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.

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.

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.

Serum Levels of Inflammatory Cytokines and Expression of BCL2 and BAX mRNA in Peripheral Blood Mononuclear Cells and in Patients with Chronic Heart Failure.

BACKGROUND This study investigated the expression of the BCL2 and BAX mRNA, inflammatory cytokines, interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-alpha (TNF-alpha), and cardiac function in patients with chronic heart failure (CHF). The New York Heart Association (NYHA) Functional Classification and measurement of the left ventricular ejection fraction (LVEF) evaluated cardiac function. MATERIAL AND METHODS Patients with CHF (n=60) due to coronary heart disease, hypertensive heart disease, and cardiomyopathy, and healthy controls (n=30) were studied. Enzyme-linked immunosorbent assay (ELISA) measured serum levels of IL-1ß, IL-6, and TNF-alpha. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) detected mRNA expression of BCL2 and BAX in peripheral blood mononuclear cells (PBMCs). Color Doppler ultrasound measured the LVEF, and the NYHA classification of CHF was used. RESULTS In patients with CHF, levels of IL-1ß, IL-6 and TNF-alpha, and mRNA expression of BAX were significantly increased compared with the control group (p<0.01); BCL2 mRNA level was significantly lower (p<0.01). There were no significant differences in the expression levels of inflammatory cytokines, or BCL2 or BAX mRNA in patients with CHF due to coronary heart disease, hypertensive heart disease, or cardiomyopathy. Expression levels of IL-1ß, IL-6, TNF-alpha, and BAX mRNA were significantly associated with the degree of CHF. Cardiac function was negatively correlated with LVEF (p<0.05). Expression levels of BCL2 mRNA level were negatively correlated with cardiac function (p<0.05), and positively correlated with LVEF (p<0.05). CONCLUSIONS Levels of IL-1ß, IL-6, TNF-alpha, and BAX mRNA were negatively correlated with cardiac function, and BCL2 mRNA expression was positively associated with CHF.

Effect of Different Methods of Administration of Diltiazem on Clinical Efficacy in Patients with Acute ST-Segment Elevation Myocardial Infarction.

BACKGROUND The aim of this study was to investigate the optimal route of administration of diltiazem in emergency PCI and to provide the best clinical treatment for ASTEMI patients. MATERIAL AND METHODS A total of 90 patients with ASTEMI treated in our hospital from January 2015 to January 2016 were selected. Prior to thrombus aspiration, a thrombus aspiration catheter was used to perform diltiazem injection at the distal end of the infarct-related artery (IRA). We chose the acute ST-elevation myocardial infarction (ASTEMI) patients treated with direct PCI to compare different administration routes of diltiazem. The occurrence of major adverse cardiac events (MACEs) was closely observed during hospitalization and was obtained through outpatient visits or telephone follow-ups over the next 6 months. RESULTS Intracoronary infusion of diltiazem at the distal end of the culprit vessel, compared to conventional coronary mouth and intravenous injection, was significantly improved in thrombolysis in myocardial infarction (TIMI) frame count immediately after PCI stent implantation, ST-segment drop rate after 90 min, and left ventricular ejection fraction (LVEF) after 1 week. Furthermore, the peak value of high-sensitivity cardiac troponin I (hs-cTnI), a marker for myocardial injury, was the lowest. White blood cell count, neutrophil count, mean platelet volume (MPV), and high-sensitivity C-reactive protein (hs-CRP) were significantly lower than with the other 2 administration routes, and there was no effect on intracoronary pressure or heart rate. CONCLUSIONS Patients with ASTEMI who underwent emergency PCI treatment had good clinical outcomes using intracoronary diltiazem at the distal end of the culprit vessel.

Cardiac Contractility Modulation Attenuate Myocardial Fibrosis by Inhibiting TGF-ß1/Smad3 Signaling Pathway in a Rabbit Model of Chronic Heart Failure.

UNLABELLED: Backgroun/Aims: To explore the effect of cardiac contractility modulation (CCM) on myocardial fibrosis in heart failure and to investigate the underlying mechanism. METHODS: Rabbits were randomly divided into sham group, HF group and CCM group. A rabbit model of chronic heart failure (CHF) was induced 12 weeks after aortic constriction by pressure unloading. Then cardiac contractility modulation was delivered to the myocardium lasting six hours per day for 4 weeks. Histology examination was carried out to evaluate the myocardial pathological changes. Protein levels of collagen I, collagen III, α-SMA, MMP2, MMP9, TIMP1, TGF-ß1 and Smad3 were measured by western blot analysis. RESULTS: Histology examination results showed that CCM therapy attenuated myocardial fibrosis and collagen deposition in rabbits with CHF. In addition, protein levels of collagen I, collagen III, α-SMA, MMP2, MMP9, TIMP1, TGF-ß1 and Smad3 were down regulated. CONCLUSION: CCM therapy exerted protective effects against myocardial fibrosis potentially by inhibiting TGF-ß1/Smad3 signaling pathway in CHF rabbits.

Effects of atorvastatin on atrial remodeling in a rabbit model of atrial fibrillation produced by rapid atrial pacing.

BACKGROUND: Accumulating evidence suggests that myeloperoxidase (MPO) is involved in atrial remodeling of atrial fibrillation (AF). Statins could reduce the MPO levels in patients with cardiovascular diseases. This study evaluated the effects of atorvastatin on MPO level and atrial remodeling in a rabbit model of pacing-induced AF. METHODS: Eighteen rabbits were randomly divided into sham, control and atorvastatin groups. Rabbits in the control and atorvastatin groups were subjected to rapid atrial pacing (RAP) at 600 bpm for 3 weeks, and treated with placebo or atorvastatin (2.5 mg/kg/d), respectively. Rabbits in the sham group did not receive RAP. After 3 weeks of pacing, atrial structural and functional changes were assessed by echocardiography, atrial effective refractory period (AERP) and AF inducibility were measured by atrial electrophysiological examination, and histological changes were evaluated by Masson trichrome-staining. The L-type calcium channel α1c (Cav1.2), collagen I and III, MPO, matrix metalloproteinase (MMP)-2 and MMP-9 were analyzed by real time polymerase chain reaction and/or western blot. RESULTS: All rabbits were found to have maintained sinus rhythm after 3 weeks of RAP. Atrial burst stimulation induced sustained AF (>30 min) in 5, 4, and no rabbits in the control, atorvastatin, and sham groups, respectively. The AERP shortened and Cav1.2 mRNA level decreased in the control group, but these changes were suppressed in the atorvastatin group. Obvious left atrial enlargement and dysfunction was found in both control and atorvastatin groups. Compared with the control group, these echocardiograhic indices of left atrium did not differ in the atorvastatin group. Prominent atrial fibrosis and increased levels of collagen I and III were observed in the control group but not in the atorvastatin group. The mRNA and protein levels of MPO, MMP-2 and MMP-9 significantly increased in the control group, but these changes were prevented in the atorvastatin group. CONCLUSION: Treatment with atorvastatin prevented atrial remodeling in a rabbit model of RAP-induced AF. The reduction of levels of atrial MPO, MMP-2 and MMP-9 may contribute to the prevention of atorvastatin on atrial remodeling.

[Impact of statin therapy on recurrence of persistent atrial fibrillation after electrical cardioversion: a meta-analysis].

OBJECTIVE: To evaluate the impact of statin therapy on the recurrence rate in patients with persistent atrial fibrillation (AF) after electrical cardioversion. METHODS: PubMed, EMBbase, Cochrane central register of controlled trials were searched up to February 2015 to identify randomized controlled trials, which reported the effect of statin therapy on AF recurrence after electrical cardioversion. The data were analyzed by RevMan 5.3 and Stata 12.0 software. RESULTS: Six trials with 572 patients were included. The result showed that statin therapy had no effect on the recurrence rate in patients with persistent AF after electrical cardioversion (OR=0.60, 95%CI: 0.32-1.11, P>0.05) compared with controls. Four out of the six trials investigated the effect of atorvastatin on the recurrence rate of AF after electrical cardioversion, subgroup analysis of these trials showed that compared with controls, atorvastatin had no effect on the recurrence of AF after electrical cardioversion (OR=0.59, 95%CI: 0.25-1.39, P>0.05). Three out of the six trials had high quality (Jadad score≥3), subgroup analysis of these trials also showed that statins did not affect the recurrence rate of AF after electrical cardioversion (OR=0.76, 95%CI: 0.49-1.16, P>0.05). CONCLUSION: This analysis suggested that statin therapy had no effect on the recurrence rate in patients with persistent AF after electrical cardioversion.

Biventricular pacing cardiac contractility modulation improves cardiac contractile function via upregulating SERCA2 and miR-133 in a rabbit model of congestive heart failure.

OBJECTIVE: To compare the effects of biventricular electrical pacing and conventional single-ventricular pacing for cardiac contractility modulation (CCM) on cardiac contractile function and to delineate the underlying molecular mechanisms. METHODS: Forty rabbits were divided into four groups before surgery: healthy control, HF sham, HF left ventricular pacing CCM (LVP-CCM), and HF biventricular pacing CCM (BVP-CCM) groups with n=10 for each group. A rabbit model of chronic heart failure was established by ligating ascending aortic root of rabbits. Then electrical stimulations during the absolute refractory period were delivered to the anterior wall of left ventricle in the LVP-CCM group and on the anterior wall of both left and right ventricles in the BVP-CCM group lasting six hours per day for seven days. Changes in ventricular structure, cardiac function and electrocardiogram were monitored before and after CCM stimulation. RESULTS: Compared with the sham-operated group, heart weight, heart weight index, LV end-systolic diameter (LVESD), LV end-diastolic diameter (LVEDD) in the LVP-CCM and BVP-CCM groups were significantly decreased (p<0.05), while LV ejection fraction (LVEF) and fractional shortening fraction (FS) were increased (p<0.05). Notably all these changes were consistently found to be greater in BVP-CCM than in LVP-CCM. Moreover, plasma BNP levels were highest in the HF sham-control group, followed by the LVP-CCM group, and lowest in the BVP-CCM group (p<0.05). Furthermore, sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA2a) protein levels were upregulated by 1.7 and 2.4 fold, along with simultaneous upregulation of a cardiac-enriched microRNA miR-133 levels by 2.6 and 3.3 fold, in LVP-CCM and BVP-CCM, respectively, compared to sham. CONCLUSIONS: Biventricular pacing CCM is superior to conventional monoventricular pacing CCM, producing greater improvement cardiac contractile function. Greater upregulation of SERCA2 and miR-133 may account, at least partially, for the improvement by BVP-CCM.

The preventive effect of atorvastatin on atrial fibrillation: a meta-analysis of randomized controlled trials.

BACKGROUND: A number of clinical and experimental studies have investigated the effect of atorvastatin on atrial fibrillation (AF), but the results are equivocal. This meta-analysis was performed to evaluate whether atorvastatin can reduce the risk of AF in different populations. METHODS: We searched PubMed, EMBASE and the Cochrane Database for all published studies that examined the effect of atorvastatin therapy on AF up to April 2014. A random effects model was used when there was substantial heterogeneity and a fixed effects model when there was negligible heterogeneity. RESULTS: Eighteen published studies including 9952 patients with sinus rhythm were identified for inclusion in the analysis. Ten studies investigated primary prevention of AF by atorvastatin in patients without AF, seven studies investigated secondary prevention of atorvastatin in patients with AF, and one study investigated mixed populations of patients. Overall, atorvastatin was associated with a decreased risk of AF (odds ratio (OR) 0.51, 95% confidence interval (CI) 0.36-0.70, P < 0.0001). However, subgroup analyses showed that in the primary prevention subgroup (OR 0.55, 95% CI 0.38-0.81, P = 0.002), atorvastatin reduced the risk of new-onset AF in patients after coronary surgery (OR 0.44, 95% CI 0.29-0.68, P = 0.0002), but had no beneficial effect in patients without coronary surgery (OR 0.97, 95% CI 0.59-1.58, P = 0.89); in the secondary prevention subgroup, atorvastatin had no beneficial effect on AF recurrence in patients with electrical cardioversion (EC) (OR 0.57, 95% CI 0.25-1.32, P = 0.19) or without EC (OR 0.38, 95% CI 0.14-1.06, P = 0.06). CONCLUSIONS: This meta-analysis suggests that atorvastatin has an overall protective effect against AF. However, this preventive effect was not seen in all types of AF. Atorvastatin was significantly associated with a decreased risk of new-onset AF in patients after coronary surgery. Moreover, atorvastatin did not prove to exert a significant protective effect against the AF recurrences in both patients who had experienced sinus rhythm restoration by means of EC and those who had obtained cardioversion by means of drug therapy. Thus, further prospective studies are warranted.

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).

[Interleukin-8 monoclonal antibody attenuates smooth muscle cell proliferation and balloon inflation-induced abdominal aorta stenosis in rabbits].

OBJECTIVE: To observe the effects of interleukin-8 monoclonal antibody on smooth muscle cell proliferation and balloon inflation-induced abdominal aorta stenosis in rabbits. METHODS: Thirty-six New Zealand white rabbits were randomly assigned to balloon inflation group (group A, n = 12), interleukin-8 monoclonal antibody pre-treated rabbits (2 mg/kg for 3 days before balloon inflation, group B, n = 12) and sham-operated control group (group C, n = 12). Peripheral blood was collected before experiment and at 4 h, 1, 3, 7, 14, and 28 days post balloon inflation or sham operation and the levels of IL-8 were measured by enzyme linked immunosorbent assay (ELISA). The ratio of positive and negative masculine cells in the high power microscopic field was determined in proliferating cell nuclear antigen (PCNA) stained slide. Histopathologic examination was performed in abdominal aorta and luminal area, intima and tunica media area were measured. RESULTS: Plasma interleukin-8 began to rise at 4 h and peaked at 1 day and remained increased up to 28 days after balloon inflation in rabbits of group A, plasma interleukin-8 level in group A was significantly higher than in group B and C at 4 h and thereafter post operation. The ratio of positive and negative masculine cells was significantly increased in group A compared to group C and was significantly lower in group B than in group A. Abdominal aorta stenosis, luminal area, intima and tunica media area were significantly reduced in group B than in group A. Correlation analysis indicated that there were positive relations between plasma IL-8 level and intima thickness, area of intima and tunica media, respectively (r = 0.894, 0.783, 0.801, 0.912, all P < 0.01). CONCLUSIONS: Plasma IL-8 level is increased in this abdominal aorta stenosis model and is positively correlated to the severity of abdominal aorta stenosis. IL-8 monoclonal antibody could significantly reduce abdominal aorta stenosis in this abdominal aorta stenosis model.

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.

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.

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.

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.