Targeting Macrophage Phenotypes and Metabolism as Novel Therapeutic Approaches in Atherosclerosis and Related Cardiovascular Diseases.

PURPOSE OF THE REVIEW: Macrophage accumulation and activation function as hallmarks of atherosclerosis and have complex and intricate dynamics throughout all components and stages of atherosclerotic plaques. In this review, we focus on the regulatory roles and underlying mechanisms of macrophage phenotypes and metabolism in atherosclerosis. We highlight the diverse range of macrophage phenotypes present in atherosclerosis and their potential roles in progression and regression of atherosclerotic plaque. Furthermore, we discuss the challenges and opportunities in developing therapeutic strategies for preventing and treating atherosclerotic cardiovascular disease. RECENT FINDINGS: Dysregulation of macrophage polarization between the proinflammatory M1 and anti-inflammatory M2 phenotypealters the immuno-inflammatory response during atherosclerosis progression, leading to plaque initiation, growth, and ultimately rupture. Altered metabolism of macrophage is a key feature for their function and the subsequent progression of atherosclerotic cardiovascular disease. The immunometabolism of macrophage has been implicated to macrophage activation and metabolic rewiring of macrophages within atherosclerotic lesions, thereby shifting altered macrophage immune-effector and tissue-reparative function. Targeting macrophage phenotypes and metabolism are potential therapeutic strategies in the prevention and treatment of atherosclerosis and atherosclerotic cardiovascular diseases. Understanding the precise function and metabolism of specific macrophage subsets and their contributions to the composition and growth of atherosclerotic plaques could reveal novel strategies to delay or halt development of atherosclerotic cardiovascular diseases and their associated pathophysiological consequences. Identifying biological stimuli capable of modulating macrophage phenotypes and metabolism may lead to the development of innovative therapeutic approaches for treating patients with atherosclerosis and coronary artery diseases.

Nomograms Based on Non-High-Density Lipoprotein to Predict Outcomes in Patients with Prior Coronary Artery Bypass Grafting with Acute Coronary Syndrome: A Single-Center Retrospective Study.

Introduction: Non-high-density-lipoprotein cholesterol (non-HDL-C) is a secondary therapeutic target in cardiovascular diseases and is used for residual risk assessment in patients with coronary artery syndrome (ACS). This study was designed to determine the association between non-HDL-C in patients with prior coronary artery bypass graft (CABG) with ACS and clinical outcomes. Methods: We retrospectively analyzed 468 patients with prior CABG with ACS and categorized them into two groups based on the median non-HDL-C level. The primary endpoints were major adverse cardiovascular events (MACEs), including cardiovascular death and recurrent myocardial infarction. Kaplan-Meier curves, Cox proportional-hazard regressions, and restricted cubic splines were used to determine the association between non-HDL-C and MACEs. The discrimination and reclassification of the nomogram based on non-HDL-C were assessed using time-dependent receiver operating characteristic (ROC) curves and net reclassification improvement (NRI). Results: During the average follow-up time of 744.5 days, non-HDL-C was independently associated with the occurrence of MACEs (hazard ratio [HR] = 5.01, 95% confidence interval [CI] = 1.65-15.24; p = 0.005) after adjusting for other lipid parameters. The spline curves indicated a linear relationship between non-HDL-C and MACEs (p-nonlinear: 0.863). The time-dependent areas under the ROC curves of prior-CABG-ACS nomograms containing non-HDL regarding MACEs in two consecutive years were 91.7 (95% CI: 85.5-97.9) and 91.5 (95% CI: 87.3-95.7), respectively. The NRI analysis indicated that the prior-CABG-ACS model improved the reclassification ability for 1- and 2-year MACEs (22.4% and 7%, p < 0.05, respectively). Discussion: Non-HDL is independently associated with the risk of MACEs in patients with prior CABG with ACS. The prior-CABG-ACS nomogram based on non-HDL-C and five convenient variables generates valid and stable predictions of MACE occurrence.

A New Predictive Model for In-Hospital Major Adverse Cardiac and Cerebrovascular Events in Chinese Patients After Major Noncardiac Surgery.

Prediction tools focused on cardiovascular and cerebrovascular events after noncardiac surgery are lacking, particularly for Chinese patients. We developed and validated what we believe is a new predictive tool for postoperative major cardiovascular and cerebrovascular events (MACCEs) in Chinese patients in this study. Overall, 401 variables derived from 598 patients who received noncardiac surgery at our center were retrospectively analyzed to develop and validate the new predictive model for MACCEs during hospitalization. The 7 strongest predictors for MACCEs in the development cohort were chronic heart failure, age, atrial fibrillation, general anesthesia, history of coronary heart disease, high-risk procedures, and lymphocyte count. The area under the receiver operating characteristic curve was 0.698 (95% confidence interval 0.616 to 0.780) for the new predictive tool with the validation cohort. Receiver operating characteristic curve analysis showed the new predictive tool had better performance than the Revised Cardiac Risk Index and the American College of Surgeons National Surgical Quality Improvement Program scores. This new predictive tool is effective for the prediction of postoperative MACCEs in patients who undergo noncardiac surgery.

Discordance of Circulating Non-HDL Cholesterol with LDL Cholesterol Concerning Long-Term Prognosis in Statin-Treated Individuals with Acute Coronary Syndrome and Previous Coronary Artery Bypass Grafting Undergoing Percutaneous Coronary Intervention.

Background: Some individuals who maintain desirable low-density lipoprotein cholesterol (LDL-C) levels still experience the progression of atherosclerosis, which may eventually lead to cardiovascular events. Non-high-density lipoprotein cholesterol (non-HDL-C) levels are quantified to assess residual risk in statin-treated patients with coronary heart disease. The study aimed to estimate the predictive performance of discordance between non-HDL-C and LDL-C on clinical prognosis in statin-treated patients with previous coronary artery bypass grafting (CABG). Methods: 468 statin-treated patients with previous CABG undergoing percutaneous coronary intervention (PCI) as a secondary coronary treatment due to acute coronary syndrome (ACS) were retrospectively enrolled in this study. The definition of major adverse cardiovascular events (MACEs) was a composite endpoint of cardiovascular death, recurring myocardial infarction, and a need for repeat revascularization. Cox proportional hazards modeling, restricted cubic splines regression, and discordance analysis were conducted to the association between all lipid parameters and the occurrence of MACEs. Discordant values were defined as LDL-C concentrations ≤ 1.8 mmol/L accompanied by non-HDL-C > 2.6 mmol/L. Results: MACEs occurred in 95 patients over a median follow-up period of 744.5 days. Cox models demonstrated that increased concentrations of non-HDL-C and LDL-C levels were independent risk indicators of MACEs (p < 0.001). The restricted cubic spline analysis revealed a linear relationship between non-HDL-C concentrations and MACEs (p-nonlinear: 0.26), whereas a nonlinear relationship was observed between LDL-C concentrations and MACEs (p < 0.01). In the subgroup analysis, the spline curves revealed that the odds of the individuals with desirable LDL-C levels suffering MACEs emerged when non-HDL-C levels were above 2.07 mmol/L. Individuals who exhibited discordance involving high non-HDL-C/low LDL-C levels had an elevated risk of experiencing MACEs compared to those with concordantly low LDL-C and low non-HDL-C levels [hazard ratios (HRs) = 2.44, 95% confidence interval (CI) = 1.14-5.22, p = 0.02]. Conclusions: Non-HDL-C levels could predict the residual risk of MACEs in ACS patients with previous CABG and statin therapy that underwent percutaneous coronary intervention. A discordance between non-HDL-C and LDL-C in individuals with desirable LDL-C levels could be useful in identifying those with a residual risk of cardiovascular complications.

Non-Traditional Risk Factors as Contributors to Cardiovascular Disease.

Cardiovascular disease (CVD) remains one of the primary causes of morbidity and mortality worldwide. Classic cardiovascular risk factors, such as hypertension, diabetes mellitus (DM), hyperlipidemia, and smoking, have been well identified and given increased attention in clinical practice. However, the incidence and prevalence of CVD remains high, especially in developing countries. Therefore, there has been more attention to non-traditional CVD risk factors such as gut microbiota, sleep disorders, dietary structure, and psychosocial factors in their important roles in the development of CVD. In this review we summarize the association of non-traditional risk factors with CVD with the aim of further reducing the risk of CVD.

Prediction of SYNTAX score II improvement by adding temporal heart rate changes between discharge and first outpatient visit in patients with acute myocardial infarction.

BACKGROUND: The prognostic ability of the temporal changes in resting heart rate (ΔHR) in patients with acute myocardial infarction (AMI) for cardiovascular (CV) mortality and clinical outcomes is rarely examined. This study investigated the predictive value of ΔHR using models with SYNTAX score II (SxS-II) for the long-term prognosis of patients with AMI. METHODS: Six hundred five AMI patients with vital signs recorded at the first outpatient visit (2-4 weeks after discharge) were retrospectively recruited into this study. The changes between discharge and outpatient resting heart rate (D-O ΔHR) were calculated by subtracting the HR at the first post-discharge visit from the value recorded at discharge. The major adverse cardiovascular and cerebrovascular events (MACCE) include cardiovascular death, recurrent myocardial infarction, revascularization, and nonfatal stroke. The predictive values and reclassification ability of the different models were assessed using a likelihood ratio test, Akaike's information criteria (AIC), receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: During the follow-up period, a drop-in resting heart rate (RHR) from discharge to first outpatient visit was independently associated with less risk of CV mortality [D-O ΔHR: hazards ratio (HR) = 0.97, 95% CI = 0.96-0.99, P < 0.001] and MACCE (HR = 0.98, 95% CI = 0.97-0.99, p = 0.001). The likelihood test indicated that the combined model of SxS-II and D-O ΔHR yielded the lowest AIC for CV mortality and MACCE (P < 0.001). Moreover, D-O ΔHR alone significantly improved the net reclassification and integrated discrimination of the models containing SxS-II for CV mortality and MACCE (CV mortality: NRI = 0.5600, P = 0.001 and IDI = 0.0759, P = 0.03; MACCE: NRI = 0.2231, P < 0.05 and IDI = 0.0107, P < 0.05). CONCLUSIONS: The change in D-O ΔHR was an independent predictor of long-term CV mortality and MACCE. The D-O ΔHR combined with SxS-II could significantly improve its predictive probability.

The Impact of Cardiac Dysfunction Based on Killip Classification on Gastrointestinal Bleeding in Acute Myocardial Infarction.

Background: Owing to limited data, the effect of cardiac dysfunction categorized according to the Killip classification on gastrointestinal bleeding (GIB) in patients with acute myocardial infarction (AMI) is unclear. The present study aimed to investigate the impact of cardiac dysfunction on GIB in patients with AMI and to determine if patients in the higher Killip classes are more prone to it. Methods: This retrospective study was comprised of patients with AMI who were admitted to the cardiac intensive care unit in the Heart Center of the Beijing Chaoyang Hospital between December 2010 and June 2019. The in-hospital clinical data of the patients were collected. Both GIB and cardiac function, according to the Killip classification system, were confirmed using the discharge diagnosis of the International Classification of Diseases, Tenth Revision coding system. Univariate and multivariate conditional logistic regression models were constructed to test the association between GIB and the four Killip cardiac function classes. Results: In total, 6,458 patients with AMI were analyzed, and GIB was diagnosed in 131 patients (2.03%). The multivariate logistic regression analysis showed that the risk of GIB was significantly correlated with the cardiac dysfunction [compared with the Killip class 1, Killip class 2's odds ratio (OR) = 1.15, 95% confidence interval (CI): 0.73-1.08; Killip class 3's OR = 2.63, 95% CI: 1.44-4.81; and Killip class 4's OR = 4.33, 95% CI: 2.34-8.06]. Conclusion: This study demonstrates that the degree of cardiac dysfunction in patients with acute myocardial infarction is closely linked with GIB. The higher Killip classes are associated with an increased risk of developing GIB.

One-Stop Hybrid Coronary Revascularization Versus Off-Pump Coronary Artery Bypass Grafting.

One-stop hybrid coronary revascularization (HCR) is a promising revascularization strategy for treating multivessel coronary artery disease (MVCAD). However, its safety and feasibility remain controversial. Therefore, we introduced our experience with midterm follow-up of HCR in patients with MVCAD and compared it with conventional off-pump coronary artery bypass grafting (CABG).Patients with MVCAD undergoing one-stop HCR at Beijing Chaoyang Hospital between March 2018 and December 2020 were retrospectively enrolled. These patients were matched in a 1:2 ratio to patients treated with off-pump CABG at the same period via a propensity score analysis with the nearest neighbor matching algorithm.In the adjusted analysis, no significant difference was found in the rate of perioperative myocardial infarction, stroke, death, prolonged ventilation, reoperation for bleeding, and renal failure between the HCR group and the CABG group. No in-hospital repeated revascularization occurred in either group. HCR was associated with lower blood transfusion rate (HCR 11.0% versus CABG 22.8%; P = 0.006) and shorter postoperative length of stay (> 10 days: 31.5% versus 81.0%; P < 0.001) compared with CABG. After the median 21-month follow-up, no significant difference was found in the major adverse cardiac and cerebrovascular events (MACCE), death, myocardial infarction, repeated revascularization, and stroke rate. Besides, the freedom-from MACCE survival rate was similar between the two groups.One-stop HCR seemed to be a safe and feasible revascularization strategy in patients with MVCAD, with faster recovery and similar outcomes when compared with off-pump CABG.

A Nomogram for Predicting In-Hospital Major Adverse Cardio- and Cerebro-Vascular Events in Patients Undergoing Major Noncardiac Surgery: A Large-Scale Nested Case-Control Study.

Purpose: Few evidence-based predictive tools are available to evaluate major adverse cardio- and cerebro-vascular events (MACCEs) before major noncardiac surgery. We sought to develop a new simple but effective tool for estimating surgical risk. Patients and Methods: Using a nested case-control study design, we recruited 105 patients who experienced MACCEs and 481 patients without MACCEs during hospitalization from 10,507 patients undergoing major noncardiac surgery in Beijing Chaoyang hospital. Least absolute shrinkage and selection operator (LASSO) regression and likelihood ratio were applied to screen 401 potential features for logistic regression. A nomogram was constructed using the selected variables. Results: Chronic heart failure, valvular heart disease, preoperative serum creatinine >2.0 mg/dL, ASA class, neutrophil count and age were most associated with in-hospital MACCEs among all the factors. A new prediction model established based on these showed a good discriminatory ability (AUC, 0.758 [95% confidence interval (CI), 0.708-0.808] and a well-performed calibration curve (Hosmer-Lemeshow χ2 = 7.549, p = 0.479), which upheld in the 10-fold cross-validation (AUC, 0.742 [95% CI, 0.718-0.767]. This model also demonstrated an improved performance in comparison to the modified Revised Cardiac Risk Index (RCRI) score (increase in AUC by 0.119 [95% CI, 0.056-0.180]; NRI, 0.445 [95% CI, 0.237-0.653]; IDI, 0.133 [95% CI, 0.087-0.178]. The decision curve analysis showed a positive net benefit of our new model. Conclusion: Our nomogram, which relies upon simple clinical characteristics and laboratory tests, is able to predict MACCEs in patients undergoing major noncardiac surgery. This prediction shows better discrimination than the standardized modified RCRI score, laying a promising foundation for further large-scale validation.

Feasibility and Safety of Drug-Coated Balloon-Only Angioplasty for De Novo Ostial Lesions of the Left Anterior Descending Artery: Two-Center Retrospective Study.

Introduction: There is limited evidence regarding the effectiveness of drug-coated balloon (DCB) angioplasty in the percutaneous treatment of complex de novo ostial coronary lesions. This study primarily aimed to explore the feasibility and safety of this innovative approach for ostial lesions in the left anterior descending artery (LAD). Methods: Patients treated with paclitaxel DCB or second-generation drug-eluting stents (DES) were retrospectively enrolled from two large centers. The primary endpoints were major adverse cardiovascular events (MACE), including cardiovascular death, target lesion revascularization (TLR), target vessel revascularization, and recurrent myocardial infarction related to target artery occlusion. Cox regression analysis was used to identify risk factors for MACE, and propensity score matching was performed to minimize selection bias. Results: A total of 388 patients were included; among them, 52 were treated with paclitaxel DCB, and 336 with DES for ostial LAD lesions. Using propensity score matching, 49 patients were treated with DCB-only and 49 with the DES strategy. The average follow-up time was 12 months; subsequently, a non-significant decrease in MACE rate was observed in the DCB-only angioplasty treatment group (MACE: 6 vs. 6%, p = 1.0; TLR: 2 vs. 4%, p = 0.56). Cox regression analysis indicated that DCB-only angioplasty was not an independent risk factor for adverse events after adjusting for confounding risk factors (hazard ratio: 1.713, p = 0.43). Conclusion: The use of the DCB-only approach is an innovative and optional strategy in the treatment of isolated ostial LAD disease. A further randomized trial is of necessity to confirm the feasibility and safety of drug-coated balloon-only angioplasty for LAD de novo ostial lesions.

Adeno-associated virus-mediated in vivo suppression of expression of EPHX2 gene modulates the activity of paraventricular nucleus neurons in spontaneously hypertensive rats.

BACKGROUND: Hypertension can be attributed to increased sympathetic activities. Presympathetic neurons in the paraventricular nucleus (PVN) of the hypothalamus are capable of modulating sympathetic outflow, thus contributing to the pathogenesis of neurogenic hypertension. Epoxyeicosatrienoic acids (EETs) were reported to have anti-hypertensive effects, which could be degraded by soluble epoxide hydrolase (sEH), encoded by EPHX2. However, the potential effect of EETs on PVN neuron activity and the underlying molecular mechanism are largely unknown. METHODS: Knockdown of EPHX2 in spontaneously hypertensive rats (SHRs) was achieved by tail-intravenous injection of AAV plasmid containing shRNA targeting EPHX2. Whole-cell patch clamp was used to record action potentials of PVN neurons. An LC-MS/MS System was employed to determine 14,15-EET levels in rat cerebrospinal fluid. qPCR and western blotting were applied to examine the expression level of EPHX2 in various tissues. ELISA and immunofluorescence staining were applied to examine the levels of ATP, D-serine and glial fibrillary acidic protein (GFAP) in isolated astrocytes. RESULTS: The expression level of EPHX2 was higher, while the level of 14,15-EET was lower in SHRs than normotensive Wistar-Kyoto rats (WKY) rats. The spike firing frequency of PNV neurons in SHRs was higher than in WKY rats at a given stimulus current, which could be reduced by either EPHX2 downregulation or 14,15-EET administration. In isolated hypothalamic astrocytes, the elevated intracellular ATP or D-serine induced by Angiotensin II (Ang II) treatment could be rescued by 14,15-EET addition or 14,15-EET combing serine racemase (SR) downregulation by siRNA, respectively. Furthermore, 14,15-EET treatment reduced the Ang II-induced elevation of GFAP immunofluorescence. CONCLUSIONS: The elevation of EET levels by EPHX2 downregulation reduced presympathetic neuronal activity in the PVN of SHRs, leading to a reduced sympathetic outflow in hypertension rats. The ATP/SR/D-serine pathway of astrocytes is involved in EET-mediated neuroprotection.

First post-discharge heart rate and long-term prognosis in patients with acute myocardial infarction.

BACKGROUND: Elevated heart rate (HR) is associated with cardiovascular mortality and other events associated with acute myocardial infarction (AMI). The heart rate after discharge is likely superior to reflect the deteriorating heart function, which negatively responds to normal physical activity. This study aimed to explore the effect of HR at the first outpatient visit on clinical outcomes. METHODS: We retrospectively identified 605 patients with AMI. HRs at admission, discharge, and first outpatient visits were measured. The primary endpoint was defined as major adverse cardiovascular events (MACEs), including cardiovascular (CV) death, readmission for worsening heart failure, recurrent nonfatal myocardial infarction (MI), repeated coronary revascularization, and ischemic stroke. RESULTS: During the follow-up period, 145 cases of MACE occurred, including 34 CV deaths, 31 recurrent MI, 89 revascularizations, 41 heart failures, and 4 strokes. The event group displayed an elevated HR at the first outpatient visit compared to the event-free group (p < 0.001). After adjustment for confounding risk factors, Cox models showed that the outpatient HR had the best correlation with MACE [Hazard ratio (HR) = 1.33, 95% confidence interval (CI) = 10.8-59.3, p < 0.01 for increments of 1 standard deviation (SD) in the outpatient HR) and CV mortality (HR = 1.18, 95% CI = 1.052-1.325, p < 0.01) compared with the other two HRs. The restricted spline model indicated that HR at the first post-discharge above 71 bpm was associated with CV mortality. CONCLUSIONS: Elevated HR at the first outpatient visit over a period of 2-4 weeks is related to the adverse outcomes of AMI and may identify AMI patients at higher risk of CV mortality.

Effect of ApoE ε4 gene polymorphism on the correlation between serum uric acid and left ventricular hypertrophy remodeling in patients with coronary heart disease.

Background: Hyperuricemia and dyslipidemia are associated with left ventricular hypertrophy (LVH), while the effect of ApoE gene polymorphism on the correlation between serum uric acid (UA) level and severity of LVH in patients with coronary heart disease (CHD) has not been clarified. Methods: This was a retrospective observational study of patients with CHD. Patients were divided into groups of ε4 carriers and non-ε4 carriers based on sanger sequencing. The association of ApoE ε4 gene polymorphism, serum UA level, and LVH, determined by cardiac color Doppler ultrasound, was evaluated by multivariate analysis. Results: A total of 989 CHD patients who underwent ApoE genotyping were enrolled and analyzed. Among them, the frequency of the ApoE ε4 genotype was 17.9% (15.7% for E3/4, 1.1% for E4/4, and 1.1% for E2/4). There were 159 patients with LVH, 262 with end-diastolic LV internal diameter (LVEDD) enlargement, 160 with left ventricular ejection fraction (LVEF) reduction, and 154 with heart failure. Multivariate analysis showed that for every increase of 10 µmol/L in serum UA level, the risk of LVH decreased in ε4 carriers (odds ratio (OR) = 0.94, 95% confidence interval (CI): 0.890-0.992, P = 0.025) and increased in non-ε4 carriers (OR = 1.03, 95% CI: 1.005-1.049, P = 0.016). The risk of LVEDD enlargement tended to decrease in ε4 carriers (OR = 0.98, 95% CI: 0.943-1.023, P = 0.391) and increased in non-ε4 carriers (OR = 1.03, 95% CI: 1.009-1.048, P = 0.003). The risk of LVEF reduction was reduced in ε4 carriers (OR = 0.996, 95% CI: 0.949-1.046, P = 0.872) and increased in non-ε4 carriers (OR = 1.02, 95% CI: 0.994-1.037, P = 0.17). The risk of LVEDD enlargement decreased in ε4 carriers (OR = 0.98, 95% CI: 0.931-1.036, P = 0.508) and increased in non-ε4 carriers (OR = 1.02, 95% CI: 0.998-1.042, P = 0.07). Conclusion: High serum UA levels decreased the risk of LVH in ApoE ε4 carriers with CHD, while increased the risk of LVH in non-ε4 carriers.

Age differences in the association between marital status and hypertension: a population-based study.

The findings on the relationship between marital status and hypertension are inconsistent. We aimed to explore age differences in their associations. We used Hainan Hypertension Survey data, including 13,088 individuals aged more than 25 years, as part of the China Hypertension Survey study, a population-based nationwide study. The marital status was classified as following three groups: the unmarried, the married, and those who formerly lived with his/her spouse. We examined the association between marital status and blood pressure levels and the odds of hypertension across different ages and sex. The participants' mean age was 49.9 ± 17 years, 49% were male, and 23% experienced hypertension. The multivariable logistic regression model showed among younger (<40 years) and older (≥60 years) participants, the married subjects appeared to have higher odds of hypertension compared with the unmarried counterparts, particular for men (Pheterogeneity = 0.039), after adjustment for age, sex, smoking, drinking, education background, employment situation, and body mass index. Compared with the unmarried and the married people, younger persons who previously had partners had a higher OR of hypertension than the older counterparts, and the ORs tended to decline with age (All Ptrend ≤ 0.005). The associations between marital status and blood pressure levels from multivariable linear regression models seemed consistent with the relationships mentioned above from logistic regression models. Our study indicates a marital status change is associated with a higher odds of hypertension, and it appears to be more obvious in young people.

Nomogram for Risk Prediction of Mortality for Patients with Critical Cardiovascular Disease Treated by Continuous Renal Replacement Therapy in Coronary Care Unit.

Aims: To establish a nomogram-scoring model for evaluating the risk of death in patients with critical cardiovascular disease after continuous renal replacement therapy (CRRT) in a coronary care unit (CCU). Methods: This retrospective cohort study included data collected on 172 patients, in whom CRRT was initiated in the CCU between January 2017 and June 2021. Predictors of mortality were selected using an adaptive least absolute shrinkage and selection operator logistic model and used to construct a nomogram. The nomogram was evaluated using the concordance index (C-index) and Hosmer-Lemeshow test. Results: The number of patients who died in-hospital after CRRT was 91 (52.9%). The results of the multivariate logistic regression analyses clarified that age, history of hypertension and/or coronary artery bypass grafting, a diagnosis of unstable angina pectoris or acute myocardial infarction, ejection fraction, systolic blood pressure, creatinine, neutrophil, and platelet counts before CRRT initiation were significant predictors of early mortality in patients treated with CRRT. The nomogram constructed on these predictors demonstrated significant discriminative power with an unadjusted C-index of 0.902 (95% CI: 0.858-0.945) and a bootstrap-corrected C-index of 0.875. Visual inspection showed a good agreement between actual and predicted probabilities (Hosmer-Lemeshow χ 2 = 5.032, p-value = 0.754). Conclusions: Our nomogram based on nine readily available predictors is a reliable and convenient tool for identifying critical patients undergoing CRRT at risk of mortality in the CCU.

Fração de Ejeção do Ventrículo Esquerdo Aumentada, Diminuída ou Estável ao Longo do Tempo em uma Série de 626 Pacientes com Insuficiência Cardíaca que Receberam Tratamento Médico / Increased, Decreased, or Stable Left Ventricle Ejection Fraction over Time in a Series of 626 Heart Failure Patients Receiving Medical Treatment

Resumo Fundamento: A fração de ejeção (FE) tem sido utilizada em análises fenotípicas e na tomada de decisões sobre o tratamento de insuficiência cardíaca (IC). Assim, a FE tornou-se parte fundamental da prática clínica diária. Objetivo: Este estudo tem como objetivo investigar características, preditores e desfechos associados a alterações da FE em pacientes com diferentes tipos de IC grave. Métodos: Foram incluídos neste estudo 626 pacientes com IC grave e classe III-IV da New York Heart Association (NYHA). Os pacientes foram classificados em três grupos de acordo com as alterações da FE, ou seja, FE aumentada (FE-A), definida como aumento da FE ≥10%, FE diminuída (FE-D), definida como diminuição da FE ≥10%, e FE estável (FE-E), definida como alteração da FE <10%. Valores p inferiores a 0,05 foram considerados significativos. Resultados: Dos 377 pacientes com IC grave, 23,3% apresentaram FE-A, 59,5% apresentaram FE-E e 17,2% apresentaram FE-D. Os resultados mostraram ainda 68,2% de insuficiência cardíaca com fração de ejeção reduzida (ICFEr) no grupo FE-A e 64,6% de insuficiência cardíaca com fração de ejeção preservada (ICFEp) no grupo FE-D. Os preditores de FE-A identificados foram faixa etária mais jovem, ausência de diabetes e fração de ejeção do ventrículo esquerdo (FEVE) menor. Já os preditores de FE-D encontrados foram ausência de fibrilação atrial, baixos níveis de ácido úrico e maior FEVE. Em um seguimento mediano de 40 meses, 44,8% dos pacientes foram vítimas de morte por todas as causas. Conclusão: Na IC grave, a ICFEr apresentou maior percentual no grupo FE-A e a ICFEp foi mais comum no grupo FE-D.

Abstract Background: Ejection fraction (EF) has been used in phenotype analyses and to make treatment decisions regarding heart failure (HF). Thus, EF has become a fundamental part of daily clinical practice. Objective: This study aims to investigate the characteristics, predictors, and outcomes associated with EF changes in patients with different types of severe HF. Methods: A total of 626 severe HF patients with New York Heart Association (NYHA) class III-IV were enrolled in this study. The patients were classified into three groups according to EF changes, namely, increased EF (EF-I), defined as an EF increase ≥10%, decreased EF (EF-D), defined as an EF decrease ≥10%, and stable EF (EF-S), defined as an EF change <10%. A p-value lower than 0.05 was considered significant. Results: Out of 377 severe HF patients, 23.3% presented EF-I, 59.5% presented EF-S, and 17.2% presented EF-D. The results further showed 68.2% of heart failure with reduced ejection fraction (HFrEF) in the EF-I group and 64.6% of heart failure with preserved ejection fraction (HFpEF) in the EF-D group. The predictors of EF-I included younger age, absence of diabetes, and lower left ventricular ejection fraction (LVEF). The predictors of EF-D were absence of atrial fibrillation, lower uric acid level, and higher LVEF. Within a median follow-up of 40 months, 44.8% of patients suffered from all-cause death. Conclusion: In severe HF, HFrEF presented the highest percentage in the EF-I group, and HFpEF was most common in the EF-D group.

Predictive value of ACEF II score in patients with multi-vessel coronary artery disease undergoing one-stop hybrid coronary revascularization.

BACKGROUND: We aimed to investigate the predictive value of recently updated ACEF II score on major adverse cardiac and cerebrovascular events (MACCE) in patients with multi-vessel coronary artery disease (MVCAD) undergoing one-stop hybrid coronary revascularization (HCR). METHODS: Patients with MVCAD undergoing one-stop HCR were retrospectively recruited from March 2018 to September 2020. Several prediction risk models, including ACEF II score, were calculated for each patient. Kaplan-Meier curve was used to evaluate freedom from cardiac death and MACCE survival rates. Differences of prediction performance among risk scores for predicting MACCE were compared by receiver operating characteristic (ROC) curve. RESULTS: According to the ACEF II score, a total of 120 patients undergoing one-stop HCR were assigned to low-score group (80 cases) and high-score group (40 cases). During the median follow-up time of 18 months, the incidence of MACCE in the low-score group and high-score group were 8.8 % and 37.5 %, respectively (p < 0.001); and the cardiac death rate of the two were 2.5% and 12.5%, respectively (p < 0.05). Moreover, the cumulative freedom from cardiac death (97.5% vs. 86.8, p < 0.05) and MACCE (75.2% vs. 52.8%, p < 0.001) survival rates in the high-score group were significantly lower than in the low-score group. According to the Cox proportional hazards regression, the ACEF II score was an independent prognostic indicator for MACCE with hazards ratio (HR) 2.24, p = 0.003. The ROC curve analysis indicated that the areas under the curve (AUC) of MACCE from the ACEF II score was 0.740 (p < 0.001), while the AUC of MACCE from the SYNTAX score II CABG was 0.621 (p = 0.070) and the AUC from the EuroSCORE II was 0.703 (p < 0.001). Thus, the accurate predictive value of ACEF II score was similar to the EuroSCORE II but much higher than the SYNTAX score II CABG. CONCLUSIONS: The updated ACEF II score is a more convenient and validated prediction tool for MACCE in patients with MVCAD undergoing one-stop HCR comparing to other risk models.

Altered synthesis of genes associated with short-chain fatty acids in the gut of patients with atrial fibrillation.

BACKGROUND: The gut microbiota provides health benefits in humans by producing short-chain fatty acids (SCFAs), whose deficiency causes multiple disorders and inflammatory diseases. However, gut bacteria producing SCFAs in patients with atrial fibrillation (AF), an arrhythmia with increasing prevalence, have not been reported. To investigate major gut microbial organisms related to SCFA synthesis, SCFAs-associated KEGG orthologues (KOs), enzymatic genes, and potential producers were examined according to metagenomic data-mining in a northern Chinese cohort comprising 50 non-AF control and 50 AF patients. RESULTS: Compared with non-AF controls, individuals with AF had marked differences in microbial genes involved in SCFA-related synthesis, including 125 KOs and 5 SCFAs-related enzymatic genes. Furthermore, there were 10 species that harbored SCFA-synthesis related enzymatic genes, and were markedly decreased in the gut of AF patients. Notably, discriminative features about SCFA-synthesis related function, including 8 KOs (K01752, K01738, K00175, K03737, K01006, K01653, K01647 and K15023), 4 genes (menI, tesB, yciA and CO dehydrogenase acetyl-CoA synthase complex) and 2 species (Coprococcus catus and Firmicutes bacterium CAG:103), were selected as key factors based on LASSO analysis. Furthermore, PLS-SEM analysis showed that 72.8 and 91.14 % of the overall effects on gut microbiota diversity and key species on AF, respectively, were mediated by the key KOs. Meanwhile, 46.31 % of the total effects of SCFA-synthesis related function on left atrial enlargement was mediated by hsCRP. Upon incorporation of clinical properties in AF, the KO score was still significantly associated with AF incidence (OR = 0.004, P = 0.001). CONCLUSIONS: The current study revealed that dysbiotic gut microbiota in AF is coupled with disrupted SCFA-synthesis related genes, characterized by decreased abundances of KEGG orthologues, synthesis enzymatic genes and harboring species.

Changes in clinical biochemical indexes of patients with heart failure with preserved ejection fraction or patients with hypertensive heart disease before and after treadmill exercise.

BACKGROUND: The incidence of hypertension is continuously increasing. This study aimed to investigate the changes in clinical biochemical indexes of patients with heart failure with preserved ejection fraction (HFpEF), or patients with hypertensive heart disease (HHD) before and after treadmill exercise. METHODS: Seventy-eight patients with HFpEF and 78 patients with HHD who were admitted to our hospital between February 2020 and February 2021 were selected to take a treadmill exercise test. All patients continued to exercise for 1 month. Clinical biochemical indexes [hemoglobin A1c (HbA1c), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), total cholesterol (TC), N-segment pro-brain natriuretic peptide (NT-proBNP), and cardiac troponin I (cTnI)] were measured before and after the treadmill exercise test and compared between the two groups. Receiver operating characteristic (ROC) curves were drawn to analyze the optimal cutoff values of the clinical biochemical indexes in the diagnosis of HFpEF. The positive diagnostic rates of the biochemical indicators for HFpEF before and after treadmill exercise were compared using the optimal cut-off value of ROC as the positive standard. RESULTS: Before exercise, there was no significant difference in HbA1c, LDL-C, HDL-C, or TC between the two groups (P>0.05), but NT-proBNP and cTnI were significantly higher in the HFpEF group than in the HHD group (P<0.05). ROC curve analysis showed that before exercise, the best cutoff values for plasma NT-proBNP and cTnI in the diagnosis of HFpEF were 2,248.24 pg/mL and 1.14 ng/mL, respectively. After exercise, no significant difference was found in HbA1c, LDL-C, HDL-C, or TC between the two groups (P>0.05). However, the levels of NT-proBNP and cTnI in both groups were higher after exercise, with more significant increases seen in the HFPEF group (P<0.05). The positive rates of plasma NT-proBNP and cTnI in HFpEF group were statistically higher after exercise than before exercise (P<0.05). CONCLUSIONS: The changes in plasma NT-proBNP and cTnI in patient after treadmill exercise can be used as sensitive indicators for the diagnosis and differentiation of HFpEF and HHD.