2022 CMICS Expert Consensus on the Management of Isolated Tricuspid Regurgitation after Left-Sided Valve Surgery.

Tricuspid regurgitation (TR) may occur late after left-sided valve surgery (LSVS). Isolated tricuspid regurgitation after left-sided valve surgery (iTR-LSVS) refers to isolated TR without significant lesions in the mitral and/or aortic position late after mitral and/or aortic replacement or repair. Severe TR has a negative impact on long-term prognosis and requires surgical or transcatheter treatment. However, there is no clear recommendation on when and how intervention should be performed for patients with iTR-LSVS in the current guidelines for the management of valvular heart disease. The historically high operative mortality may be reduced by current minimally invasive techniques and transcatheter therapy. To further understand iTR-LSVS, standardize the treatment, improve the prognosis, and promote the collaboration, the Chinese Minimally Invasive Cardiovascular Surgery Committee (CMICS) wrote this expert consensus on the management of iTR-LSVS from the aspects of etiology, preoperative evaluation, indications for intervention, surgical treatment, transcatheter therapy, and postoperative management.

Interpretable machine learning models for early prediction of acute kidney injury after cardiac surgery.

OBJECTIVE: Postoperative acute kidney injury (PO-AKI) is a common complication after cardiac surgery. We aimed to evaluate whether machine learning algorithms could significantly improve the risk prediction of PO-AKI. METHODS: The retrospective cohort study included 2310 adult patients undergoing cardiac surgery in a tertiary teaching hospital, China. Postoperative AKI and severe AKI were identified by the modified KDIGO definition. The sample was randomly divided into a derivation set and a validation set based on a ratio of 4:1. Exploiting conventional logistic regression (LR) and five ML algorithms including decision tree, random forest, gradient boosting classifier (GBC), Gaussian Naive Bayes and multilayer perceptron, we developed and validated the prediction models of PO-AKI. We implemented the interpretation of models using SHapley Additive exPlanation (SHAP) analysis. RESULTS: Postoperative AKI and severe AKI occurred in 1020 (44.2%) and 286 (12.4%) patients, respectively. Compared with the five ML models, LR model for PO-AKI exhibited the largest AUC (0.812, 95%CI: 0.756, 0.860, all P < 0.05), sensitivity (0.774, 95%CI: 0.719, 0.813), accuracy (0.753, 95%CI: 0.719, 0.781) and Youden index (0.513, 95%CI: 0.451, 0.573). Regarding severe AKI, GBC algorithm showed a significantly higher AUC than the other four ML models (all P < 0.05). Although no significant difference (P = 0.173) was observed in AUCs between GBC (0.86, 95%CI: 0.808, 0.902) and conventional logistic regression (0.803, 95%CI: 0.746, 0.852), GBC achieved greater sensitivity, accuracy and Youden index than conventional LR. Notably, SHAP analyses showed that preoperative serum creatinine, hyperlipidemia, lipid-lowering agents and assisted ventilation time were consistently among the top five important predictors for both postoperative AKI and severe AKI. CONCLUSION: Logistic regression and GBC algorithm demonstrated moderate to good discrimination and superior performance in predicting PO-AKI and severe AKI, respectively. Interpretation of the models identified the key contributors to the predictions, which could potentially inform clinical interventions.

Peak Blood Lactate at 24 h after ECMO Can Predict 30-day Mortality in Infants after Complex Cardiac Surgery.

OBJECTIVE: Peak blood lactate at 24 h after extracorporeal membrane oxygenation (ECMO) can predict 30-day mortality in infants after complex cardiac surgery. METHODS: Twenty-eight infants with ECMO after complex congenital heart disease surgery were selected from March 2019 to March 2022 in our hospital. The infants were divided into survival group (n = 11) and non-survival group (n = 17) according to 30-day survival after discharge from hospital. The risk factors at 30-day mortality after discharge were analyzed by Cox regression analysis. RESULTS: When compared to the non-survival group, there were significant differences in peak blood lactate at 24 h after ECMO, liver dysfunction and multiple organ dysfunction syndrome (MODS) in the survival group (p < 0.05). Cox regression analysis showed that peak blood lactate at 24 h after ECMO (HR = 1.074, 95% CI: 1.005-1.149, p = 0.036) and MODS (HR = 4.120, 95% CI: 1.373-12.362, p = 0.012) were related risk factors affecting the prognosis of infants. The best cutoff value for the peak blood lactate at 24 h after ECMO was 10.2 mmol/L. The area under the curve (AUC) for predicting the 30-day survival rate of the ECMO assisted infants after discharge from hospital was 0.770 (95% CI: 0.592-0.948, p = 0.018), with a sensitivity of 94.1% and specificity of 54.5%. CONCLUSION: The peak blood lactate at 24 h after ECMO can predict the 30-day mortality after discharge of infants treated with ECMO after complex cardiac surgery. The best cut-off value for peak blood lactate at 24 h after ECMO was 10.2 mmol/L.

GAS5/METTL14/ESR1 genetic variants are related to the susceptibility of coronary heart disease.

The prevention and treatment of coronary heart disease (CHD) is a difficult problem to be solved urgently. Genetic factors play a crucial role in CHD development. This study aimed to investigate the association of GAS5/METTL14/ESR1 polymorphisms with CHD susceptibility. We carried out a case-control study that included 506 patients and 506 healthy subjects to detect the correlation between GAS5/METTL14/ESR1 polymorphisms and CHD risk in a Chinese population. Odds ratios (OR) and 95% confidence intervals (CI) were computed to assess the associations. Our study showed that GAS5 rs17359906 (OR 2.32, p = 0.020) and rs75315904 (OR 0.41, p = 0.039) were related to the risk of CHD in females. ESR1 rs6927072 (OR 1.76, p = 0.007) and rs4870061 (OR 0.74, p = 0.036) correlated with CHD risk in age ≤ 60 years. GAS5 rs17359906 (OR 0.10, p = 0.032) and ESR1 rs3020308 (OR 2.73, p = 0.041) were associated with an increased susceptibility to CHD in smokers. We also found that METTL14 rs4834698 (OR 1.57, p = 0.044) and ESR1 rs4870061 (OR 0.62, p = 0.040) were associated with CHD susceptibility in non-drinkers. Besides, METTL14 rs17050450 (OR 0.48, p = 0.029) and ESR1 rs3853248 (OR 1.61, p = 0.018) had the susceptibility of CHD patients with diabetes. Our study indicated that GAS5/METTL14/ESR1 polymorphisms were associated with CHD risk, which might provide a new understanding of CHD in a Chinese population.

Silencing of Long Noncoding RNA MIAT Contributes to Relieving Sepsis-Induced Myocardial Depression via the NF-κB Axis.

INTRODUCTION: Sepsis represents a life-threatening disease caused by a series of infections, which may be complicated with severe myocardial depression (MD). Long noncoding RNAs (lncRNAs) are closely related to sepsis-induced myocardial depression (SIMD). This study aimed to seek out the mechanism of lncRNA myocardial infarction-associated transcript (MIAT) in the growth of SIMD. METHODS: Venous blood samples were collected from 62 patients with sepsis; the sepsis rat model was established with 15 mg/kg lipopolysaccharide (LPS), and the H9C2 cardiomyocyte injury model was established with 1 µg/mL LPS. In the rat and cardiomyocyte models, MIAT was inhibited. The expression of MIAT in normal tissues and SIMD tissues was detected. Then, the functional assays of MIAT were performed in rats and H9C2 cells for detection of cardiac function, hemodynamics, inflammation response, myocardial function, oxidative stress, tissue stainings, and cardiomyocyte viability and apoptosis. Western blot analysis was used to measure the levels of apoptosis-related proteins and the nuclear factor kappa B (NF-κB) axis-related proteins. RESULTS: MIAT was highly expressed in SIMD patients. Silencing MIAT alleviated inflammation and apoptosis and improved myocardial function in SIMD rats by downregulating the NF-κB axis. In LPS-induced H9C2 cardiomyocytes, silencing MIAT alleviated inflammation and oxidative stress and inhibited apoptosis by downregulating the NF-κB axis, thus mitigating cardiomyocyte injury. CONCLUSIONS: MIAT could assist the diagnosis of SIMD and might affect the progression of SIMD by regulating the NF-κB pathway.

Histone Deacetylase 1 Depletion Alleviates Coronary Heart Disease Via the MicroRNA-182-Mediated Transforming Growth Factor ß/Smad Signaling Pathway.

ABSTRACT: Histone deacetylase (HDAC) determines the acetylation status of histones, thereby regulating gene expression. HDAC inhibitors have been demonstrated to suppress cardiomyocyte growth in vitro and in vivo. We assessed here whether HDAC1 exerts an aggravating effect on coronary heart disease (CHD). Epigenetic probe array revealed that HDAC1 was overexpressed in patients with CHD. HDAC1 was then downregulated in rat cardiomyocytes, and microRNA microarray analysis was performed to detect downstream targets of HDAC1, followed by chromatin immunoprecipitation validation. HDAC1 inhibited miR-182 expression through deacetylation. miR-182 was poorly expressed in patients with CHD. Using enzyme-linked immunosorbent assay, Reverse transcription-quantitative PCR, hematoxylin-eosin staining, terminal deoxynucleotidyl transferase (TdT)-mediated 2'-deoxyuridine 5'-triphosphate (dUTP) nick-end labeling assay, and immunohistochemistry, we observed that HDAC1 downregulation promoted cardiac function, restored lipid levels, reduced myocardial injury markers and inflammatory factors, and alleviated myocardial tissue damage and apoptosis in CHD rats. By contrast, miR-182 downregulation exacerbated injury in rats in the presence of HDAC1 knockdown. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes of miR-182 were mainly enriched in the transforming growth factor (TGF)-ß/Smad pathway. Western blot also validated that HDAC1/miR-182 modulated the TGF-ß/Smad pathway activity. Our results demonstrated that HDAC1 repressed miR-182 and activated the TGF-ß/Smad pathway to promote CHD.

Update on surgical repair in functional mitral regurgitation.

BACKGROUND: Functional mitral regurgitation (FMR) is common in patients with myocardial infarction or dilated cardiomyopathy, and portends a poor prognosis despite guideline-directed medical therapy (GDMT). Surgical or transcatheter mitral repair for FMR from recent randomized clinical trials showed disappointing or conflicting results. AIMS: To provide an update on the role of surgical repair in the management of FMR. MATERIALS AND METHODS: A literature search was conducted utilizing PubMed, Ovid, Web of Science, Embase, and Cochrane Library. The search terms included secondary/FMR, ischemic mitral regurgitation, mitral repair, mitral replacement, mitral annuloplasty, transcatheter mitral repair, and percutaneous mitral repair. Randomized clinical trials over the past decade were the particular focus of the current review. RESULTS: Recent data underlined the complexity and poor prognosis of FMR. GDMT and cardiac resynchronization, when indicated, should always be applied. Accurate assessment of the interplay between ventricular geometry and mitral valve function is essential to differentiate proportionate FMR from the disproportionate subgroup, which could be helpful in selecting appropriate transcatheter intervention strategies. Surgical repair, most commonly performed with an undersized ring annuloplasty, remains controversial. Adjunctive valvular or subvalvular repair techniques are evolving and may produce improved results in selected FMR patients. CONCLUSION: FMR resulted from complex valve-ventricular interaction and remodeling. Distinguishing proportionate FMR from disproportionate FMR is important in exploring their underlying mechanisms and to guide medical treatment with surgical or transcatheter interventions. Further studies are warranted to confirm the clinical benefit of appropriate surgical repair in selected FMR patients.

Effect of High- vs Low-Dose Tranexamic Acid Infusion on Need for Red Blood Cell Transfusion and Adverse Events in Patients Undergoing Cardiac Surgery: The OPTIMAL Randomized Clinical Trial.

Importance: Tranexamic acid is recommended for reducing blood loss and transfusion in cardiac surgery. However, it remains unknown whether a high dose of tranexamic acid provides better blood-sparing effect than a low dose without increasing the risk of thrombotic complications or seizures in cardiac surgery. Objective: To compare the efficacy and adverse events of high-dose vs low-dose tranexamic acid in patients undergoing cardiac surgery with cardiopulmonary bypass. Design, Setting, and Participants: Multicenter, double-blind, randomized clinical trial among adult patients undergoing cardiac surgery with cardiopulmonary bypass. The study enrolled 3079 patients at 4 hospitals in China from December 26, 2018, to April 21, 2021; final follow-up was on May 21, 2021. Interventions: Participants received either a high-dose tranexamic acid regimen comprising a 30-mg/kg bolus, a 16-mg/kg/h maintenance dose, and a 2-mg/kg prime (n = 1525) or a low-dose regimen comprising a 10-mg/kg bolus, a 2-mg/kg/h maintenance dose, and a 1-mg/kg prime (n = 1506). Main Outcomes and Measures: The primary efficacy end point was the rate of allogeneic red blood cell transfusion after start of operation (superiority hypothesis), and the primary safety end point was a composite of the 30-day postoperative rate of mortality, seizure, kidney dysfunction (stage 2 or 3 Kidney Disease: Improving Global Outcomes [KDIGO] criteria), and thrombotic events (myocardial infarction, ischemic stroke, deep vein thrombosis, and pulmonary embolism) (noninferiority hypothesis with a margin of 5%). There were 15 secondary end points, including the individual components of the primary safety end point. Results: Among 3079 patients who were randomized to treatment groups (mean age, 52.8 years; 38.1% women), 3031 (98.4%) completed the trial. Allogeneic red blood cell transfusion occurred in 333 of 1525 patients (21.8%) in the high-dose group and 391 of 1506 patients (26.0%) in the low-dose group (risk difference [RD], -4.1% [1-sided 97.55% CI, -∞ to -1.1%]; relative risk, 0.84 [1-sided 97.55% CI, -∞ to 0.96; P = .004]). The composite of postoperative seizure, thrombotic events, kidney dysfunction, and death occurred in 265 patients in the high-dose group (17.6%) and 249 patients in the low-dose group (16.8%) (RD, 0.8%; 1-sided 97.55% CI, -∞ to 3.9%; P = .003 for noninferiority). Fourteen of the 15 prespecified secondary end points were not significantly different between groups, including seizure, which occurred in 15 patients (1.0%) in the high-dose group and 6 patients (0.4%) in the low-dose group (RD, 0.6%; 95% CI, -0.0% to 1.2%; P = .05). Conclusions and Relevance: Among patients who underwent cardiac surgery with cardiopulmonary bypass, high-dose compared with low-dose tranexamic acid infusion resulted in a modest statistically significant reduction in the proportion of patients who received allogeneic red blood cell transfusion and met criteria for noninferiority with respect to a composite primary safety end point consisting of 30-day mortality, seizure, kidney dysfunction, and thrombotic events. Trial Registration: ClinicalTrials.gov Identifier: NCT03782350.

Preliminary Study of Genome-Wide Association Identified Novel Susceptibility Genes for Hemorheological Indexes in a Chinese Population.

Background: Genome-wide association studies for various hemorheological characteristics have not been reported. We aimed to identify genetic loci associated with hemorheological indexes in a cohort of healthy Chinese Han individuals. Methods: Genotyping was performed using Applied Biosystems Axiom™ Precision Medicine Diversity Array in 838 individuals, and 6,423,076 single nucleotide polymorphisms were available for genotyping. The relations were examined in an additive genetic model using mixed linear regression and combined with identical by descent matrix. Results: We identified 38 genetic loci (p < 5 × 10-6) related to hemorheological traits. In which, LOC102724502-OLIG2 rs28371438 was related to the levels of nd30 (p = 8.58 × 10-07), nd300 (p = 1.89 × 10-06), erythrocyte rigidity (p = 1.29 × 10-06), assigned viscosity (p = 6.20 × 10-08) and whole blood high cut relative (p = 7.30 × 10-08). The association of STK32B rs4689231 for nd30 (p = 3.85 × 10-06) and nd300 (p = 2.94 × 10-06) and GTSCR1-LINC01541 rs11661911 for erythrocyte rigidity (p = 9.93 × 10-09) and whole blood high cut relative (p = 2.09 × 10-07) was found. USP25-MIR99AHG rs1297329 was associated with erythrocyte rigidity (p = 1.81 × 10-06) and erythrocyte deformation (p = 1.14 × 10-06). Moreover, the association of TMEM232-SLC25A46 rs3985087 and LINC00470-METTL4 rs9966987 for fibrinogen (p = 1.31 × 10-06 and p = 4.29 × 10-07) and plasma viscosity (p = 1.01 × 10-06 and p = 4.59 × 10-07) was found. Conclusion: These findings may represent biological candidates for hemorheological indexes and contribute to hemorheological study.

Knockdown of Long Noncoding RNA SNHG14 Protects H9c2 Cells Against Hypoxia-induced Injury by Modulating miR-25-3p/KLF4 Axis in Vitro.

ABSTRACT: Cyanotic congenital heart disease (CCHD) is the main cause of death in infants worldwide. Long noncoding RNAs (lncRNAs) have been pointed to exert crucial roles in development of CHD. The current research is designed to illuminate the impact and potential mechanism of lncRNA SNHG14 in CCHD in vitro. The embryonic rat ventricular myocardial cells (H9c2 cells) were exposed to hypoxia to establish the model of CCHD in vitro. Quantitative real-time polymerase chain reaction was conducted to examine relative expressions of SNHG14, miR-25-3p, and KLF4. Cell viability was determined by the MTT assay. Lactate dehydrogenase (LDH) was measured by an LDH assay kit. Apoptosis-related proteins (Bax and Bcl-2) and KLF4 were detected by Western Blot. The targets of SNHG14 and miR-25-3p were verified by the dual-luciferase reporter assay. SNHG14 and KLF4 were upregulated, whereas miR-25-3p was downregulated in hypoxia-induced H9c2 cells and cardiac tissues of patients with CCHD compared with their controls. Knockdown of SNHG14 or overexpression of miR-25-3p facilitated cell viability, while depressing cell apoptosis and release of LDH in hypoxia-induced H9c2 cells. MiR-25-3p was a target of SNHG14 and inversely modulated by SNHG14. MiR-25-3p could directly target KLF4 and negatively regulate expression of KLF4. Repression of miR-25-3p or overexpression of KLF4 reversed the suppression impacts of sh-SNHG14 on cell apoptosis and release of LDH as well as the promotion impact of sh-SNHG14 on cell viability in hypoxia-induced H9c2 cells. Sh-SNHG14 protected H9c2 cells against hypoxia-induced injury by modulating miR-25-3p/KLF4 axis in vitro.

Anti-inflammatory cytokine IL10 loaded cRGD liposomes for the targeted treatment of atherosclerosis.

AIM: Atherosclerosis (AS) is one of the main causes of cardiovascular disease which might lead to myocardial infarction or stroke and further leads to fatality. METHOD: In this study, we have designed an anti-inflammatory cytokine interleukin-10 (IL10) delivery system to effectively alleviate the inflammation of atherosclerosis plaque. The targeted delivery of IL10 to the atherosclerotic plaques was achieved by cRGD conjugated liposomes (IL10-cRGD-Lip). RESULTS: The IL10-cRGD-Lip of size 179.4 ± 10.91 nm having PDI 0.14 ± 0.04 with a surface charge of +18.34 ± 1.36 mV was prepared. The in-vitro analysis clearly suggests that IL10-cRGD-Lip sustains the release of IL10 and could significantly reduce ROS and NO. The immuno-staining results revealed that IL-1ß and TNF-α were down-regulated after the treatment with IL10-cRGD-Lip in Lipopolysaccharide (LPS) stimulated RAW 264.7 cells. CONCLUSION: the in-vitro results clearly suggest that anti-inflammatory cytokine IL10 could be used for the cure of inflammatory maladies including atherosclerosis.

IRAK3 gene silencing prevents cardiac rupture and ventricular remodeling through negative regulation of the NF-κB signaling pathway in a mouse model of acute myocardial infarction.

Cardiac rupture and ventricular remodeling are recognized as the severe complications and major risk factors of acute myocardial infarction (AMI). This study aims to evaluate the regulatory roles of interleukin-1 receptor-associated kinase 3 (IRAK3) and nuclear factor-κB (NF-κB) signaling pathway in cardiac rupture and ventricular remodeling. Microarray analysis was performed to screen AMI-related differentially expressed genes and IRAK3 was identified. The models of AMI were established in male C57BL/6 mice to investigate the functional role of IRAK3. Afterwards, lentivirus recombinant plasmid si-IRAK3 was constructed for IRAK3 silencing. Next, cardiac function parameters were measured in response to IRAK3 silencing. The regulatory effects that IRAK3 had on myocardial infarct size and the content of myocardial interstitial collagen were analyzed. The regulation of IRAK3 silencing on the NF-κB signaling pathway was further assayed. The obtained results indicated that highly expressed IRAK3 and activated NF-κB signaling pathway were observed in myocardial tissues of mouse models of AMI, accompanied by increased expression of matrix metalloproteinase (MMP)-2/9 and tissue inhibitor of metalloproteinase 2 (TIMP-2). Notably, IRAK3 gene silencing inhibited the activation of NF-κB signaling pathway. Furthermore, IRAK3 gene silencing led to the decreased thickness of infarct area and collagen content of myocardial interstitium, alleviated diastolic, and systolic dysfunctions, as well as, facilitated cardiac functions in mice with AMI, corresponding to decreased expression of MMP-2/9 expression and increased expression of TIMP-2. Taken together, silencing of IRAK3 inactivates the NF-κB signaling pathway, and thereby impeding the cardiac rupture and ventricular remodeling, which eventually prevents AMI progression.

Promotion of PTEN on apoptosis through PI3K/Akt signal in vascular smooth muscle cells of mice model of coronary heart disease.

Previous studies have shown that phosphatase and tensin homolog (PTEN) are key regulators of the development of many malignant tumors and other diseases. However, its regulatory effect on coronary heart disease (CHD) has rarely been reported. Therefore, the regulatory effect of PTEN on the survival and cell death of vascular smooth muscle cells (VSMCs) in CHD mice was elucidated in this study. It was found that the protein and messenger RNA expressions of PTEN in VSMCs of 10 CHD mice were lower than those of normal mice. Then PTEN was overexpressed in VSMCs. It was suggested that the upregulation of PTEN was not conducive to the proliferation and survival of VSMCs in the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assay. The flow cytometry (Annexin V-Fluorescein isothiocyanate (FITC)/propidium iodide) and the terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used to detect the apoptotic rate of overexpressing PTEN cells. Some data showed that the expression of PTEN could lead to increased apoptotic rate. It was shown that antiapoptotic Bcl-2 levels were decreased, but cleaved caspase-3 and proapoptotic Bax levels were promoted by SIRT6 overexpression in Western blot analysis. Moreover, PI3K/Akt expression and phosphorylation were significantly decreased in cells expressing PTEN. Recovery of PI3K expression inhibited the suppressive influence of PTEN on VSMC survival, as evidenced by the activated PI3K/Akt pathway, increased cell proliferative rate, reduced the apoptotic level, and reversed expression patterns of Bcl-2 and Bax. Therefore, the findings in this study provide a new idea on the occurrence and development mechanism of CHD and may promote the discovery of innovative therapies.

microRNA-135a protects against myocardial ischemia-reperfusion injury in rats by targeting protein tyrosine phosphatase 1B.

microRNAs are an emerging class of molecules that regulate pathogenesis of cardiovascular diseases. Here we aim to elucidate the effects and mechanism of miR-135a, a previously reported regulator of ischemia-reperfusion (I/R) injury, in myocardial I/R injury. Quantitative real-time polymerase chain reaction analysis revealed that the expression level of miR-135a was significantly decreased both in the rat I/R group and H9c2 cells subjected to hypoxia/reoxygenation. Overexpression of miR-135a in vivo markedly decreased the infarct size and inhibited the I/R-induced cardiomyocyte apoptosis. Overexpression of miR-135a in H9c2 also exerted antiapoptosis effects. Furthermore, bioinformatics analysis, luciferase activity, and the Western blot assay indicated that protein tyrosine phosphatase 1B (PTP1B) is a direct target of miR-135a. In addition, the expression of proapoptotic-related genes, such as p53, Bax, and cleaved caspase3, were decreased in association with the downregulation of PTP1B. In summary, this study demonstrates that miR-135a exerts protective effects against myocardial I/R injury by targeting PTP1B.

Effect of Ticagrelor Plus Aspirin, Ticagrelor Alone, or Aspirin Alone on Saphenous Vein Graft Patency 1 Year After Coronary Artery Bypass Grafting: A Randomized Clinical Trial.

Importance: The effect of ticagrelor with or without aspirin on saphenous vein graft patency in patients undergoing coronary artery bypass grafting (CABG) is unknown. Objective: To compare the effect of ticagrelor + aspirin or ticagrelor alone vs aspirin alone on saphenous vein graft patency 1 year after CABG. Design, Setting, and Participants: Randomized, multicenter, open-label, clinical trial among 6 tertiary hospitals in China. Eligible patients were aged 18 to 80 years with indications for elective CABG. Patients requiring urgent revascularization, concomitant cardiac surgery, dual antiplatelet or vitamin K antagonist therapy post-CABG, and who were at risk of serious bleeding were excluded. From July 2014 until November 2015, 1256 patients were identified and 500 were enrolled. Follow-up was completed in January 2017. Interventions: Patients were randomized (1:1:1) to start ticagrelor (90 mg twice daily) + aspirin (100 mg once daily) (n = 168), ticagrelor (90 mg twice daily) (n = 166), or aspirin (100 mg once daily) (n = 166) within 24 hours post-CABG. Neither patients nor treating physicians were blinded to allocation. Main Outcomes and Measures: Primary outcome was saphenous vein graft patency 1 year after CABG (FitzGibbon grade A) adjudicated independently by a committee blinded to allocation. Saphenous vein graft patency was assessed by multislice computed tomographic angiography or coronary angiography. Results: Among 500 randomized patients (mean age, 63.6 years; women, 91 [18.2%]), 461 (92.2%) completed the trial. Saphenous vein graft patency rates 1 year post-CABG were 88.7% (432 of 487 vein grafts) with ticagrelor + aspirin; 82.8% (404 of 488 vein grafts) with ticagrelor alone; and 76.5% (371 of 485 vein grafts) with aspirin alone. The difference between ticagrelor + aspirin vs aspirin alone was statistically significant (12.2% [95% CI, 5.2% to 19.2%]; P < .001), whereas the difference between ticagrelor alone vs aspirin alone was not statistically significant (6.3% [95% CI, -1.1% to 13.7%]; P = .10). Five major bleeding episodes occurred during 1 year of follow-up (3 with ticagrelor + aspirin; 2 with ticagrelor alone). Conclusions and Relevance: Among patients undergoing elective CABG with saphenous vein grafting, ticagrelor + aspirin significantly increased graft patency after 1 year vs aspirin alone; there was no significant difference between ticagrelor alone and aspirin alone. Further research with more patients is needed to assess comparative bleeding risks. Trial Registration: clinicaltrials.gov Identifier: NCT02201771.

Application of Autologous Blood Cell Salvage in Off-Pump Coronary Artery Bypass Graft Operation.

OBJECTIVE: To analyze whether application of autologous blood cell salvage can reduce the transfusion volume of allogeneic blood and complications of blood transfusion in off-pump coronary artery bypass operations. Methods: We randomly divided 120 patients into autologous blood cell salvage group (experimental group, n = 60) and non-autologous blood cell salvage group (control group, n = 60). Volume of perioperative allogeneic blood transfusion of each patient was recorded. Moreover, complications and ICU retention times (H) of each patient were also recorded. The data were analyzed using t tests. Results: The volume of allogeneic blood transfusion was significantly less in the experimental group than in the control group. Conclusion: Application of autologous blood cell salvage in off-pump coronary artery bypass graft operation can reduce the volume of allogeneic blood transfusion, alleviate blood shortage, and reduce the incidence of postoperative complications, leading to medical, economic, and social benefits.

Level of perioperative B-type natriuretic peptide associates with heart function after on-pump coronary artery bypass graft surgery on a beating heart.

OBJECTIVE: To explore the relationship of the perioperative B-type natriuretic peptide (BNP) level with heart function among patients undergoing on-pump coronary artery bypass graft surgery on a beating heart. METHODS: Total 90 patients expected to undergo coronary artery bypass graft surgery were selected and their left ventricular ejection fraction (LVEF) were examined before operation. Patients with LVEF greater than or equal to 50% were selected as the A group (n=46), and those less than 50% formed the B group (n=44). BNP levels of the patients were examined and its relationship with cardiac function was analyzed. RESULTS: BNP levels of group A was lower than that in group B pre-and post-operatively (until 7 days after the surgery), the difference is statistically significant (p<0.05). Pearson analysis showed that the BNP level was negatively correlated with the LVEF (r = 0.767, p< 0.05). The area under the Roc curve is 0.865. CONCLUSION: BNP level was negatively correlated with the LVEF. Perioperative BNP level can be used as the prediction for heart function of patients with on-pump coronary artery bypass graft surgery on a beating heart.

Application of Real-Time Three-Dimensional Echocardiography to Evaluate the Pre- and Postoperative Right Ventricular Systolic Function of Patients with Tetralogy of Fallot.

UNLABELLED: Tetralogy of Fallot (ToF) can be challenging for clinicians to both diagnose and treat, given the multiple heart defects that are by definition associated with the illness. This study investigates the value of real-time three- dimensional echocardiography (RT-3DE) in evaluating the pre-and postoperative right ventricular systolic function of patients with tetralogy of Fallot. A total of 41 ToF patients were divided into two groups: the child group (CG) and the adult group (AG) according to age. The right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV), and the right ventricular ejection fraction (RVEF) of ToF patients were measured before surgery, 7 days, and 3 months after the surgery. The correlation between the preoperative Nakata index and RVEF was then analyzed. Compared with the RVEDV and RVESV prior to surgery, those of the postoperative 7-day and 3-month were not statistically significant (p > 0.05). However, RVEF decreased, and the difference was statistically significant (p < 0.05). The differences in RVEDV, RVESV, and RVEF between postoperative 3-month and 7-day were not significant (p > 0.05). Compared with the pre-and postoperative RVEDV and RVESV of CG, those of AG increased. However, RVEF decreased, and the differences were statistically significant (p < 0.05). Our study indicated that the correlation between preoperative Nakata index and RVEF was good. Ultimately, we did confirm that RT-3DE can quantitatively evaluate the right ventricular volume and systolic function of ToF patients, thereby providing clinical significance in determining postoperative efficacy and prognosis evaluation. KEY WORDS: Echocardiography; Right; Tetralogy of Fallot; Three-dimensional; Ventricular function.

Investigation of the long-term patency of a transmural heparinized polycaprolactone and poly(D,L-lactic/glycolic acid) scaffold.

BACKGROUND: The transmural biodegradable polycaprolactone/poly(D,L-lactic/glycolic acid) (PCL/PLGA) scaffold is a promising modality for diffuse coronary atherosclerosis cases that are not suitable for bypass grafting. The purpose of this study was to evaluate the long-term performance of the PCL/PLGA scaffold in vivo in the setting of polymer and heparin degradation. MATERIALS AND METHODS: After mechanical drilling through the ventricular wall was performed in the whole ventricular wall, two scaffolds were implanted into the ventricular wall. Animals were grouped into the single drilling group (SD group), the blank scaffold group (BS group), and the heparinized scaffold group (HS group) and were allowed to survived for 6 mo. Next, the patency and integrity of the scaffolds were evaluated by echocardiography and 3D-DOCTOR software. Endothelium coverage of the lumen was evaluated by scanning electron microscopy. Neovessels and collagen fiber within the scaffolds were identified by histologic staining. Metabolite production of prostacyclin (PGI2) and thromboxane A2 (TXA2) in the plasma was measured by an enzyme-linked immunosorbent assay. The expression levels of PGI2 synthase and cyclooxygenase 2 (COX-2) involved in PGI2 production and COX-1 involved in TXA2 production were measured by Western blot analysis. RESULTS: The heparinized scaffolds were patent for up to 6 mo and the lumen was covered with confluent endothelial cells. Histologic staining revealed collagen fiber remodeling and reconstruction of the neovascular network immediately surrounding the lumen. The expression of PGI2 synthase and COX-2 in the HS group was significantly higher compared with the SD and BS groups (P < 0.01). The expression of COX-1 was similar in the three groups (P > 0.05). Consistent with synthetase expression, a PGI2 metabolite (6-keto-PGF1a) also showed a significant increase in the HS group relative to the SD and BS groups (P = 0.021 and P = 0.015, respectively). Concomitantly, as a PGI2 antagonist, the TXA2 metabolite (TXB2) did not exhibit a significant difference among the three groups (P = 0.17). CONCLUSIONS: Despite polymer and heparin degradation, the scaffold could continuously maintain the structural integrity and lumen patency for up to 6 mo by reinforcement of host collagen fiber and the balance of PGI2/TXA2.

Effect of preoperative moderate-dose statin and duration on acute kidney injury after cardiac surgery: a retrospective cohort study.

BACKGROUND: The impact of preoperative statin use on postoperative acute kidney injury (AKI) is uncertain. We aimed to examine the association of statin therapy before cardiac surgery with postoperative AKI. METHODS: The retrospective cohort study consisted of 1581 patients undergoing cardiac surgery. Postoperative AKI were identified by the modified KDIGO definition. Propensity-score matching was employed to control for selection bias, and logistic regression was used to control for confounders. Subgroup and interaction analyses were performed to evaluate the robustness of the findings. RESULTS: The overall incidence of postoperative AKI and severe AKI were 42.19% and 12.27%, respectively. Preoperative moderate-dose statin was significantly associated with a reduced incidence of postoperative AKI (28.9% vs 43.0%, OR (95%CI): 0.54 (0.38, 0.77), p < 0.001) and severe AKI (6.9% vs 13.7%, OR (95%CI): 0.46 (0.26, 0.83), p = 0.009). The beneficial effect on postoperative AKI persisted after adjusting for major confounding factors (OR (95%CI): 0.47 (0.34, 0.66)). Decreased risk of postoperative AKI was observed in patients with preoperative statin duration of 7 ∼ 14 days (OR (95%CI): 0.41 (0.25, 0.65)) and over 14 days (OR (95%CI): 0.43 (0.28, 0.65)), but not in those with preoperative statin duration of <7 days. Similar favorable effects were noted in most subgroup patients, except for those with high-risk factors such as diabetes mellitus, previous congestive cardiac failure, arrhythmia, preoperative ACEI/ARB, aortic cross-clamping or IABP. CONCLUSION: Preoperative moderate-dose statin was significantly related to a decreased risk of postoperative AKI, especially in patients who received statins for a longer duration. Further large-scale multicenter randomized controlled trials are needed to ascertain the impact of statin dose, duration, and timing on postoperative AKI in cardiac surgery patients.