Extended Clopidogrel Monotherapy vs DAPT in Patients With Acute Coronary Syndromes at High Ischemic and Bleeding Risk: The OPT-BIRISK Randomized Clinical Trial.

Importance: Purinergic receptor P2Y12 (P2Y12) inhibitor monotherapy after a certain period of dual antiplatelet therapy (DAPT) may be an attractive option of maintenance antiplatelet treatment for patients undergoing percutaneous coronary intervention (PCI) who are at both high bleeding and ischemic risk (birisk). Objective: To determine if extended P2Y12 inhibitor monotherapy with clopidogrel is superior to ongoing DAPT with aspirin and clopidogrel after 9 to 12 months of DAPT after PCI in birisk patients with acute coronary syndromes (ACS). Design, Setting, and Participants: This was a multicenter, double-blind, placebo-controlled, randomized clinical trial including birisk patients with ACS who had completed 9 to 12 months of DAPT after drug-eluting stent implantation and were free from adverse events for at least 6 months at 101 China centers between February 2018 and December 2020. Study data were analyzed from April 2023 to May 2023. Interventions: Patients were randomized either to clopidogrel plus placebo or clopidogrel plus aspirin for an additional 9 months. Main Outcomes and Measures: The primary end point was Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding 9 months after randomization. The key secondary end point was major adverse cardiac and cerebral events (MACCE; the composite of all-cause death, myocardial infarction, stroke or clinically driven revascularization). The primary end point was tested for superiority, and the MACCE end point was tested for sequential noninferiority and superiority. Results: A total of 7758 patients (mean [SD] age, 64.8 [9.0] years; 4575 male [59.0%]) were included in this study. The primary end point of BARC types 2, 3, or 5 bleeding occurred in 95 of 3873 patients (2.5%) assigned to clopidogrel plus placebo and 127 of 3885 patients (3.3%) assigned to clopidogrel plus aspirin (hazard ratio [HR], 0.75; 95% CI, 0.57-0.97; difference, -0.8%; 95% CI, -1.6% to -0.1%; P = .03). The incidence of MACCE was 2.6% (101 of 3873 patients) in the clopidogrel plus placebo group and 3.5% (136 of 3885 patients) in the clopidogrel plus aspirin group (HR, 0.74; 95% CI, 0.57-0.96; difference, -0.9%; 95% CI, -1.7% to -0.1%; P < .001 for noninferiority; P = .02 for superiority). Conclusions and Relevance: Among birisk patients with ACS who completed 9 to 12 months of DAPT after drug-eluting stent implantation and were free from adverse events for at least 6 months before randomization, an extended 9-month clopidogrel monotherapy regimen was superior to continuing DAPT with clopidogrel in reducing clinically relevant bleeding without increasing ischemic events. Trial Registration: ClinicalTrials.gov Identifier: NCT03431142.

Cellular-level analyses of SCN5A mutations in left ventricular noncompaction cardiomyopathy suggest electrophysiological mechanisms for ventricular tachycardia.

Left ventricular noncompaction cardiomyopathy (LVNC) is a cardiovascular disease characterized by arrhythmia and heart failure. In this study, LVNC myocardial samples were collected from patients who underwent heart transplantation and were analyzed using exome sequencing. Approximately half of the LVNC patients carried SCN5A variants, which are associated with clinical symptoms of ventricular tachycardia. To investigate the electrophysiological functions of these SCN5A variants and the underlying mechanism by which they increase arrhythmia susceptibility in LVNC patients, functional evaluations were conducted in CHO-K1 cells and human embryonic stem cell-derived cardiomyocytes (hESC-CMs) using patch-clamp or microelectrode array (MEA) techniques. These findings demonstrated that these SCN5A mutants exhibited gain-of-function properties, leading to increased channel activation and enhanced fast inactivation in CHO-K1 cells. Additionally, these mutants enhanced the excitability and contractility of the cardiomyocyte population in hESC-CMs models. All SCN5A variants induced fibrillation-like arrhythmia and increased the heart rate in cardiomyocytes. However, the administration of Lidocaine, an antiarrhythmic drug that acts on sodium ion channels, was able to rescue or alleviate fibrillation-like arrhythmias and secondary beat phenomenon. Based on these findings, it is speculated that SCN5A variants may contribute to susceptibility to arrhythmia in LVNC patients. Furthermore, the construction of cardiomyocyte models with SCN5A variants and their application in drug screening may facilitate the development of precise therapies for arrhythmia in the future.

Whole-genome sequencing of Salmonella pullorum and Sanguinarine-induced mutant.

This work was performed on commercially purchased Salmonella pullorum CVCC519 originally isolated from chicken intestinal content. The Sanguinarine-resistant strain XM3104 was isolated from Sanguinarine-induced CVCC519. To identify possible mechanisms underlying resistance, the complete genomes of CVCC519 and XM3104 were sequenced using PromethION and next-generation sequencing.

Correlation Analysis and Diagnostic Value of Serum Homocysteine, Cystatin C and Uric Acid Levels with the Severity of Coronary Artery Stenosis in Patients with Coronary Heart Disease.

Background: Coronary angiography (CAG) is an invasive examination with high risks and costs and various complications may occur. It is necessary to find a diagnostic method, non-invasiveness, inexpensive with low risk. This study aims to analyze the correlation between the levels of serum homocysteine (Hcy), cystatin C (Cys C) and uric acid (UA) and Gensini score in patients with coronary heart disease (CHD) and assess their diagnostic value for CHD. Methods: A retrospective analysis was conducted on 1412 patients underwent CAG from October 2019 to December 2021, and we conducted this study from January to July 2022. A total of 765 patients with CHD confirmed by CAG were selected as the research group, while 647 patients revealed as non-obstructive stenosis by CAG as the control group. The serum Hcy, Cys C and UA levels were detected and the correlation between Gensini score and variables was analyzed. The receiver-operating characteristic (ROC) curve was performed to assess the diagnostic value of the Hcy, Cys C and UA for CHD. Results: The serum Hcy, Cys C and UA levels in the research group were higher as compared with the control group (p<0.05). Spearman correlation and multivariate linear regression analysis showed that there was a significantly positive correlation between Gensini score and serum Hcy, Cys C and UA levels (p<0.05). The ROC curve analysis presented the combined Hcy and Cys C with UA having the highest specificity of diagnostic value for CHD (area under the curve (AUC)=0.768, 95% CI 0.706-0.823, specificity = 72.34%, sensitivity = 67.88%, Youden Index = 0.4022). Conclusion: The serum Hcy, Cys C and UA levels in patients with CHD were significantly increased, positive correlation with Gensini score. The combined Hcy and Cys C with UA could be used to assess the severity of coronary artery stenosis and provide predictive and early intervention treatment values for CHD and a new way of diagnosing CHD, which is cheap, safe, effective and deserving of clinical application.

Prevalence, predictors, and management for balloon uncrossable or undilatable lesions in patients undergoing percutaneous coronary intervention with in-stent restenosis chronic total occlusion.

Background: Percutaneous coronary intervention for in-stent restenosis (ISR) chronic total occlusion (CTO) has been a great challenge. There are occasions when the balloon is uncrossable or undilatable (BUs) even though the guidewire has passed, leading to failure of the procedure. Few studies have focused on the incidence, predictors, and management of BUs during ISR-CTO intervention. Methods: Patients with ISR-CTO were recruited consecutively between January 2017 and January 2022 and divided into two groups based on the presence of BUs. The clinical data of the two groups (BUs group and non-BUs group) were retrospectively analyzed and compared to explore the predictors and clinical management strategies of BUs. Results: A total of 218 patients with ISR-CTO were included in this study, 23.9% (52/218) of whom had BUs. The percentage of ostial stents, stent length, CTO length, the presence of proximal cap ambiguity, moderate to severe calcification, moderate to severe tortuosity, and J-CTO score were higher in the BUs group than in the non-BUs group (p < 0.05). The technical success rate and the procedural success rate were lower in the BUs group than in the non-BUs group (p < 0.05). Multivariable logistic regression analysis showed that ostial stents (OR: 2.011, 95% CI: 1.112-3.921, p = 0.031), the presence of moderate to severe calcification (OR: 3.383, 95% CI: 1.628-5.921, p = 0.024) and moderate to severe tortuosity (OR: 4.816, 95% CI: 2.038-7.772, p = 0.033) were independent predictors of BUs. Conclusion: The initial rate of BUs in ISR-CTO was 23.9%. Ostial stents, presence of moderate to severe calcification, and moderate to severe tortuosity were independent predictors of BUs.

Predictors and prognosis of PCI-related myocardial injury in chronic total occlusion.

BACKGROUND: Periprocedural myocardial injury (PMI) is associated with major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI). However, the incidence predictors and prognosis of PMI in chronic total occlusion (CTO) undergoing PCI remains unclear. METHOD: To evaluate the predictors and prognostic impact of PMI following PCI in patients with CTO. We consecutively enrolled 132 individuals and 8 of whom with procedural failure were excluded in this study. Thus, a total of 124 CTO patients successfully received PCI were included in this study. And patients were divided into the PMI group (n = 42) and the non-PMI group (n = 82) according to their c-TnI levels measured after procedure. The baseline and angiographic characteristics of the two groups were compared. The predictors of PMI and the correlation between PMI and MACE were investigated. RESULTS: Overall, PMI occurred in 42 patients (33.9%). Comparing with control group, PMI group had more diabetes (54.8% vs. 31.7%,P = 0.013) and dyslipidemia (54.8% vs. 13.4%, P＜0.001). Also, there were significant differences between the two groups in left ventricular ejection fraction(43.2 ± 7.2 vs 47.2 ± 8.0, P = 0.027), prior myocardial infarction(54.8%vs43.1%, P = 0.020), prior PCI(57.1% vs 22.0%, P＜0.001) and prior CABG(14.3% vs 2.4%, P = 0.011). Also, patients with PMI had more calcified lesions (52.4% vs 24.4%, P = 0.002) and were more likely to have multivessel disease (71.4% vs 35.4%, P＜0.001). In addition, patients in the PMI group had higher J-CTO scores (3.3 ± 1.0 vs 1.9 ± 0.5, P＜0.001) and were more likely to have wire-crossing difficulties (64.3% vs 37.8%, P = 0.005), require more use of retrograde approach (38.1% vs 7.3%, P＜0.001) and have more procedural complications (19.0% vs 2.4%, P = 0.003). In the multivariate analysis, multivessel artery disease (odd ratio [OR], 4.347;95% confidence interval [CI], 1.601- 11.809;P = 0.004), retrograde approach (OR, 4.036; 95%CI, 1.162- 14.020;P = 0.028) and the presence of procedural complications (OR, 16.480;95%CI, 2.515-107.987;P = 0.003) were predictors of PMI. CONCLUSION: The incidence of PMI in CTO patients after PCI was 33.9%. Multivessel artery disease, retrograde approach, and the presence of procedural complications were predictors of PMI after CTO-PCI. Patients who develop PMI tend to have a poorer clinical prognosis and more MACE than those who do not develop PMI.

Relationship between increased systemic immune-inflammation index and coronary slow flow phenomenon.

BACKGROUND: Systemic immune-inflammation index (SII, platelet × neutrophil/lymphocyte ratio), a new marker of inflammation, is associated with adverse cardiovascular events, but its relationship with coronary slow flow phenomenon (CSFP) is unclear. Therefore, we aimed to investigate the relationship between SII and CSFP. METHODS: We enrolled consecutive patients who presented with chest pain, with normal/near-normal coronary angiography findings (n = 89 as CSFP group; n = 167 as control group). The baseline characteristics, laboratory parameters and angiographic characteristics of the two groups were compared. RESULTS: SII levels were significantly higher in the CSFP group than in the control group (409.7 ± 17.7 vs. 396.7 ± 12.7, p < 0.001). A significant positive correlation between SII and the mean thrombolysis in myocardial infarction frame count (mTFC) was found (r = 0.624, p < 0.001). SII increased with the number of coronary arteries involved in CSFP. In multivariate logistic regression analysis, SII/10 was an independent predictor of CSFP (odds ratio: 1.739, p < 0.001). In addition, the SII level > 404.29 was a predictor of CSFP with 67.4% sensitivity and 71.9% specificity. CONCLUSIONS: SII can predict the occurrence of CSFP.

Predictive Value of Soluble Growth Stimulator Gene 2 Protein for Coronary Slow Flow/No-Reflow in ST-Elevation Myocardial Infarction Patients Receiving Percutaneous Coronary Intervention.

Background: Soluble growth stimulator gene 2 protein (sST2) is associated with heart failure and myocardial infarction; however, the predictive value of plasma sST2 level for coronary slow flow/no-reflow (CSF/NRF) is unclear. This study aimed to explore the predictive value of plasma sST2 levels for CSF/NRF in patients with ST-elevation myocardial infarction (STEMI) who underwent emergency percutaneous coronary intervention (PCI). Methods: A total of 242 STEMI patients who underwent emergency PCI at our hospital between November 2020 and July 2021 were enrolled in this study. According to the postprocedural procedure, these patients were divided into the CSF/NRF and control groups. Clinical data were collected from both groups and were used to explore the predictive value of serum sST2 levels for CSF/NRF. Results: Of the total 242 patients, CSF/NRF was observed in 50 patients (20.7%). Statistically significant differences (P < 0.05) were observed in age, diabetes mellitus, sST2 level, neutrophil-to-lymphocyte ratio (NLR), fasting blood sugar, preprocedural blood pressure, intraprocedural hypotension, N-terminal pro-B-type natriuretic peptide, MB isoenzyme of creatine kinase (CK-MB), and cardiac troponin I (cTNI). Multivariate analysis showed that the sST2 level, NLR, and intraoperative hypotension were independent risk factors for CSF/NRF. ROC curve analysis showed that the sensitivity and specificity of the sST2 level for predicting CSF/NRF were 68.0% and 75.5%, respectively, when the sST2 level was more than 64.6 ng/mL (AUC = 0.780, 95% CI: 1.003-1.020, P=0.009). Conclusion: For STEMI patients, preprocedural sST2 levels significantly correlated with CSF/NRF occurring in PCI. sST2 level is a potential predictor for CSF/NRF occurrence.

Accuracy of the Euro CTO(CASTLE) score obtained on coronary computed tomography angiography for Predicting 30-minute wire crossing in chronic total occlusions.

BACKGROUND: To investigate the feasibility and accuracy of the Euro CTO (CASTLE)CTA score obtained on coronary computed tomography angiography (CCTA) for predicting the success of percutaneous coronary intervention (PCI) and the 30-min wire crossing in chronic total occlusions (CTO). METHOD: One hundred and fifty patients (154 CTO cases; median age, 61 (interquartile range [IQR], 54-68) years; 75.3% male) received CCTA at the People's Hospital of Liaoning Provincce within 1 month before the procedure. The Euro CTO (CASTLE) score obtained on CCTA(CASTLECTA) was calculated and compared with the Euro CTO (CASTLE) score obtained based on coronary angiography (CASTLECAG) for the predictive value of 30-min wire crossing and CTO procedural success. RESULTS: In our study, the CTO-PCI success rate was 89.0%, with guidewires of 65 cases (42.2%) crossing within 30 min. There were no significant differences in the median CASTLECTA and CASTLECAG scores in the procedure success group (3 [IQR, 2-4] vs 3 (IQR, 2-3]; p = 0.126). However, the median CASTLECTA score was significantly higher than the median CASTLECAG score in the procedure failure group (4 [IQR, 3-5.5] vs 4 [IQR, 2.5-5.5]; p = 0.021). There was no significant difference between the median CASTLECTA score and the median CASTLECAG score in the 30-min wire crossing failure group (3 [IQR, 3-4] vs 3 [IQR, 2-4]; p = 0.254). However, the median CASTLECTA score was significantly higher than the median CASTLECAG score in the 30-min wire crossing group (3 [IQR, 2-3] vs 2 [IQR, 2-3]; p < 0.001). The CASTLECTA score described higher levels of calcification than the CASTLECAG score (48.1% vs 33.8%; p = 0.015). There was no significant difference between the CASTLECTA score (area under the curve [AUC], 0.643; 95% confidence interval [CI], 0.561-0.718) and the CASTLECAG score (AUC, 0.685; 95% CI, 0.606-0.758) for predicting procedural success (p = 0.488). The CASTLECTA score (AUC, 0.744; 95% CI, 0.667-0.811) was significantly better than the CASTLECAG score (AUC, 0.681; 95% CI, 0.601-0.754; p = 0.046) for predicting 30-min wire crossing with the best cut-off value being CASTLECTA ≤ 3. The sensitivity, specificity, positive predictive value, and negative predictive value were 90.8%, 55.2%, 54.6%, and 87.0%, respectively. CONCLUSION: The CASTLECTA scores obtained from noninvasive CCTA perform better for the prediction of the 30-min wire crossing than the CASTLECAG score.

Revascularization of Coronary Artery Chronic Total Occlusion by Active Antegrade Reverse Wire Technique.

OBJECTIVES: To assess the effectiveness and safety of ARW for vascular recanalization in CTO patients. BACKGROUND: Chronic total occlusion (CTO) of coronary artery accompanied with large branch distal to the occluded segment (<2 mm) is one of the challenges physicians are facing during the coronary intervention. In cases where the antegrade wire passed the occluded segment reaching the branch vessel, but could not access the main vessel through various adjustments, application of active antegrade reverse wire technique (ARW) could be considered. Patients and Methods. A total of 301 consecutive CTO patients who received the antegrade percutaneous coronary intervention (PCI) between December 2015 and December 2019 at our institution were included, of whom 11 were treated with ARW (10 successfully) for vascular recanalization. The applicability and safety of ARW were assessed. RESULTS: Among the 301 CTO patients who received antegrade vascular recanalization, 11 were treated with ARW. ARW was successful in 10 patients as follows: from the diagonal branch (D) to anterior descending branch (LAD) in 4 patients; from the septal branch (S) to LAD in 1 patient; from D to S and LAD in 1 patient; from the circumflex branch (LCX) to obtuse marginal branch (OM) in 1 patient; from OM to LCX in 1 patient; from a posterior descending artery (PDA) to the posterior lateral vein (PLV) in 2 patients. Yet, ARW in patient with RCAm CTO failed, while the consequent retrograde PCI succeeded. The mean J-CTO score of the 11 patients was 2.7 ± 0.65, among whom eight were accompanied with calcifications. Sion Black and Fielder XTR reverse wires were used in 9 and 2 patients, respectively. No loss of side branches or severe procedure-related complications occurred in 11 patients. CONCLUSION: Therefore, ARW can improve procedural efficiency and should be popularized for further application.

Incidence, Predictors, and Strategies for Failure of Retrograde Microcatheter Tracking After Successful Wiring of Septal Collateral Channels in Chronic Total Occlusions.

BACKGROUND: Retrograde microcatheter collateral channel (CC) tracking after successful wiring of septal CC is crucial for retrograde revascularization of coronary chronic total occlusion (CTO). However, the incidence, predictors, and strategies for failure of retrograde microcatheter CC tracking after successful wiring of septal CC remain unclear. METHODS: In total, 298 patients with CTO who underwent retrograde septal CC PCI between January 2015 and May 2019 were retrospectively analyzed. Clinical data were compared to investigate the predictors of initial microcatheter tracking failure. RESULTS: The initial and final microcatheter tracking success rates were 79.2% (236/298) and 96.6% (288/298), respectively. The procedural success rate was 94.0% (280/298). The right coronary artery-to-left anterior descending artery septal ratio (48.4% vs 33.1%, p=0.037) and CC tortuosity (34.6% vs 20.8%, p=0.045) were significantly higher in the initial microcatheter CC tracking failure group than in the successful tracking group. Multivariate logistic regression analysis revealed that severe collateral tortuosity (odds ratio [OR]: 13.241, 95% confidence interval [CI]: 3.429-27.057, p=0.038), CC entry angle of <90° (OR:4.921, 95% CI: 1.128-9.997, p=0.002), CC exit angle of <90° (OR:5.037, 95% CI: 2.237-11.182, p=0.004), use of Finecross MG as initial microcatheter (OR:1.826, 95% CI: 1.127-3.067, p=0.035), and shunning initial retrograde application of Guidezilla (OR:0.321, 95% CI: 0.267-0.915, p=0.024) were variables independently associated with initial microcatheter CC tracking failure in patients with CTO undergoing retrograde septal CC PCI. CONCLUSION: The overall initial microcatheter CC tracking failure was 20.8%. Severecollateral tortuosity, CC entry, and exit angle of <90°, use of Finecross MG as initial microcatheter, and shunning initial retrograde application of Guidezilla were variables independently associated with initial microcatheter CC tracking failure in patients with CTO undergoing retrograde septal PCI.

Active Retrograde Extra Backup with a Mother-and-Child Catheter to Facilitate Retrograde Microcatheter Collateral Channel Tracking in Recanalization of Coronary Chronic Total Occlusion.

OBJECTIVE: To explore the feasibility and safety of the active retrograde backup (ARB) for treatment of chronic total occlusion (CTO) during retrograde percutaneous coronary intervention (PCI). BACKGROUND: Guiding support plays an important role in guidewire and microcatheter coronary channel (CC) tracking in retrograde PCI therapy for patients with CTO. However, the feasibility and safety of retrograde active use of a mother-and-child catheter are still unclear. Patients and Methods. A total of 271 consecutive patients with CTO who underwent retrograde PCI between January 2015 and January 2020 were retrospectively analyzed. Clinical data of two groups were compared to evaluate the feasibility and safety of ARB. RESULTS: Of the 271 patients, 69.0% (187/271) underwent therapy through the septal branch, 31.0% (84/271) through the epicardial collateral channel, and 47.6% (129/271) through active retrograde extra backup with a mother-and-child catheter to facilitate retrograde microcatheter collateral CC tracking. The time of wire CC tracking was shorter in the ARB group than that in the non-ARB group (25.4 ± 8.5 vs 26.4 ± 9.7, p=0.348), but there was no significant difference. The duration of the retrograde microcatheter tracking (10.2 ± 3.8 vs 15.5 ± 6.8, p=0.012) and the retrograde approach (62.8 ± 20.3 vs 70.4 ± 24.3, p=0.026) in the ARB group was significantly shorter than that in the non-ARB group. The radiation dose (223.6 ± 112.7 vs. 295.2 ± 129.3, p=0.028), fluoroscopy time (50.6 ± 21.3 vs 62.3 ± 32.1, p=0.030), and contrast volume (301.8 ± 146.7 vs 352.2 ± 179.5, p=0.032) in the ARB group were significantly lower than that in the non-ARB group. There were no life-threatening procedural complications in either group. Complications unrelated to ARB included two cases of donor-vessel dissection, one case of CC perforation, and two cases of target-vessel perforation. There was no statistically significant difference in major adverse cardiac and cerebrovascular events between the groups during hospitalization (p > 0.05). CONCLUSION: ARB is feasible, safe, and conducive to guidewire and microcatheter CC tracking in the recanalization of coronary CTO. It improves procedural efficiency and is worthy of further promotion.

Gender Disparities in Clinical Outcome After Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy in the Chinese Han Population: A Cohort Study.

BACKGROUND: Sex differences in the long-term prognosis of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients undergoing alcohol septal ablation (ASA) remain unclear, especially in the Chinese Han population. METHOD: This cohort study included 320 HOCM Chinese Han patients who underwent ASA because of symptomatic left ventricular outflow tract (LVOT) obstruction. Patients were grouped according to sex: females (mean±standard deviation age [SD] 50.7±6.8 years) and males (mean±SD age 52.6±7.3 years). Individuals were followed over the long term. RESULTS: Pre-procedure, women had more symptoms (New York Heart Association [NYHA] class III-IV 67.3% vs 56.3%, p=0.03), more atrial fibrillation (23.5% vs 14.6%, p=0.047) than men. Transient complete atrioventricular block after ASA was more common in woman than in men (34.0 vs 23.4%; p=0.048). Residual LVOT gradient, post-procedural residual left ventricular wall thickness, NYHA functional class, and adverse arrhythmic events were comparable between the two groups. The 10-year survival rate (77% vs 89%, p=0.037) and the annual adverse arrhythmic event rate (1.3% vs 0.4%, p<0.01) following ASA were significantly worse in women compared with men. Kaplan-Meier analysis showed a significantly lower survival in women compared with men (p=0.023). In multivariable modelling, female sex remained independently associated with higher all-cause mortality (hazard ratio, 1.12; 95% confidence interval, 1.08-1.27; p=0.03) when adjusted for age, NYHA class III-IV symptoms, and other cardiovascular comorbidities. CONCLUSIONS: Female patients with HOCM undergoing ASA tended to have more severe symptoms and adverse arrhythmic events. The 10-year survival rate after ASA was significantly worse in women compared with men with HOCM. Sex may need to be considered as an important factor in the clinical management of patients with symptomatic HOCM.

Efficacy and safety of standard and low dose ticagrelor versus clopidogrel in east AsianPatients with chronic total occlusion undergoing percutaneous coronary intervention: a single center retrospective study.

BACKGROUND: Patients with coronary chronic total occlusion (CTO) require effective antiplatelet therapy after percutaneous coronary intervention (PCI). Ticagrelor has more pronounced platelet inhibition than clopidogrel. However, the most appropriate dose of ticagrelor in East Asian populations remains unclear. METHOD: We compared ticagrelor (180 mg loading dose, 90 mg twice daily thereafter and 120 mg loading dose, 60 mg twice daily thereafter) and clopidogrel (300 mg loading dose, 75 mg daily thereafter) for prevention of cardiovascular events in 525patients with CTO undergoing PCI. RESULTS: The rate of in-hospital major adverse cardiac and cerebral events (MACCE) was not different between the groups. At 1-year follow-up, target vessel revascularization (TVR) in both ticagrelor groups were significantly lower than that in the clopidogrel group (p = 0.047); TVR was significantly decreased in 60 mg ticagrelor compared to standard dose clopidogrel (p = 0.046). At 1-year follow-up, overall MACCE in both ticagrelor groups were significantly lower than that in the clopidogrel group (p = 0.023). Kaplan-Meier analysis showed MACCE-free survival was significantly higher in both ticagrelor groups than in the clopidogrel group (p = 0.024). During hospitalization, minor bleeding was significant increased in the 90 mg ticagrelor group (p = 0.021). At 1-year follow-up, risk of major and minor bleeding were significantly increased in the 90 mg ticagrelor group. CONCLUSION: In East Asian patients with CTO undergoing PCI, 60 mg ticagrelor was as effective as 90 mg, at the same time significantly reduced risk of bleeding.

Incidence, Predictors, and Prognosis of Coronary Slow-Flow and No-Reflow Phenomenon in Patients with Chronic Total Occlusion Who Underwent Percutaneous Coronary Intervention.

BACKGROUND: The incidence and prognosis of coronary slow-flow (CSF) and no-reflow phenomenon (NRP) in patients with coronary chronic total occlusion (CTO) who underwent percutaneous coronary intervention (PCI) remain unclear. METHODS: This single-center prospective study aimed to investigate the incidence of CSF/NRP during CTO interventional therapy, determine predictors of CSF/NRP, and evaluate its effect on patient outcomes. RESULTS: In this study, 552 patients with CTO who underwent PCI were included. CSF/NRP occurred in 16.1% of them. They had higher incidences of diabetes mellitus (53.9% vs 36.3%, p=0.002) and hypertension (50.6% vs 37.1%, p=0.018) and a lower incidence of retrograde filling grade >2 (34.8% vs 47.1%, p=0.036). Patients with CSF/NRP had a higher neutrophil ratio (55.6±19.4 vs 52.4±18.3, p=0.038) and levels of low-density lipoprotein (LDL; 3.0±0.8 vs 2.8±0.6, p=0.029), fasting glucose (FG; 8.3±1.3 vs 6.8±1.1, p=0.005), uric acid (332.6±82.9 vs 308.2±62.8, p=0.045), and high-sensitivity C-reactive protein (Hs-CRP; 9.8±4.8 vs 7.3±3.9, p=0.036). A multivariate logistic regression analysis revealed that diabetes mellitus (odds ratio [OR], 1.962; 95% confidence interval [CI]: 1.198-2.721; p=0.042), mean platelet volume (MPV; OR,1.284; 95% CI, 1.108-1.895; p=0.046), LDL cholesterol (LDL-C; OR, 1.383; 95% CI, 1.105-2.491; p=0.036), FG (OR, 2.095; 95% CI, 1.495-2.899; p=0.018), Hs-CRP(OR, 2.218; 95% CI, 1.556-3.519; p=0.029), and retrograde filling of grade >2 (OR, 0.822; 95% CI, 0.622-0.907; p=0.037) were independent predictors of CSF/NRP in CTO patients who underwent PCI. Kaplan-Meier analysis revealed that the patients in the CSF/NRP group had a significantly lower cumulative major cardiac and cerebrovascular events (MACCE)-free survival than those in the non-CSF/NRP group (p<0.0001). CONCLUSION: Of the patients with CTO who underwent PCI, 16.1% developed CSF/NRP and had a significantly lower cumulative MACCE-free survival rate. Diabetes mellitus; higher levels of MPV, LDL-C, FG, and Hs-CRP; and a lower incidence of retrograde filling grade >2 were independent predictors of CSF/NRP in CTO patients who underwent PCI. Thus, they can be used for risk stratification.

The Impact of Sacrubitril/Valsartan on Clinical Treatment and hs-cTnT and NT-ProBNP Serum Levels and the Left Ventricular Function in Patients with Chronic Heart Failure.

Chronic heart failure (CHF) seriously affects the quality of patients' lives. Sacrubitril/valsartan is a combination angiotensin receptor-neprilysin inhibitor, a new therapeutic drugs to treat CHF.This study aims to observe the impact of sacrubitril/valsartan on clinical treatment and high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-brain natriuretic peptide (NT-ProBNP) serum levels, the improvement of the left atrial diameter (LAD) and left ventricular end diastolic dimension (LVEDD), and the left ventricular ejection fraction (LVEF) in patients with CHF.120 patients were randomly divided into a sacrubitil/valsartan group and a valsantan group, with 60 cases in each. Patients in the sacrubitil/valsartan group were administered sacrubitril/valsartan; while in the valsantan group, they were administered valsartan. The clinical effects, adverse reactions, and rehospitalization were observed eight weeks later, and hs-cTnT and NT-ProBNP serum levels and LAD, LVEDD, and LVEF were assayed.There were 53 cases of positive effect in the sacrubitil/valsartan group and 42 in the valsartan group (P < 0.05). Eight participants demonstrated adverse reactions in the sacrubitil/valsartan group, while 17 in the control group (P < 0.05). Hs-cTnT and NT-ProBNP serum levels, the measurements of LAD, LVEDD, and LVEF in the sacrubitil/valsartan group before the treatments were (24.47 ± 7.54) pg/mL, (10,356.94 ± 5,447.68) pg/mL, (49.41 ± 5.22) mm, (68.06 ± 6.20) mm and (31.12 ±6.65) %; in the valsartan group were (29.752 ± 10.03) pg/mL, (9,518.17 ± 5,905.17) pg/mL, (49.65 ± 4.91) mm, (67.06 ± 3.97) mm, and (30.41 ± 6.11) % (P > 0.05), while in the sacrubitil/valsartan group, the values decreased after the treatments to (17.92 ± 4.74) pg/mL, (3,881.59 ± 2,087.79) pg/mL, (42.18 ± 4.87) mm, (60.35 ± 7.12) mm and (45.35 ± 4.49) %; in the valsartan group to (25.81 ± 7.36) pg/mL, (6,278.35 ± 2,643.11) pg/mL, (46.53 ± 4.80) mm, (64.51 ± 4.34) mm, and (36.47 ± 5.21) % (P < 0.05). There were significant differences within the same group, before and after treatments (P < 0.05).Sacrubitril/valsartan treatment of patients with CHF improves their symptoms and is deserving of clinical application. This is also evident from significantly improved levels of serum hs-cTnT and NT-ProBNP and the left ventricular function.

CHA2DS2-VASC score as a preprocedural predictor of contrast-induced nephropathy among patients with chronic total occlusion undergoing percutaneous coronary intervention: a single-center experience.

BACKGROUND: The usefulness of the CHA2DS2-VASC risk score (CVRS) in predicting the occurrence of contrast-induced nephropathy (CIN) among patients with chronic total occlusion (CTO) undergoing percutaneous coronary intervention (PCI) remains unclear. METHOD: A total of 239 patients with CTO who underwent PCI were included in this study. They were divided into 3 groups according to the CVRS: low-risk group (1 point, n = 64), intermediate-risk group (2 points, n = 135), and high-risk group (≥3 points, n = 40). Baseline serum creatinine was determined upon admission before the procedure. The serum creatinine level was monitored for 72 h post-procedure to determine the occurrence of CIN. RESULTS: The total incidence of CIN in patients with CTO who underwent PCI was 16.3%. The average CVRS in the CIN group was significantly higher than that in the non-CIN group (3.1 ± 1.2 VS 2.1 ± 1.1, P < 0.001). The incidence of CIN in the high-risk group was 5.6 times higher than that in the low-risk group (37.5% VS 6.3%, P < 0.001). Similar to the Mehran risk score (AUC, 0.754; 95% CI, 0.698-0.810; P < 0.001), the receiver operating characteristic curve analysis showed a good diagnostic value of the CVRS in predicting CIN among patients with CTO who underwent interventional therapy for having CVRS≥3 (sensitivity, 69.2%; specificity, 78.0%; AUC, 0.742; 95% CI, 0.682-0.797; P < 0.001). The multivariate analysis showed that the higher pulse pressure and contrast volume, lower baseline glomerular filtration rate, and CVRS ≥3 were independent predictors of CIN. CONCLUSIONS: The CVRS can be used as a simple pre-procedural predictor of CIN among patients with CTO undergoing PCI.

Efficacy and safety of bivalirudin during percutaneous coronary intervention in high-bleeding-risk elderly patients with chronic total occlusion: A prospective randomized controlled trial.

OBJECTIVES: To assess the efficacy and safety of bivalirudin during percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) in high-bleeding-risk elderly patients. BACKGROUND: Bivalirudin reduces PCI-related bleeding; however, its efficacy and safety in patients with CTO, especially elderly patients with a high bleeding risk, remain unclear. METHODS: This single-center prospective randomized controlled trial assigned 123 high-bleeding-risk elderly patients with CTO to either the unfractionated heparin (UFH) group (n = 55) or the bivalirudin group (n = 68). The primary efficacy endpoint was the incidence of major adverse cardiac events (MACEs) during hospitalization and at the 6-month follow-up. The safety endpoint was bleeding or procedure (access)-related complications after PCI. RESULTS: MACE incidence was 17.6% and 20.0% in the bivalirudin and UFH groups, respectively (P = 0.82). Bleeding Academic Research Consortium (BARC) type 1-2 bleeding events during hospitalization were comparable between the groups (UFH: 10.9% vs. bivalirudin: 8.8%, P = 0.77). No BARC type 3-5 bleeding events or severe procedure (access)-related complications (subcutaneous hematoma >5 cm) occurred in either group. At the 6-month follow-up, MACE incidence was comparable between the groups (UFH: 3.6% vs. bivalirudin: 1.5%, P = 0.59). The Kaplan-Meier analysis revealed that MACE-free survival rates were comparable between the groups (P = 0.43). One case of BARC type 3-5 bleeding (fatal intracranial hemorrhage) was observed in the UFH group at the 6-month follow-up. CONCLUSIONS: Bivalirudin and UFH showed comparable efficacy and safety in elderly patients with a high bleeding risk, undergoing PCI for CTO lesions.

Ginsenoside Rb1 Ameliorates Autophagy of Hypoxia Cardiomyocytes from Neonatal Rats via AMP-Activated Protein Kinase Pathway.

OBJECTIVE: To investigate whether ginsenoside-Rb1 (Gs-Rb1) improves the CoCl-induced autophagy of cardiomyocytes via upregulation of adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway. METHODS: Ventricles from 1- to 3-day-old Wistar rats were sequentially digested, separated and incubated in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum for 3 days followed by synchronization. Neonatal rat cardiomyocytes were randomly divided into 7 groups: control group (normal level oxygen), hypoxia group (500 µmol/L CoCl2), Gs-Rb1 group (200 µmol/L Gs-Rb1 + 500 µmol/L CoCl2), Ara A group (500 µmol/L Ara A + 500 µmol/L CoCl2), Ara A+ Gs-Rb1 group (500 µmol/L Ara A + 200 µmol/L Gs-Rb1 + 500 µmol/L CoCl2), AICAR group [1 mmol/L 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) + 500 µmol/L CoCl2], and AICAR+Gs-Rb1 group (1 mmol/L AICAR + 200 µmol/L Gs-Rb1 + 500 µmol/L CoCl2). Cells were treated for 12 h and cell viability was determined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and cardiac troponin I (cTnI) levels were detected by enzyme-linked immunosorbent assay (ELISA). AMPK activity was assessed by 2',7'-dichlorofluorescein diacetate (DCFH-DA) ELISA assay. The protein expressions of Atg4B, Atg5, Atg6, Atg7, microtubule-associated protein 1A/1B-light chain 3 (LC3), P62, and active-cathepsin B were measured by Western blot. RESULTS: Gs-Rb1 significantly improved the cell viability of hypoxia cardiomyocytes (P<0.01). However, the viability of hypoxia-treated cardiomyocytes was significantly inhibited by Ara A (P<0.01). Gs-Rb1 increased the AMPK activity of hypoxia-treated cardiomyocytes. The AMPK activity of hypoxia-treated cadiomyocytes was inhibited by Ara A (P<0.01) and was not affected by AICAR =0.983). Gs-Rb1 up-regulated Atg4B, Atg5, Beclin-1, Atg7, LC3B II, the LC3B II/I ratio and cathepsin B activity of hypoxia cardiomyocytes (P<0.05), each of these protein levels was significantly enhanced by Ara A (all P<0.01), but was not affected by AICAR (all P>0.05). Gs-Rb1 significantly down-regulated P62 levels of hypoxic cardiomyocytes (P<0.05). The P62 levels of hypoxic cardiomyocytes were inhibited by Ara A (P<0.05) and were not affected by AICAR (P=0.871). CONCLUSION: Gs-Rb1 may improve the viability of hypoxia cardiomyocytes by ameliorating cell autophagy via the upregulation of AMPK pathway.

The effects of ginsenoside Rb1 on fatty acid ß-oxidation, mediated by AMPK, in the failing heart.

OBJECTIVES: This study intended to investigate the effects of Ginsenoside-Rbl (Gs-Rbl) on fatty acid ß-oxidation (FAO) in rat failing heart and to identify potential mechanisms of Gs-Rbl improving heart failure (HF) by FAO pathway dependent on AMP-activated protein kinase (AMPK). MATERIALS AND METHODS: Rats with chronic HF, induced by adriamycin (Adr), were randomly grouped into 7 groups. Gs-Rb1, adenine 9-ß-D-arabinofuranoside (Ara A, specific AMPK inhibitor), and 5'-aminoimidazole-4-carboxamide riboside (Aicar, specific AMPK activator) were administered to rats with HF, singly and/or combinedly. Myocardial high-energy phosphate (such as phosphocreatine, ADP, and ATP), free L-Carnitine, malonyl-CoA, and the activity of FAO-related enzymes in left ventricle from different groups were measured by using the corresponding molecular biological techniques. RESULTS: Gs-Rb1 improved HF significantly, accompanied by a significant increase in phosphocreatine (PCr), ADP, ATP, PCr/ATP ratio, free carnitine, malonyl-CoA, mRNA, activity of carnitine palmitoyltransferase (Cpt), medium-chain Acyl-CoA Dehydrogenase (MCAD) and long-chain acyl-CoA Synthetase (ACSL) and a significant decrease of the ADP/ATP ratio in the left ventricular myocardium. However, all those effects were almost abolished by Ara A and were not further improved by Aicar. CONCLUSION: Taken together, it suggests that Gs-Rb1 may modulate cardiac metabolic remodeling by improving myocardial fatty acid ß-oxidation in failing heart. In addition, the effects of Gs-Rb1 may be mediated via activating AMPK.