Electroacupuncture improves myocardial fibrosis in heart failure rats by attenuating ECM collagen deposition through modulation of TGF-β1/Smads signaling pathway

Background: To explore the effects of electroacupuncture on cardiac function and myocardial fibrosis in rat models of heart failure, and to elucidate the underlying mechanism of electroacupuncture in heart failure treatment. Methods: Healthy male Sprague-Dawley rats were allocated into three groups: Sham group, Model group, and electroacupuncture (Model + EA) group, with each group comprising 8 rats. The model underwent a procedure involving the ligation of the left anterior descending coronary artery to induce a model of heart failure. The Model + EA group was used for 7 consecutive days for electroacupuncture of bilateral Shenmen (HT7) and Tongli (HT5), once a day for 30 min each time. Left ventricular parameters in rats were assessed using a small-animal ultrasound machine to analyze changes in left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction, and left ventricular fractional shortening. Serum interleukin-1β (IL-1β), cardiac troponin (cTn), and N-terminal brain natriuretic peptide precursor levels were measured using ELISA. Histopathological changes in rat myocardium were observed through HE staining, while collagen deposition in rat myocardial tissue was assessed using the Masson staining method. Picro sirius red staining, immunohistochemical staining, and RT-qPCR were utilized to distinguish between the various types of collagen deposition. The expression level of TGF-β1 and SMAD2/3/4/7 mRNA in rat myocardial tissues was determined using RT-qPCR. Additionally, western blot analysis was conducted to assess the protein expression levels of TGF-β1, SMAD3/7, and p-SMAD3 in rat myocardial tissues. Results: Compared with the Sham group, the left ventricular ejection fraction and left ventricular fractional shortening values of the Model group were significantly decreased (P < 0.01);the left ventricular end-diastolic volume and left ventricular end-systolic volume values were remarkably increased (P < 0.01);serum N-terminal brain natriuretic peptide precursor content was increased (P < 0.01);serum IL-1β and cTn levels were increased (P < 0.01);myocardial collagen volume fraction were increased (P < 0.01);and those of the expression of TGF-β1 and SMAD2/3/4 mRNA was increased (P < 0.01);the expression of SMAD7 mRNA was decreased (P < 0.01);the protein expression levels of TGF-β1, SMAD3, and p-Smad3 were increased (P < 0.01);the protein expression level of SMAD7 was decreased (P < 0.01) in the Model group. Compared to the Model group, the expression levels of the proteins TGF-β1, SMAD3, and p-Smad3 in myocardial tissue were found to be decreased (P < 0.01), and the expression level of the protein SMAD7 was found to be increased (P < 0.01) in the Model + EA group;the collagen volume fraction and deposition of type Ⅰ /Ⅲ collagen were decreased (P < 0.01) in the Model + EA group. Conclusion: Electroacupuncture alleviates myocardial fibrosis in rats with heart failure, and this effect is likely due to attributed to the modulation of the TGF-β1/Smads signaling pathway, which helps reduce collagen deposition in the extracellular matrix.

Dapagliflozin and sacubitril on myocardial microperfusion in patients with post-acute myocardial infarction heart failure and type 2 diabetes

BACKGROUND Coronary heart disease and type 2 diabetes mellitus(T2DM)frequently coexist,creating a complex and challenging clinical scenario,particularly when complicated with acute myocardial infarction(AMI).AIM To examine the effects of dapagliflozin combined with sakubactrovalsartan sodium tablets on myocardial microperfusion.METHODS In total,98 patients were categorized into control(n=47)and observation(n=51)groups.The control group received noxital,while the observation group was treated with dapagliflozin combined with noxital for 6 months.Changes in myocardial microperfusion,blood glucose level,cardiac function,N-terminal prohormone of brain natriuretic peptide(NT-proBNP)level,growth differentiation factor-15(GDF-15)level,and other related factors were compared between the two groups.Additionally,the incidence of major adverse cardiovascular events(MACE)and adverse reactions were calculated.RESULTS After treatment,in the observation and control groups,the corrected thrombolysis in myocardial infarction frame counts were 37.12±5.02 and 48.23±4.66,respectively.The NT-proBNP levels were 1502.65±255.87 and 2015.23±286.31 pg/mL,the N-terminal pro-atrial natriuretic peptide(NT-proANP)levels were 1415.69±213.05 and 1875.52±241.02 ng/mL,the GDF-15 levels were 0.87±0.43 and 1.21±0.56 g/L,and the high-sensitivity C-reactive protein(hs-CRP)levels were 6.54±1.56 and 8.77±1.94 mg/L,respectively,with statistically significant differences(P<0.05).The cumulative incidence of MACEs in the observation group was significantly lower than that in the control group(P<0.05).The incidence of adverse reactions was 13.73%(7/51)in the observation group and 10.64%(5/47)in the control group,with no statistically significant difference(P>0.05).CONCLUSION Dapagliflozin combined with nocinto can improve myocardial microperfusion and left ventricular remodeling and reduce MACE incidence in patients with post-AMI heart failure and T2DM.The underlying mechanism may be related to the reduction in the expression levels of NT-proANP,GDF-15,and hs-CRP.

Yiqi Huoxue traditional Chinese decoction affect ventricular remodeling in rats with heart failure after myocardial infarction by regulating osteopontin expression

Objective:To investigate the mechanism of Yiqi Huoxue traditional Chinese medicine affecting the osteopontin(OPN)level in myocardial tissue and improving ventricular remodeling in heart failure rats after myocardial infarction.Methods:Forty SPF-grade SD male rats were prepared,and 10 rats were reserved as blank controls.The remaining rats were prepared by anterior descending coronary artery ligation combined with reduced diet and exhausted swimming to prepare a rat model of heart failure after myocardial infarction.The rats in the blank group and the model group were orally administered with distilled water,the Chinese medicine group was administered with Yiqi Huoxue Chinese medicine decoction,and the western medicine group was administered with captopril.After 6 weeks of treatment,small animal ultrasound was used to detect changes in ventricular structure and function in rats.Kill all the rats,and take myocardial tissue,observe the morphological changes of myocardial tissu under a light microscope.Use real-time quantitative PCR to detect the expression of OPN mRNA in rat myocardial tissue,and use immunohistochemical method to detect the expression of OPN protein in myocardial tissue.Results:Compared with the blank group,the left ventricular ejection fraction(EF),left ventricular short axis shortening fraction(FS)of the model group were significantly reduced,and the left ventricular end-diastolic diameter(LVEDD)and left ventricular end-systolic diameter(LVESD)were significantly increased,OPN mRNA and protein expression were significantly up-regulated(P<0.01),and myocardial structure disorder was seen under light microscope.Compared with the model group,the EF and FS of the Chinese medicine group and the Western medicine group were both significantly increased,the LVEDD and LVESD were significantly reduced,the expressions of OPN mRNA and protein were significantly reduced(P<0.01),and the myocardial structure was significantly improved under light microscopy.There was no statistically significant difference between the western medicine group and the traditional Chinese medicine group(P>0.05).Conclusion:Yiqi Huoxue Chinese medicine may reduce the expression of OPN in myocardial tissue,improve ventricular remodeling,improve cardiac function and prevent heart failure after myocardial infarction.

Effects of rh BNP after PCI on non-invasive hemodynamic in acute myocardial infarction patients with left heart failure

Objective: To investigate the effects of exogenous recombinant human brain natriuretic peptide(rh BNP) after primary percutaneous coronary intervention(PCI) on non-invasive hemodynamic in acute myocardial infarction patients with left ventricular failure. Methods: A number of 96 acute myocardial infarction patients accompanied with heart failure after PCI hospitalized in the People's Hospital of Sanya during February 2012 to October 2015 were selected. They were randomly divided into the therapy group(n = 50) and control group(n = 46). On the basis of routine treatment, patients in the therapy group were treated with intravenous rh BNP(1.5 μg/kg was intravenous injection with uniform speed of 3 min, followed by continuous infusion 0.007 5 μg/kg·min for 72 h), while the control group received conventional treatment. Bio Z-2011 non-invasive hemodynamic real-time monitoring system was used to monitor the hemodynamic parameters changes and the leves of plasma pro-BNP, serum creatinine, serum potassium, serum sodium and urine volume of each group before and after treating for 30 min, 1 h, 3 h, 6 h, 12 h, 24 h, 48 h, 72 h. Results: Patients in the therapy group showed no effect on heart rate, while after 30 min of intravenous injection of rh BNP, CO, CI, SV, and SI increased significantly and LVET and TFC reduced at the same time, which had certain effect on blood pressure(SBP/DBP). Compared with the control group, the therapy group showed a faster and more effective improvement on haemodynamics. Conclusions: Acute myocardial infarction patients complicated with left heart failure after primary PCI can significantly improve hemodynamics by treating with rh BNP.

Heart failure after myocardial infarction in the era of primary percutaneous coronary intervention:Mechanisms,incidence and identification of patients at risk

Myocardial infarction(MI) remains the most common cause of heart failure(HF) worldwide. For almost 50 years HF has been recognised as a determinant ofadverse prognosis after MI, but efforts to promote myocardial repair have failed to translate into clinical therapies. Primary percutaneous coronary intervention(PPCI) has driven improved early survival after MI, but its impact on the incidence of downstream HF is debated. The effects of PPCI are confounded by the changing epidemiology of MI and HF, with an ageing patient demographic, an increasing proportion of non-STelevation myocardial infarction, and the recognition of HF with preserved ejection fraction. Herein we review the mechanisms of HF after MI and discuss contemporary data on its incidence and outcomes. We review current and emerging strategies for early detection of patients at risk of HF after MI, with a view to identification of patient cohorts for novel therapeutic agents.

Development and course of heart failure after a myocardial infarction in younger and older people

Background Acute myocardial infarction （AMI） is a common cause of heart failure （HF）, which can develop soon after AMI and may persist or resolve or develop late. HF after an MI is a major source of mortality. The cumulative incidence, prevalence and resolution of HF after MI in different age groups are poorly described. This study describes the natural history of HF after AMI according to age. Methods Patients with AMI during 1998 were identified from hospital records. HF was defined as treatment of symptoms and signs of HF with loop diuretics and was considered to have resolved if loop diuretic therapy could be stopped without recurrence of symptoms. Patients were cate- gorised into those aged 〈 65 years, 65-75 years, and 〉 75 years. Results Of 896 patients, 311,297 and 288 were aged 〈 65, 65-75 and 〉75 years and of whom 24%, 57% and 82% had died respectively by December 2005. Of these deaths, 24 （8%）, 68 （23%） and 107 （37%） oc- curred during the index admission, many associated with acute HF. A further 37 （12%）, 63 （21%） and 82 （29%） developed HF that persisted until discharge, of whom 15, 44 and 62 subsequently died. After discharge, 53 （24%）, 55 （40%） and 37 （47%） patients developed I-IF for the first time, of whom 26%, 62% and 76% subsequently died. Death was preceded by the development of HF in 35 （70%）, 93 （91%） and 107 （85%） in aged 〈 65 years, 65-75 years and 〉75 years, respectively. Conclusions The risk of developing HF and of dying after an MI in- creases progressively with age. Regardless of age, most deaths after a MI are preceded by the development of HF.

Peripheral blood stem cells transplantation in patients with heart failure after myocardial infarction:their efficiency and safety

Objective To compare the efficiency and safety of intracoronary transplantation of peripheral blood stem cells (PBSC) between elderly and younger patients with heart failure after myocardial infarction (MI). Methods Twenty-five patients with heart failure after MI were divided into aged group(≥60 years,n=13) and non-aged group(<60years,n=12)to receive intracoronary PBSC transplantation (PBSCT) following bone marrow cells mobilized by granulocyte colony-stimulating factor(G-CSF). Clinical data including coronary lesion characteristic, left ventricular shape,infarct region area and cardiac function, as well as adverse side effects between the two groups were compared. Left ventricular function was evaluated before and 6 months after the treatment by single photon emission computed tomography(SPECT). Results At 6 months, the left ventricular ejection fraction (LVEF) and 6 minute walk test (6MWT) distance increased, while the left ventricular diastolic diameter (LVDd) decreased significantly in both groups. There were no significant difference between the two groups in absolute change in the cardiac function parameters. Conclusions The present study demonstrated that autologous intracoronary PBSCT might be safe and feasible for both old and younger patients with heart failure after MI and left ventricular function is significantly improved.(J Geriatr Cardiol 2007;4:233-237.)

Protective Role of Wumen Jianzhong Qiangxin Granules in Rats with Post-myocardial Infarction Heart Failure and Effect on Myocardial Energy Metabolism

[Objectives]The paper was to determine the effect of Wumen Jianzhong Qiangxin granules(WJQG)on myocardial energy metabolism in a chronic heart failure rat model after myocardial infarction(MI).[Methods]Totally 40 normal male SD rats were randomly divided into sham operation group,model group,trimetazidine group and WJQG group(n=10).The model of MI was established by ligation of the left anterior descending branch except sham operation group.The rats in trimetazidine and WJQG groups were gavaged with 60 mg/kg and 16 g/kg emodin daily,respectively.After administration for 4 weeks,the changes in heart rate(HR),R-R interval(RRI),systolic arterial pressure(SAP),diastolic arterial pressure(DAP),mean arterial pressure(MAP),pulse pressure(PP),left ventricular end-diastolic pressure(LVEDP),rates of maximum positive left ventricular pressure development(+dp/dtmax)and rates of maximum negative left ventricular pressure development(-dp/dtmax)were analyzed.Morphology of myocardial tissues was observed by HE staining,the levels of myocardial tissue adenosine triphosphate(ATP)and glucose transporter type 4(GLUT-4)were determined using scientific research kit,and the expressions of mitochondrial creatine kinase(mit-CK),creatine kinase MM isoenzyme(CK-MM)and adenine nucleotide translocator(ANT)in myocardial tissues were determined by Western blotting.[Results](i)Compared with sham group,LVEDP obviously increased,while+dp/dtmax and-dp/dtmax significantly decreased in model group,with extremely significant difference in statistics(P<0.01).Compared with model group,LVEDP decreased,while+dp/dtmax and-dp/dtmax increased in trimetazidine group and WJQG group,with significant difference in statistics(P<0.05 orP<0.01).(ii)The cardiomyocytes ultrastructure of rats in sham group was normal,while in model group,extensive focus of MI can be seen under optic microscope.In the infarction focus,we can see outline of the necrotic tissue,infiltration of inflammatory cells,few fibroblasts,as well as the slow growth of granulation tissue.Focus of MI in both trimetazidine group and WJQG group were located in a certain part.In the infarction focus,we can see living myocardial cells distributing as islands and islets,more fibroblasts than in model group,as well as active hyperplasia of granulation tissue.(iii)Compared with sham group,the levels of myocardial tissues ATP and GLUT-4 in left ventricular myocardial cells in model group went down,with extremely significant difference(P<0.01).Compared with model group,the levels of myocardial tissues ATP and GLUT-4 in left ventricular myocardial cells in both trimetazidine group and WJQG group went up,with extremely significant difference(P<0.05).(iv)Compared with sham group,the expression level of CK-MM,mit-CK and ANT in left ventricular myocardial cells in model group went down,with extremely significant difference(P<0.01 orP<0.001).Compared with model group,the expression levels of CK-MM,mit-CK and ANT in left ventricular myocardial cells in both trimetazidine group and WJQG group went up,with extremely significant difference in statistics(P<0.05 orP<0.01 orP<0.001).[Conclusions]WJQG can effectively increase the levels of myocardial tissues ATP and GLUT-4,as well as the expression levels of CK-MM,mit-CK and ANT of rats with heart failure after MI,and thus enhance the full exchange between ATP and ADP on the inner membrane of mitochondria conducted by ANT.The prescription also helps to ensure myocardial energy supply and remodel the process of myocardial energy metabolism,and finally protects the cardiac function of rats.

Effect of perindopril on the myocardial energy consumption in patients with heart failure after myocardial infarction

Objective:To explore the clinical efficacy of perinodopril in the treatment of heart failure in patients after myocardial infarction and effect on the myocardial energy consumption. Methods:A total of 87 patients with heart failure after myocardial infarction who were admitted in our hospital from August, 2014 to October, 2015 were included in the study and divided into the routine dose group (n=43, perinodopril 4 mg/d) and high dose group (n=44, perinodopril 8 mg/d) according to the long-term oral dose. All the patients were given perinodopril, continuously for 6 months. The changes of blood pressure and serum biochemical indicators before and after treatment in the two groups were compared. The changes of cardiac function indicators and myocardial energy consumption indicators before and after treatment in the two groups were compared. 6MWT 6 months and 1 year after treatment in the two groups was calculated.Results: The plasma BNP and H-FABP levels, LVEDD, LVESD, MEE, and cESS after treatment in the two groups were significantly reduced when compared with before treatment, and those in the high dose group were significantly lower than those in the low dose group. LVEF and FS after treatment in the two groups were significantly increased, and those in the high dose group were significantly greater than those in the routine dose group. The seurm potassium level after treatment in the high dose group was significantly elevated when compared with before treatment, but was not significantly different from that in the routine dose group. SBP, DBP, and Scr levels after treatment in the two groups were not significantly changed. 6MWT 6 months and 1 year after treatment in the high dose group was significantly greater than that in the routine dose group.Conclusions: Perinodopril in a high dose can significantly reduce the plasma BNP and H-FABP levels in patients with heart failure after myocardial infarction, inhibit the ventricular remodeling, promote the recovery of systolic function, reduce the myocardial energy consumption, and will not affect the blood pressure, serum potassium, and renal function, with efficacy significantly superior to that in a low dose;moreover, it has a certain safety.

Dapagliflozin in heart failure and type 2 diabetes:Efficacy,cardiac and renal effects,safety

BACKGROUND Heart failure(HF),especially HF with reduced ejection fraction(HFrEF),presents complex challenges,particularly in the aging population where it often coexists with type 2 diabetes mellitus(T2DM).AIM To analyze the effect of dapagliflozin treatment on cardiac,renal function,and safety in patients with HFrEF combined with T2DM.METHODS Patients with T2DM complicated with HFrEF who underwent treatment in our hospital from February 2018 to March 2023 were retrospectively analyzed as the subjects of this study.The propensity score matching method was used,and a total of 102 eligible samples were scaled.The clinical efficacy of the two groups was evaluated at the end of the treatment,comparing the results of blood glucose,insulin,cardiac function,markers of myocardial injury,renal function indexes,and 6-min walk test(6MWT)before and after the treatment.We compared the occurrence of adverse effects on the treatment process of the two groups of patients.The incidence of adverse outcomes in patients within six months of treatment was counted.RESULTS The overall clinical efficacy rate of patients in the study group was significantly higher than that of patients in the control group(P=0.013).After treatment,the pancreatic beta-cell function index,left ventricular ejection fraction,and glomerular filtration rate of patients in the study group were significantly higher than control group(P<0.001),while their fasting plasma glucose,2-h postprandial glucose,glycosylated hemoglobin,insulin resistance index,left ventricular end-systolic diameter,left ventricular end-diastolic diameter,cardiac troponin I,creatine kinase-MB,N-terminal pro b-type natriuretic peptide,serum creatinine,and blood urea nitrogen were significantly lower than those of the control group.After treatment,patients in the study group had a significantly higher 6MWT than those in the control group(P<0.001).Hypoglycemic reaction(P=0.647),urinary tract infection(P=0.558),gastrointestinal adverse effect(P=0.307),respiratory disturbance(P=0.558),and angioedema(P=0.647)were not statistically different.There was no significant difference between the incidence of adverse outcomes between the two groups(P=0.250).CONCLUSION Dapagliflozin significantly enhances clinical efficacy,cardiac and renal function,and ambulatory capacity in patients with HFrEF and T2DM without an increased risk of adverse effects or outcomes.

Coronary artery disease and heart failure:Late-breaking trials presented at American Heart Association scientific session 2023

The late-breaking science presented at the 2023 scientific session of the American Heart Association paves the way for future pragmatic trials and provides meaningful information to guide management strategies in coronary artery disease and heart failure(HF).The dapagliflozin in patient with acute myocardial infarction(DAPA-MI)trial showed that dapagliflozin use among patients with acute MI without a history of diabetes mellitus or chronic HF has better cardiometabolic outcomes compared with placebo,with no difference in cardiovascular outcomes.The MINT trial showed that in patients with acute MI and anemia(Hgb<10 g/dL),a liberal transfusion goal(Hgb≥10 g/dL)was not superior to a restrictive strategy(Hgb 7-8 g/dL)with respect to 30-day all-cause death and recurrent MI.The ORBITA-2 trial showed that among patients with stable angina and coronary stenoses causing ischemia on little or no antianginal therapy,percutaneous coronary intervention results in greater improvements in anginal frequency and exercise times compared with a sham procedure.The ARIES-HM3 trial showed that in patients with advanced HF who received a HeartMate 3 levitated left ventricular assist device and were anticoagulated with a vitamin K antagonist,placebo was noninferior to daily aspirin with respect to the composite endpoint of bleeding and thrombotic events at 1 year.The TEAMMATE trial showed that everolimus with low-dose tacrolimus is safe in children and young adults when given≥6 months after cardiac transplantation.Providing patients being treated for HF with reduced ejection fraction(HFrEF)with specific out-of-pocket(OOP)costs for multiple medication options at the time of the clinical encounter may reduce‘contingency planning’and increase the extent to which patients are taking the medications decided upon.The primary outcome,which was cost-informed decisionmaking,defined as the clinician or patient mentioning costs of HFrEF medication,occurred in 49%of encounters with the checklist only control group compared with 68%of encounters in the OOP cost group.

Repeated measurement of growth-differentiation factor-15in Chinese Han patients with post-myocardial infarction chronic heart failure

Background Growth-differentiation factor-15(GDF-15)is a promising prognostic biomarker in patients with chronic heart failure (CHF).Comparatively little is known about the value of repeated measurement of GDF-15with CI-IF in Chinese Han population.This study sought to identify the clinical value of repeated measurement of GDF-15in Chinese Han patients with post-myocardial infarction CHF. Methods In total,232consecutive Chinese Hart patients with post-myocardial infarction CHF were enrolled prospectively from January 2014to June 2016.The plasma concentration of GDF-15was determined on admission and over 12months.Patients were followed up for all-cause death and a composite outcome of major adverse cardiac events (MACE)included all-cause death,myocardial infarction and first heart failure (HF)re-hospitalization.Association with other clinical variables and adverse outcomes of repeated measurement of GDF-15 was explored.Results The median baseline GDF-15level was 2025ng/L.Baseline GDF-15was moderately associated with baseline N-terminal pro-B type nalriuretic peptide (NT-proBNP)(coefficient 0.561,P <0.001).During a median follow-up of 20months,there were 53deaths and 100MACE.GDF-I5remained an independent predictor of all-cause death (adjusted hazard ratio 1.826per 1Ln U,95%CI: 1.037-8.360;P =0.037)and MACE (adjusted hazard ratio 2.243per I Ln U,95%CI:1.181-1.775;P <0.001)adjusted for established risk factors.Repeated measurement of GDF-15was performed in 173survivals over 12months.Increase of GDF-15over 12months was associ- ated with dilatation of left ventricle and acted as an independent predictor of subsequent all-canse death (adjusted HR =3.164,95%CI: 1.245~.041;P =0.015).In the joint model,GDF-15was also shown to be a risk factor for all-cause death (HR =2.749,95%CI: 1.667-3.831;P <0.001)and MACE (FIR =2.434,95%CI:1.425-3.443;P <0.001).Conclusions Repeated measurements of GDF-15 have promising prognostic value of the risk of all-cause death in Chinese Han patients with CI-IF post-myocardial infarction.GDF-15may influence the post-myocardial infarction CI-IF through the path physiological pathway of myocardial remodeling.

Correlation between growth differentiation factor-15 and collagen metabolism indicators in patients with myocardial infarction and heart failure

BackgroundGrowth differentiation factor （GDF）-15, a divergent member of the transforming growth factor beta super-family does appear to be up-regulated in response to experimental pressure overload and progression of heart failure （HF）. HF frequently develops after myocardial infarction （MI）, contributing to worse outcome. The aim of this study is to assess the correlation between GDF-15 levels and markers related to collagen turnover in different stages of HF.MethodsThe study consists of a cohort of 179 patients, including stable angina pectoris patients （AP group,n= 50）, old MI patients without HF （OMI group,n = 56）, old MI patients with HF （OMI-HF group,n= 38） and normal Control group （n = 35）. Both indicators reflecting the synthesis and degradation rates of collagen including precollagen I N-terminal peptide （PINP）, type I collagen carboxy-terminal peptide （ICTP）, precollagen III N-terminal peptide （PIIINP） and GDF-15 were measured using an enzyme-linked inmunosorbent assay.ResultsThe plasma GDF-15 level was higher in OMI-HF group （1373.4 ± 275.4 ng/L） than OMI group （1036.1 ± 248.6 ng/L）, AP group （784.6 ± 222.4 ng/L） and Control group （483.8 ± 186.4 ng/L） （P〈 0.001）. The indi-cators of collagen turnover （ICTP, PINP, PIIINP） all increased in the OMI-HF group compared with Control group （3.03 ± 1.02μg/Lvs. 2.08 ± 0.95μg/L, 22.2 ± 6.6μg/Lvs. 16.7 ± 5.1μg/L and 13.2 ± 7.9μg/Lvs. 6.4 ± 2.1μg/L, respectively;P〈 0.01）. GDF-15 positively cor-related with ICTP and PIIINP （r = 0.302,P〈 0.001 andr= 0.206,P= 0.006, respectively）. GDF-15 positively correlated to the echocardio-graphic diastolic indicators E/Em and left atrial pressure （r= 0.349 and r= 0.358, respectively;P〈 0.01）, and inversely correlated to the systolic indicators left ventricular ejection fraction and the average of peak systolic myocardial velocities （Sm） （r=-0.623 and r=-0.365, respectively;P〈 0.01）.ConclusionPlasma GDF-15 is associated with the indicators of type I and III collagen turnover.

Paeoniflorin Attenuates Myocardial Fibrosis in Isoprenaline-induced Chronic Heart F ailure Rats via Inhibiting P38 MA PK Pathway

Paconiflorin(Pae)is a monoterpenoid glycoside compound and has many biological activitics,such as immunosuppression,anti-inflammation and anti-cell proliferation.However,the effects and mechanisms of Pae on chronic heart failure(CHF)remain unclear.This study was conducted to assess the effects and mechanisms of Pae on myocardial fibrosis in isoprenaline(Iso)-induced CHF rats.Pae(20 mgkg)was intragastrically administrated to CHF rats for 6 weeks.Cardiac structure and function were assessed.The protein and mRNA levels of transforming growth factorβ1(TGF-β1)and p38 were detected.C ompared to Iso group,Pae could alleviate myocardial fbrosis and improve cardiac function in CHF rats.The levels of collagen volume fraction(13.75%+3.77%vs.30.97%+4.22%,P<0.001)and perivascular collagen volume area(14.32%+2.50%v8.28.31%+3.16%,P<0.001)were significantly reduced in Pae group as compared with those in Iso group.The expression of TGF-BI protein(0.30+0.07 vs.0.66+0.07,P<0.05)and mRNA(3.51+0.44 vs.7.58+0.58,P<0.05)decreased significantly in Pac group as compared with that in Iso group.The expression of p38 protein(0.36+0.12 vs.0.81+0.38,P<0.05)and mRNA(3.84+0.05 vs.4.40+0.17,P<0.05)also decreased markedly in Pae group as compared with that in Iso group.Pae could attenuate myocardial fibrosis and improve cardiac function in CHF rats by down-regulating the p38 MAPK signaling pathway.

Digoxin:A systematic review in atrial fibrillation,congestive heart failure and post myocardial infarction

AIM: To review digoxin use in systolic congestive heart failure, atrial fibrillation, and after myocardial infarction. METHODS: A comprehensive Pub Med search was performed using the key words "digoxin and congestive heart failure", "digoxin and atrial fibrillation", "digoxin, atrial fibrillation and systolic congestive heart failure", and "digoxin and myocardial infarction". Only articles written in English were included in this study. We retained studies originating from randomized controlled trials, registries and included at least 500 patients. The studies included patients with atrial fibrillation or heart failure or myocardial infarction and had a significant proportion of patients(at least 5%) on digoxin. A table reviewing the different hazard ratios was developed based on the articles selected. Our primary endpoint was the overall mortality in the patients on digoxin vs those without digoxin, among patients with atrial fibrillation and also among patients with atrial fibrillation and systolic heart failure. We reviewed the most recent international guidelines to discuss current recommendations.RESULTS: A total of 18 studies were found that evaluated digoxin and overall mortality in different clinical settings including systolic congestive heart failure and normal sinus rhythm(n = 5), atrial fibrillation with and without systolic congestive heart failure(n = 9), and myocardial infarction(n = 4). Overall, patients with systolic congestive heart failure with normal sinus rhythm, digoxin appears to have a neutral effect on mortality especially if close digoxin level monitoring is employed. However, most of the observational studies evaluating digoxin use in atrial fibrillation without systolic congestive heart failure showed an increase in overall mortality when taking digoxin. In the studies evaluated in this systematic review, the data among patients with atrial fibrillation and systolic congestive heart failure, as well as post myocardial infarction were more controversial. The extent to which discrepancies among studies are based on statistical methods is currently unclear, as these studies' findings are generated by retrospective analyses that employed different techniques to address confounding. CONCLUSION: Based on the potential risks and benefits, as well as the presence of alternative drugs, there is a limited role for digoxin in the management of patients with normal sinus rhythm and congestive heart failure. Based on the retrospective studies reviewed there is a growing volume of data showing increased mortality in those with only atrial fibrillation. The pro-per role of digoxin is, however, less certain in other subgroups of patients, such as those with both atrial fibrillation and systolic congestive heart failure or after a myocardial infarction. Further studies may provide helpful information for such subgroups of patients.

Post-myocardial infarction giant left ventricular pseudoaneurysm presenting with severe heart failure

Left ventricle(LV) pseudoaneurysm is a late mechanical complication of myocardial infarction.A giant LV pseudoaneurysm is a rare presentation.We report a case of giant LV pseudoaneurysm in a post-MI patient who presented with gross congestive heart failure.The patient had a successful surgical repair of the aneurysm and had a favorable 3-mo outcome.The imaging modality and surgical treatment of the pseudoaneurysm are discussed.

Effects of renal sympathetic denervation on cardiac systolic function after myocardial infarction in rats

This study investigated the therapeutic effects of renal denervation on cardiac systolic function after myocardial infarction （MI） in rats and the mechanism involved. Fifty male SD rats were randomly assigned to the sham group （n = 15）, the MI group （n = 20）, and the MI plus renal denervation group （n = 15）. MI was established through thoracotomic ligation of the anterior descending artery. Renal denervation was achieved by laparotomic stripping of the renal arterial adventitial sympathetic nerve, approximately 3 mm from the abdominal aorta. Left ventricular function and hemodynamics were measured several weeks following MI. The left ventricular systolic function of the MI group was significantly reduced and the systolic blood pressure （SBP） remarkably declined. In rats with MI treated with renal denervation, the left ventricular ejection fraction （EF）, fractional shortening （FS） and SBP markedly improved compared with the MI group. However, heart rate and fibrosis decreased significantly. These findings suggest that renal denervation has therapeutic effects on post-MI cardiac dysfunction. These effects are associated with increased left ventricular ejection fraction （LVEF） and SBP, as well as reduced heart rate and fibrosis. This may represent a new approach to the treatment of post-MI remodeling and subsequent heart failure.

Renal impairment and heart failure with preserved ejection fraction early post-myocardial infarction

AIM:To study if impaired renal function is associated with increased risk of peri-infarct heart failure (HF) in patients with preserved ejection fraction (EF).METHODS:Patients with occluded infarct-related arteries (IRAs) between 1 to 28 d after myocardial infarction (MI) were grouped into chronic kidney disease (CKD) stages based on estimated glomerular filtration rate (eGFR).Rates of early post-MI HF were compared among eGFR groups.Logistic regression was used to explore independent predictors of HF.RESULTS:Reduced eGFR was present in 71.1% of 2160 patients,with significant renal impairment (eGFR < 60 mL/min every 1.73 m2) in 14.8%.The prevalence of HF was higher with worsening renal function:15.5%,17.8% and 29.4% in patients with CKD stages 1,2 and 3 or 4,respectively (P < 0.0001),despite a small absolute difference in mean EF across eGFR groups:48.2 ± 10.0,47.9 ± 11.3 and 46.2 ± 12.1,respectively (P=0.02).The prevalence of HF was again higher with worsening renal function among patients with preserved EF:10.1%,13.6% and 23.6% (P < 0.0001),but this relationship was not significant among patients with depressed EF:27.1%,26.2% and 37.9% (P= 0.071).Moreover,eGFR was an independent correlate of HF in patients with preserved EF (P=0.003) but not in patients with depressed EF (P=0.181).CONCLUSION:A significant proportion of post-MI patients with occluded IRAs have impaired renal function.Impaired renal function was associated with an increased rate of early post-MI HF,the association being strongest in patients with preserved EF.These findings have implications for management of peri-infarct HF.

Myocardial Protection with Beta Blocker Treatment in Infants with Heart Failure Due to Congenital Heart Defects and Duchenne Muscular Dystrophy

Our first intention to treat infants’ heart failure with beta blockers was to improve the clinical condition as shown in our prospective randomized trial. We only use non-selective beta blockers in these infants, carvedilol in those with left ventricular dysfunction and propranolol in those with congenital heart disease without ventricular dysfunction. Despite a significant improvement of Ross’s heart failure score, we could not convince most colleagues within the last 25 years if the concept of neurohumoral activation in heart failure is not well-established pediatric cardiology. Recently, Honghai Liu et al. published that cardiomyocyte cytokinesis failure was increased in congenital heart disease. Inactivation of the beta adreno receptors genes and administration of the beta-blocker propranolol increased cardiomyocyte division in neonatal mice, which increased the number of cardiomyocytes (endowment) and conferred benefit after myocardial infarction in adults. We currently realize that propranolol in infants with congenital heart disease not only decrease highly elevated NT-Pro-BNP values but also decrease cardiac troponin T values that may indicate myocardial injury due to neurohumoral activation. We reproduce this observation, primarily seen in infants with congenital heart disease, in an infant with Duchenne muscular dystrophy. These observations were in good accordance with current data from H. Liu et al., who showed that treatment with non-selective beta blockers early after birth might rescue cytokinesis defects and prevent heart dysfunction in adulthood in a mouse model.

Clinical study of recombinant human brain natriuretic peptide in patients with acute myocardial infarction complicating congestive heart failure

Objectives To observe the efficacy and safety of recombinant human brain natriuretic peptide(rh-BNP) on patients with acute myocardial infarction complicating congestive heart failure.Methods 40 patients with acute myocardial infarction complicated by congestive heart failure were randomly divided into control group and treatment group of 20 cases.The control group,15 cases of acute anterior myocardial infarction,5 cases of acute inferior wall myocardial infarction, 15 males and 5 females,aged 55-70 years,mean age 58±12 years;treated 16 cases of acute anterior myocardial infarction,4 cases of acute myocardial infarction,16 males and 4 females,aged 56-70 years,mean age 59±11 years;two groups of age,gender,severity of disease and vascular lesions no significant difference and comparable(P】0.05).Conventional group were given aspirin,clopidogrel, statins,Inotropic,diuretic and vasodilator therapy.In the con- ventional treatment group based on the use of recombinant human brain natriuretic peptide(new bios,Tibet Pharmaceutical Co.,Ltd.Chengdu Nuodikang biopharmaceutical production, usage:1.5μg/Kg intravenous injection(impact), then 0.0075μg-0.01μg/(kg·min)infusion rate).Continuous medication 72 h.The clinical symptoms observed for 3 days in patients before treatment and after treatment,heart rate,blood pressure and left ventricular ejection fraction (LVEF) and tumor necrosis factor(TNF-α),brain natriuretic peptide(BNP) levels were measured.Results In control group,8 cases markedly effect,5 cases effect and 7 cases no effect,the total effective rate was 65%;In treatment group,13 cases markedly effect,6 cases effect and 1 cases no effect,the total effective rate was 95%,compared with two groups P New bios treatment group significantly increased cardiac index(CI) in patients with heart failure and left ventricular ejection fraction(LVEF) than the control group(all P【0.05),further reduce the levels of tumor necrosis (TNF-α) and brain natriuretic peptide(BNP).Conclusions rh-BNP can improve symptoms and heart function,reduced plasma tumor necrosis factor(TNF-α) and BNP levels of acute myocardial infarction patients with congestive heart failure,the treatment safe and reliable.As small sample size observed,larger sample to be accumulated to further evaluate its efficacy and safety.