levels upon activation. Consistent with their channel phenotypes, the production of interferon-γ and perforin in CD4(+)CD28null T cells was suppressed by the specific Kv1.3 blocker 5-(4-phenoxybutoxy)psoralen PAP-1. Therefore, selective targeting of Kv1.3 in CD4(+)CD28null T cells may hold potential therapeutic promise for ACS.

The Identification and Validation of Hub Genes Associated with Acute Myocardial Infarction Using Weighted Gene Co-Expression Network Analysis.

Acute myocardial infarction (AMI), one of the most severe and fatal cardiovascular diseases, remains the main cause of mortality and morbidity worldwide. The objective of this study is to investigate the potential biomarkers for AMI based on bioinformatics analysis. A total of 2102 differentially expressed genes (DEGs) were screened out from the data obtained from the gene expression omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) explored the co-expression network of DEGs and determined the key module. The brown module was selected as the key one correlated with AMI. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses demonstrated that genes in the brown module were mainly enriched in 'ribosomal subunit' and 'Ribosome'. Gene Set Enrichment Analysis revealed that 'TNFA_SIGNALING_VIA_NFKB' was remarkably enriched in AMI. Based on the protein-protein interaction network, ribosomal protein L9 (RPL9) and ribosomal protein L26 (RPL26) were identified as the hub genes. Additionally, the polymerase chain reaction (PCR) results indicated that the expression levels of RPL9 and RPL26 were both downregulated in AMI patients compared with controls, in accordance with the bioinformatics analysis. In summary, the identified DEGs, modules, pathways, and hub genes provide clues and shed light on the potential molecular mechanisms of AMI.

Functional comparison of different jailed balloon techniques in treating non-left main coronary bifurcation lesions.

BACKGROUND: There is a paucity of data comparing functional difference between active jailed balloon technique (A-JBT) and conventional jailed balloon technique (C-JBT) in treating non-left main coronary bifurcation lesions (CBLs). METHODS: In this retrospective cohort study, we consecutively enrolled 232 patients with non-left main CBLs who underwent percutaneous coronary intervention (PCI) using JBTs between January 2018 and March 2019. Among them, 191 patients entered the final analysis with 12-months angiographic follow-up. We stratified patients into A-JBT group (130 patients) and C-JBT group (61 patients). The functional analysis by Murray law-based quantitative flow ratio (µQFR) and Seattleanginaquestionnaire (SAQ) were performed to compare the two techniques. RESULTS: Compared with C-JBT group, A-JBT group observed a lower abrupt (0.8% vs. 11.1%, p = 0.002) and final SB occlusion (0 vs. 7.9%, p = 0.005). Meanwhile, A-JBT group had a significantly higher µQFR of side branch (SB) both post-PCI and 12-months follow-up (median [interquartile range (IQR)]: 0.91 (0.86-0.96) vs. 0.82 (0.69-0.92), p < 0.001; median [IQR]: 0.95 (0.89-0.98) vs. 0.85 (0.74-0.93), p < 0.001) than C-JBT group. Besides, A-JBT group gained a µQFR improvement at follow-up period compared with post-PCI data (median [IQR]: 0.95 [0.89-0.98] vs. 0.91[0.86-0.96] of SB, p < 0.001) and a higher SAQ scores at 12-months follow-up compared with C-JBT group (p < 0.001). CONCLUSIONS: Compared with C-JBT, A-JBT provided excellent SB protection during MV stenting and improved the SB functional blood flow as well as the angina relief even after 12 months.

[Effect of antiarrhythmic peptide on ventricular arrhythmia induced by lysophosphatidic acid].

OBJECTIVE: To investigate the effect and potential mechanism of lysophosphatidic acid (LPA) and antiarrhythmic peptide (AAP10) on rabbit ventricular arrhythmia. METHODS: Twenty-four rabbits were randomly divided into three groups (n = 8 each): control group, LPA group and AAP10 + LPA group. Using arterially perfused rabbit ventricular wedge preparations, transmural ECG and action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments with two separate floating microeletrodes. The incidence of ventricular arrhythmia post S1S2 stimulation was recorded. Protein levels of nonphosphorylated Cx43 and total Cx43 were evaluated by Western blot. The distribution of nonphosphorylated Cx43 was observed by confocal immunofluorescence microscopy. RESULTS: Compared with the control group, the QT interval, endocardial action potential duration, transmural repolarization dispersion (TDR) and incidence of ventricular arrhythmia were significantly increased and nonphosphorylated Cx43 expression was significantly upregulated in the LPA group. Compared with the LPA group, cotreatment with AAP10 can reduce the QT interval, endocardial action potential duration, TDR and incidence of ventricular arrhythmia (25.0% vs 62.5%, P < 0.01) and downregulate nonphosphorylated Cx43. CONCLUSIONS: LPA could promote the arrhythmia possibly by upregulating nonphosphorylated Cx43 and subsequent gap junction transmission inhibition. Gap junction enhancer AAP10 could attenuate the pro-arrhythmic effect of LPA probably by downregulating myocardial nonphosphorylated Cx43 expression.