Heart failure with preserved ejection fraction and the first law of thermodynamics

In heart failure with preserved ejection fraction,significant left ventricular diastolic abnormalities are present,despite a normal systolic ejection fraction.This article will consider whether this is consistent with the law of conservation of energy,also know as the first law of thermodynamics.

Epicardial adipose tissue in obesity with heart failure with preserved ejection fraction: Cardiovascular magnetic resonance biomarker study

BACKGROUND Obesity has become a serious public health issue,significantly elevating the risk of various complications.It is a well-established contributor to Heart failure with preserved ejection fraction(HFpEF).Evaluating HFpEF in obesity is crucial.Epicardial adipose tissue(EAT)has emerged as a valuable tool for validating prognostic biomarkers and guiding treatment targets.Hence,assessing EAT is of paramount importance.Cardiovascular magnetic resonance(CMR)imaging is acknowledged as the gold standard for analyzing cardiac function and mor-phology.We hope to use CMR to assess EAT as a bioimaging marker to evaluate HFpEF in obese patients.AIM To assess the diagnostic utility of CMR for evaluating heart failure with preserved ejection fraction[HFpEF;left ventricular(LV)ejection fraction≥50%]by measuring the epicardial adipose tissue(EAT)volumes and EAT mass in obese patients.METHODS Sixty-two obese patients were divided into two groups for a case-control study based on whether or not they had heart failure with HFpEF.The two groups were defined as HFpEF+and HFpEF-.LV geometry,global systolic function,EAT volumes and EAT mass of all subjects were obtained using cine magnetic resonance sequences.RESULTS Forty-five patients of HFpEF-group and seventeen patients of HFpEF+group were included.LV mass index(g/m2)of HFpEF+group was higher than HFpEF-group(P<0.05).In HFpEF+group,EAT volumes,EAT volume index,EAT mass,EAT mass index and the ratio of EAT/[left atrial(LA)left-right(LR)diameter]were higher compared to HFpEF-group(P<0.05).In multivariate analysis,Higher EAT/LA LR diameter ratio was associated with higher odds ratio of HFpEF.CONCLUSION EAT/LA LR diameter ratio is highly associated with HFpEF in obese patients.It is plausible that there may be utility in CMR for assessing obese patients for HFpEF using EAT/LA LR diameter ratio as a diagnostic biomarker.Further prospective studies,are needed to validate these proof-of-concept findings.

Heart failure with preserved ejection fraction in the elderly: pathophysiology, diagnostic and therapeutic approach

Heart failure with preserved ejection fraction(HFpEF)is a clinical syndrome characterized by symptoms and sings of heart failure with elevated left ventricular filling pressures at rest or during exercise.It is the most common type of heart failure in the elderly and its prevalence increases with age and is higher in females at any given age.HFpEF is frequently accompanied of comorbid conditions such as diabetes mellitus,obesity,atrial fibrillation and renal dysfunction.The diagnosis relies in the integration of clinical information,laboratory data and interpretation of cardiac imaging and hemodynamic findings at rest and during exercise.Conditions that have a specific treatment such as coronary artery disease,valvular disease,cardiac amyloidosis and constrictive pericarditis should be considered and evaluated as appropriate.Aggressive management of comorbidities,optimization of blood pressure control and volume status using diuretics as needed are among the current treatment recommendations.There are no specific therapies that have shown to decrease mortality in HFpEF.In symptomatic patients with history of hospital admission for decompensated heart failure,the implantation of a wireless pulmonary artery pressure monitor should be considered.Finally,given the high mortality of this condition,goals of care discussion should be initiated early and involvement of palliative care medicine should be considered.

Diagnostic and prognostic value of circulating micro RNAs in heart failure with preserved and reduced ejection fraction

micro RNAs(mi RNAs) are powerful regulators of posttranscriptional gene expression and play an important role in pathophysiological processes. Circulating mi RNAs can be quantified in body liquids and are promising biomarkers in numerous diseases. In cardiovascular disease mi RNAs have been proven to be reliable diagnostic biomarkers for different disease entities. In cardiac fibrosis(CF) and heart failure(HF) dysregulated circulating mi RNAs have been identified,indicating their promising applicability as diagnostic biomarkers. Some mi RNAs were successfully tested in risk stratification of HF implementing their potential use as prognostic biomarkers. In this respect mi RNAs might soon be implemented in diagnostic clinical routine. In the young field of mi RNA based research advances have been made in identifying mi RNAs as potential targets for the treatment of experimental CF and HF. Promising study results suggest their potential future application as therapeutic agents in treatment of cardiovascular disease. This article summarizes the current state of the various aspects of mi RNA research in the field of CF and HF with reduced ejection fraction as well as preserved ejection fraction. The review provides an overview of the application of circulating mi RNAs as biomarkers in CF and HF and current approaches to therapeutically utilize mi RNAs in this field of cardiovascular disease.

Therapeutic interventions for heart failure with preserved ejection fraction:A summary of current evidence

Heart failure with preserved ejection fraction(HFPEF)is common and represents a major challenge in cardiovascular medicine.Most of the current treatment of HFPEF is based on morbidity benefits and symptom reduction.Various pharmacological interventions available for heart failure with reduced ejection fraction have not been supported by clinical studies for HFPEF.Addressing the specific aetiology and aggressive risk factor modification remain the mainstay in the treatment of HFPEF.We present a brief overview of the currently recommended therapeutic options with available evidence.

Risks of incident heart failure with preserved ejection fraction in Chinese patients hospitalized for cardiovascular diseases

Background Endogenous aldehyde damages DNA and potentiates an ageing phenotype. The aldehyde dehydrogenase 2(ALDH2) rs671 polymorphism has a prevalence of 30%–50% in Asian populations. In this study, we aimed to analyze risk factors contributing to the development of heart failure with preserved ejection fraction(HFpEF) along with the genetic exposure in Chinese patients hospitalized with cardiovascular diseases(CVD). Methods From July 2017 to October 2018, a total of 770 consecutive Chinese patients with normal left ventricular ejection fractions(LVEF) and established CVD(hypertension, coronary heart diseases, or diabetes) were enrolled in this prospective cross-sectional study. HFpEF was defined by the presence of at least one of symptom(dyspnoea and fatigue) or sign(rales and ankle swelling) related to heart failure;N-terminal pro-B-Type natriuretic peptide(NT pro-BNP ≥ 280 pg/mL);LVEF ≥ 50%;and at least one criterion related to elevated ventricular filling pressure or diastolic dysfunction(left atrial diameter > 40 mm, E/E’ ≥ 13, E’/A’ < 1 or concurrent atrial fibrillation). Logistic regression was performed to yield adjusted odds ratios(ORs) for HFp EF incidence associated with traditional and/or genetic exposures. Results Finally, among 770 patients with CVD, 92(11.9%) patients were classified into the HFpEF group according to the diagnostic criteria. The mean age of the participants was 67 ± 12 years, and 278(36.1%) patients were females. A total of 303(39.4%) patients were ALDH2*2 variant carriers. In the univariate analysis, eight exposures were found to be associated with HFpEF: atrial fibrillation, ALDH2*2 variants, hypertension, age, anaemia, smoking, alcohol consumption and sex. Multivariable logistic regression showed that 4 ‘A’ variables(atrial fibrillation, ALDH2*2 variants, age and anaemia) were significantly associated with an increased risk of HFpEF. Atrial fibrillation was associated with a 3.8-fold increased HFpEF risk(95% CI: 2.21–6.61, P < 0.001), and the other three exposures associated with increased HFpEF risk were the ALDH2*2 variant(OR = 2.41, 95% CI: 1.49–3.87, P < 0.001), age(OR = 2.14, 95% CI: 1.27–3.60, P = 0.004), and anaemia(OR = 1.79, 95% CI: 1.05–3.03, P = 0.032). These four variables predicted HFpEF incidence in Chinese CVD patients(C-statistic = 0.745, 95% CI: 0.691–0.800, P < 0.001). Conclusions 4 A traits(atrial fibrillation, ALDH2*2 variants, age and anaemia) were associated with an increased risk of HFpEF in Chinese CVD patients. Our results provide potential clues to the aetiology, pathophysiology and therapeutic targets of HFpEF.

Therapies for patients with coexisting heart failure with reduced ejection fraction and non-alcoholic fatty liver disease

Heart failure with reduced ejection fraction(HFrEF)and nonalcoholic fatty liver disease(NAFLD)are two common comorbidities that share similar pathophysiological mechanisms.There is a growing interest in the potential of targeted therapies to improve outcomes in patients with coexisting HFrEF and NAFLD.This manuscript reviews current and potential therapies for patients with coexisting HFrEF and NAFLD.Pharmacological therapies,including angiotensinconverting enzyme inhibitors/angiotensin receptor blockers,mineralocorticoids receptor antagonist,and sodium-glucose cotransporter-2 inhibitors,have been shown to reduce fibrosis and fat deposits in the liver.However,there are currently no data showing the beneficial effects of sacubitril/valsartan,ivabradine,hydralazine,isosorbide nitrates,digoxin,or beta blockers on NAFLD in patients with HFrEF.This study highlights the importance of considering HFrEF and NAFLD when developing treatment plans for patients with these comorbidities.Further research is needed in patients with coexisting HFrEF and NAFLD,with an emphasis on novel therapies and the importance of a multidisciplinary approach for managing these complex comorbidities.

Impact of vericiguat on heart failure with reduced ejection fraction:a review

Introduction:Heart failure is a major public health issue with a prevalence of about 26 million people worldwide.Reduced nitric oxide availability,lower soluble guanylate cyclase(sGC)activity,and decreased cyclic guanosine monophosphate(cGMP)production are the causes of HF's development.Vericiguat prescribed under the brand name Verquvo was approved by U.S.Food and Drug Administration(FDA)in January 2021.It is a novel agent and the first sGC stimulator which helps to treat patients suffering from heart failure with reduced ejection fraction(HFrEF).Objective:The mechanism of action(cGMP pathway)of vericiguat,its clinical trials,its use in the treatment of heart failure,and its possible future aspects in therapeutic recommendations are all covered in this review.It will also raise awareness amongst healthcare professionals about the pharmacokinetic and pharmacodynamic parameters,dosing,administration,and drug-related problems of this new drug.Methods:Various databases for drug review were used in this review like PubMed,Medline,Google scholar,Drug bank,U.s.FDA,Medscape,and European society of cardiology guidelines.A total of 58 articles were screened out of which 39 articles were included in this review.Results:This review discusses vericiguat's mechanism of action(cGMP pathway),clinical studies,application in the treatment of heart failure,and potential future considerations in therapeutic recommendations.It will also educate healthcare professionals about the new drug's pharmacokinetics and pharmacodynamics,dose,administration,and drug-related problems.Conclusion:After hospitalization for HFrEF,the 5-year survival rate is just 25%,and disease morbidity and death are stil significant.As adjunctive therapy for individuals with heart failure and a low ejection fraction,vericiguat has a moderate level of effectiveness.Vericiguat's efficacy as an adjunct therapy to different drugs used to cure HF has to be further investigated.Vericiguat's safety and dosage in patients who have severe renal or hepatic illness need to be studied further.

Thirty-day readmission in patients with heart failure with preserved ejection fraction:Insights from the nationwide readmission database

BACKGROUND There are rising numbers of patients who have heart failure with preserved ejection fraction(HFpEF).Poorly understood pathophysiology of heart failure with preserved and reduced ejection fraction and due to a sparsity of studies,the management of HFpEF is challenging.AIM To determine the hospital readmission rate within 30 d of acute or acute on chronic heart failure with preserved ejection fraction and its effect on mortality and burden on health care in the United States.METHODS We performed a retrospective study using the Agency for Health-care Research and Quality Health-care Cost and Utilization Project,Nationwide Readmissions Database for the year 2017.We collected data on hospital readmissions of 60514 adults hospitalized for acute or acute on chronic HFpEF.The primary outcome was the rate of all-cause readmission within 30 d of discharge.Secondary outcomes were cause of readmission,mortality rate in readmitted and index patients,length of stay,total hospitalization costs and charges.Independent risk factors for readmission were identified using Cox regression analysis.RESULTS The thirty day readmission rate was 21%.Approximately 9.17%of readmissions were in the setting of acute on chronic diastolic heart failure.Hypertensive chronic kidney disease with heart failure(1245;9.7%)was the most common readmission diagnosis.Readmitted patients had higher in-hospital mortality(7.9%vs 2.9%,P=0.000).Our study showed that Medicaid insurance,higher Charlson co-morbidity score,patient admitted to a teaching hospital and longer hospital stay were significant variables associated with higher readmission rates.Lower readmission rate was found in residents of small metropolitan or micropolitan areas,older age,female gender,and private insurance or no insurance were associated with lower risk of readmission.CONCLUSION We found that patients hospitalized for acute or acute on chronic HFpEF,the thirty day readmission rate was 21%.Readmission cases had a higher mortality rate and increased healthcare resource utilization.The most common cause of readmission was cardio-renal syndrome.

Targeting epicardial adipose tissue:A potential therapeutic strategy for heart failure with preserved ejection fraction with type 2 diabetes mellitus

Heart failure with preserved ejection fraction(HFpEF)is a heterogeneous syndrome with various comorbidities,multiple cardiac and extracardiac pathophysiologic abnormalities,and diverse phenotypic presentations.Since HFpEF is a heterogeneous disease with different phenotypes,individualized treatment is required.HFpEF with type 2 diabetes mellitus(T2DM)represents a specific phenotype of HFpEF,with about 45%-50% of HFpEF patients suffering from T2DM.Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM,which is intimately related to the expansion and dysfunction(inflammation and hypermetabolic activity)of epicardial adipose tissue(EAT).EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms.Therefore,suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM.Although there is no treatment specifically for EAT,lifestyle management,bariatric surgery,and some pharmaceutical interventions(anti-cytokine drugs,statins,proprotein convertase subtilisin/kexin type 9 inhibitors,metformin,glucagon-like peptide-1 receptor agonists,and especially sodium-glucose cotransporter-2 inhibitors)have been shown to attenuate the inflammatory response or expansion of EAT.Importantly,these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF.Accordingly,well-designed randomized controlled trials are needed to validate the efficacy of current therapies.In addition,more novel and effective therapies targeting EAT are needed in the future.

Dapagliflozin in Heart Failure with Reduced Ejection Fraction:A Real-World Study

Aims:We aimed to observe the improvements in cardiac function indexes and the occurrence of adverse events in patients with heart failure with reduced ejection fraction(HFrEF)after dapagliflozin administration in a real-world setting.Methods:We retrospectively included 201 patients with HFrEF who were treated at a tertiary hospital in Zhengzhou and started to take dapagliflozin(10 mg/d)from March 2020 to June 2021.Their New York Heart Association(NYHA)functional class,cardiac ultrasound indexes,laboratory indexes,and vital signs between baseline and the last follow-up visit were compared,and their adverse events during the follow-up period were recorded.Results:The follow-up period was 173(67–210)days.The cardiac function indexes of patients at follow-up,com-pared with baseline,indicated significant improvement(proportion of NYHA functional class I and II:40.8%vs.56.2%;left ventricular ejection fraction:28.4±5.3%vs.34.7±5.9%;left ventricular end-diastolic diameter:70.1±6.4 mm vs.64.7±5.6 mm;N-terminal pro-B-type natriuretic peptide:5421.9±2864.4 pg/mL vs.2842.8±1703.4 pg/mL at baseline vs.at follow-up;all P<0.05).The rates of hypotension,deterioration of renal function,and genital infection during the follow-up period were 6.5%,4.0%,and 3.5%,respectively.Conclusions:We believe that dapagliflozin is safe and effective in patients with HFrEF in the real world.

Heterogeneity in cardiorenal protection by Sodium glucose cotransporter 2 inhibitors in heart failure across the ejection fraction strata:Systematic review and meta-analysis

BACKGROUND Gliflozins or Sodium glucose cotransporter 2 inhibitors(SGLT2i)are relatively novel antidiabetic medications that have recently been shown to represent favorable effects on patients’cardiorenal outcomes.However,there is shortage of data on potential disparities in this therapeutic effect across different patient subpopulations.AIM To investigate differential effects of SGLT2i on the cardiorenal outcomes of heart failure patients across left ventricular ejection fraction(LVEF)levels.METHODS Literature was searched systematically for the large randomized double-blind controlled trials with long enough follow up periods reporting cardiovascular and renal outcomes in their patients regarding heart failure status and LVEF levels.Data were then meta-analyzed after stratification of the pooled data across the LVEF strata and New York Heart Associations(NYHA)classifications for heart failure using Stata software version 17.0.RESULTS The literature search returned 13 Large clinical trials and 13 post hoc analysis reports.Meta-analysis of the effects of gliflozins on the primary composite outcome showed no significant difference in efficacy across the heart failure subtypes,but higher efficacy were detected in patient groups at lower NYHA classifications(I2=46%,P=0.02).Meta-analyses across the LVEF stratums revealed that a baseline LVEF lower than 30%was associated with enhanced improvement in the primary composite outcome compared to patients with higher LVEF levels at the borderline statistical significance(HR:0.70,95%CI:0.60 to 0.79 vs 0.81,95%CI:0.75 to 0.87;respectively,P=0.06).Composite renal outcome was improved significantly higher in patients with no heart failure than in heart failure patients with preserved ejection fraction(HFpEF)(HR:0.60,95%CI:0.49 to 0.72 vs 0.94,95%CI:0.74 to 1.13;P=0.04).Acute renal injury occurred significantly less frequently in heart failure patients with reduced ejection fraction who received gliflozins than in HFpEF(HR:0.67,95%CI:51 to 0.82 vs 0.94,95%CI:0.82 to 1.06;P=0.01).Volume depletion was consistently increased in response to SGLT2i in all the subgroups.CONCLUSION Heart failure patients with lower LVEF and lower NYHA sub-classifications were found to be generally more likely to benefit from therapy with gliflozins.Further research are required to identify patient subgroups representing the highest benefits or adverse events in response to SGLT2i.

Effect of Angiotensin Receptor-Neprilysin Inhibitor versus Valsartan on Cardiac Status in Patients with Chronic Heart Failure with Reduced Ejection Fraction: A Randomized Clinical Trial in Rangpur Medical College Hospital, Bangladesh

Background: Heart failure with reduced ejection fraction has a significant association with considerable morbidity and mortality, but there is still inadequacy in appropriate treatment to prevent this condition. We observed the effect of angiotensin receptor neprilysin inhibitor (ARNi) with such disorder compared to valsartan. Methods: In this single-blind trial, the patients were enrolled with chronic HF aged on or above 40 years, symptomatic NYHA class II - IV, an elevated NT-proBNP above 400 pg/ml level and a reduced LVEF of 40% or less. The patients were randomly assigned 1:1 to the treatment arms either ARNi (50 mg titrated to 100 mg twice a day) or valsartan (40 mg titrated to 80 mg twice a day) and followed for a median of 88 days. The primary outcome was mode of cardiovascular death and re-hospitalization for heart failure. Changes in the level of NT-proBNP and rate of ejection fraction were also measured. Results: Cardiovascular deaths occurred 4 (8%) in the ARNi treatment arm, while 11 (22%) in the valsartan treatment arm with significant hazard ratio in the ARNi group [Hazard Ratio = 0.37;95% CI: 0.34, 0.64;p = 0.042] during a median of 88 days of follow up period and 2 (4%) of the patients from the ARNi treatment arm were hospitalized due to HF, while in the valsartan treatment arm, 10 (20%) patients were hospitalized due to HF followed by receiving treatment respectively with hazard ratio in the ARNi group [Hazard Ratio = 0.80;95% CI: 0.57, 0.92;p Conclusion: Chronic treatment with the angiotensin receptor neprilysin inhibitor (ARNi) strongly decreases the NT-proBNP as well as morbidity and mortality and increases LVEF in patients with heart failure compared to valsartan.

The Relationship between Abnormal Circadian Blood Pressure Rhythm and Risk of Readmission in Patients with Heart Failure with Preserved Ejection Fraction

Objective:Abnormal circadian blood pressure rhythm has been revealed to be associated with hypertensive target organ damage and cardiovascular events,but its association with readmission risk in patients with heart failure with preserved ejection fraction(HFpEF)remains unknown.We conducted a retrospective study to explore the relationship between circadian blood pressure rhythm and readmission risk in HFpEF patients.Methods:We retrospectively collected baseline and follow-up data on HFpEF patients who underwent ambulatory blood pressure monitoring(ABPM)from May 2015 to October 2019.Patient circadian blood pressure rhythms defi ned by ABPM were grouped as dipper,nondipper,or riser patterns.Univariate and multivariate linear regression analyses were performed to assess the association between circadian blood pressure rhythm and readmission risk.Results:A total of 122 patients were enrolled in this study.The mean age and ejection fraction were 69.87 years and 61.44%,respectively,with mean the N-terminal pro-B-type natriuretic peptide(NT-proBNP)level being 1048.15 pg/mL.There were signifi cant differences in the 24-hour systolic blood pressure(SBP),sleep SBP,and sleep diastolic blood pressure(DBP)among the three groups,where the 24-hour SBP,sleep SBP,and sleep DBP in the riser pattern group were markedly higher than in the dipper pattern group.Notably,serum NT-proBNP levels,the proportion of patients readmitted for heart failure and the mean number of admissions differed markedly among three groups.Instructively,multivariate linear regression analysis showed that the riser pattern was a signifi cant and independent risk factor for increased serum NT-proBNP level(β=929.16,95%confi dence interval 178.79–1679.53,P=0.016).In multivariate logistic regression analysis,the riser pattern was demonstrated to be a signifi cant risk factor for readmission(odds ratio 11.23,95%confi dence interval 2.01–62.67,P=0.006)in HFpEF patients.Conclusion:The riser blood pressure pattern is a potential risk factor for elevated serum NT-proBNP level and readmission in HFpEF patients.

Air pollution and heart failure: Relationship with the ejection fraction

AIM: To study whether the concentrations of particulate matter in ambient air are associated with hospitaladmission due to heart failure in patients with heart failure with preserved ejection fraction and reduced ejection fraction. METHODS: We studied 353 consecutive patients admitted into a tertiary care hospital with a diagnosis of heart failure. Patients with ejection fraction of ≥ 45% were classified as having heart failure with preserved ejection fraction and those with an ejection fraction of < 45% were classified as having heart failure with reduced ejection fraction. We determined the average concentrations of different sizes of particulate matter (< 10, < 2.5, and < 1 μm) and the concentrations of gaseous pollutants (carbon monoxide, sulphur dioxide, nitrogen dioxide and ozone) from 1 d up to 7 d prior to admission. RESULTS: The heart failure with preserved ejection fraction population was exposed to higher nitrogen dioxide concentrations compared to the heart failure with reduced ejection fraction population (12.95 ± 8.22 μg/m 3 vs 4.50 ± 2.34 μg/m 3 , P < 0.0001). Multivariate analysis showed that nitrogen dioxide was a significant predictor of heart failure with preserved ejection fraction (odds ratio ranging from (1.403, 95%CI: 1.003-2.007, P = 0.04) to (1.669, 95%CI: 1.043-2.671, P = 0.03). CONCLUSION: This study demonstrates that shortterm nitrogen dioxide exposure is independently associated with admission in the heart failure with preserved ejection fraction population.

Progress in the Pathogenesis and Treatment of Heart Failure with Preserved Ejection Fraction

Heart failure with preserved ejection fraction(HFpEF)is a special and common clinical heart failure with left ventricular diastolic dysfunction.It has attracted much attention at home and abroad in recent years because of its high heterogeneity and complex pathogenesis.Compared with heart failure with reduced ejection fraction(HFrEF),HFpEF has complex clinical manifestations,many complications,limited clinical treatment,and poor prognosis.In recent years,the research on the pathogenesis and treatment of HFpEF has made certain progress,but there are no specific guidelines for clinical practice.By combing the latest research at home and abroad,the pathogenesis and treatment of HFpEF are systematically reviewed in order to provide a relevant basis for reference its clinical treatment.

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.

Kill two birds with one stone:Hapatologist’s approach to metabolic dysfunction-associated steatotic liver disease and heart failure

Heart failure(HF)is a major global public health concern,and one of the less commonly known risk factors for HF development is metabolic dysfunction-associated steatotic liver disease(MASLD),as they share a similar pathophysio-logical background.In this article,we evaluated a recently published review article by Arriola-Montenegro et al.This article briefly summarizes the common pathophysiology of HF and MASLD development and evaluates the available therapeutic options to treat both conditions.Clinical practice guidelines highlight the importance of initiating and titrating guideline-directed medication therapy(GDMT)for patients with HF with reduced ejection fraction.GDMT is comprised of the four pillars currently proposed in most clinical practice guidelines,namely angiotensin-converting enzyme inhibitors(ACEIs),angiotensin receptor blockers(ARBs),angiotensin receptor-neprilysin inhibitors,beta-blockers,mineralocor-ticoid receptor antagonists,and sodium-glucose co-transporter 2 inhibitors(SGLT-2i).Given the similarity of pathophysiology and risk factors,recent studies for GDMT regarding ACEIs,ARBs,mineralocorticoid receptor antagonists,and SGLT-2i have shown beneficial effects on MASLD.Nonetheless,other medications for both conditions and novel therapies require more robust data and well-designed clinical studies to demonstrate their efficacies in both conditions.

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.