2022年 · 第02卷第04期

Objective: The effectiveness of statins in reducing atherosclerotic calcification remains controversial. The aim of this study was to confirm that simvastatin reduces atherosclerotic calcification and stabilizes plaque by restricting endoplasmic reticulum stress (ERS)-mediated apoptosis. Methods: Twenty-four 8-week-old male apolipoprotein E (ApoE)-/- mice (C57BL/6J genetic background) were selected and randomly divided into model (n = 12) and simvastatin (n = 12) groups. Twelve male C57BL/6J mice were selected as control group (n = 12). The mice were adaptively fed for 2 weeks and were put on a high-fat diet thereafter. After 9 weeks, they were treated with simvastatin (20 mg/kg) or phosphate-buffered saline daily for 8 weeks. Aortic sinus samples were obtained from ApoE-/- and C57BL/6J mice for hematoxylin and eosin, von Kossa, alizarin Red S, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and immunohistochemical staining after in vivo treatment with simvastatin. In addition, mouse vascular smooth muscle cells were analyzed after exposure to simvastatin in vitro. Results: Administration of simvastatin in vivo drastically attenuated the atherosclerosis, calcification, and apoptosis, and decreased the serum levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The expression levels of glucose-regulated protein, 78 kDa (GRP78), C/EBP homologous protein (CHOP), and caspase 12 (CASP12) in the aortic sinus decreased in the simvastatin group compared with the model group. In vitro, simvastatin or simvastatin plus ERS inhibitor (taurine) attenuated calcification and apoptosis, and reduced the expression of ERS-related proteins GRP78, CHOP, and CASP12. Conclusion: Treatment with simvastatin suppressed atherosclerotic calcification. This effect may be mediated through the inhibition of ERS-related apoptosis.

Objective: Annulus-sparing (AS) repair for tetralogy of Fallot (TOF) with a dysplastic pulmonary valve annulus (PVA) is a challenging procedure and is controversial. This study aimed to assess the feasibility and surgical effect of AS repair versus transannular patch enlargement (TAPE) repair, especially in individuals with dysplastic pulmonary valves. Methods: This retrospective cohort study included 375 pediatric patients with a primary diagnosis of TOF in the Center for Pediatric Cardiac Surgery of Fuwai hospital from January 2014 to June 2017. Among them, 60 consecutive and nonselective patients underwent 1-stage repair of TOF with aggressive PVA-preserving strategies performed by a single surgeon were enrolled in AS cohort. In AS cohort, patients were divided into AS, PVA z-score ≥-2 group (33 patients) and AS, PVA z-score <-2 group (27 patients). During the same period, 315 patients underwent TAPE repair by other surgeons were enrolled as TAPE cohort, of these, 87 patients with PVA z-score ≥-2 were excluded. From the 228 patients in the TAPE group, 27 cases were selected as TAPE, PVA z-score <-2 group according to the propensity score and 1:1 ratio with AS, PVA z-score <-2 group. The primary outcome was a composite of reintervention, significant pulmonary regurgitation, and significant annular peak gradient (APG). Kaplan-Meier curve was plotted to show the survival rate of severe pulmonary regurgitation. Results: One death occurred after the TAPE operation in TAPE group, and 1 patient in the AS z ≥-2 group needed reintervention with a balloon. After a median follow-up of (30.3±11.6) months, compared with AS z ≥-2 group, there was no difference in the technical performance score for severe pulmonary stenosis (APGs > 20 mmHg) in the AS z <-2 group. Compared with TAPE, AS repair was often accompanied by a postoperative APGs over 20 mmHg (P = 0.001). More patients underwent TAPE suffered from moderate or severe pulmonary regurgitation than those who received AS repair (20 (74.1%) vs. 7 (26.0%), P < 0.001). AS repair was associated with a shorter duration of mechanical ventilation (20 vs. 29 hours, P = 0.039), faster discharge from the intensive care unit (2.0 vs. 4.0 days, P = 0.022) and shorter postoperative hospitalization (8.0 vs. 11.0 days, P = 0.008) compared with TAPE. Conclusions: APG demonstrated an upward trend in the TAPE group and a downtrend in the AS group after discharge from hospital. AS repair had an acceptable surgical effect in TOF patients, even in those with a dysplastic PVA. A higher APG remained upon hospital discharge in dysplastic patients with AS, but a downward trend was observed over time.

Intravenous anticoagulant therapy is critical to prevent ischemic events without increasing the risk of bleeding in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Heparin and bivalirudin are the most commonly used adjunctive anticoagulant agents during PPCI. However, the superiority of the 2 most optimal regimens with these agents in patients undergoing PPCI remains controversial. The BivaliRudin with prolonged high-dose Infusion durinG PPCI versus Heparin Trial 4 (BRIGHT-4) is a large-scale, prospective, multicenter, active-control, parallel-group, open-label, randomized trial designed to test whether bivalirudin with a post-PCI high-dose infusion is superior to heparin monotherapy in STEMI patients undergoing PPCI. A total of 6000 patients will be enrolled and randomly assigned to receive bivalirudin or heparin in a 1:1 ratio. Patients allocated to the bivalirudin group will be treated with a high-dose bivalirudin infusion (1.75 mg/(kg·h)) after PCI for 2 to 4 hours. In the heparin group, the use of glycoprotein IIb/IIIa inhibitors will be reserved for the development of procedural thrombotic complications. The efficacy and safety of bivalirudin will be evaluated at 30 days, 6 months, and 12 months after the randomization. The primary endpoint is a composite of all-cause death or Bleeding Academic Research Consortium (BARC) types 3 to 5 bleeding at 30 days after randomization. The BRIGHT-4 study protocol has received approval from the ethics committee of General Hospital of Northern Theater Command (Shenyang, China). The procedures set out in this protocol are in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines. The results will be published following the Consolidated Standards of Reporting Trials statement in a peer-reviewed scientific journal (Trial registration number: NCT03822975).

Heart failure (HF) is a major public health problem around the world. Although currently available therapies have improved outcomes, morbidity and mortality in patients with HF remain unacceptably high. Most guideline-recommended therapies for HF are indicated for patients with a reduced left ventricular ejection fraction (HFrEF). Until recently, treatment options that improved outcomes in patients with HF and preserved left ventricular ejection fraction or mildly reduced ejection fraction were limited. Over the past several years, however, several new drugs including angiotensin receptor neprilysin inhibitors (ARNIs), sodium glucose cotransporter 2 inhibitors (SGLT2 inhibitors), soluble guanylate cyclase stimulators, and a cardiac myotrope, omecamtiv mecarbil have all reported positive results in pivotal phase III clinical trials. Moreover, the results of these studies have provided evidence that both ARNIs and SGLT2 inhibitors can improve clinical outcomes in patients with HF across a broad spectrum of LVEF, not just in HFrEF. This article presents the rationale for the use of each of these 4 new classes of drugs, reviews the results from pivotal clinical trials showing their safety and efficacy, and provides a framework for how each drug has begun to be integrated into new HF management guidelines. Collectively, these new drugs provide hope for the millions of patients around the world who suffer from HF.

The outcomes of patients with myocardial infarction (MI) have substantially improved given the rapid progress that has occurred in revascularization techniques and secondary prevention, and the majority of MI patients subsequently enter a chronic stable phase. Therefore, the long-term management of patients with MI has become a core issue in daily clinical practice for cardiologists. The long-term incidence of adverse events can be further reduced using newly developed medications and therapies ranging from lipid-lowering agents (eg, proprotein convertase subtilisin/kexin type 9 inhibitors) to anti-thrombotic treatments (eg, shortened dual anti-platelet therapy). However, a considerable number of patients still experience adverse events, as some residual risk can remain despite intensive secondary prevention, such as continuously elevated cholesterol levels, chronic cardiovascular inflammation, and rapid atherosclerosis progression due to increased plaque instability. Therefore, the present review sought to summarize and discuss recent advances in several key aspects regarding the long-term management of MI patients, with the expectation of clarifying the available treatment strategies for various clinical scenarios, examining the gaps between trial evidence and clinical practice, and providing possible directions for future research.

Treatment of aortic arch (AA) diseases is challenging for surgeons. Conventional open surgery remains the "gold standard" but is associated with significant morbidity and mortality despite improvements in techniques. In the last 2 decades, thoracic endovascular aortic repair (TEVAR) has become the first-line treatment for diseases of the descending aorta, and its indications have expanded gradually. Various strategies have been proposed to preserve supra-aortic branches in TEVAR: hybrid technique, chimney technique, fenestration technique (including custom-made fenestrated or "scalloped" stent grafts, in situ fenestration, and physician-modified fenestration), and branched stent grafts. Though acceptable outcomes of endovascular aortic repair have been documented, the evidence regarding its long-term safety and efficacy is lacking, and concerns remain about the risk of cerebrovascular events, retrograde type-A dissection, endoleaks, and branch occlusion. This review discusses the current status and progress of endovascular repair of the AA, and looks toward future trends. We believe that multidisciplinary collaboration of a "HENDO" team (professionals in hybrid repair, endovascular repair, open surgery, cardiovascular anesthesia, and genetics) is essential for future repair of the AA to provide the optimal treatment.