Punicalagin prevents obesity-related cardiac dysfunction through promoting DNA demethylation in mice

The aim of this study was to investigate whether punicalagin(PU)could prevent obesity-related cardiac dysfunction by promoting DNA demethy lation,and to explore its possible mechanism.C57BL/6J mice were fed with standard diet,high-fat diet(HFD),HFD supplemented with resveratrol,low-dose PU(LPU)and high-dose PU(HPU)for 8 weeks.Compared with HFD group,body weight was significantly lower in PU treatment groups,number of cardionwocytes and the protein level of myosin heavy chain 7B were significantly higher in PU treatment groups.Levels of 5-hydroxymethylcytosine and 5-formylcytosine were significantly lower in HFD group than in other groups.Compared with the HFD group,the protein level of ten-eleven translocation enzyme(TET)2 was significantly higher in PU treatment groups,p-AMP-activated protein kinase(AMPK)was significantly higher in LPU group.Levels of total antioxidant capacity and the protein levels of complexesⅡ/Ⅲ/Ⅴ,oxoglutarate dehydrogenase,succinate dehydrogenase B and fumarate hdrolase were significantly lower in HFD group than PU treatment group.The ratio of(succinic acid+fumaric acid)/a-ketoglutarate was significantly higher in HFD group than other groups.In conclusion,PU up-regulated TETs enzyme activities and TET2 protein stability through alleviating mitochondrial dysfunction and activating AMPK,so as to promote DNA demethylation,thus preventing obesity-related cardiac dysfunction.

Protective and therapeutic potentials of Dunaliella salina on aging-associated cardiac dysfunction in rats

Objective: To investigate the possible protective and/or therapeutic potentials of Dunaliella salina(D. salina) biomass, its carotenoid and polar fractions on cardiac dysfunction associated with D-galactose(D-GAL) induced aging in rats. Methods: Aging associated cardiac dysfunction was induced in rats by injection of D-GAL(200 mg/kg; i.p) for 8 weeks. D-GAL injected rats were treated with two regimens; protective regimen where D. salina biomass(250 mg/kg), its carotenoid(250 μg/kg) and polar(250 μg/kg) fractions were given orally for two weeks concurrently with D-GAL injection as well as treatment regimen where the three treatments were given orally for 28 consecutive days after D-GAL injection. Results: D-GAL injection for 8 weeks was accompanied with dramatic electrocardiographic changes as well as profound elevation in serum levels of homocysteine, creatinine kinase isoenzyme and lactate dehydrogenase in addition to the reduction of the cardiac content of glucose trasporter 4. D-GAL also induced reduction in cardiac superoxide dismutase activity and elevation of inducible nitric oxide synthetase and interleukin-6. On the other hand, oral administration of D. salina carotenoid fraction as well as the total biomass significantly attenuated the D-GAL-induced disturbances in the above mentioned parameters where the protective regimen appeared more successful in controlling the manifestations of cardiac dysfunction. The histopathological examination further emphasized the promising results. Besides, the HPLC analysis of the carotenoid fraction of D. salina revealed the presence of 2.31%. salina carotenoid fraction as well as the total biomass amelior β-carotene. Conclusions: Date D-GAL-induced aging associated cardiac dysfunction which is attributed to the potent antioxidant activity of β-carotene.

Targeting PPARαin low ambient temperature exposure-induced cardiac dysfunction and remodeling

The present study demonstrates that the down-regulation of peroxisome proliferator-activated receptor-α(PPARα)results in chronic low ambient temperature(LT)exposure-induced cardiac dysfunction and remodeling,emphasizing the therapeutic potential of PPARαactivation strategies(e.g.,fenofibrate treatment)in LT-associated cardiac injury.

COVID-19 vaccination and cardiac dysfunction

The coronavirus disease 2019(COVID-19)mRNA vaccine against severe acute respiratory syndrome coronavirus 2 infections has reduced the number of symptomatic patients globally.A case series of vaccine-related myocarditis or pericarditis has been published with extensive vaccination,most notably in teenagers and young adults.Men seem to be impacted more often,and symptoms commonly occur within 1 wk after immunization.The clinical course is mild in the majority of cases.Based on the evidence,a clinical framework to guide physicians to examine,analyze,identify,and report suspected and confirmed cardiac dysfunction cases is needed.A standardized workup for every patient with strongly suspicious symptoms associated with the COVID-19 mRNA vaccine comprises serum cardiac troponin measurement and a 12-lead electrocardiogram(ECG).For patients with unexplained elevation of cardiac troponin and pathologic ECG,echocardiography is recommended.Consultation with a cardiovascular expert and hospitalization should be considered in this group of patients.Treatment is primarily symptomatic and supportive.Deferring a 2^(nd) dose of the COVID-19 mRNA vaccination in individuals with suspected myocarditis or pericarditis after the 1^(st) dose is suggested until further safety data become available.

Inflammation and cardiac dysfunction during sepsis, muscular dystrophy, and myocarditis

Inflammation plays an important role in cardiac dysfunction under different situations. Acute systemic inflammation occurring in patients with severe burns, trauma, and inflammatory diseases causes cardiac dysfunction, which is one of the leading causes of mortality in these patients. Acute sepsis decreases cardiac contractility and impairs myocardial compliance. Chronic inflammation such as that occurring in Duchenne muscular dystropshy and myocarditis may cause adverse cardiac remodeling including myocyte hypertrophy and death, fibrosis, and altered myocyte function. However, the underlying cellular and molecular mechanisms for inflammatory cardiomyopathy are still controversial probably due to multiple factors involved. Potential mechanisms include the change in circulating blood volume;a direct inhibition of myocyte contractility by cytokines (tumor necrosis factor (TNF)-?, interleukin (IL)-1?);abnormal nitric oxide and reactive oxygen species (ROS) signaling;mitochondrial dysfunction;abnormal excitation-contraction coupling;and reduced calcium sensitivity at the myofibrillar level and blunted ?-adrenergic signaling. This review will summarize recent advances in diagnostic technology, mechanisms, and potential therapeutic strategies for inflammation-induced cardiac dysfunction.

Macrophage-NLRP3 Inflammasome Activation Exacerbates Cardiac Dysfunction after Ischemic Stroke in a Mouse Model of Diabetes

Ischemic stroke is one of the leading causes of death worldwide.In the post-stroke stage,cardiac dysfunction is common and is known as the brain-heart interaction.Diabetes mellitus worsens the post-stroke outcome.Stroke-induced systemic inflammation is the major causative factor for the sequential complications,but the mechanism underlying the brain-heart interaction in diabetes has not been clarified.The NLRP3(NLR pyrin domain-containing 3) inflammasome,an important component of the inflammation after stroke,is mainly activated in M1-polarized macrophages.In this study,we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes.Meanwhile,M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke.Importantly,the NLRP3 inflammasome inhibitor CY-09 restored cardiac function,indicating that the Ml-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.

Effect of impaired glucose tolerance on cardiac dysfunction in a rat model of prediabetes

Background The effect of impaired glucose tolerance （IGT） on cardiac function during the chronic prediabetes state is complicated and plays an important role in clinical outcome. However, the molecular mechanisms are not fully understood. This study was designed to observe cardiac dysfunction in prediabetic rats with IGT and to determine whether glucose metabolic abnormalities, inflammation and apoptosis are linked to it.Methods The IGT rat models were induced by streptozocin, and the heart functions were assessed by echocardiography. Myocardial glucose metabolism was analyzed by glycogen periodic acid-Schiff staining, and the pro-apoptotic effect of IGT was evaluated by TUNEL staining. Additionally, caspase-3 activation, macrophage migration inhibitory factor （MIF） and G-protein coupled receptor kinase 2 （GRK2） were detected by Western blotting in cardiac tissue lysates.Results Area-under-the-curve of blood glucose in rats injected with streptozotocin was higher than that in controls, increased by 16.28%, 38.60% and 38.61% at 2, 4 and 6 weeks respectively （F=15.370, P=0.003）. Abnormal cardiac functions and apoptotic cardiomyocytes were observed in the IGT rats, the ejection fraction （EF） being （68.594-6.62）% in IGT rats vs. （81.07±4.59）% in controls （t=4.020, P=0.002）. There was more glucose which was converted to glycogen in the myocardial tissues of IGT rats, especially in cardiac perivascular tissues. Compared to controls, the cleaved caspase-3, MIF and GRK2 were expressed at higher levels in the myocardial tissues of IGT rats.Conclusions IGT in the prediabetes period resulted in cardiac dysfunction linked to abnormal glycogen storage and apoptosis. Additionally, MIF and GRK2 may be involved in the pathogenesis of cardiac dysfunction in prediabetes and their regulation may contribute to the design of novel diagnostic and therapeutic strategies for those who have potential risks for diabetic cardiovascular complications.

Chronic intermittent hypoxia induces cardiac inflammation and dysfunction in a rat obstructive sleep apnea model

Chronic intermittent hypoxia is considered to play an important role in cardiovascular pathogenesis during the development of obstructive sleep apnea（OSA）.We used a well-described OSA rat model induced with simultaneous intermittent hypoxia.Male Sprague Dawley rats were individually placed into plexiglass chambers with air pressure and components were electronically controlled.The rats were exposed to intermittent hypoxia 8 hours daily for 5weeks.The changes of cardiac structure and function were examined by ultrasound.The cardiac pathology,apoptosis,and fibrosis were analyzed by H＆E staining,TUNNEL assay,and picosirius staining,respectively.The expression of inflammation and fibrosis marker genes was analyzed by quantitative real-time PCR and Western blot.Chronic intermittent hypoxia/low pressure resulted in significant increase of left ventricular internal diameters（LVIDs）,endsystolic volume（ESV）,end-diastolic volume（EDV）,and blood lactate level and marked reduction in ejection fraction and fractional shortening.Chronic intermittent hypoxia increased TUNNEL-positive myocytes,disrupted normal arrangement of cardiac fibers,and increased Sirius stained collagen fibers.The expression levels of hypoxia induced factor（HIF）-l α,NF-κB,IL-6,and matrix metallopeptidase 2（MMP-2） were significantly increased in the heart of rats exposed to chronic intermittent hypoxia.In conclusion,the left ventricular function was adversely affected by chronic intermittent hypoxia,which is associated with increased expression of HIF-lα and NF-κB signaling molecules and development of cardiac inflammation,apoptosis and fibrosis.

Depletion of Kindlin-2 induces cardiac dysfunction in mice

Kindlin-2, a member of the Kindlin family focal adhesion proteins, plays an important role in cardiac development. It is known that defects in the Z-disc proteins lead to hypertrophic cardiomyopathy(HCM) or dilated cardiomyopathy(DCM). Our previous investigation showed that Kindlin-2 is mainly localized at the Z-disc and depletion of Kindlin-2 disrupts the structure of the Z-Disc. Here, we reported that depletion of Kindlin-2 leads to the disordered myocardial fibers, fractured and vacuolar degeneration in myocardial fibers. Interestingly, depletion of Kindlin-2 in mice induced cardiac myocyte hypertrophy and increased the heart weight. Furthermore, decreased expression of Kindlin-2 led to cardiac dysfunction and also markedly impairs systolic function. Our data indicated that Kindlin-2 not only maintains the cardiac structure but also is required for cardiac function.

Outcomes of cardiac surgery in senior aged patients with ventricular dysfunction:analysis of a large national database

OBJECTIVE In patients undergoing cardiac surgery,reduced preoperative ejection fraction(EF)and senior age are associated with a worse outcome.As most outcome data available for these patients are mainly from Western surgical populations involving specific surgery types,our aim is to evaluate the real-world characteristics and perioperative outcomes of surgery in senior-aged heart failure patients with reduced EF across a broad range cardiac surgeries.METHODS Data were obtained from the China Heart Failure Surgery Registry(China-HFSR)database,a nationwide multicenter registry study in China's Mainland.Multiple variable regression analysis was performed in patients over 75 years old to identify risk factors associated with mortality.RESULTS From 2012 to 2017,578 senior-aged(>75 years)patients were enrolled in China HFSR,21.1%of whom were female.Isolated coronary bypass grafting(CABG)were performed in 71.6%of patients,10.1%of patients underwent isolated valve surgery and 8.7%received CABG combined with valve surgery.In-hospital mortality was 10.6%,and the major complication rate was 17.3%.Multivariate analysis identified diabetes mellitus(odds ratio(OR)=1.985),increased creatinine(OR=1.007),New York Heart Association(NYHA)Class III(OR=1.408),NYHA class IV(OR=1.955),cardiogenic shock(OR,6.271),and preoperative intra-aortic balloon pump insertion(OR=3.426)as independent predictors of in-hospital mortality.CONCLUSIONS In senior-aged patients,preoperative evaluation should be carefully performed,and strict management of reversible factors needs more attention.Senior-aged patients commonly have a more severe disease status combined with more frequent comorbidities,which may lead to a high risk in mortality.

Dysfunction of branded-chain amino acids catabolism in rat cardiac allograft

Objective Allograft vasculopathy ( AV) ,feature of chronic rejection,is a major serious long - term post - operation complication in organ transplantation. The accurate mechanisms for AV have not been definitively established,but extensive basic and clinical studies dem-

Hepatocardiorenal syndrome in liver cirrhosis:Recognition of a new entity?

Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome(HRS),outside of conventional understanding that liver cirrhosis is traditionally considered the sole origin of a cascade of pathophysiological mechanisms directly affecting the kidneys in this context.In the absence of established heart disease,cirrhotic cardiomyopathy may occur more frequently in those with liver cirrhosis and kidney disease.It is a specific form of cardiac dysfunction characterized by blunted contractile responsiveness to stress stimuli and altered diastolic relaxation with electrophysiological abnormalities.Despite the clinical description of these potential cardiac-related complications of the liver,the role of the heart has traditionally been an overlooked aspect of circulatory dysfunction in HRS.Yet from a physiological sense,temporality(prior onset)of cardiorenal interactions in HRS and positive effects stemming from portosystemic shunting demonstrated an important role of the heart in the development and progression of kidney dysfunction in cirrhotic patients.In this review,we discuss current concepts surrounding how the heart may influence the development and progression of HRS,and the role of systemic inflammation and endothelial dysfunction causing circulatory dysfunction within this setting.The temporality of heart and kidney dysfunction in HRS will be discussed.For a subgroup of patients who receive portosystemic shunting,the dynamics of cardiorenal interactions following treatment is reviewed.Continued research to determine the unknowns in this topic is anticipated,hopefully to further clarify the intricacies surrounding the liver-heart-kidney connection and improve strategies for management.

Correlation of cardiac troponin T levels with inotrope requirement,hypoxic-ischemic encephalopathy,and survival in asphyxiated neonates

BACKGROUND Cardiac involvement in neonates with perinatal asphyxia not only complicates perinatal management but also contributes to increased mortality.AIM To assess cardiac troponin T(cTnT)levels in asphyxiated neonates and their correlation with echocardiography findings,inotrope requirement,hypoxicischemic encephalopathy(HIE)stages,and mortality.METHODS cTnT levels,echocardiographic findings,the requirement of inotropes,HIE stages,and outcome were studied in neonates of gestational age≥34 wk with perinatal asphyxia.RESULTS Among 57 neonates with perinatal asphyxia,male gender,cesarean section,forceps/vacuum-assisted vaginal delivery and late preterm included 33(57.9%),23(40.4%),3(5.3%),and 12(21.1%)respectively.The mean gestational age was 38.4 wk(1.6 wk).HIE stages I,II,and III were observed in 7(12.3%),37(64.9%),and 9(15.8%)neonates respectively.26(45.6%)neonates had echocardiographic changes and 19(33.3%)required inotropes.cTnT levels were elevated in 41(71.9%)neonates[median(IQR);0.285(0.211-0.422)ng/mL].The Median cTnT level showed an increasing trend with increasing changes in echocardiography(P=0.002).Two neonates with mitral regurgitation and global hypokinesia had the highest cTnT levels(1.99 and 0.651 ng/mL).Of 31 neonates with normal echocardiography,18(58.06%)showed elevated cTnT.cTnT levels were significantly higher in those who required inotropic support than those who did not(P=0.007).Neonates with HIE stage III had significantly higher cTnT levels compared to those with HIE stage I/II(P=0.013).Survivors had lower median cTnT levels[0.210(0.122-0.316)ng/mL]than who succumbed[0.597(0.356-1.146)ng/mL].CONCLUSION cTnT levels suggestive of cardiac involvement were observed in 71.9%of asphyxiated neonates.cTnT levels correlated with echocardiography findings,inotrope requirement,HIE stages,and mortality.

Signaling Pathways Involved in Cardiac Hypertrophy

Cardiac hypertrophy is the heart＇s response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress. Traditionally, it has been considered a beneficial mechanism; however, sustained hypertrophy has been associated with a significant increase in the risk of cardiovascular disease and mortality. Delineating intracellular signaling pathways involved in the different aspects of cardiac hypertrophy will permit future improvements in potential targets for therapeutic intervention. Generally, there are two types of cardiac hypertrophies, adaptive hypertrophy, including eutrophy （normal growth） and physiological hypertrophy （growth induced by conditioning）, and maladaptive hypertrophy, physical including pathologic or reactive hypertrophy （growth induced by pathologic stimuli） and hypertrophic growth caused by genetic mutations affecting sarcomeric or cytoskeletal proteins. Accumulating observations from animal models and human patients have identified a number of intracellular signaling pathways that characterized as important transducers of the hypertrophic response, including calcineurin/nuclear factor of activated Tcells, phosphoinositide 3-kinases/Akt （PI3Ks/Akt）, G protein-coupled receptors, small G proteins, MAPK, PKCs, Gp130/STAT3, Na＋/H＋ exchanger, peroxisome proliferator-activated receptors, myocyte enhancer factor 2/histone deacetylases, and many others. Furthermore, recent evidence suggests that adaptive cardiac hypertrophy is regulated in large part by the growth hormone/insulin-like growth factors axis via signaling through the PI3K/Akt pathway. In contrast, pathological or reactive hypertrophy is triggered by autocrine and paracrine neurohormonal factors released during biomechanical stress that signal through the Gq/phosphorlipase C pathway, leading to an increase in cytosolic calcium and activation of PKC.

Analysis of differential genes of ischemic stroke-induced heart tissue in mice based on GEO database

Objective:The differential genes of left ventricle in middle cerebral artery occlusion model(MCAO)mice and Sham mice(Sham)mice at 24h and 72h after ischemia were compared respectively,and the differential genes and their regulated functional pathways were analyzed at different time points after ischemic stroke,so as to analyze the mechanism of inducing cardiac dysfunction after ischemic stroke and provide evidence for its treatment.Methods:Gene-chip data from the left ventricle of MCAO mice and Sham mice were downloaded from the GEO database at the National Center for Biotechnology Information(NCBI).The differentially expressed genes were obtained by R language software programming.The GO functional enrichment and KEGG pathway enrichment analysis of the obtained differential genes were performed using DAVID 6.8 online analysis tool,and the Omicshare online analysis tool was used to visualize the enrichment analysis results.Results:At 24h after ischemia,187 differentially expressed genes were obtained,including 56 GO enrichment pathways and 5 KEGG enrichment pathways with significant significance.After 72h after ischemia,51 differentially expressed genes were obtained,14 GO enrichment pathways and 3 KEGG enrichment pathways with significant significance.The two time points involved Aplnr and Itgb6 gene targets and PI3K-Akt signaling pathway.Conclusion:①By analyzing the gene expression profile data,the differentially expressed genes and related pathways of cardiac dysfunction induced by ischemic stroke were obtained.②PI3K-AKT signaling pathway is closely related to the regulation of cardiac function,and regulation of PI3K-AKT signaling pathway may be an important direction for the treatment of cardiac dysfunction after ischemic stroke.

Effects of Chinese Medicine Shen-Fu Injection(参附注射液)on the Expression of Inflammatory Cytokines and Complements during Post-Resuscitation Immune Dysfunction in A Porcine Model

Objective：To investigate the action of Shen-Fu Injection（参附注射液,SFI） in regulating the expression of the serum complements and inflammatory cytokines synthesized and released in response to the stress of global ischemia accompanying cardiac arrest（CA） and resuscitation.Methods：Thirty pigs were randomly divided into the sham（n=6） and 3 returns of spontaneous circulation（ROSC） groups（n=24）.After 8-min untreated ventricular fibrillation and 2-min basic life support,24 pigs of the ROSC groups were randomized into three groups（n=8 per group）,which received central venous injection of SFI（SFI group）,epinephrine（EP group）,or saline（SA group）.Hemodynamic status and blood samples were obtained at 0,0.5,1,2,4,6,12,and 24 h after ROSC.Results：Serum concentrations of specific activation markers of the complement system C3,C4 and C5b-9 were increased during cardiopulmonary resuscitation th rough1 24 h after ROSC.There were intense changes of various pro-inflammatory cytokines and anti-inflammatory cytokines as early as 0.5 h after CA.Compared with the EP and SA groups,SFI treatment reduced the proinflammatory cytokines levels of interleukin（IL）-6,IL-8and tumor necrosis factor α（TNF-α,P〈0.05）,and increased the anti-inflammatory cytokine levels of IL-4 and IL-10（P〈0.05）.Further,SFI treatment decreased the values of C3,C4 and C5b-9 compared with the EP and SA groups.Conclusions：SFI,derived from the ancient Chinese medicine,has significant effects in attenuating post-resuscitation immune dysfunction by modulating the expression of complements and cytokines levels.The current study provided an experimental basis for the clinical application of a potential pharmacologic target for post resuscitation immune dysfunction.

Evaluation of respiratory dysfunction in a pig model of severe acute dichlorvos poisoning

Background Respiratory failure is the main cause of death in acute organophosphorus pesticide poisoning. In this study, a pulse-induced contour cardiac output monitor was used to evaluate the respiratory status in a pig model of acute dichlorvos poisoning. Methods Twenty female pigs were randomly allocated to dichlorvos （n=7）, atropine （n=7）, and control （n=6） groups. In the dichlorvos group, pigs were administered 80% emulsifiable dichlorvos （100 mg/kg） via a gastric tube. In the atropine group, pigs were similarly administered dichlorvos, and 0.5 hours later, atropine was injected to attain and maintain atropinization. The control group was administered saline solution. Arterial blood gas was measured at 0, 0.5, 1, 2, 4, and 6 hours post-injection. The extravascular lung water index and pulmonary vascular permeability index were recorded by the pulse-induced contour cardiac output monitor. At termination of the study, the animals were euthanized, the lung wet-to-dry weight ratio was determined, and histopathology was observed. Results In the dichlorvos group, the extravascular lung water index and pulmonary vascular permeability index were substantially increased from 0.5 hours and were particularly high within 1 hour. In the atropine group, these indices increased initially, but decreased from the 1-hour mark. The control group exhibited no obvious changes. In both the dichlorvos and atropine groups, the extravascular lung water index was negatively correlated with partial pressure of oxygen/fraction of inspiration oxygen （POz/FiO2） and positively correlated with the pulmonary vascular permeability index. Compared with the control group, the lung wet-to-dry weight ratio markedly increased and the histopathological findings obviously changed in the dichlorvos group, but only mildly increased and changed, respectively, in the atropine group. Conclusion The extravascular lung water index is an appropriate and valuable parameter for assessment of respiratory function in acute dichlorvos poisoning.

Energy metabolism disorders and potential therapeutic drugs in heart failure

Heart failure(HF)is a global public health problem with high morbidity and mortality.A large number of studies have shown that HF is caused by severe energy metabolism disorders,which result in an insufficient heart energy supply.This deficiency causes cardiac pump dysfunction and systemic energy metabolism failure,which determine the development of HF and recovery of heart.Current HF therapy acts by reducing heart rate and cardiac preload and afterload,treating the HF symptomatically or delaying development of the disease.Drugs aimed at cardiac energy metabolism have not yet been developed.In this review,we outline the main characteristics of cardiac energy metabolism in healthy hearts,changes in metabolism during HF,and related pathways and targets of energy metabolism.Finally,we discuss drugs that improve cardiac function via energy metabolism to provide new research ideas for the development and application of drugs for treating HF.

Analysis of Renal Artery Stenosis in Patients with Heart Failure： A RASHEF Study

Background： Previous data are controversial about the association of renal artery stenosis （RAS） with clinical outcome in patients with heart failure. Definition of RAS in previous studies might not be appropriate. By definition of RAS with renal duplex sonography, we investigated the association of RAS with clinical outcome in patients with heart failure. Methods： In this retrospective study, we identified 164 patients with heart failure （New York Heart Association classification ≥11; left ventricular ejection fraction 〈50%） who had received renal duplex sonography during hospital stay. RAS was defined as renal-aortic ratio 〉3.5 or a peak systolic velocity ≥200 cm/s （or both）, or occlusion of the renal artery. Categorical data of patients were compared using the Chi-square test or Fisher＇s exact test. Cox proportional hazards regression modeling technique was used to investigate the prognostic significance of possible predictors. Results： Finally, 143 patients were enrolled, Median follow-up time was 32 months （1-53 months）. Twenty-two patients were diagnosed as RAS by renal duplex sonography, including 13 unilateral RAS （3 left RAS, l0 right RAS） and 9 bilateral RAS. There were more all-cause mortality and cardiovascular death in patients with RAS than patients without RAS. By multivariate analysis, RAS was a significant predictor for all-cause death and cardiovascular death （hazard ratio [HR] = 4.155, 95% confidence interval [（7/]： 1.546-1 1. 164, P = 0.005; and MR = 3.483, 95% CI： 1.200-10.104, P = 0.022, respectively）. As for composite endpoint events, including death, nonfatal myocardial infarction, ischemic stroke or intracranial hemorrhage, rehospitalization for cardiac failure, and renal replacement therapy, only angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker was significant predictor. RAS was not a significant predictor for composite endpoint events. Conclusions： Our data suggested that RAS is associated with a poorer clinical outcome in patients with heart failure.