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.

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.

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.

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.

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.

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.

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.

The potential of herbal drugs to treat heart failure:The roles of Sirt1/AMPK

Heart failure(HF)is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic burden.In addition to cardiac myocyte oxidative stress and apoptosis,which are considered mechanisms for the development of HF,alterations in cardiac energy metabolism and pathological autophagy also contribute to cardiac abnormalities and ultimately HF.Silent information regulator 1(Sirt1)and adenosine monophosphate-activated protein kinase(AMPK)are nicotinamide adenine dinucleotide(NAD+)-dependent deacetylases and phosphorylated kinases,respectively.They play similar roles in regulating some pathological processes of the heart through regulating targets such as peroxisome proliferator-activated receptorγcoactivator 1α(PGC-1α),protein 38 mitogen-activated protein kinase(p38 MAPK),peroxisome proliferator-activated receptors(PPARs),and mammalian target of rapamycin(mTOR).We summarized the synergistic effects of Sirt1 and AMPK in the heart,and listed the traditional Chinese medicine(TCM)that exhibit cardioprotective properties by modulating the Sirt1/AMPK pathway,to provide a basis for the development of Sirt1/AMPK activators or inhibitors for the treatment of HF and other cardiovascular diseases(CVDs).

Latest updates on structure and recommendations of cardiac rehabilitation programs in chronic heart failure

Chronic heart failure(HF)is a clinical syndrome with high morbidity and mor-tality worldwide.Cardiac rehabilitation(CR)is a medically supervised program designed to maintain or improve cardiovascular health of people living with HF,recommended by both American and European guidelines.A CR program con-sists of a multispecialty group including physicians,nurses,physiotherapists,trainers,nutritionists,and psychologists with the common purpose of improving functional capacity and quality of life of chronic HF patients.Physical activity,lifestyle,and psychological support are core components of a successful CR program.CR has been shown to be beneficial in all ejection fraction categories in HF and most patients,who are stable under medication,are capable of participating.An individualized exercise prescription should be developed on the basis of a baseline evaluation in all patients.The main modalities of exercise training are aerobic exercise and muscle strength training of different intensity and frequency.It is important to set the appropriate clinical outcomes from the beginning,in order to assess the effectiveness of a CR program.There are still significant limitations that prevent patients from participating in these programs and need to be solved.A significant limitation is the generally low quality of research in CR and the presence of negative trials,such as the rehabilitation after myocardial infarction trial,where comprehensive rehabilitation following myocardial infraction had no important effect on mortality,morbidity,risk factors,or health-related quality of life or activity.In the present editorial,we present all the updated knowledge and recommendations in CR programs.

Cardioprotective effects of glucagon-like peptide 1 receptor agonists in heart failure: Myth or truth?

Therapy with glucagon-like peptide 1(GLP1)receptor agonists has raised great interest for its beneficial cardiovascular effects in preventing atherosclerosis and heart failure-related outcomes.However,while evidence about atherosclerosis consistently suggests a cardioprotective potential with class effect,controversies remain on its impact on heart failure.GLP1 receptor agonists appear to prevent hospitalization for new-onset heart failure and reduce symptoms in heart failure with preserved ejection fraction(as demonstrated by the recent STEP-HFpEF Trial).Still,GLP1 agonism has resulted in neutral or even harmful effects in patients with established heart failure with reduced ejection fraction(the LIVE trial).GLP1 receptor agonists benefit the cardiovascular system indirectly through their marked metabolic effects(improved weight management,glycemic control,blood pressure,systemic and tissue inflammation),while direct effects on the heart have been questioned.Nonetheless,weight loss alone achieved through GLP1 receptor agonists has failed in improving left ventricular functions.Tirzepatide is a dual agonist of GLP1 and glucose-dependent insulinotropic polypeptide,representing an innovative treatment option in diabetes with a major impact on weight loss and promising cardiovascular benefits.Whether this class of therapies is going to change the history of heart failure is an ongoing debate.

Chlorogenic acid ameliorates heart failure by attenuating cardiomyocyte ferroptosis Author links open overlay panel

Objective To elucidate the effects of chlorogenic acid(CGA),a bioactive polyphenol compound prevalent in traditional Chinese medicine and various foods,including Lonicera japonica Thunb.(Jin Yin Hua),Eucommia ulmoides Oliv.(Du Zhong Ye),tea,and coffee,on cardiomyocyte ferroptosis and heart failure.Methods We assessed the effect of CGA on cardiac function using a mouse model of heart failure induced by transverse aortic constriction(TAC).These indicators included the left ventricular ejection fraction(LVEF),fractional shortening(LVFS),end-systolic volume(LVESV),end-diastolic volume(LVEDV),end-systolic diameter(LVESD),and end-diastolic diameter(LVEDD).An isoprenaline hydrochloride(ISO)-induced H9c2 cardiomyocyte cell model was also established,and the cells were treated with various concentrations of CGA.To assess the effect of CGA on ferroptosis in cardiomyocytes,we measured cell viability and evaluated the levels of intracellular reactive oxygen species(ROS),ferrous ions(Fe^(2+)),and lipid peroxidation using fluorescent staining.To clarify the ferroptosis signaling pathway regulated by CGA,western blotting was used to examine the expression of ferroptosis biomarkers,specifically solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),in H9c2 cardiomyocytes and mouse myocardial tissues.Results CGA significantly enhanced cardiac performance indices such as LVEF,LVFS,LVESV,LVEDV,LVESD,and LVEDD.H9c2 cardiomyocytes exposed to ISO showed decreased cell viability and increased ROS levels,Fe^(2+)content,and lipid peroxidation levels.However,CGA treatment significantly ameliorated these changes.Additionally,in both H9c2 cardiomyocytes and myocardial tissue obtained from mice with TAC,CGA increased the expression of ferroptosis-related proteins,including SLC7A11 and GPX4.Conclusion CGA has the potential to enhance cardiac function and diminish lipid peroxidation and ROS levels in cardiomyocytes via the SLC7A11/GPX4 signaling pathway.This process alleviates ferroptosis in cardiomyocytes.These results provide new insights into the clinical use of CGA and the management of heart failure.

Cardiovascular mechanisms of thyroid hormones and heart failure:Current knowledge and perspectives

A multiple hormonal imbalance that accompanies heart failure(HF)may have a significant impact on the clinical course in such patients.The non-thyroidal illness syndrome(NTIS),also referred to as euthyroid sick syndrome or low triiodothyronine syndrome,can be found in about 30%of patients with HF.NTIS represents a systemic adaptation to chronic illness that is associated with increased cardiac and overall mortality in patients with HF.While conclusions on thyroid-stimulating hormone,free triiodothyronine,total and free thyroxine are currently unresolved,serum total triiodothyronine levels and the ratio of free triiodothyronine to free thyroxine seem to provide the best correlates to the echocardiographic,laboratory and clinical parameters of disease severity.HF patients with either hyper-or hypothyroidism should be treated according to the appropriate guidelines,but the therapeutic approach to NTIS,with or without HF,is still a matter of debate.Possible treatment options include better individual titration of levothyroxine therapy,combined triiodothyronine plus thyroxine therapy and natural measures to increase triiodothyronine.Future research should further examine the cellular and tissue mechanisms of NTIS as well as new therapeutic avenues in patients with 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.

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.

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.

Ultrasound unveiling:Decoding venous congestion in heart failure for precision management of fluid status

This editorial discusses the manuscript by Di Maria et al,published in the recent issue of the World Journal of Cardiology.We here focus on the still elusive pathophysiological mechanisms underlying cardio-renal syndrome(CRS),despite its high prevalence and the substantial worsening of both kidney function and heart failure.While the measure of right atrial pressure through right cardiac catheterization remains the most accurate albeit invasive and costly procedure,integrating bedside ultrasound into diagnostic protocols may substantially enhance the staging of venous congestion and guide therapeutic decisions.In particular,with the assessment of Doppler patterns across multiple venous districts,the Venous Excess Ultrasound(VExUS)score improves the management of fluid overload and provides insight into the underlying factors contributing to cardio-renal interactions.Integrating specific echocardiographic parameters,particularly those concerning the right heart,may thus improve the VExUS score sensitivity,offering perspective into the nuanced comprehension of cardio-renal dynamics.A multidisciplinary approach that consistently incorporates the use of ultrasound is emerging as a promising advance in the understanding and management of CRS.

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.

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.

Effectiveness and mechanisms of sodium-dependent glucose transporter 2 inhibitors in type 2 diabetes and heart failure patients

We comment on an article by GrubićRotkvićet al published in the recent issue of the World Journal of Cardiology.We specifically focused on possible factors affecting the therapeutic effectiveness of sodium-dependent glucose transporter inhibitors(SGLT2i)in patients with type 2 diabetes mellitus(T2DM)and their impact on comorbidities.SGLT2i inhibits SGLT2 in the proximal tubules of the kidneys,lowering blood glucose levels by inhibiting glucose reabsorption by the kidneys and causing excess glucose to be excreted in the urine.Previous studies have demonstrated a role of SGLT2i in cardiovascular function in patients with diabetes who take metformin but still have poor glycemic control.In addition,SGLT2i has been shown to be effective in anti-apoptosis,weight loss,and cardiovascular protection.Accordingly,it is feasible to treat patients with T2DM with cardiovascular or renal diseases using SGLT2i.