Drug-Coated Balloon-Only Angioplasty Outcomes in Diabetic and Nondiabetic Patients with De Novo Small Coronary Vessels Disease.

BACKGROUND: The revascularization of small vessels using drug-eluting stents remains challenging. The use of the drug-coated balloon is an attractive therapeutic strategy in de novo lesions in small coronary vessels, particularly in the diabetic group. This study aimed to assess the outcomes of DCB-only angioplasty in small vessel disease. METHODS: A total of 1198 patients with small vessel disease treated with DCB-only strategy were followed. Patients were divided into the diabetic and nondiabetic groups. Clinical and angiographical follow-up were organized at 12 months. The primary endpoints were target lesion failure and secondary major adverse cardiac events. RESULTS: There was a significantly higher rate of target lesion failure among diabetic patients compared to nondiabetic [17 (3.9%) vs. 11 (1.4%), P=0.006], taken separately, the rate of target lesion revascularization significantly differed between groups with a higher rate observed in the diabetic group [9 (2%) vs. 4 (0.5%), P=0.014]. Diabetes mellitus remained an independent predictor for TLF (HR: 2.712, CI: 1.254-5.864, P=0.011) and target lesion revascularization (HR: 3.698, CI: 1.112-12.298, P=0.033) after adjustment. However, no significant differences were observed between groups regarding the target vessel myocardial infarction (0.6% vs. 0.1%, P=0.110) and MACE [19 (4.4%) vs. 21 (2.7%), P=0.120]. CONCLUSION: Drug-coated balloon-only treatment achieved lower incidence rates of TLF and MACE. Diabetes is an independent predictor for target lesion failure and target lesion revascularization at one year following DCB treatment in small coronary vessels. We observed no significant differences between groups regarding MACE in one year.

Relationship of sarcopenia with steatohepatitis and advanced liver fibrosis in non-alcoholic fatty liver disease: a meta-analysis.

BACKGROUND: Several studies have emerged indicating that sarcopenia is associated with nonalcoholic fatty liver disease, we aimed to systematically review and quantify the association between sacropenia and the histological severity of nonalcoholic fatty liver disease. METHODS: Pubmed, the Cochrane Library and EMBASE were searched (until August 2017) for studies examining the relationship of sarcopenia with steatohepatitis and advanced liver fibrosis in nonalcoholic fatty liver disease. Pooled odds ratios were estimated by fixed effects models. RESULTS: Three articles met our inclusion criteria, with a total of 3226 individuals. Two of the studies examined the association between sacropenia and steatohepatitis, a significant association was documented between sarcopenia and steatohepatitis (OR = 2.35, 95%CI 1.45, 3.81). All of the three studies assessed the association between sacropenia and advanced liver fibrosis, a significant association between sarcopenia and advanced liver fibrosis (OR = 2.41, 95%CI 1.94, 2.98). No significant heterogeneity was detected among studies in all comparisons. These results remained essentially unchanged after excluding any of the studies in the sensitivity analysis. CONCLUSIONS: Sarcopenia in patients with nonalcoholic fatty liver disease is associated with a higher likelihood of having steatohepatitis or advanced liver fibrosis. Demonstration of the role of sarcopenia in nonalcoholic fatty liver disease development in future studies could have important therapeutic implications.

Plasma MicroRNA-126-5p is Associated with the Complexity and Severity of Coronary Artery Disease in Patients with Stable Angina Pectoris.

BACKGROUND: Coronary artery disease (CAD) is a major problem worldwide. As an endothelium-enriched microRNA (miRNA), miR-126 has been reported to serve as a potential biomarker of acute myocardial infarction. However, the relationship between miR-126 and the severity of CAD remains unknown. This study was designed to test whether circulating miR-126 levels are associated with the severity of CAD. METHODS: The present study enrolled 40 patients who had risk factors for CAD without angiographically significant CAD, and 110 patients presenting with stable angina pectoris, who were validated left main coronary artery disease (LMCA) and/or multi-vessel disease by coronary angiography. The expression levels of plasma miR-126-5p from all enrolled subjects were estimated by quantitative real-time polymerase chain reaction (qRT-PCR). Then, the relationships between plasma miR-126-5p levels, number of diseased vessels and the corresponding Synergy between PCI with Taxus and Cardiac surgery (SYNTAX) score were analyzed. RESULTS: The expression of circulating miR-126-5p was affected by some CAD risk factors including aging, dyslipidemia and DM. Furthermore, plasma miR-126-5p levels were significantly down-regulated in CAD patients with multi-vessel disease, higher SYNTAX score, rather than isolated LMCA and low SYNTAX score. CONCLUSION: Circulating miR-126-5p has emerged as a potential biomarker for complexity and severity of CAD in patients with stable angina pectoris.

microRNA-29b Mediates the Antifibrotic Effect of Tanshinone IIA in Postinfarct Cardiac Remodeling.

BACKGROUND: Tanshinone IIA (TSN) is one of the main components isolated from Danshen, which is widely used for the treatment of cardiovascular diseases. The transforming growth factor beta (TGF-ß) signaling pathway and microRNA (miR)-29b play important roles in the progression of cardiac fibrosis and the modulation of cardiac fibroblast (CF) function. Our study investigated the role of miR-29b in the cardioprotective effects of TSN in postinfarct cardiac remodeling. METHODS AND RESULTS: Echocardiography demonstrated that medium-dose TSN (TSN-M) and high-dose TSN (TSN-H) significantly inhibited postinfarct cardiac fibrosis and improved the impaired left ventricular function in rats subjected to acute myocardial infarction. Moreover, quantitative real-time polymerase chain reaction and Western blot demonstrated that TSN-M and TSN-H downregulated the expression of TGF-ß1, Col1a1, Col3a1, and α-SMA but upregulated the expression of miR-29b. CFs treated with TSN showed inhibited TGF-ß signaling pathway, downregulated expression of Col1a1, Col3a1, and α-SMA, and upregulated miR-29b expression in vitro. Furthermore, treatment with a miR-29b inhibitor dramatically inhibited these TSN-induced antifibrotic effects, suggesting that miR-29b may be responsible for the antifibrotic effects of TSN. In addition, treatment with Smad3 siRNA significantly inhibited miR-29b expression in CFs, which implies that Smad3 signaling promotes miR-29b expression on CFs. CONCLUSIONS: TSN exerts antifibrotic effects in postinfarct cardiac fibrosis by upregulating the expression of miR-29b, which is mediated by the TGF-ß-Smad3 signaling pathway.

Long-term outcomes of drug-coated balloon treatment of calcified coronary artery lesions: a multicenter, retrospective, propensity matching study.

Background: Coronary artery calcification (CAC) is associated with high rates of restenosis and adverse clinical events after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Objectives: The aim of this study was to evaluate the long-term clinical outcomes of drug-coated balloon (DCB)-only treatment for de novo lesions with and without CAC. Methods: Patients with de novo coronary disease treated with the DCB-only strategy were retrospectively enrolled from three centers and categorized into a CAC group and a non-CAC group. The primary endpoint was the target lesion failure (TLF) rate during the 3-year follow-up. Secondary endpoints included the occurrence of major adverse cardiac events (MACEs), target lesion revascularization (TLR), cardiac death, myocardial infarction (MI) and any revascularization. Propensity score matching (PSM) was conducted to assemble a cohort of patients with similar baseline characteristics. Results: A total of 1,263 patients with 1,392 lesions were included, and 243 patients were included in each group after PSM. Compared with the non-CAC group, the incidence rates of TLF (9.52% vs. 4.94%, odds ratio [OR]: 2.080; 95% confidence interval [CI]: 1.083-3.998, P = 0.034) and TLR (7.41% vs. 2.88%, OR: 2.642; 95% CI: 1.206-5.787, P = 0.020) in the CAC group were higher. The incidence rates of MACE (12.35% vs. 7.82%, OR: 1.665; 95% CI: 0.951-2.916, P = 0.079), cardiac death (2.06% vs. 2.06%, OR: 0.995; 95% CI: 0.288-3.436, P = 0.993), MI (1.23% vs. 0.82%, OR: 2.505; 95% CI: 0.261-8.689, P = 0.652) and any revascularization (12.76% vs. 9.67%, OR: 1.256; 95% CI: 0.747-2.111, P = 0.738) were similar between groups. Conclusions: CAC increased the incidence of TLF and TLR without a substantial increase in the risk of MACE, cardiac death, MI, or any revascularization in patients treated with DCB-only angioplasty during the 3-year follow-up.

Long-term outcomes of less drug-eluting stents by the use of drug-coated balloons in de novo coronary chronic total occlusion intervention: A multicenter observational study.

Background: Data on drug-coated balloons (DCB) for de novo coronary chronic total occlusion (CTO) are limited. We aimed to investigate the long-term outcomes of substitution of drug-eluting stents (DES) by DCB. Methods: We compared the outcomes of less DES strategy (DCB alone or combined with DES) and DES-only strategy in treating de novo coronary CTO in this prospective, observational, multicenter study. The primary endpoints were major adverse cardiovascular events (MACE), target vessel revascularization, myocardial infarction, and death during 3-year follow-up. The secondary endpoints were late lumen loss (LLL) and restenosis until 1-year after operation. Results: Of the 591 eligible patients consecutively enrolled between January 2015 and December 2019, 281 (290 lesions) were treated with DCB (DCB-only or combined with DES) and 310 (319 lesions) with DES only. In the DCB group, 147 (50.7%) lesions were treated using DCB-only, and the bailout stenting rate was relatively low (3.1%). The average stent length per lesion in the DCB group was significantly shorter compared with the DES-only group (21.5 ± 25.5 mm vs. 54.5 ± 26.0 mm, p < 0.001). A total of 112 patients in the DCB group and 71 patients in the DES-only group (38.6% vs. 22.3%, p < 0.001) completed angiographic follow-up until 1-year, and LLL was much less in the DCB group (-0.08 ± 0.65 mm vs. 0.35 ± 0.62 mm, p < 0.001). There were no significant differences in restenosis occurrence between the two groups (20.5% vs. 19.7%, p > 0.999). The Kaplan-Meier estimates of MACE at 3-year (11.8% vs. 12.0%, log-rank p = 0.688) was similar between the groups. Conclusion: Percutaneous coronary intervention with DCB is a potential "stent-less" therapy for de novo CTO lesions with satisfactory long-term clinical results compared to the DES-only approach.

The Relationship Between Collagen Proportionate Area and Hepatitis B Surface Antigen Levels in E Antigen Positive Hepatitis B Cirrhosis.

BACKGROUND: Quantitative serum hepatitis B surface antigen (HbsAg) has been widely used as a biomarker for treatment response and prognosis in chronic hepatitis B infection, and has recently been found associated with liver histology in e-antigen positive patients. A histological measurement as a continuous variable-collagen proportionate area (CPA)-is appropriate to assess liver fibrosis degree and substages cirrhosis. We, therefore, aimed to explore the association between serum quantitative HBsAg and CPA in e antigenpositive hepatitis B cirrhosis. METHODS: Liver fibrosis staging was evaluated by METAVIR semiquantitative scoring system, only patients with METAVIR fibrosis stage 4 were included. All liver sections were stained with picroSirius red for determination of collagen quantification by digital image analysis. RESULTS: Mean CPA value was 23.46%. The percentage of patients with different classification of CPA (30%) were 25.8%, 57.8%, and 16.4%, respectively. A modest correlation was found between CPA and serum HBsAg level (r = -0.306, P =.001). Hepatitis B surface antigen level is independently associated with CPA in multivariable linear regression analyses. CONCLUSION: Serum HBsAg levels can predict liver fibrosis determined by CPA in HBeAg-positive hepatitis B cirrhosis.

Clinical outcomes of drug-coated balloon in coronary lesions: a real-world, all-comers study.

BACKGROUNDS: Although drug-eluting stents are the most common interventional devices for patients with coronary disease, drug-coated balloons (DCBs) represent a novel therapeutic alternative in certain scenarios. This prospective, observational all-comers study explored the clinical outcomes of DCB use in patients with coronary lesions. METHODS AND RESULTS: All patients treated with DCBs were enrolled in this study, including patients with in-stent restenosis (ISR) or de novo lesions. The primary outcome was the target lesion revascularization (TLR) rate at one year. We enrolled 2306 patients with 2660 lesions and performed DCB angioplasty in 399 patients (17.3%) with ISR and 1907 patients (82.7%) with de novo lesions. During follow-up (366 ± 46 days), the TLR rate was lower in the de novo lesion group (1.31%) compared to the ISR group (7.02%) [odds ratio (OR) 0.176, 95% confidence interval (CI) 0.101-0.305, p < 0.001]. Patients with de novo lesions had a lower yearly incidence of MACE compared to ISR patients (2.73 vs. 9.27%, respectively, OR 0.274, 95% CI 0.177-0.424, p < 0.001) and a lower incidence of any revascularization (5.09 vs. 13.03%, OR 0.358, 95% CI 0.251-0.510, p < 0.001). No significant differences between groups were observed in the rates of cardiac death (OR 0.783, 95% CI 0.258-2.371, p = 0.655) or MI (OR 0.696, 95% CI 0.191-2.540, p = 0.573). CONCLUSIONS: DCB angioplasty in this all-comers, real-world, prospective study was safe and efficient with low TLR and MACE rates. Thus, DCB appears to be an attractive alternative for the stent-less treatment of de novo coronary lesions. ISR in-stent restenosis; OR odds ratio; CI confidence interval; TLR target lesion revascularization; MACE major adverse cardiovascular events; MI myocardial infraction. MACE defined as the composite outcome of cardiac death, myocardial infarction, and target vessel revascularization. Any revascularization includes any percutaneous coronary intervention, and coronary artery bypass grafting.

Circ_0004872 promotes platelet-derived growth factor-BB-induced proliferation, migration and dedifferentiation in HA-VSMCs via miR-513a-5p/TXNIP axis.

The proliferation, migration and dedifferentiation of vascular smooth muscle cells (VSMCs) exert crucial roles in atherosclerosis (AS) progression. The aim of our study was to explore the influences of circular RNA 0004872 (circ_0004872) in platelet-derived growth factor-BB (PDGF-BB)-induced AS cell model and investigate the underlying mechanisms. Real-time quantitative polymerase chain reaction (RT-qPCR) was implemented for the expression detection of circ_0004872, mitogen-activated protein kinase 1 (MAPK1) messenger RNA (mRNA), microRNA-513a-5p (miR-513a-5p) and thioredoxin interacting protein (TXNIP). Cell proliferation was analyzed via Cell Counting Kit 8 (CCK8) assay. Cell migration was assessed via wound healing assay and transwell migration assay. Western blot assay was used to measure the expression of alpha smooth muscle actin (α-SMA), osteopontin (OPN), calponin and TXNIP. Dual-luciferase reporter assay and RNA-pull down assay were used for confirmation of interaction between miR-513a-5p and circ_0004872 or TXNIP. Circ_0004872 expression was elevated in PDGF-BB-induced human aortic vascular smooth muscle cells (HA-VSMCs) and carotid plaque tissues. Circ_0004872 silencing alleviated PDGF-BB-induced proliferation, migration and dedifferentiation in HA-VSMCs. MiR-513a-5p bound to circ_0004872, and circ_0004872 knockdown-induced effects in PDGF-BB-treated HA-VSMCs were largely attenuated by the silencing of miR-513a-5p. MiR-513a-5p bound to the 3' untranslated region (3'UTR) of TXNIP, and miR-513a-5p overexpression-mediated effects were counteracted by the transfection of pcDNA-TXNIP in PDGF-BB-induced HA-VSMCs. TXNIP was modulated by circ_0004872/miR-513a-5p signaling cascade in HA-VSMCs. Circ_0004872 accelerated PDGF-BB-induced proliferation, migration and dedifferentiation in HA-VSMCs through enhancing TXNIP level via sponging miR-513a-5p.

Clinical Outcomes of Drug-Coated Balloon in Coronary Patients with and without Diabetes Mellitus: A Multicenter, Propensity Score Study.

BACKGROUND: Relative to nondiabetic patients, percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM) is associated with inferior clinical outcomes. We aimed to evaluate the outcomes of drug-coated balloon (DCB) in diabetic versus nondiabetic patients. METHODS AND RESULTS: In this observational, prospective, multicenter study, we compared the outcomes of patients with and without DM after undergoing PCI with DCBs. Target lesion failure (TLF) was analyzed as primary endpoint. Secondary endpoints were the rates of target lesion revascularization (TLR), major adverse cardiovascular events (MACE), cardiac death, myocardial infarction (MI), and any revascularization. Propensity score matching was used to assemble a cohort of patients with similar baseline characteristics. Among 2,306 eligible patients, 578 with DM and 578 without DM had similar propensity scores and were included in the analyses. During follow-up (366 ± 46 days), compared with DM patients, patients without DM were associated with a lower yearly incidence of TLF (2.77% vs. 5.36%; OR, 1.991; 95% CI, 1.077 to 3.681; P = 0.025) and TLR (1.90% vs. 4.15%; OR, 2.233; 95% CI, 1.083 to 4.602; P = 0.026). No significant differences were observed with regards to rates of MACE (OR: 1.580, 95% CI: 0.912-2.735; P = 0.100), cardiac death (OR: 1.608, 95% CI: 0.523-4.946; P = 0.403), MI (OR: 4.042, 95% CI: 0.855-19.117; P = 0.057), and any revascularization (OR: 1.534, 95% CI: 0.983-2.393; P = 0.058). CONCLUSIONS: Diabetic patients experience higher TLF and TLR rates following DCB angioplasty without substantial increase in the risk of MACE, cardiac death, MI, or revascularization.

TBC1D25 Regulates Cardiac Remodeling Through TAK1 Signaling Pathway.

Cardiac remodeling is a major early event of heart failure, which is regulated by multiple signaling pathways. Here, we demonstrate that TBC1D25 is upregulated during pathological cardiac remodeling. The aim of this study is to determine the role of TBC1D25 in cardiac remodeling and to illustrate the underlying molecular mechanism. Specifically, cardiac remodeling was induced in TBC1D25-KO mice and their wild-type control mice through partial transverse aortic constriction (TAC) of aortic arch. Knockout TBC1D25 exacerbated cardiac hypertrophy, fibrosis and dysfunction. Meanwhile, TBC1D25 overexpression in both H9C2 cells and NRCMs alleviate Angiotensin II-induced cardiomyocyte hypertrophy in vitro. Moreover, TBC1D25 deficiency increases the phosphorylation levels of TAK1 and its downstream molecular (JNK and p38), whereas overexpressed TBC1D25 inhibits phosphorylation of TAK1, JNK and p38. And TAK1 is the key molecule in this process. Furthermore, we demonstrated that TBC1D25 could directly interacts with TAK1 by immunoprecipitation assay and GST pull-down assay, and the interaction needs the amino acids from at least 138 to 226 in the C-terminal region of TBC1D25 and from 1 to 300 in the C-terminal region of TAK1. We conclude that TBC1D25 suppresses pathological cardiac remodeling via regulating TAK1-JNK/p38 signaling pathway, which suggests that TBC1D25 will likely become a promising therapeutic target for heart failure.

Downregulation of microRNA­34b is responsible for the elevation of blood pressure in spontaneously hypertensive rats.

The present study aimed to identify the microRNA (miRNA) responsible for the development of primary hypertension, and examine the downstream signaling pathway, which mediates the effect of the miRNA. Reverse transcription­quantitative polymerase chain reaction analysis was performed to identify which miRNA may be involved in the pathogenesis of hypertension. In silico analysis and a luciferase assay were used to validate the target of the selected miRNA, and miRNA mimics and small interfering (si)RNA of the target were transfected into smooth muscle cells to examine its effect on the biological activity of the cells. miR­34b was found to be upregulated in spontaneously hypertensive rats (SHRs), compared with Wistar Kyoto (WKY) rats. Therefore, the present study used online miRNA target prediction tools to predict the candidate target genes of miR­34b in the database, and consequently identified cyclin G1 (CCNG1) and cyclin­dependent kinase 6 (CDK6) as its possible target genes. CDK6 subsequently identified to be the direct target gene of miR­34b using a luciferase reporter assay in vascular smooth muscle cells (VSMCs). The present study also established the possible negative regulatory association between miR­34b and CDK6 via investigating the mRNA and protein expression levels of CDK6 and CCNG1 in VSMCs collected from the SHRs and WKY rats, respectively. To investigate the signaling pathways between miR­34b and CDK6, the mRNA and protein expression levels of CDK6, and the proliferation rates were compared in VSMCs transfected with CDK6 siRNA or miR­34b mimics, the results of which indicated that the miR­34b mimics exerted the same effects on the expression of CDK6 and cell proliferation as CDK6 siRNA. The negative regulatory association between miR­34b and its target, CDK6, was confirmed, which may offer potential as a novel therapeutic target in the treatment of hypertension.

Relationship between obstructive sleep apnea and coronary microcirculatory function among patients with cardiac syndrome X.

OBJECTIVES: Obstructive sleep apnea (OSA) is an emerging risk factor for cardiovascular disease. Microcirculatory dysfunction has been proposed as a potential mechanism in the pathogenesis of cardiovascular disease in OSA. This study aims to investigate the relationship between OSA and coronary microcirculatory function. PATIENTS AND METHODS: One thousand and thirty-eight patients (598 female, mean age 60±9 years) with angiographically normal coronary arteries were divided into three groups with non-OSA of apnea-hypopnea index (AHI) less than 5 (n=403), mild-to-moderate OSA of AHI 5-30 (n=386), and severe OSA of AHI more than 30 (n=249). RESULTS: The prevalence of OSA was very high in patients with syndrome X (635/1038). Patients with higher AHI values had a lower coronary flow reserve, were more likely to have a higher total cholesterol, low-density lipoprotein cholesterol, and high sensitive C-reactive protein, and were more likely to be obese. Compared with the non-OSA group, the multivariable-adjusted odds ratio of coronary microcirculatory function for an AHI of 5-30 events/h was 1.93, 95% confidence interval 1.66-3.47, P=0.038, and for an AHI of more than 30 events/h was 2.18, 95% confidence interval 1.62-4.23, P=0.024, in model 1; and coronary microcirculatory function for an AHI of 5-30 events/h and more than 30 events/h odds ratio 1.31, 95% confidence interval 1.06-2.88, P=0.043, versus odds ratio 2.08, 95% confidence interval 1.03-2.16, P=0.036, in model 2. CONCLUSION: As compared with having no sleep apnea, categories with higher AHI were associated with increased odds of lower coronary flow reserve. The data suggested a close relationship between OSA and coronary microcirculatory function in atherosclerosis.