Comparison of Drug-Coated Balloon and Drug-Eluting Stent for the Treatment of Small Vessel Disease (from the Dissolve SVD Randomized Trial).

The Dissolve drug-coated balloons (DCBs) is a new-generation DCB coated with paclitaxel of balloon surface, with midchain triglyceride excipient. Although the use of DCBs is a promising technique, little is known about the the clinical efficacy of the novel Dissolve DCB in coronary small vessel disease. This study was a prospective, randomized, multicenter, noninferiority trial comparing the Dissolve DCB with the Resolute drug-eluting stent (DES) in patients with a reference vessel diameter ≥2.25 and ≤2.75 mm. Patients with a reference vessel diameter ≥2.00 and <2.25 mm were enrolled in the very small vessel registry. The angiographic and clinical follow-up were planned at 9 months and 1 year in all patients, respectively. The primary end point was 9-month in-segment percentage diameter stenosis. A total of 247 patients with small vessel disease from 10 Chinese sites were included (Dissolve DCB, n = 118; Resolute DES, n = 129); 30 patients were treated with the DCB in the very small vessel cohort. The 9-month in-segment percentage diameter stenosis was 31.2 ± 2.0% with Dissolve DCB versus 26.1 ± 2.1% with Resolute DES; the 1-sided 97.5% upper confidence limit of the difference was 10.3% (p for noninferiority = 0.0002). At 12 months, the DCB and DES groups were associated with similar rates of target lesion failure (8.5% vs 6.1%, p = 0.28) and major adverse cardiac and cerebrovascular events (20.9% vs 13.6%, p = 0.12). In conclusion, the Dissolve DCB was noninferior to the Resolute DES for the primary end point of 9-month in-segment percentage diameter stenosis in this multicenter, head-to-head, randomized trial (a safety and efficacy study of Dissolve In Treatment Of Coronary Small Vessel Disease; NCT03376646).

Long Noncoding RNA and mRNA Expression Profiles in Rats with LPS-induced Myocardial Dysfunction.

Background: Sepsis is an uncontrolled systemic inflammatory response. Long noncoding RNAs (lncRNAs) are involved in the pathogenesis of sepsis. However, little is known about the roles of lncRNAs in sepsis-induced myocardial dysfunction. Objective: We aimed to determine the regulatory mechanism of lncRNAs in sepsis-induced myocardial dysfunction. Methods: In this study, we analysed the lncRNA and mRNA expression profiles using microarray analysis. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, protein-protein interaction network, and gene set enrichment analysis were used to evaluate the data. We also constructed coding and noncoding coexpression and competing endogenous RNA networks to investigate the mechanisms. Results: In vivo lipopolysaccharide -induced sepsis rat model was established. A total of 387 lncRNAs and 1,952 mRNAs were identified as significantly changed in the left ventricle. Kyoto Encyclopedia of Genes and Genomes analysis of mRNAs showed that the upregulated genes were mainly enriched in the "complement and coagulation cascade pathway" and "immune-related biological processes" terms. Eight significantly changed lncRNAs detected by RT-qPCR may be responsible for these processes. A competing endogenous RNA network was generated, and the results indicated that eight lncRNAs were related to the "calcium ion binding" process. Conclusion: These results demonstrate that crosstalk between lncRNAs and mRNAs may play important roles in the development of sepsis-induced myocardial dysfunction.

Diagnosis, Genetics, and Management of 24 Patients With Cardiac Paragangliomas: Experience From a Single Center.

Context: Paragangliomas located within the pericardium represent a rare yet challenging clinical situation. Objective: The current analysis aimed to describe the clinical characteristics of cardiac paragangliomas, with emphasis on the diagnostic approach, genetic background, and multidisciplinary management. Methods: Twenty-four patients diagnosed with cardiac paraganglioma (PGL) in Peking Union Medical College Hospital, Beijing, China, between 2003 and 2021 were identified. Clinical data was collected from medical record. Genetic screening and succinate dehydrogenase subunit B immunohistochemistry were performed in 22 patients. Results: The median age at diagnosis was 38 years (range 11-51 years), 8 patients (33%) were females, and 4 (17%) had familial history. Hypertension and/or symptoms related to catecholamine secretion were present in 22 (92%) patients. Excess levels of catecholamines and/or metanephrines were detected in 22 (96%) of the 23 patients who have completed biochemical testing. Cardiac PGLs were localized with 131I-metaiodobenzylguanidine scintigraphy in 11/22 (50%), and 99mTc-hydrazinonicotinyl-tyr3-octreotide scintigraphy in 24/24 (100%) patients. Genetic testing identified germline SDHx mutations in 13/22 (59%) patients, while immunohistochemistry revealed succinate dehydrogenase (SDH) deficiency in tumors from 17/22 (77%) patients. All patients were managed by a multidisciplinary team through medical preparation, surgery, and follow-up. Twenty-three patients received surgical treatment and perioperative death occurred in 2 cases. Overall, 21 patients were alive at follow-up (median 7.0 years, range 0.6-18 years). Local recurrence or metastasis developed in 3 patients, all of whom had SDH-deficient tumors. Conclusion: Cardiac PGLs can be diagnosed based on clinical manifestations, biochemical tests, and appropriate imaging studies. Genetic screening, multidisciplinary approach, and long-term follow-up are crucial in the management of this disease.

Coronary artery ectasia associated with IgG4-related disease: a case report and literature review.

BACKGROUND: Coronary artery ectasia is defined as a local or diffuse dilatation of the coronary artery more than 1.5 times the diameter of the adjacent normal segment. The etiology of coronary artery ectasia is diverse, and rarely complicated with immunoglobulin G4-related disease (IgG4-related disease). A limited number of cases have been reported, with insidious onset, slow progression but poor prognosis. CASE PRESENTATION: we report a patient with coronary artery ectasia combined with IgG4-related disease. He has been diagnosed with IgG4-related disease 5 years after his first percutaneous coronary intervention (PCI). Despite routine treatment with steroids, he develops a large coronary aneurysm and eventually died. CONCLUSIONS: It is suggested that a thorough evaluation should be performed when coronary artery ectasia is diagnosed. The factors such as manifestations of coronary artery thickening, typical imaging features, other aortas involvement, increased serum IgG4 level, etc. should be considered for early diagnosis of key etiologies.

A Randomized Comparison of 2 Different Drug-Coated Balloons for In-Stent Restenosis.

BACKGROUND: Although use of drug-coated balloons (DCB) is a promising technique, little is known about the clinical efficacy of the Dissolve DCB in drug-eluting stent (DES) in-stent restenosis (ISR). OBJECTIVES: This study sought to evaluate the efficacy and safety of the Dissolve DCB in patients with DES ISR. METHODS: This was a prospective, multicenter, randomized, noninferiority trial comparing Dissolve DCB with SeQuent Please DCB in patients with DES ISR. Angiographic and clinical follow-up was planned at 9 months in all patients. The primary endpoint was 9-month in-segment late loss. RESULTS: A total of 260 patients with ISR from 10 Chinese sites were included (Dissolve DCB, n = 128; SeQuent Please DCB, n = 132). Nine-month in-segment late loss was 0.50 ± 0.06 mm with Dissolve DCB vs 0.47 ± 0.07 mm with SeQuent Please DCB; the 1-sided 97.5% upper confidence limit of the difference was 0.18 mm (P for noninferiority = 0.03). Rates of target lesion failure and binary restenosis were numerical higher in the Dissolve DCB cohort compared with the SeQuent Please DCB cohort at 9 months (17.5% vs 10.7%; P = 0.12; 23.4% vs 16.4%; P = 0.19, respectively). At 9 months, major adverse cardiac and cerebrovascular events occurred in 36 patients (28.3%) vs 30 patients (22.9%) in the Dissolve DCB and SeQuent Please DCB groups, respectively. CONCLUSIONS: In this head-to-head randomized trial, the Dissolve DCB was noninferior to the SeQuent Please DCB for 9-month in-segment late loss. However, Dissolve DCB with its numerical increase in target lesion failure and binary restenosis warrants assessment in larger clinical trials (A Safety and Efficacy Study of Dissolve™ in Treatment of Coronary In-Stent Restenosis; NCT03373695).

LncRNA-mRNA expression profile and functional network of vascular dysfunction in septic rats.

BACKGROUND: We used microarrays to analyse the changes in long non-coding RNAs (lncRNAs) and mRNAs in aorta tissue in model rats with lipopolysaccharide-induced sepsis and determined the lncRNA-mRNA and lncRNA-miRNA-mRNA functional networks. METHODS: Wistar rats were intraperitoneally injected with lipopolysaccharide, and the lncRNA and mRNA expression profiles in the aorta were evaluated using microarrays. The functions of the differentially expressed mRNAs were analysed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. We then constructed coding/non-coding co-expression and competing endogenous RNA networks to study the mechanisms related to sepsis in rats. RESULTS: We identified 503 differentially expressed lncRNAs and 2479 differentially expressed mRNAs in the model rats with lipopolysaccharide-induced sepsis. Mitochondrial fission process 1 (MTFP1) was the most significantly down-regulated mRNA. Bioinformatics analysis showed that the significantly down-regulated mRNAs in the sepsis models were in pathways related to mitochondrial structure, function, and energy metabolism. Coding/non-coding co-expression and competing endogenous RNA analyses were conducted using 12 validated lncRNAs in combination with all mRNAs. The coding/non-coding co-expression analysis showed that the 12 validated lncRNAs were mainly regulatory factors for abnormal energy metabolism, including mitochondrial structure damage and aberrant mitochondrial dynamics. The competing endogenous RNA analysis revealed that the potential functions of these 12 lncRNAs might be related to the inflammatory response. CONCLUSION: We determined the differentially expressed lncRNAs and mRNAs in the aorta of septic rats using microarrays. Further studies on these lncRNAs will help elucidate the mechanism of sepsis at the genetic level and may identify potential therapeutic targets.

Genome-wide identification of altered RNA m6A profiles in vascular tissue of septic rats.

Sepsis is the leading cause of death in hospital intensive care units. In light of recent studies showing that variations in N6-methyladenosine (m6A) levels in different RNA transcripts influence inflammatory responses, we evaluated the m6A profiles of rat aortic mRNAs and lncRNAs after lipopolysaccharide (LPS)-induced sepsis. LC-MS-based mRNA modification analysis showed that global m6A levels were significantly decreased in aortic tissue of rats injected intraperitoneally with LPS. This finding was consistent with downregulated expression of METTL3 and WTAP, two members of the m6A writer complex, in LPS-exposed aortas. Microarray analysis of m6A methylation indicated that 40 transcripts (31 mRNAs and 9 lncRNAs) were hypermethylated, while 223 transcripts (156 mRNAs and 67 lncRNAs) were hypomethylated, in aortic tissue from LPS-treated rats. On GO and KEGG analyses, 'complement and coagulation cascades', 'transient receptor potential channels', and 'organic anion transmembrane transporter activity' were the major biological processes modulated by the differentially m6A methylated mRNAs. In turn, competing endogenous RNA network analysis suggested that decreased m6A levels in lncRNA-XR_343955 may affect the inflammatory response through the cell adhesion molecule pathway. Our data suggest that therapeutic modulation of the cellular m6A machinery may be useful to preserve vascular integrity and function during sepsis.

[Clinical Value of 1.5-T Non-contrast Whole-heart Magnetic Resonance Coronary Angiography in Evaluating the Severity of Coronary Stenosis].

Objective To evaluate the diagnostic performance of 1.5-T non-contrast free-breathing whole-heart magnetic resonance coronary angiography(MRCA)for≥50% and≥70% coronary artery stenosis in coronary artery disease(CAD).Methods Forty-one patients clinically scheduled for invasive coronary angiography(ICA)underwent 1.5-T non-contrast free-breathing whole-heart MRCA.The diagnostic performance for≥50% and≥70% stenosis was evaluated and compared using ICA as a reference standard.Results MRCA was completed in all the 41 patients with the total acquisition time of(10.1 ± 2.2)min.The sensitivity,specificity,and accuracy of MRCA for≥50% and≥70% stenosis were 100%(95% CI:89%-100%)and 82%(95%CI:63%-94%),38%(95%CI:9%-76%)and 54%(95%CI:25%-81%),and 88%(95%CI:73%-95%)and 73%(95%CI:57%-85%)on a per-patient basis,respectively;they were 95%(95%CI:87%-99%)and 86%(95%CI:73%-95%),58%(95%CI:45%-71%)and 76%(95%CI:65%-85%),and 78%(95%CI:69%-84%)and 80%(95%CI:71%-86%)on a per-vessel basis,respectively.The sensitivity of MRCA for≥50% stenosis was higher than that for≥70% stenosis(97%vs.88%,χ 2=5.73,P=0.017),and the specificity showed an opposite trend(86% vs. 94%,χ 2=14.12,P<0.001)on a per-segment basis.Conclusions The 1.5-T non-contrast whole-heart MRCA can detect both≥50% and≥70% coronary artery stenosis with high sensitivity and accuracy.MRCA showed lower sensitivity while higher specificity for≥70% stenosis than for≥50% stenosis on a per-segment basis.

Restoration of NRF2 attenuates myocardial ischemia reperfusion injury through mediating microRNA-29a-3p/CCNT2 axis.

Accumulated studies have been implemented for comprehending the mechanism of myocardial ischemia reperfusion injury (MI/RI). Nuclear factor erythroid-2 related factor 2 (NRF2)-mediated transcription activity in MI/RI has not been completely interpreted from the perspective of microRNA-29a-3p (miR-29a-3p) and cyclin T2 (CCNT2). Therein, this study intends to decode the mechanism of NRF2/miR-29a-3p/CCNT2 axis in MI/RI. Rat MI/RI models were established by left anterior descending artery ligation. Rats were injected with NRF2 or CCNT2 overexpression plasmids or miR-29a-3p agomir to explore their effects on MI/RI. Hypoxia/reoxygenation (H/R) cardiomyocytes were established and transfected with restored NRF2 or miR-29a-3p or CCNT2 for further exploration of their roles. NRF2, miR-29a-3p, and CCNT2 expression in myocardial tissues in rats with MI/RI and in cardiomyocytes in H/R injury were detected. ChIP assay verified the relationship between miR-29a-3p and NRF2, and the bioinformatics software and dual-luciferase reporter experiment verified the interaction between miR-29a-3p and CCNT2. NRF2 and miR-29a-3p were down-regulated while CCNT2 was up-regulated in myocardial tissues in rats with MI/RI and in H/R-treated cardiomyocytes. Restoration of NRF2 or miR-29a-3p improved hemodynamics and myocardial injury and suppressed serum inflammation and cardiomyocyte apoptosis via CCNT2 in rats with MI/RI. Upregulation of NRF2 or miR-29a-3p inhibited LDH and CK-MB activities, oxidative stress, and apoptosis and promoted viability of cardiomyocytes with H/R injury. NRF2 bound to the promoter of miR-29a-3p and CCNT2 was targeted by miR-29a-3p. This study elucidates that up-regulating NRF2 or miR-29a-3p attenuates MI/RI via inhibiting CCNT2, which may renew the existed knowledge of MI/RI-related mechanism and provide a novel guidance toward MI/RI treatment.

Efficacy of adaptive servo-ventilation and continuous positive airway pressure treatment in chronic heart failure with sleep-disordered breathing: a systematic review and meta-analysis.

Noninvasive positive-pressure ventilation (NPPV) is recognized as an effective adjuvant therapy for sleep-disordered breathing (SDB) in heart failure patients with reduced ejection fraction (HFrEF + SDB). In recent years, some studies have found that adaptive servo-ventilation (ASV) has a negative impact on survival, especially among patients with central sleep apnea (CSA), the use of which is controversial. This study aims to explore the effects of NPPV on cardiac function and survival in patients with sleep-disordered breathing and chronic congestive heart failure. This meta-analysis was based on literature searches of publications published before August 31, 2019, in the PubMed, EMBASE, Cochrane Library, and Web of Science databases. A total of 88 independent studies were summarized and compared, comprising a sampling of 19,259 subjects. Compared with the nontreatment group, treatment with ASV had no effect on all-cause mortality in patients with HFrEF + CSA (hazard ratio (HR) = 1.13 [0.84, 1.51]). Short-term treatment with ASV, e.g., 3-6 months, was significantly beneficial regarding event-free survival in patients with HFrEF + CSA (HR = 0.13 [0.04, 0.45]). Periodic short-term (e.g., 3-6 months) positive-pressure ventilation can significantly improve cardiac function, which is beneficial for the survival of patients with HFrEF + CSA. Attention should be paid to the length and period of treatment, as prolonged treatment may have negative effects.

Prognostic value of fasting glucose on the risk of heart failure and left ventricular systolic dysfunction in non-diabetic patients with ST-segment elevation myocardial infarction.

Recent studies have shown that acute blood glucose elevation in patients with ST-segment elevation myocardial infarction (STEMI) suggests a poor prognosis. To investigate the effect of fasting blood glucose (FBG) on the risk of heart failure (HF) and left ventricular systolic dysfunction (LVSD) in non-diabetic patients undergoing primary percutaneous coronary intervention (PCI) for acute STEMI, we retrospectively recruited consecutive non-diabetic patients who underwent primary PCI for STEMI in our hospital from February 2003 to March 2015. The patients were divided into two groups according to the FBG level. A total of 623 patients were recruited with an age of 61.3 ± 12.9 years, of whom 514 (82.5%) were male. The HF risk (odds ratio 3.401, 95% confidence interval (CI) 2.144-5.395, P < 0.001) was significantly increased in patients with elevated FBG than those with normal FBG. Elevated FBG was also independently related to LVSD (ß 1.513, 95%CI 1.282-1.785, P < 0.001) in a multiple logistics regression analysis. In conclusion, elevated FBG was independently associated with 30-day HF and LVSD risk in non-diabetic patients undergoing primary PCI for STEMI.

Analyses of circRNA and mRNA profiles in the submandibular gland in hypertension.

The aim of this study was to elucidate the roles played by circular RNAs (circRNAs) in the mechanism underlying submandibular gland (SMG) dysfunction in hypertension. We employed RNA-seq to analyze the circRNA and mRNA expression profiles of SMGs. Seventy-five differentially expressed (DE) circRNAs and 691 DE mRNAs were determined to be significantly altered in spontaneously hypertensive rats. Altered mRNAs were primarily related to the immune system and immune response. Eight circRNAs were selected for further analysis. Cell adhesion molecules were determined to be the most strongly enriched pathway through analysis of DE mRNAs, the coding noncoding gene co-expression (CNC) network and the competitive endogenous RNA (ceRNA) network. The salivary secretion pathway was observed to be notably enriched through analysis of the ceRNA network. These results suggest that the crosstalk among circRNAs may play a crucial role in the development of SMG dysfunction in hypertension.

A clinical strategy to improve the diagnostic accuracy of 1.5-T non-contrast MR coronary angiography for detection of coronary artery disease: combination of whole-heart and volume-targeted imaging.

OBJECTIVES: To evaluate the diagnostic performance of 1.5-T non-contrast MR coronary angiography (MRCA) for detection of coronary artery disease (CAD) using whole-heart imaging combined with volume-targeted imaging. METHODS: Forty-five patients scheduled for conventional coronary angiography (CAG) underwent 1.5-T free-breathing non-contrast steady-state free-precession MRCA, including whole-heart and subsequent three-vessel volume-targeted imaging. Coronary stenosis was evaluated as follows: (1) by whole-heart MRCA alone; (2) by combined MRCA (whole-heart plus volume-targeted images). The diagnostic performance for significant stenosis (≥ 50% diameter reduction) was evaluated and compared using CAG as a reference standard. RESULTS: Combined MRCA was completed in all 45 patients with a total acquisition time of 16.6 ± 3.3 min. The sensitivity, specificity, and accuracy of combined MRCA per patient were 97% (95% confidence interval 84-100%), 83% (52-98%), and 93% (82-98%), respectively. The areas under the receiver operating characteristic curve of combined MRCA were significantly higher than those of whole-heart MRCA on a per patient (0.97 versus 0.85, p = 0.0078) and per vessel (0.96 versus 0.86, p < 0.0001) basis. Compared with whole-heart MRCA, combined MRCA showed equally high sensitivity but significantly improved specificity on a per patient (83% versus 25%, p = 0.016) and per vessel (85% versus 50%, p < 0.0001) basis. CONCLUSIONS: 1.5-T non-contrast MRCA combining whole-heart and volume-targeted imaging can detect significant CAD with high sensitivity and moderate specificity. Combined MRCA significantly improves specificity compared with whole-heart imaging alone. KEY POINTS: • 1.5-T non-contrast MRCA with combined whole-heart and volume-targeted imaging can detect CAD with high sensitivity and moderate specificity comparable with coronary CTA. • Compared with whole-heart imaging alone, combined imaging provides improved diagnostic accuracy, especially specificity.

Low-dose CT perfusion with combined use of CTP and CTP-derived coronary CT angiography at 70 kVp: validation with invasive fractional flow reserve.

OBJECTIVES: To investigate the diagnostic performance of 70-kVp stress dynamic myocardial CT perfusion (CTP) as a low-dose, one-stop cardiac CT examination in clinical application. MATERIALS AND METHODS: Consecutive symptomatic patients were prospectively recruited and scanned with stress dynamic myocardial CTP. The CTP phase with the best enhancement of the coronary arteries was selected and extracted as the CTP-derived single-phase coronary CT angiography (SP-CTA). The diagnostic performance of CTP and CTP+SP-CTA for functionally significant CAD was assessed. Invasive coronary angiography and fractional flow reserve were used as the reference standard for the myocardial ischemia evaluation. RESULTS: In total, 71 patients (43 men and 28 women; 63.6 ± 8.8 years old) underwent the stress dynamic myocardial CTP; 63 vessels (36.2%) from 42 of the patients (59.2%) were identified as causing ischemia. On a per-vessel basis, the sensitivity, specificity, PPV, NPV, and diagnostic accuracy for CTP and CTP+SP-CTA were 77.8%, 93.7%, 87.5%, 88.1%, and 87.9% and 84.1%, 93.7%, 88.3%, 91.2%, and 90.2%, respectively. The area under the curve (AUC) of CTP+SP-CTA (AUC = 0.963; 95%CI, 0.938-0.989) was significantly superior to that of CTP (AUC = 0.922; 95%CI, 0.880-0.964) and that of SP-CTA (AUC = 0.833; 95%CI, 0.765-0.900) alone (all p < 0.01). The mean radiation dose of the CTP examination was 3.8 ± 1.4 mSv. CONCLUSION: CTP-derived SP-CTA improved the diagnostic value of CTP. With a promising performance of myocardial ischemia detection and low radiation dose, the innovative low-dose, one-stop CTP examination is clinically feasible for patients who need to receive a myocardial perfusion assessment. KEY POINTS: • Myocardial CTP performed well in the evaluation of hemodynamically significant CAD. • CTP-derived single-phase CCTA improved the diagnostic value of CTP. • The combined use of low-dose CTP and CTP-derived CCTA at 70 kVp is clinically feasible for CAD patients who need to receive a myocardial perfusion assessment.

LncRNA and mRNA expression profiles and functional networks of hyposalivation of the submandibular gland in hypertension.

Hyposalivation is a complication of hypertension. However, little is known about the role of long non-coding RNAs (lncRNAs) in salivary glands in hypertension. This study aimed to compare the lncRNA and mRNA expression profiles between spontaneous hypertension rats (SHRs) and Wistar-Kyoto (WKY) rats through microarray analysis and apple bioinformatics methods to analyse their potential roles in hyposalivation. The differentially expressed (DE) lncRNAs and mRNAs were confirmed by quantitative real-time PCR (qRT-PCR). Compared with WKY rats, 225 DE lncRNAs and 473 DE mRNAs were identified in the SMG of SHRs. The pathway analyses of DE mRNAs showed that inflammatory mediator regulation of transient receptor potential channels was involved in hyposalivation in SHRs. Ten DE lncRNAs were chosen for further research. A coding-non-coding gene co-expression (CNC) network and competing endogenous RNA (ceRNA) network analysis revealed that the potential functions of these 10 DE lncRNAs were closely connected with the processes of the immune response. This study showed abundant DE lncRNAs and mRNAs in hypertensive SMGs. Furthermore, our results indicated strong associations between the immune response and hyposalivation and showed the potential of immune-related genes as novel and therapeutic targets for hyposalivation.

Active SB-P Versus Conventional Approach to the Protection of High-Risk Side Branches: The CIT-RESOLVE Trial.

OBJECTIVES: The aim of this study was to determine whether an active side branch protection (SB-P) strategy is superior to the conventional strategy in reducing side branch (SB) occlusion in high-risk bifurcation treatment. BACKGROUND: Accurate prediction of SB occlusion after main vessel stenting followed by the use of specific strategies to prevent occlusion would be beneficial during bifurcation intervention. METHODS: Eligible patients who had a bifurcation lesions with high risk for occlusion as determined using the validated V-RESOLVE (Visual Estimation for Risk Prediction of Side Branch Occlusion in Coronary Bifurcation Intervention) score were randomized to an active SB-P strategy group (elective 2-stent strategy for large SBs and jailed balloon technique for small SBs) or a conventional strategy group (provisional stenting for large SBs and jailed wire technique for small SBs) in a 1:1 ratio stratified by SB vessel size. The primary endpoint of SB occlusion was defined as an angiography core laboratory-assessed decrease in TIMI (Thrombolysis In Myocardial Infarction) flow grade or absence of flow in the SB immediately after full apposition of the main vessel stent to the vessel wall. RESULTS: A total of 335 subjects at 16 sites were randomized to the SB-P group (n = 168) and conventional group (n = 167). Patients in the SB-P versus conventional strategy group had a significantly lower rate of SB occlusion (7.7% [13 of 168] vs. 18.0% [30 of 167]; risk difference: -9.1%; 95% confidence interval: -13.1% to -1.8%; p = 0.006), driven mainly by the difference in the small SB subgroup (jailed balloon technique vs. jailed wire technique: 8.1% vs. 18.5%; p = 0.01). CONCLUSIONS: An active SB-P strategy is superior to a conventional strategy in reducing SB occlusion when treating high-risk bifurcation lesions. (Conventional Versus Intentional Strategy in Patients With High Risk Prediction of Side Branch Occlusion in Coronary Bifurcation Intervention [CIT-RESOLVE]; NCT02644434).

Identification of circRNA and mRNA expression profiles and functional networks of vascular tissue in lipopolysaccharide-induced sepsis.

Sepsis is the most common cause of death in intensive care units. This study investigated the circular RNA (circRNA) and mRNA expression profiles and functional networks of the aortic tissue in sepsis. We established a lipopolysaccharide (LPS)-induced rat sepsis model. High-throughput sequencing was performed on the aorta tissue to identify differentially expressed (DE) circRNAs and mRNAs, which were validated by real-time quantitative polymerase chain reaction (RT-qPCR). Bioinformatic analysis was carried out and coding and non-coding co-expression (CNC) and competing endogenous RNA (ceRNA) regulatory networks were constructed to investigate the mechanisms. In total, 373 up-regulated and 428 down-regulated circRNAs and 2063 up-regulated and 2903 down-regulated mRNAs were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of mRNAs showed that the down-regulated genes were mainly enriched in the process of energy generation. CNC and ceRNA regulatory networks were constructed with seven DE circRNAs. The results of functional enrichment analysis of CNC target genes revealed the important role of circRNAs in inflammatory response. The ceRNA network also highlighted the significant enrichment in calcium signalling pathway. Significant alterations in circRNAs and mRNAs were observed in the aortic tissue of septic rats. In addition, CNC and ceRNA networks were established.

Apolipoprotein A-IV Enhances Fatty Acid Uptake by Adipose Tissues of Male Mice via Sympathetic Activation.

Apolipoprotein A-IV (ApoA-IV) synthesized by the gut regulates lipid metabolism. Sympathetic innervation of adipose tissues also controls lipid metabolism. We hypothesized that ApoA-IV required sympathetic innervation to increase fatty acid (FA) uptake by adipose tissues and brown adipose tissue (BAT) thermogenesis. After 3 weeks feeding of either a standard chow diet or a high-fat diet (HFD), mice with unilateral denervation of adipose tissues received intraperitoneal administration of recombinant ApoA-IV protein and intravenous infusion of lipid mixture with radioactive triolein. In chow-fed mice, ApoA-IV administration increased FA uptake by intact BAT but not the contralateral denervated BAT or intact white adipose tissue (WAT). Immunoblots showed that, in chow-fed mice, ApoA-IV increased expression of lipoprotein lipase and tyrosine hydroxylase in both intact BAT and inguinal WAT (IWAT), while ApoA-IV enhanced protein levels of ß3 adrenergic receptor, adipose triglyceride lipase, and uncoupling protein 1 in the intact BAT only. In HFD-fed mice, ApoA-IV elevated FA uptake by intact epididymal WAT (EWAT) but not intact BAT or IWAT. ApoA-IV increased sympathetic activity assessed by norepinephrine turnover (NETO) rate in BAT and EWAT of chow-fed mice, whereas it elevated NETO only in EWAT of HFD-fed mice. These observations suggest that, in chow-fed mice, ApoA-IV activates sympathetic activity of BAT and increases FA uptake by BAT via innervation, while in HFD-fed mice, ApoA-IV stimulates sympathetic activity of EWAT to shunt FAs into the EWAT.

Comparing the effects of different management strategies on long-term outcomes for significant coronary stenosis in patients with Takayasu arteritis.

BACKGROUND: The long-term outcomes and optimal treatment strategy for patients with Takayasu arteritis (TA) and significant coronary stenosis remain unclear. We aim to investigate the prognosis of these patients according to the initial management strategy. METHODS: A total of 57 consecutive patients with TA and significant coronary stenosis were included between 2002 and 2018. The cohort was divided into the percutaneous coronary intervention (PCI) group (n = 18), coronary artery bypass graft (CABG) group (n = 10), and medical-therapy group (n = 29). The primary outcome was major adverse cardiac events (MACEs) defined as a composite of cardiac death, myocardial infarction, and coronary revascularization. RESULTS: Over a median follow-up of 4.5 (IQR 3.5-8.0) years, 24 (42.1%) patients experienced at least one MACE. The long-term rates of MACEs and re-revascularization were significantly higher in the PCI group than in the other 2 groups (HR 5.306, 95% CI 2.160-13.036, p < 0.001; HR 12.286, 95% CI 3.257-46.343, p < 0.001, respectively). The cumulative incidences of MACEs and subsequent revascularization were similar between the CABG and medical-therapy group. Active disease at baseline and PCI were independent predictors of MACEs (HR, 7.039, 95% CI 2.031-24.396; p = 0.002; HR, 4.400; 95% CI 1.804-10.727; p = 0.001, respectively) and revascularization (HR 4.632, 95% CI 1.010-21.235, p = 0.048; HR 9.820, 95% CI 2.641-36.514, p = 0.001, respectively). CONCLUSIONS: The initial baseline active disease is an important predictor of long-term outcome and subsequent revascularization in patients with TA and significant coronary artery stenosis. Also, PCI is independently associated with higher risk of MACEs and re-revascularization.