Efficacy and safety of sympathetic mapping and ablation of renal nerves for the treatment of hypertension (SMART): 6-month follow-up of a randomised, controlled trial.

Background: Previous trials of renal denervation (RDN) have been designed to investigate reduction of blood pressure (BP) as the primary efficacy endpoint using non-selective RDN without intraoperatively verified RDN success. It is an unmet clinical need to map renal nerves, selectively denervate renal sympathetic nerves, provide readouts for the interventionalists and avoid futile RDN. We aimed to examine the safety and efficacy of renal nerve mapping/selective renal denervation (msRDN) in patients with uncontrolled hypertension (HTN) and determine whether antihypertensive drug burden is reduced while office systolic BP (OSBP) is controlled to target level (＜140 mmHg). Methods: We conducted a randomized, prospective, multicenter, single-blinded, sham-controlled trial. The study combined two efficacy endpoints at 6 months as primary outcomes: The control rate of patients with OSBP ＜140 mmHg (non-inferior outcome) and change in the composite index of antihypertensive drugs (Drug Index) in the treatment versus Sham group (superior outcome). This design avoids confounding from excess drug-taking in the Sham group. Antihypertensive drug burden was assessed by a composite index constructed as: Class N (number of classes of antihypertensive drugs) × (sum of doses). 15 hospitals in China participated in the study and 220 patients were enrolled in a 1:1 ratio (msRDN vs Sham). The key inclusion criteria included: age (18-65 years old), history of essential HTN (at least 6 months), heart rate (≥70 bpm), OSBP (≥150 mmHg and ≤180 mmHg), ambulatory BP monitoring (ABPM, 24-h SBP ≥130 mmHg or daytime SBP ≥135 mmHg or nighttime SBP ≥120 mmHg), renal artery stenosis (＜50%) and renal function (eGFR ＞45 mL/min/1.73 m2). The catheter with both stimulation and ablation functions was inserted in the distal renal main artery. The RDN site (hot spot) was selected if SBP increased (≥5 mmHg) by intra-renal artery (RA) electrical stimulation; an adequate RDN was confirmed by repeated electronic stimulation if no increase in BP otherwise, a 2nd ablation was performed at the same site. At sites where there was decreased SBP (≥5 mmHg, cold spot) or no BP response (neutral spot) to stimulation, no ablation was performed. The mapping, ablation and confirmation procedure was repeated until the entire renal main artery had been tested then either treated or avoided. After msRDN, patients had to follow a predefined, vigorous drug titration regimen in order to achieve target OSBP (＜140 mmHg). Drug adherence was monitored by liquid chromatography-tandem mass spectrometry analysis using urine. This study is registered with ClinicalTrials.gov (NCT02761811) and 5-year follow-up is ongoing. Findings: Between July 8, 2016 and February 23, 2022, 611 patients were consented, 220 patients were enrolled in the study who received standardized antihypertensive drug treatments (at least two drugs) for at least 28 days, presented OSBP ≥150 mmHg and ≤180 mmHg and met all inclusion and exclusion criteria. In left RA and right RA, mapped sites were 8.2 (3.0) and 8.0 (2.7), hot/ablated sites were 3.7 (1.4) and 4.0 (1.6), cold spots were 2.4 (2.6) and 2.0 (2.2), neutral spots were 2.0 (2.1) and 2.0 (2.1), respectively. Hot, cold and neutral spots was 48.0%, 27.5% and 24.4% of total mapped sites, respectively. At 6 M, the Control Rate of OSBP was comparable between msRDN and Sham group (95.4% vs 92.8%, p = 0.429), achieved non-inferiority margin -10% (2.69%; 95% CI -4.11%, 9.83%, p ＜ 0.001 for non-inferiority); the change in Drug Index was significantly lower in msRDN group compared to Sham group (4.37 (6.65) vs 7.61 (10.31), p = 0.010) and superior to Sham group (-3.25; 95% CI -5.56, -0.94, p = 0.003), indicating msRDN patients need significantly fewer drugs to control OSBP ＜140 mmHg. 24-hour ambulatory SBP decreased from 146.8 (13.9) mmHg by 10.8 (14.1) mmHg, and from 149.8 (12.8) mmHg by 10.0 (14.0) mmHg in msRDN and Sham groups, respectively (p < 0.001 from Baseline; p > 0.05 between groups). Safety profiles were comparable between msRDN and Sham groups, demonstrating the safety and efficacy of renal mapping/selective RDN to treat uncontrolled HTN. Interpretation: The msRDN therapy achieved the goals of reducing the drug burden of HTN patients and controlling OSBP <140 mmHg, with only approximately four targeted ablations per renal main artery, much lower than in previous trials. Funding: SyMap Medical (Suzhou), LTD, Suzhou, China.

Endomyocardial fibrosis and apical calcification: A case report with unusual presentations of apical hypertrophic cardiomyopathy.

RATIONALE: Apical hypertrophic cardiomyopathy (ApHCM) is a phenotypic variant of hypertrophic cardiomyopathy. Endomyocardial fibrosis and endocardial calcification are especially rare in ApHCM. PATIENT CONCERNS: The main symptoms was chest tightness, palpitation, shortness of breath, and fatigue. Echocardiography and imaging examinations found apical hypertrophy along with endocardial calcification and endomyocardial fibrosis. Abnormal structural changes led to thrombosis and made the left ventricle a flat shape resembling an "apple." DIAGNOSES: The typical presentations, hypertrophic apex on echocardiography and an elevated N-terminal pro-brain natriuretic peptide level indicated the diagnosis of ApHCM and heart failure with preserved ejection fraction. INTERVENTIONS: Optimal medical therapy including the administration of ApHCM, heart failure and atrial fibrillation to improve symptoms and life quality. OUTCOMES: Since discharge, the patient could perform normal daily activities and had no discomfort based on the optimal medical therapy. LESSONS: We report a ApHCM patients with unusual presentations of endomyocardial fibrosis and apical calcification. This case highlights the importance of understanding the specific pathological changes of ApHCM for treatment and prognosis.

Prognostic Value of GRACE Risk Score Combined With Systemic Immune-Inflammation Index in Patients With ST-Segment Elevation Myocardial Infarction After Percutaneous Coronary Intervention.

The Global Registry of Acute Coronary Events (GRACE) score and the systemic immune-inflammation index (SII) were used independently to predict adverse outcomes in patients with ST-elevation myocardial infarction (STEMI). In this study, 1041 patients with STEMI were divided into 4 groups based on GRACE scores and optimal cutoff values for SII. SII was positively correlated with GRACE score (r = 0.164; P < .001). SII (HR, hazard ratio: 2.051; 95%CI: 1.249-3.368; P = .005) and GRACE score (HR: 7.625; 95%CI: 3.692-15.746; P < .001) were independent risk predictors of short-term major adverse cardiovascular events (MACEs). Taking the low SII+low GRACE group as the reference group, the short-term MACE HR of the high SII+high GRACE group was 40.470 (95%CI: 5.547-295.253). Comparing the area under the curve, the combined use of SII and GRACE scores can significantly improve the prediction efficiency of short-term MACE compared with the single use of SII and GRACE scores. In conclusion, SII may be positively correlated with GRACE score, and the combination of the two accurately predicted the occurrence of short-term MACE in STEMI patients after percutaneous coronary intervention (PCI).

Efficacy and safety of hybutimibe in combination with atorvastatin for treatment of hypercholesteremia among patients with atherosclerotic cardiovascular disease risk equivalent: A multicenter, randomized, double-blinded phase III study.

Background: To evaluate the safety and efficacy of hybutimibe plus atorvastatin for lipid control in hypercholesterolemia patients with atherosclerotic cardiovascular disease risk equivalent. Methods: In this double-blind phase III study, we 1:1 randomly assigned 255 hypercholesterolemia patients with atherosclerotic cardiovascular disease to receive hybutimibe plus atorvastatin or placebo plus atorvastatin. The primary endpoint was the rate of change of plasma low-density lipoprotein-cholesterol (LDL-C) level at 12 weeks from baseline. The secondary endpoints were plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), non-HDL-C, apoprotein (Apo) B, and 2-, 4-, 8-, and 12-week Apo A1 levels change rate and rates of change of plasma LDL-C levels at 2, 4, and 8 weeks from baseline. Results: From April 2016 to January 2018, 128 in the hybutimibe plus atorvastatin group and 125 in the atorvastatin group were included in modified intention-to-treat (mITT) analysis. After 12 weeks of treatment, LDL-C level changed from 2.61 mmol/L (±0.30) at baseline to 2.18 mmol/L (±0.45) in the hybutimibe plus atorvastatin group and from 2.58 (±0.31) mmol/L to 2.40 (± 0.46) mmol/L in the atorvastatin group (P < 0.0001), in mITT. The change rate in the hybutimibe plus atorvastatin group was significantly higher than that in the atorvastatin group (P < 0.0001); the estimated mean rates of change were -16.39 (95% confidence interval: -19.04, -13.74) and -6.75 (-9.48, -4.02), respectively. Consistently, in per-protocol set (PPS) analysis, the rate of change of LDL-C in the hybutimibe plus atorvastatin group was significantly higher than that in atorvastatin group. Significant decreases in the change rates of non-HDL-C, TC, and Apo B at 2, 4, 8, and 12 weeks (all P < 0.05) were observed for hybutimibe plus atorvastatin, while the differences were not significant for HDL-C, TG, and Apo-A1 (all P > 0.05). During the study period, no additional side effects were reported. Conclusions: Hybutimibe combined with atorvastatin resulted in significant improvements in LDL-C, non-HDL-C, TC, and Apo B compared with atorvastatin alone. The safety and tolerability were also acceptable, although additional benefits of hybutimibe plus atorvastatin were not observed compared with atorvastatin alone in HDL-C, TG, and Apo-A1.

Dapagliflozin Attenuates Myocardial Fibrosis by Inhibiting the TGF-ß1/Smad Signaling Pathway in a Normoglycemic Rabbit Model of Chronic Heart Failure.

Recent studies have shown that sodium-glucose cotransporter-2 (SGLT2) inhibitors play a beneficial role for normoglycemic patients with heart failure (HF). However, the underlying mechanism remains largely unexplored. In the present study, we aimed to investigate the cardioprotective effect of SGLT2 inhibitors in a normoglycemic rabbit model of chronic heart failure (CHF) and its potential mechanism was also explored. A total of 24 male New Zealand white rabbits were randomly divided into the sham group, HF group, perindopril group, and dapagliflozin (DAPA) group. The normoglycemic CHF model was established by aortic constriction for 12 weeks. In the 13th week, DAPA (1 mg/kg/day) or perindopril (0.5 mg/kg/day) was administered by oral gavage daily for 10 weeks. Both the sham group and HF group were given normal saline via gavage. After 10 weeks, the heart structure and function were evaluated by echocardiography and plasma NT-proBNP. Moreover, cardiac fibrosis was analyzed using immunohistochemistry, Masson's trichrome staining, and Western blotting analysis. The results showed that DAPA improved the myocardial structure and function of normoglycemic CHF rabbits and ameliorated myocardial fibrosis. Further study indicated that DAPA suppressed cardiac fibrosis by inhibiting the transforming growth factor ß1 (TGF-ß1)/Smad signaling pathway. Collectively, our findings showed that DAPA could ameliorate cardiac fibrosis in normoglycemic CHF rabbits by inhibiting the TGF-ß1/Smad signaling pathway.

Pentraxin 3 depletion (PTX3 KD) inhibited myocardial fibrosis in heart failure after myocardial infarction.

BACKGROUND: HF is a common complication of MI. The underlying mechanisms of myocardial fibrosis in HF after MI are incompletely defined. Here, this study aims to investigate the role of PTX3 KD in HF after MI. METHODS: Bioinformatics analysis based on GSE86569 dataset was performed to explore the potential role of PTX3 in HF. Male C57/BL6J mice were administered with lentiviral vector encoding PTX3 KD or empty vector, and then underwent either coronary ligation or sham surgery. Echocardiography, Masson staining, and immunofluorescence counterstaining were conducted to evaluate the cardiac function and fibrosis. Cardiac fibroblasts were isolated and transfected with lentiviral vector encoding PTX3 KD in vitro to verify the in vivo findings. RESULTS: Bioinformatics analysis based on GSE86569 revealed the aberrant expression of PTX3 in HF patients. Echocardiography showed that PTX3 KD reversed the HF-induced cardiac dysfunction with better cardiac function parameters. Masson staining demonstrated that the obvious infarct and high fibrosis ratio in HF mice were remarkably improved after PTX3 KD. Immunofluorescence staining indicated that the HF-induced increase expression of α-SMA was significantly suppressed by PTX3 KD. Additionally, both in vivo and in vitro results confirmed that PTX3 KD decreased the fibrosis-related up-regulation of collagen I, collagen III, and p-STAT3. However, the result was opposite after IL-6 treatment. CONCLUSIONS: PTX3 KD protects the cardiac function and counteracts the myocardial fibrosis by down-regulating IL-6/STAT3 pathway in HF.

Association between total ischemic time and in-hospital mortality after emergency PCI in patients with acute ST-segment elevation myocardial infarction: a retrospective study.

BACKGROUND: Symptom-to-balloon time (SBT) represents the total ischemic time in ST-elevated myocardial infarction (STEMI) and is associated with poor long-term outcomes. The study aimed to explore the association between SBT and in-hospital mortality after emergency percutaneous coronary intervention (PCI) in patients with acute STEMI. METHODS: This retrospective, multicenter, observational study included patients admitted to the Hebei General Hospital, Baoding No. 1 Central Hospital, and Cangzhou Central Hospital from January 2016 to December 2018. The outcome was all-cause mortality during the hospital stay. Logistic regression models were established to explore the association between SBT and all-cause mortality during the hospital stay. RESULTS: This study included 1169 patients: 876 males of 59.6 ± 11.4 years of age, and 293 females 66.3 ± 13.3 years of age. A first analysis showed EF had an interaction with SBT (P = 0.01). In patients with EF ≥ 50%, SBT was not an independent risk factor for postoperative all-cause mortality in the hospital (all P > 0.05). In patients with EF < 50%, SBT was an independent risk factor for postoperative all-cause mortality in the hospital [model 3: 1.51 (1.17, 1.54), P for trend = 0.01]. CONCLUSIONS: SBT was independently associated with all-cause mortality in the hospital after PCI in patients with acute STEMI and EF < 50%. Specifically, the risk of in-hospital mortality for those with SBT ≥ 361 min is increased by 51% compared with those with SBT ≤ 120 min.

Nomogram for Predicting In-Hospital Mortality in Patients with Acute ST-Elevation Myocardial Infarction Complicated by Cardiogenic Shock after Primary Percutaneous Coronary Intervention.

Background: Mortality after percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) patients with cardiogenic shock (CS) remains high. However, the real-world risk factors for mortality in these patients are poorly defined. Objective: The aim of this study is to establish a clinical prognostic nomogram for predicting in-hospital mortality after primary PCI in STEMI patients with CS. Methods: This retrospective, multicenter, observational study included STEMI patients with CS who underwent PCI at 39 hospitals in Hebei Province from January 2018 to December 2019. A multivariate logistic regression model was used to identify the factors associated with in-hospital mortality. These factors were then incorporated into a nomogram and its performance was evaluated by discrimination, calibration, and clinical utility. Results: This study included 274 patients, among whom 179 died in hospital. Sex, random blood glucose on admission, ejection fraction after PCI, no-reflow, and intra-aortic balloon pump (IABP) were independently associated with in-hospital mortality (all P < 0.05). In the training set, the nomogram showed a C-index of 0.819, goodness-of-fit of 0.08, and area under the receiver operating characteristic curve (AUC) of 0.819 (95%CI = 0.759-0.879). In the testing set, the C-index was 0.842, goodness-of-fit was 0.585, and AUC was 0.842 (95%CI = 0.715-0.970). The results indicate that the nomogram had good discrimination and good prediction accuracy and could achieve a good net benefit. Conclusion: We established and validated a nomogram that provided individual prediction of in-hospital mortality for STEMI patients with CS after PCI in a Chinese population.

Inhibition of Kruppel-like factor 7 attenuates cell proliferation and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis through nuclear factor κB and mitogen-activated protein kinase signaling pathway.

Rheumatoid arthritis (RA) is an autoimmune disease, which can lead to joint inflammation and progressive joint destruction. Kruppel-like factor 7 (KLF7) is the member of KLF family and plays an important role in multiple biological progresses. However, its precise roles in RA have not been described. Present study aimed to investigate the role of KLF7 in RA-fibroblast-like synoviocytes (FLSs). Data showed that KLF7 expression was obviously upregulated in synovial tissues of rats with adjuvant-induced arthritis. Functional studies demonstrated that the loss of KLF7 may suppress cell proliferation and the expression of pro-inflammatory factors (IL-6, IL-1ß, IL-17A) and matrix metalloproteinase (MMP-1, MMP-3, MMP-13) in FLSs through the inhibition of phosphorylation of nuclear factor κB (NF-κB) p65 and JNK. We further showed that miR-9a-5p specifically interacts with KLF7 to negatively regulate the expression of KLF7 in RA-FLSs. Taken together, our results demonstrated that KLF7 which targeted by miR-9a-5p might participate in the pathogenesis of RA by promoting cell proliferation, pro-inflammatory cytokine release and MMP expression through the activation of NF-κB and JNK pathways in RA-FLSs. Hence, KLF7 could be a novel target for RA therapy.

Development of a nomogram for the prediction of in-hospital mortality in patients with acute ST-elevation myocardial infarction after primary percutaneous coronary intervention: a multicentre, retrospective, observational study in Hebei province, China.

OBJECTIVES: To establish a clinical prognostic nomogram for predicting in-hospital mortality after primary percutaneous coronary intervention (PCI) among patients with ST-elevation myocardial infarction (STEMI). DESIGN: Retrospective, multicentre, observational study. SETTING: Thirty-nine hospitals in Hebei province. PARTICIPANTS: Patients with STEMI who underwent PCI from January 2018 to December 2019. INTERVENTIONS: A multivariable logistic regression model was used to identify the factors associated with in-hospital mortality, and a nomogram was established using these factors. The performance of the nomogram was evaluated by the discrimination, calibration and clinical usefulness. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome was the factors associated with in-hospital mortality. RESULTS: This study included 855 patients, among whom 223 died in hospital. Age, body mass index, systolic pressure on admission, haemoglobin, random blood glucose on admission, ejection fraction after PCI, use aspirin before admission, long lesions, thrombolysis in myocardial infarction flow grade and neutrophils/lymphocytes ratio were independently associated with in-hospital mortality (all p<0.05). In the training set, the nomogram showed a C-index of 0.947, goodness-of-fit of 0.683 and area under the receiver operating characteristic curve (AUC) of 0.947 (95% CI 0.927 to 0.967). In the testing set, the C-index was 0.891, goodness-of-fit was 0.462 and AUC was 0.891 (95% CI 0.844 to 0.939). The results indicate that the nomogram had good discrimination and good prediction accuracy and could achieve a good net benefit. CONCLUSIONS: A nomogram to predict in-hospital mortality in patients with STEMI after PCI was developed and validated in Hebei, China and showed a satisfactory performance. Prospective studies will be necessary to confirm the performance and clinical applicability and practicality of the nomogram.

Ginsenoside Rg2 Attenuated Trastuzumab-Induced Cardiotoxicity in Rats.

AIM: Trastuzumab (TZM) is a monoclonal antibody drug for HER2-positive breast cancer by targeting epidermal growth factor 2, but it has significant cardiotoxicity. Ginsenoside Rg2 has shown a variety of biological activities. This study was aimed at investigating whether Rg2 attenuates TZM-induced cardiotoxicity. METHODS: A model of TZM-induced cardiotoxicity was established in Wistar rats, and the rats were pretreated with Rg2. After echocardiography analysis, the rats were killed and the hearts were dissected for RNAseq analysis. Primary human cardiomyocytes (HCMs) were treated with TZM with or without pretreatment with Rg2 and then subjected to a colony formation assay, flow cytometry analysis, and Western blot analysis for the detection of caspase-3, caspase-9, and BAX. RESULTS: TZM induced LV dysfunction in rats, but Rg2 could attenuate TZM-induced LV dysfunction. The mRNA levels of caspase-3, caspase-9, and BAX were significantly higher in TZM-treated rats. The colony formation ability of HCMs was significantly lower in TZM-treated cells but was recovered after pretreatment with Rg2. The apoptosis rate of HCMs was significantly higher in TZM-treated cells but was significantly lower after pretreatment with Rg2. Moreover, protein levels of caspase-3, caspase-9, and BAX were significantly higher in TZM-treated cells but were significantly lower after pretreatment with Rg2. CONCLUSION: Ginsenoside Rg2 inhibited TZM-induced cardiotoxicity, and the mechanism may be related to the downregulation of the expression of proapoptotic proteins caspase-3, caspase-9, and BAX and the inhibition of TZM-induced apoptosis in cardiomyocytes. Ginsenoside Rg2 has a potential to be applied in patients with breast cancer to prevent TZM-induced cardiotoxicity.

Risk factors for in-hospital death in acute ST-segment elevation myocardial infarction after emergency percutaneous coronary intervention: a multicenter retrospective study.

BACKGROUND: For some acute ST-segment elevation myocardial infarction (STEMI) cases, the risk of in-hospital death remains high even after emergency percutaneous coronary intervention (PCI). This study sought to identify predictors of in-hospital mortality in STEMI patients after PCI. METHODS: Patients with acute STEMI, who underwent emergency PCI at Hebei General Hospital, Baoding First Central Hospital, and Cangzhou Central Hospital, from January 2016 to December 2018, were retrospectively included in this study. The patients' general data, previous medical history, clinical data and medication data were collected and compared between the survival and mortality groups. The primary outcome was in-hospital mortality. In-hospital mortality was defined as all-cause death during admission. RESULTS: Of the 1,169 patients (876 male and 293 female) enrolled in this study, 95 (8.13%) died during hospitalization. The multivariate logistic regression analysis showed that being female [odds ratio (OR) =5.86, 95% confidence interval (CI): 2.03-16.92, P=0.001], a Killip class of 2 (OR =8.13, 95% CI: 2.03-32.61, P=0.003), a Killip class of 4 (OR =17.31, 95% CI: 3.69-81.27, P=0.001), a left main coronary artery lesion (OR =44.25, 95% CI: 3.96-494.05, P=0.002), a final TIMI flow of 1 (OR =171.83, 95% CI: 28.46-1037.51, P=0.001), a final TIMI flow of 2 (OR =72.93, 95% CI: 38.54-138.00, P=0.001), symptom onset-to-door time (SDT) (OR =1.01, 95% CI: 1.00-1.02, P=0.001), symptom onset-to-balloon dilatation time (SBT) (OR =1.01, 95% CI: 1.00-1.02, P=0.001), and the Synergy Between PCI With Taxus and CABG (SYNTAX) score (OR =1.07, 95% CI: 1.01-1.12, P=0.019) were risk factors; while postoperative ß-receptor blockers (OR =0.10, 95% CI: 0.03-0.30, P=0.001) postoperative angiotensin-converting enzymes/angiotensin receptor blockers (OR =0.13, 95% CI: 0.04-0.44, P=0.001), BMI (OR =0.85, 95% CI: 0.74-0.98, P=0.024), the percentage of the ejection fraction (OR =0.81, 95% CI: 0.75-0.86, P=0.001), and low-density lipoprotein cholesterol (OR =0.44, 95% CI: 0.21-0.91, P=0.027) were protective factors for in-hospital mortality. CONCLUSIONS: Female, Killip grade, a left main lesion, TIMI grade, SDT, SBT, and SYNTAX score were associated with a higher risk of in-hospital death. Conversely, BMI, ejection fraction, LDL-C level, and postoperative use of ß-blocker and ACEI/ARB drugs were associated with a lower in-hospital death risk.

Silencing ferritin alleviates atherosclerosis in mice via regulating the expression levels of matrix metalloproteinases and interleukins.

This study was conducted to investigate the roles of ferritin in atherosclerosis. The mouse model of atherosclerosis was established by feeding ApoE knockout mice with a high-fat diet. The mice were then treated with ferritin-overexpressing and -silencing constructs, and assessed for interleukins (ILs) and matrix metalloproteinases (MMPs) levels using ELISA and Western blot analysis. After being fed with a high-fat diet, the ApoE knockout mice developed pro-atherogenic lipid profiles with elevated total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C). They also showed increased atherosclerotic lesions including narrowed lumen diameter, reduced lumen area, and increased plaque size. Following injection of the overexpression and silencing constructs, mRNA levels of ferritin were increased and decreased, respectively, and at the same time the atherosclerotic lesions were aggravated and alleviated, respectively. Further analysis indicated that silencing of ferritin gene reduced IL-1ß and IL-10 levels while overexpressing ferritin increased them. On other hand, the TNF-α levels showed an opposite trend. MMP8, MMP12 and MMP13 levels were increased or decreased significantly after the mice were injected with ferritin over-expression or silencing vectors, respectively. Western blot analysis showed that compared to the control, overexpressing ferritin resulted in increased expression of p-JNK while silencing ferritin decreased the expression. Meanwhile, the levels of pc-Jun remained unchanged. Our work demonstrates that ferritin can regulate the progress of atherosclerosis via regulating the expression levels of MMPs and interleukins. Silencing ferritin inhibits the development of atherosclerosis and is, therefore, worth being further investigated as a potential therapeutic approach for this disease.

Lipid goal attainment in post-acute coronary syndrome patients in China: Results from the 6-month real-world dyslipidemia international study II.

BACKGROUND: Dyslipidemia International Study II (DYSIS II)-China was conducted to determine the low-density lipoprotein cholesterol (LDL-C) goal (<1.8 mmol/L) attainment rate in patients with post-acute coronary syndrome (ACS). HYPOTHESIS: Compliance with treatment guideline recommendations improves the LDL-C goal attainment rate in post-ACS patients. METHODS: This multicenter prospective observational study conducted at 28 tertiary hospitals determined the LDL-C goal attainment rates at admission and 6-month follow-up in patients on lipid-lowering treatment (LLT) for ≥3 months and those not on LLT (LLT-naive or off LLT for ≥3 months) at admission. Predictors of goal attainment at 6 months were identified using multivariate logistic regression. RESULTS: The LDL-C goal attainment rate at admission in 1102/1103 enrolled patients was 17.1%; it was 41.2% among 752 patients with available lipid results at 6 months. The distance to goal was 0.7 mmol/L at 6 months. Statin monotherapy was the most prescribed LLT. Only 7.7% of patients were receiving statin + ezetimibe and 8.4% of patients were receiving an atorvastatin-equivalent dose of ≥40 mg/day at 6 months. Being male (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.1-2.6) and undergoing percutaneous coronary intervention during index hospitalization (OR 1.5, 95% CI 1.1 to 2.1) were the independent predictors for LDL-C goal attainment. CONCLUSIONS: This real-world DYSIS II study in China reports a low LDL-C goal attainment rate in post-ACS patients even after 6 months of LLT. Lack of intensification of statin therapy and underutilization of combinations suggest gaps between real-world treatment practices and guideline recommendations.

Successful optical coherence tomography-guided treatment in a 19-year-old patient with ST-segment elevation myocardial infarction caused by plaque erosion.

ST-segment elevation myocardial infarction is a type of coronary atherosclerotic heart disease, and its pathophysiological mechanism is formation of lipid plaques. We report a 19-year-old patient with ST-segment elevation myocardial infarction caused by plaque erosion, but he did not have any common traditional risk factors of lipid plaques. His treatment was guided by optical coherence tomography. He received successful treatment and had a good prognosis. Optical coherence tomography can be used to help understand the pathogenesis of myocardial infarction and visualize the real lumen.

Ginsenoside Rg2 protects cardiomyocytes against trastuzumab-induced toxicity by inducing autophagy.

Trastuzumab (TZM) significantly improves the outcomes of patients with breast cancer; however, it is associated with severe cardiotoxicity. Ginsenoside Rg2 was reported to exert protective effects against myocardial injury and apoptosis in human cardiomyocytes (HCMs). However, whether ginsenoside Rg2 protects HCMs against TZM-induced toxicity remains unclear. The present study investigated the proliferation of HCMs using a Cell Counting Kit-8 assay and Ki67 immunofluorescence staining. Apoptotic cells were detected by Annexin V/propidium iodide staining and flow cytometry. Furthermore, monodansylcadaverine staining was performed to detect cell autophagy. In addition, western blotting was used to detect the expression levels of phosphorylated (p)-Akt, p-mTOR, beclin 1, microtubule associated protein 1 light chain 3α (LC3) and autophagy protein 5 (ATG5) in HCMs. Pretreatment with ginsenoside Rg2 significantly protected HCMs against TZM-induced cytotoxicity by inhibiting apoptosis. Furthermore, pretreatment with ginsenoside Rg2 induced autophagy in HCMs by upregulating the expression levels of p-Akt, p-mTOR, beclin 1, LC3 and ATG5. The results obtained in the present study suggested that ginsenoside Rg2 could protect HCMs against TZM-induced cardiotoxicity by activating autophagy. Therefore, ginsenoside Rg2 may serve as a potential therapeutic agent to prevent TZM-related cardiotoxicity in patients with breast cancer.

Sacubitril/valsartan inhibits ox­LDL­induced MALAT1 expression, inflammation and apoptosis by suppressing the TLR4/NF­κB signaling pathway in HUVECs.

The therapeutic effect of sacubitril/valsartan (S/V) on heart failure has been confirmed, while its role in atherosclerosis remains largely unexplored. The present study aimed to investigate the effects of S/V on the expression of metastasis­associated lung adenocarcinoma transcript 1 (MALAT1), inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs) induced by oxidized low­density lipoprotein (ox­LDL) and to elucidate its possible mechanism. Cell Counting Kit­8 assay was used to detect cell viability. Reverse transcription­quantitative PCR was performed to detect the MALAT1 expression. ELISA was performed to detect the levels of IL­1ß, IL­6 and TNF­α. Flow cytometry was conducted to detect the apoptotic rate of cells. A nitric oxide (NO) detection kit was used to determine the concentration of NO. Western blotting analysis was performed to determine the levels of intercellular cell adhesion molecule (ICAM)­1, vascular cell adhesion molecule (VCAM)­1, endothelin­1, caspase­3, Bax, Bcl­2, Toll­like receptor 4 (TLR4), p65 and p­p65. Compared with the ox­LDL group, S/V treatment significantly increased the cell viability, NO concentration and Bcl­2 expression, decreased the levels of IL­1ß, IL­6 and TNF­α and reduced the expressions of MALAT1, ICAM­1, VCAM­1, cleaved­caspase­3, Bax, TLR4 and p­p65. Overall, the findings suggested that S/V could downregulate the expression of MALAT1, inhibit inflammation and apoptosis and improve endothelial function in ox­LDL­induced HUVECs via inactivating the TLR4/NF­κB signaling pathway. Therefore, S/V might be utilized as a promising therapeutic strategy for the prevention and treatment of atherosclerosis.

Effectiveness of Levoamlodipine Maleate for Hypertension Compared with Amlodipine Besylate: a Pragmatic Comparative Effectiveness Study.

PURPOSE: Antihypertensive treatment is the most important method to reduce the risk of cardiovascular events in hypertensive patients. However, there is scant evidence of the benefits of levoamlodipine maleate for antihypertensive treatment using a head-to-head comparison in the real-world. This study aims to examine the effectiveness of levoamlodipine maleate used to treat outpatients with primary hypertension compared with amlodipine besylate in a real-world setting. METHODS: This was a pragmatic comparative effectiveness study carried out at 110 centers across China in outpatients with primary hypertension treated with levoamlodipine maleate or amlodipine besylate, with 24 months of follow-up. The primary outcomes used for evaluating the effectiveness were composite major cardiovascular and cerebrovascular events (MACCE), adverse reactions, and cost-effectiveness. RESULTS: Among the included 10,031 patients, there were 482 MACCE, 223 (4.4%) in the levoamlodipine maleate group (n = 5018) and 259 (5.2%) in the amlodipine besylate group (n = 5013) (adjusted hazard ratio = 0.90, 95%CI: 0.75-1.08, P = 0.252). The levoamlodipine maleate group had lower overall incidences of any adverse reactions (6.0% vs. 8.4%, P < 0.001), lower extremity edema (1.1% vs. 3.0%, P < 0.001) and headache (0.7% vs. 1.1%, P = 0.045). There was a nearly 100% chance of the levoamlodipine maleate being cost-effective at a willingness to pay threshold of 150,000 Yuan per quality-adjusted life years (QALYs) gained, resulting in more QALYs (incremental QALYs: 0.00392) and cost savings (saving 2725 Yuan or 28.8% reduction in overall costs) per patient. CONCLUSION: In conclusion, levoamlodipine maleate could reduce cost by 29% with a similar MACCE incidence rate and lower occurrence of adverse reactions (especially edema and headache) compared with amlodipine besylate. TRIAL REGISTRATION: Clinicaltrials.gov NCT01844570 registered at May 1, 2013.

Establishment and validation of a risk model for prediction of in-hospital mortality in patients with acute ST-elevation myocardial infarction after primary PCI.

BACKGROUND: Currently, how to accurately determine the patient prognosis after a percutaneous coronary intervention (PCI) remains unclear and may vary among populations, hospitals, and datasets. The aim of this study was to establish a prediction model of in-hospital mortality risk after primary PCI in patients with acute ST-elevated myocardial infarction (STEMI). METHODS: This was a multicenter, observational study of patients with acute STEMI who underwent primary PCI. The outcome was in-hospital mortality. The least absolute shrinkage and selection operator (LASSO) method was used to select the features that were the most significantly associated with the outcome. A regression model was built using the selected variables to select the significant predictors of mortality. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. RESULTS: Totally, 1169 and 316 patients were enrolled in the training and validation sets, respectively. Fourteen predictors were identified by the LASSO analysis: sex, Killip classification, left main coronary artery disease (LMCAD), grading of thrombus, TIMI classification, slow flow, application of IABP, administration of ß-blocker, ACEI/ARB, symptom-to-door time (SDT), symptom-to-balloon time (SBT), syntax score, left ventricular ejection fraction (LVEF), and CK-MB peak. The mortality risk prediction nomogram achieved good discrimination for in-hospital mortality (training set: C-statistic = 0.987; model calibration: P = 0.722; validation set: C-statistic = 0.984, model calibration: P = 0.669). Area under the curve (AUC) values for the training and validation sets are 0.987 (95% CI: 0.981-0.994, P = 0.003) and 0.990 (95% CI: 0.987-0.998, P = 0.007), respectively. DCA shows that the nomogram can achieve good net benefit. CONCLUSIONS: A novel nomogram was developed and is a simple and accurate tool for predicting the risk of in-hospital mortality in patients with acute STEMI who underwent primary PCI.

LncRNA A2M-AS1 lessens the injury of cardiomyocytes caused by hypoxia and reoxygenation via regulating IL1R2.

BACKGROUND: Myocardial ischemia and reperfusion injury (MI/RI) is a complex pathophysiological process, which can lead to severe myocardial injury. The long noncoding RNA alpha-2-macroglobulin antisense RNA 1 (A2M-AS1) has been revealed to be abnormally expressed in MI, However, its function in MI and the potential mechanism are still unclear. OBJECTIVE: To evaluate the functional role of A2M-AS1 in hypoxia/reoxygenation (H/R)-induced neonatal cardiomyocytes and its potential molecular mechanism. METHODS: Dataset GSE66360 was obtained from GEO database for analyzing the RNA expression of A2M-AS1 and interleukin 1 receptor type 2 (IL1R2). KEGG pathway enrichment analysis of the genes that co-expressed with A2M-AS1 was performed. Human neonatal cardiomyocytes were subjected to H/R to construct in vitro models. QRT-PCR and Western blot were adopted to test the levels of mRNA and protein. The viability and apoptosis of cardiomyocytes were tested by CCK-8 and flow cytometry assays, respectively. RESULTS: The expression of A2M-AS1 was notably downregulated in H/R-treated cardiomyocytes. Overexpression of A2M-AS1 can notably enhance the cell viability of H/R-damaged cardiomyocytes, whereas knockdown of A2M-AS1 showed the opposite outcomes. Besides, a negative correlation was showed between A2M-AS1 and IL1R2 expression. In H/R-treated cardiomyocytes, overexpression of IL1R2 weakened the promoting proliferation and anti-apoptosis effects caused by overexpressing A2M-AS1, however, IL1R2-knockdown abolished the anti-proliferation and pro-apoptosis effects caused by silencing A2M-AS1. CONCLUSION: This study demonstrates the potential regulatory role of A2M-AS1/ IL1R2 axis in cardiomyocytes suffered from H/R, and provides insight into the protection of MI/RI.