Living biodrugs and how tissue source influences mesenchymal stem cell therapeutics for heart failure

In this editorial we comment on the article by Safwan M et al.We especially fo-cused on the cardiac function restoration by the use of mesenchymal stem cells(MSCs)therapy for heart failure(HF),which has emerged as a new treatment approach as“Living Biodrugs”.HF remains a significant clinical challenge due to the heart’s inability to pump blood effectively,despite advancements in medical and device-based therapies.MSCs have emerged as a promising therapeutic approach,offering benefits beyond traditional treatments through their ability to modulate inflammation,reduce fibrosis,and promote endogenous tissue rege-neration.MSCs can be derived from various tissues,including bone marrow and umbilical cord.Umbilical cord-derived MSCs exhibit superior expansion ca-pabilities,making them an attractive option for HF therapy.Conversely,bone marrow-derived MSCs have been extensively studied for their potential to im-prove cardiac function but face challenges related to cell retention and delivery.Future research is focusing on optimizing MSC sources,enhancing differentiation and immune modulation,and improving delivery methods to overcome current limitations.

Effect of Cardiac Rehabilitation on Physical Capacity of Heart Failure Patients in Senegal

Background: Heart failure is a chronic and severe condition that often results from various heart diseases. Cardiac rehabilitation (CR) is currently a crucial component in managing this condition. The aim was to assess the effects of cardiac rehabilitation on physical capacity of heart failure patients. Methods: This was a cross-sectional study conducted from February 1, 2021, to June 30, 2023. We included all patients with heart failure who underwent cardiac rehabilitation. Data analysis was performed using SPSS software version 24.0, with a significance level set at p Results: The study included 87 heart failure patients, with a male-to-female ratio of 1.8. Mean age was 57.10 years (±11.75). Coronary artery disease was the primary cause of heart failure, accounting for 75.9% of cases. Atrial fibrillation was present in 4.7% of cases. Following cardiac rehabilitation, Left Ventricular Ejection Fraction increased from 40.15% to 49.48% (p = 0.001). Resting heart rate decreased significantly from 81.4 bpm to 68.3 bpm (p = 0.000), and the number of METS increased from 4.3 to 6.57 (+56.8%;p = 0.000). The mean distance covered in the 6-minute walk test significantly increased from 337.8 meters to 522.7 meters (p = 0.000), reflecting a gain of 183.5 meters. Moreover, the increase in the number of METS was more pronounced in females (p = 0.001), non-obese individuals (p = 0.000), non-diabetics (p = 0.001), non-sedentary individuals (p = 0.000), and non-smokers (p = 0.000). The study reported a low readmissions rate of 2.2% and a mortality rate of 1.1%. Conclusion: Our study demonstrates that cardiac rehabilitation is beneficial for black African heart failure patients, resulting in significant improvements in symptoms, physical and capacity.

Congestive Heart Failure: Treatment of Symptoms or Causes

This paper is based on the author’s 20+ years of experience treating patients with congestive heart failure (CHF) as a cardiologist. In the 20+ years, 64 patients were treated, including both with reduced and preserved left ventricular function. Most patients had a 4 - 5 days hospitalization in their first admission with one readmission (1.6%) over seven years. This paper will help us understand the physiology and pathophysiology of congestive heart failure, especially how to use beta blockers and diuretics. It will shorten the length of hospitalization and lower the readmission rate and cost of CHF treatment. This paper will help us to open another research direction for CHF.

Predictive Effect of CA125 on Adverse Cardiovascular Events in Patients with Chronic Heart Failure

Objective: To study the expression of CA125 in the serum of patients with CHF and the relationship between CA125 level and the occurrence of adverse cardiovascular events. Methods: The clinical data of 132 patients with CHF admitted to Shizuishan Second People’s Hospital from January 2023 to December 2023 were collected and divided into heart function II group, heart function III group, heart function IV group according to cardiac function. 44 healthy subjects who underwent physical examination during the same period were selected as the control group. The clinical data of CA125, NT-proBNP, echocardiography and other clinical data of the four groups were compared, and the incidence of major adverse cardiovascular events was followed up for 12 months. Results: Compared with the control group, the CA125 level in the CHF group was significantly increased (P Conclusion: Serum CA125 level is related to the cardiac function level in CHF patients and increases with the deterioration of cardiac function. The increase of the index is related to the mortality rate and re-hospitalization rate, suggesting that CA125 can be used as an indicator to reflect the severity of heart failure and prognosis monitoring.

Efficacy and safety of Yangxinshi tablet for chronic heart failure:A systematic review and meta-analysis

BACKGROUND The specific benefits of Yangxinshi tablet(YXST)in the treating chronic heart failure(CHF)remain uncertain.AIM To systematically evaluate the efficacy and safety of YXST in the treatment of CHF.METHODS Randomized controlled trials(RCTs)investigating YXST for CHF treatment were retrieved from eight public databases up to November 2023.Meta-analyses of the included clinical studies were conducted using Review Manager 5.3.RESULTS Twenty RCTs and 1845 patients were included.The meta-analysis results showed that the YXST combination group,compared to the conventional drug group,significantly increased the clinical efficacy rate by 23%[relative risk(RR)=1.23,95%CI:1.17-1.29],(P<0.00001),left ventricular ejection fraction by 6.69%[mean difference(MD)=6.69,95%CI:4.42-8.95,P<0.00001]and 6-min walk test by 49.82 m(MD=49.82,95%C:38.84-60.80,P<0.00001),and reduced N-terminal pro-Btype natriuretic peptide by 1.03 ng/L[standardized MD(SMD)=-1.03,95%CI:-1.32 to-0.74,P<0.00001],brain natriuretic peptide by 80.95 ng/L(MD=-80.95,95%CI:-143.31 to-18.59,P=0.01),left ventricular end-diastolic diameter by 3.92 mm(MD=-3.92,95%CI:-5.06 to-2.78,P<0.00001),and left ventricular endsystolic diameter by 4.34 mm(MD=-4.34,95%CI:-6.22 to-2.47,P<0.00001).Regarding safety,neither group reported any serious adverse events during treatment(RR=0.54,95%CI:0.15-1.90,P=0.33).In addition,Egger's test results indicated no significant publication bias(P=0.557).CONCLUSION YXST effectively improves clinical symptoms and cardiac function in patients with CHF while maintaining a favorable safety profile,suggesting its potential as a therapeutic strategy for CHF.

Effect of Luhong formula on the cardiac rehabilitation of patients with chronic heart failure

BACKGROUND Current treatments for chronic heart failure(CHF)are therapeutically ineffective.The optimization of treatments for this disease needs to be explored and analyzed.AIM To analyze the effect of using Luhong Formula in the cardiac rehabilitation of patients with CHF and its influence on cardiopulmonary function(CPF)and prognosis.METHODS In total,160 patients with CHF admitted between June 2022 and June 2023 were selected,including 75 receiving perindopril(control group)and 85 receiving Luhong Formula(research group).We conducted comparative analyses on the curative effects of traditional Chinese medicine(TCM)syndromes and cardiac function,CPF[oxygen consumption at the anaerobic threshold(VO2 AT)and at peak exercise(peak VO2)],echocardiographic indexes[left atrial volume index(LAVI),left ventricular muscle mass index(LVMI),left ventricular ejection fraction(LVEF)],and prognosis[major adverse cardiovascular events(MACEs)at 6 months follow-up].RESULTS The research group showed markedly higher curative effects of TCM syndromes and cardiac function than the control group.In addition,post-treatment VO2 AT,peak VO2,LVMI and LVEF in the research group were significantly higher,whereas LAVI was significantly lower,than those of the control group.Furthermore,fewer patients in the research group developed MACEs at the 6-month follow-up.CONCLUSION Luhong Formula is more therapeutically effective than perindopril for the cardiac rehabilitation of patients with CHF,specifically in enhancing CPF and prognosis.

Assessing myocardial indices and inflammatory factors to determine anxiety and depression severity in patients with chronic heart failure

BACKGROUND Patients with chronic heart failure(CHF)have a progressive disease that is associated with poor quality of life and high mortality.Many patients experience anxiety and depression(A&D)symptoms,which can further accelerate disease progression.We hypothesized that indicators of myocardial function and inflammatory stress may reflect the severity of A&D symptoms in patients with CHF.Changes in these biomarkers could potentially predict whether A&D symptoms will deteriorate further in these individuals.AIM To measure changes in cardiac and inflammatory markers in patients with CHF to determine A&D severity and predict outcomes.METHODS We retrospectively analyzed 233 patients with CHF treated at the Jingzhou Hospital,Yangtze University between 2018-2022 and grouped them according to Self-Rating Anxiety Scale(SAS)and Self-Rating Depression Scale(SDS)scores.We compared clinical data in the no-A&D,mild-A&D,moderate-A&D,and severe-A&D groups,the SAS and SDS scores with the New York Heart Association(NYHA)functional classification,and cardiac markers and inflammatory factors between the no/mild-A&D and moderate/severe-A&D groups.Regression analysis was performed on the markers with P<0.05 to determine their ability to predict A&D severity in patients and the area under the receiver operating characteristic curve(AUROC)was used to evaluate their accuracy.RESULTS In the inter-group comparison,the following variables had an effect on A&D severity in patients with CHF:NYHA class,left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter,N-terminal pro-brain natriuretic peptide(NT-proBNP),interleukin-6(IL-6),and tumor necrosis factor-alpha(P<0.05).Other variables did not differ significantly between the A&D groups(P>0.05).In addition,we found that higher NYHA classes were associated with higher the SAS and SDS scores(P<0.05).Regression analysis showed that LVEF,NTproBNP,and IL-6 were independent risk factors for A&D severity(P<0.05).Among them,NT-proBNP had the best predictive ability as a single indicator(AUROC=0.781).Furthermore,the combination of these three indicators exhibited a good predictive effect toward discriminating the extent of A&D severity among patients(AUROC=0.875).CONCLUSION Cardiac and inflammatory biomarkers,such as LVEF,NT-proBNP,and IL-6,are correlated with A&D severity in patients with CHF and have predictive value.

Effect of dapagliflozin on uric acid in patients with chronic heart failure and hyperuricemia

BACKGROUND Patients with chronic heart failure(CHF)frequently develop hyperuricemia,an elevated serum uric acid level,associated with adverse outcomes.Dapagliflozin,a sodium-glucose cotransporter-2 inhibitor,demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction(HFrEF),irrespective of diabetes.However,dapagliflozin’s effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear.AIM To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia.METHODS We conducted a randomized,double-blind,placebo-controlled trial in 200 patients with CHF and hyperuricemia,with HFrEF and serum uric acid levels≥7 mg/dL(≥416μmol/L).The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months.The primary endpoint was the change in serum uric acid level from baseline to 24 months.Secondary endpoints included changes in left ventricular ejection fraction(LVEF),Nterminal pro-B-type natriuretic peptide(NT-proBNP),and quality of life(QoL)scores,as well as the incidence of cardiovascular death and hospitalization for heart failure.RESULTS At 24 months,dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL(71μmol/L)compared with placebo(95%CI:-1.5 to-0.9;P<0.001).Dapagliflozin also significantly improved LVEF by 3.5%(95%CI:2.1-4.9;P<0.001),NT-proBNP by 25%(95%CI:18-32;P<0.001),and QoL scores by 10 points(95%CI:7-13;P<0.001)and reduced the risk of cardiovascular death and hospitalization for heart failure by 35%(95%CI:15–50;P=0.002)compared with the placebo.Adverse events were similar between the two groups,except for a higher rate of genital infections in the dapagliflozin group(10%vs 2%,P=0.01).CONCLUSION Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia.Therefore,dapagliflozin may be a useful therapeutic option for this high-risk population.

Clinical intervention effect of Xuefu Zhuyu decoction on chronic heart failure complicated with depression

BACKGROUND The diagnosis and treatment of depression in patients with chronic heart failure(CHF)is challenging,with no ideal treatment at present.AIM To analyze the clinical intervention effect of Xuefu Zhuyu decoction(XFZYD)on CHF complicated with depression.METHODS The study cohort comprised 116 patients with CHF complicated with depression who received treatment from July 2020 to July 2023,of which 55 received Western medicine(control group)and 61 received XFZYD(research group).Data on clinical effectiveness,traditional Chinese medicine(TCM)syndrome score,cardiac function,negative emotions,and serum inflammatory factors,were collected for comparative analyses.RESULTS Compared with the control group,the research group had an evidently higher total effective rate.Furthermore,there were marked reductions in TCM symptom score,left ventricular end-diastolic diameter,left ventricular end-systolic diameter,Self-Rating Depression Scale,Hamilton Depression Scale,high-sensitivity C-reactive protein,monocyte chemoattractant protein-1,and matrix metalloproteinase-9 in the research group after treatment,and these were lower than the corresponding values in the control group.Left ventricular ejection fraction was increased and higher in the research group compared with the control group after treatment.CONCLUSION Our findings conclusively proved that XFZYD was considerably superior to Western medicine for treating CHF complicated with depression because it significantly alleviated patients’symptoms,improved cardiac function,relieved negative emotions,and reduced the levels of serum inflammatory factors.

Bioinformatics Analysis of the Relationship between Dilated Cardiomyopathy and Chronic Heart Failure

Objective: To screen and analyze the differentially expressed genes between dilated cardiomyopathy (DCM) and chronic heart failure (CHF) based on bioinformatics methods. Methods: The Gene Expression Omnibus (GEO) database was used for data retrieval, and the chip data GSE3585 was downloaded, which was the original data of DCM and normal control group. At the same time, the chip data GSE76701 was downloaded, which was the original data of CHF and control group. Differentially expressed mRNAs (DEmRNAs) were screened by R language limma package, the data were standardized, and the common differentially expressed genes were screened. GO function and KEGG pathway enrichment analysis were performed on the common differentially expressed genes. String11.0 online tool was used for data analysis to obtain differentially expressed genes, and the results were imported into Cytoscape 3.9.1 software. The results were imported into Cytoscape 3.9.1 software, and the common expression gene module was obtained by MOCDE algorithm. Nine Hub genes were obtained by 10 algorithms such as MCC. Results: A total of 248 differentially expressed genes were screened. GO analysis showed that differentially expressed genes were mainly concentrated in 9 different physiological and pathological processes. KEGG analysis showed that the main signaling pathways involved in differentially expressed genes were 2, and 9 key differentially expressed genes were predicted: NPPB, NPPA, MYH6, FRZB, ASPN, SFRP4, RPS4Y1, DDX3Y. Conclusion: This study preliminarily explored the molecular mechanism of DCM and CHF, and obtained the common differentially expressed genes of the two diseases. Further experimental studies are needed to verify the correlation between gene expression and clinicopathological features. Provide new ideas for clinical drug treatment research.

Network pharmacology-based exploration of molecular mechanisms underlying therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure with spleen Qi deficiency syndrome

BACKGROUND Chronic heart failure is a complex clinical syndrome.The Chinese herbal compound preparation Jianpi Huatan Quyu recipe has been used to treat chronic heart failure;however,the underlying molecular mechanism is still not clear.AIM To identify the effective active ingredients of Jianpi Huatan Quyu recipe and explore its molecular mechanism in the treatment of chronic heart failure.METHODS The effective active ingredients of eight herbs composing Jianpi Huatan Quyu recipe were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The target genes of chronic heart failure were searched in the Genecards database.The target proteins of active ingredients were mapped to chronic heart failure target genes to obtain the common drugdisease targets,which were then used to construct a key chemical componenttarget network using Cytoscape 3.7.2 software.The protein-protein interaction network was constructed using the String database.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed through the Metascape database.Finally,our previously published relevant articles were searched to verify the results obtained via network pharmacology.RESULTS A total of 227 effective active ingredients for Jianpi Huatan Quyu recipe were identified,of which quercetin,kaempferol,7-methoxy-2-methyl isoflavone,formononetin,and isorhamnetin may be key active ingredients and involved in the therapeutic effects of TCM by acting on STAT3,MAPK3,AKT1,JUN,MAPK1,TP53,TNF,HSP90AA1,p65,MAPK8,MAPK14,IL6,EGFR,EDN1,FOS,and other proteins.The pathways identified by KEGG enrichment analysis include pathways in cancer,IL-17 signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,calcium signaling pathway,cAMP signaling pathway,NF-kappaB signaling pathway,AMPK signaling pathway,etc.Previous studies on Jianpi Huatan Quyu recipe suggested that this Chinese compound preparation can regulate the TNF-α,IL-6,MAPK,cAMP,and AMPK pathways to affect the mitochondrial structure of myocardial cells,oxidative stress,and energy metabolism,thus achieving the therapeutic effects on chronic heart failure.CONCLUSION The Chinese medicine compound preparation Jianpi Huatan Quyu recipe exerts therapeutic effects on chronic heart failure possibly by influencing the mitochondrial structure of cardiomyocytes,oxidative stress,energy metabolism,and other processes.Future studies are warranted to investigate the role of the IL-17 signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,and other pathways in mediating the therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure.

Investigation on the mechanism of Qiangxinhuoli prescription in the treatment of chronic heart failure based on p38-MAPK signaling pathway

Background:The aim of this study is to investigate the mechanism of action underlying the therapeutic effects of the national patent Chinese medicine compound“Qiangxinhuoli prescription(QXHLF)”on chronic heart failure(CHF).Methods:In vitro,the H_(9)C_(2) cell model was induced by ANGII,and cell proliferation and related protein expression were detected by Cell Counting Kit-8 and Western blot.In vivo,A rat model of CHF was prepared by ligation of the left anterior descending coronary artery.The effects of QXHLF on cardiac function in CHF rats were evaluated by cardiac index,hemodynamic changes,enzyme-linked immunosorbent assay,hematoxylin-eosin staining,immunohistochemistry,Western blot and RT-PCR.The expression of pro-apoptotic factors and anti-apoptotic factors,as well as TGFβ1,p-p38,TAK 1 mRNA,and protein,were detected.Results:In vitro,QXHLF has a significant inhibitory effect on the proliferation of H_(9)C_(2) cells.QXHLF can reduce the expression levels of TAK 1,TGFβ1,p-p38,Caspase3 and BAX proteins in H_(9)C_(2) cells,and increase the expression level of BCL_(2) protein.In vivo,QXHLF has the potential to increase left ventricular systolic pressure,m aximum rate of change in left ventricular pressure while decreasing left ventricular end diastolic pressure,and inhibiting the serum levels of brain natriuretic peptide.Moreover,QXHLF exhibits significant improvements in the pathological alterations of myocardial cells and fibers in CHF rats,leading to enhanced myocardial tissue morphology and notable advantages in combating myocardial fibrosis.QXHLF can reduce the levels of BAX and Caspase3 and up-regulate the expression of BCL_(2),thereby inhibiting cardiomyocyte apoptosis.Furthermore,QXHLF demonstrates inhibitory effects on the mRNA and protein expression levels of TGFβ_(1),TAK_(1),and p-p38 in the heart tissue of the CHF rat model.Conclusion:These findings indicate that QXHLF has a therapeutic effect on CHF by inhibiting the p38-MAPK signaling pathway,reducing myocardial fibrosis,preventing apoptosis,inhibiting cell proliferation,and restoring myocardial injury.

Left bundle branch pacing vs biventricular pacing in heart failure patients with left bundle branch block:A systematic review and meta-analysis

BACKGROUND Left bundle branch pacing(LBBP)is a novel pacing modality of cardiac resynchronization therapy(CRT)that achieves more physiologic native ventricular activation than biventricular pacing(BiVP).AIM To explore the validity of electromechanical resynchronization,clinical and echocardiographic response of LBBP-CRT.METHODS Systematic review and Meta-analysis were conducted in accordance with the standard guidelines as mentioned in detail in the methodology section.RESULTS In our analysis,the success rate of LBBP-CRT was determined to be 91.1%.LBBP CRT significantly shortened QRS duration,with significant improvement in echocardiographic parameters,including left ventricular ejection fraction,left ventricular end-diastolic diameter and left ventricular end-systolic diameter in comparison with BiVP-CRT.CONCLUSION A significant reduction in New York Heart Association class and B-type natriuretic peptide levels was also observed in the LBBP-CRT group vs BiVP-CRT group.Lastly,the LBBP-CRT cohort had a reduced pacing threshold at follow-up as compared to BiVP-CRT.

Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure

BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of action.We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy.Two groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control.AIM To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body weight.METHODS The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood pressure.To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMI)decrease,and lack of heart rate increase,linear regression analysis was performed.RESULTS There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up.Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI,while the predictor of stroke volume index increase was SGLT2i therapy itself.CONCLUSION SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic response.Glycemic control contributes to the improvement of heart function,blood pressure control,oxidative stress,and reduction in inflammation.

Serum cystatin C,monocyte/high-density lipoprotein-C ratio,and uric acid for the diagnosis of coronary heart disease and heart failure

BACKGROUND Coronary heart disease(CHD)and heart failure(HF)are the major causes of morbidity and mortality worldwide.Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis.However,conventional diagnostic methods such as electrocardiography,echocardiography,and cardiac biomarkers have certain limitations,such as low sensitivity,specificity,availability,and cost-effectiveness.Therefore,there is a need for simple,noninvasive,and reliable biomarkers to diagnose CHD and HF.AIM To investigate serum cystatin C(Cys-C),monocyte/high-density lipoprotein cholesterol ratio(MHR),and uric acid(UA)diagnostic values for CHD and HF.METHODS We enrolled 80 patients with suspected CHD or HF who were admitted to our hospital between July 2022 and July 2023.The patients were divided into CHD(n=20),HF(n=20),CHD+HF(n=20),and control groups(n=20).The serum levels of Cys-C,MHR,and UA were measured using immunonephelometry and an enzymatic method,respectively,and the diagnostic values for CHD and HF were evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Serum levels of Cys-C,MHR,and UA were significantly higher in the CHD,HF,and CHD+HF groups than those in the control group.The serum levels of Cys-C,MHR,and UA were significantly higher in the CHD+HF group than those in the CHD or HF group.The ROC curve analysis showed that serum Cys-C,MHR,and UA had good diagnostic performance for CHD and HF,with areas under the curve ranging from 0.78 to 0.93.The optimal cutoff values of serum Cys-C,MHR,and UA for diagnosing CHD,HF,and CHD+HF were 1.2 mg/L,0.9×10^(9),and 389μmol/L;1.4 mg/L,1.0×10^(9),and 449μmol/L;and 1.6 mg/L,1.1×10^(9),and 508μmol/L,respectively.CONCLUSION Serum Cys-C,MHR,and UA are useful biomarkers for diagnosing CHD and HF,and CHD+HF.These can provide information for decision-making and risk stratification in patients with CHD and HF.

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.

Establishing delivery route-dependent safety and efficacy of living biodrug mesenchymal stem cells in heart failure patients

BACKGROUND Mesenchymal stem cells(MSCs)as living biopharmaceuticals with unique properties,i.e.,stemness,viability,phenotypes,paracrine activity,etc.,need to be administered such that they reach the target site,maintaining these properties unchanged and are retained at the injury site to participate in the repair process.Route of delivery(RoD)remains one of the critical determinants of safety and efficacy.This study elucidates the safety and effectiveness of different RoDs of MSC treatment in heart failure(HF)based on phase II randomized clinical trials(RCTs).We hypothesize that the RoD modulates the safety and efficacy of MSCbased therapy and determines the outcome of the intervention.AIM To investigate the effect of RoD of MSCs on safety and efficacy in HF patients.METHODS RCTs were retrieved from six databases.Safety endpoints included mortality and serious adverse events(SAEs),while efficacy outcomes encompassed changes in left ventricular ejection fraction(LVEF),6-minute walk distance(6MWD),and pro-B-type natriuretic peptide(pro-BNP).Subgroup analyses on RoD were performed for all study endpoints.RESULTS Twelve RCTs were included.Overall,MSC therapy demonstrated a significant decrease in mortality[relative risk(RR):0.55,95%confidence interval(95%CI):0.33-0.92,P=0.02]compared to control,while SAE outcomes showed no significant difference(RR:0.84,95%CI:0.66-1.05,P=0.11).RoD subgroup analysis revealed a significant difference in SAE among the transendocardial(TESI)injection subgroup(RR=0.71,95%CI:0.54-0.95,P=0.04).The pooled weighted mean difference(WMD)demonstrated an overall significant improvement of LVEF by 2.44%(WMD:2.44%,95%CI:0.80-4.29,P value≤0.001),with only intracoronary(IC)subgroup showing significant improvement(WMD:7.26%,95%CI:5.61-8.92,P≤0.001).Furthermore,the IC delivery route significantly improved 6MWD by 115 m(WMD=114.99 m,95%CI:91.48-138.50),respectively.In biochemical efficacy outcomes,only the IC subgroup showed a significant reduction in pro-BNP by-860.64 pg/mL(WMD:-860.64 pg/Ml,95%CI:-944.02 to-777.26,P=0.001).CONCLUSION Our study concluded that all delivery methods of MSC-based therapy are safe.Despite the overall benefits in efficacy,the TESI and IC routes provided better outcomes than other methods.Larger-scale trials are warranted before implementing MSC-based therapy in routine clinical practice.

Digitalis Medication in Treatment of Heart Failure

In Mexico, digitalis was known since the 16th century and was used to treat patients with bloating, and it was not until the 20th century that it began to be used as a medicine for heart failure. In conjunction with diuretics. Digitalis was later used in combination individualized with the new medications, for this purpose and research has shown that the combination of medications on an individualized basis is what is currently successfully available for the medical treatment of heart failure.

A Chinese Multi-Specialty Delphi Consensus to Optimize RAASi Usage and Hyperkalaemia Management in Patients with Chronic Kidney Disease and Heart Failure

Objective Variations are present in common clinical practices regarding best practice in managing hyperkalaemia(HK),there is therefore a need to establish a multi-specialty approach to optimal renin angiotension-aldosterone system inhibitors(RAASi)usage and HK management in patients with chronic kidney disease(CKD)&heart failure(HF).This study aimed to establish a multi-speciality approach to the optimal use of RAASi and the management of HK in patients with CKD and HF.Methods A steering expert group of cardiology and nephrology experts across China were convened to discuss challenges to HK management through a nominal group technique.The group then created a list of 41 statements for a consensus questionnaire,which was distributed for a further survey in extended panel group of cardiologists and nephrologists across China.Consensus was assessed using a modified Delphi technique,with agreement defined as"strong"(≥75%and<90%)and"very strong"(≥90%).The steering group,data collection,and analysis were aided by an independent facilitator.Results A total of 150 responses from 21 provinces across China were recruited in the survey.Respondents were comprised of an even split(n=75,50%)between cardiologists and nephrologists.All 41 statements achieved the 75%consensus agreement threshold,of which 27 statements attained very strong consensus(≥90%agreement)and 14 attained strong consensus(agreement between 75%and 90%).Conclusion Based on the agreement levels from respondents,the steering group agreed a set of recommendations intended to improve patient outcomes in the use of RAASi therapy and HK management in China.

Sodium glucose cotransporter 2 inhibitors in the management of heart failure:Veni,Vidi,and Vici

Heart failure(HF)is a chronic disease associated with high morbidity and mortality rates.Renin-angiotensin-aldosterone system blockers(including angiotensin receptor/neprilysin inhibitors),beta-blockers,and mineralocorticoid receptor blockers remain the mainstay of pharmacotherapy for HF with reduced ejection fraction(HFrEF).However,despite the use of guideline-directed medical therapy,the mortality from HFrEF remains high.HF with preserved ejection fraction(HFpEF)comprises approximately half of the total incident HF cases;however,unlike HFrEF,there are no proven therapies for this condition.Sodium glucose cotransporter-2 inhibitors(SGLT-2is)represent a new class of pharmacological agents approved for diabetes mellitus(DM)that inhibit SGLT-2 receptors in the kidney.A serendipitous finding from seminal trials of SGLT-2is in DM was the significant improvement in renal and cardiovascular(CV)outcomes.More importantly,the improvement in HF hospitalization(HHF)in the CV outcomes trials of SGLT-2is was striking.Multiple mechanisms have been proposed for the pleiotropic effects of SGLT-2is beyond their glycemic control.However,as patients with HF were not included in any of these trials,it can be considered as a primary intervention.Subsequently,two landmark studies of SGLT-2is in patients with HFrEF,namely,an empagliflozin outcome trial in patients with chronic HF and a reduced ejection fraction(EMPEROR-Reduced)and dapagliflozin and prevention of adverse outcomes in HF(DAPA-HF),demonstrated significant improvement in HHF and CV mortality regardless of the presence of DM.These impressive results pitchforked these drugs as class I indications in patients with HFrEF across major guidelines.Thereafter,empagliflozin outcome trial in patients with chronic HF with preserved ejection fraction(EMPEROR-Preserved)and dapagliflozin evaluation to improve the lives of patients with preserved ejection fraction HF(DELIVER)trials successively confirmed that SGLT-2is also benefit patients with HFpEF with or without DM.These results represent a watershed as they constitute the first clinically meaningful therapy for HFpEF in the past three decades of evolution of HF management.Emerging positive data for the use of SGLT-2is in acute HF and post-myocardial infarction scenarios have strengthened the pivotal role of these agents in the realm of HF.In a short span of time,these classes of drugs have captivated the entire scenario of HF.