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.

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.

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.

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.

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.

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.

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.

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.

Biomechanical Manifestations of Diastolic and Systolic Function in Rats with Heart Failure with Preserved Ejection Fraction

Objective Heart failure(HF)is divided into two types:Heart failure with reduced ejection fraction(HFrEF)and heart failure with preserved ejection fraction(HFpEF).The latter always results in diastolic dysfunction,characterized by changes in mechanical properties.The objective of this study is to build a finite element(FE)model of HFpEF and analyze diastolic and systolic function in rats.Methods Ten Dahl salt-sensitive rats were fed either a low-salt(LS)(n=5)or highsalt(HS)(n=5)diet beginning at 7 weeks of age and scanned by ultrasonic machine at 14 weeks of age.A non-linear FE model of the left ventricle(LV)was built from cardiac echo images at end-diastole and passive material properties of the LV were prescribed using Fung’s transversely isotropic constitutive law.Fiber angles of the endocardium and epicardium were prescribed as 53°°and-52°,respectively,with respect to the circumferential direction and varied linearly through the LV wall.The method developed by Krishnamurthywas used to determine the unloaded geometry to estimate the Fung passive material parameters.LV end-diastolic pressure(EDP)was determined from the measured pressure waves and applied to the endocardium at the unloaded geometry to simulate passive filling.Active material properties of the LV were prescribed using Guccione’s time-varying elastance model and maximum isometric tension was scaled to match the measured peak systolic pressure.The finite element model was then coupled to the Windkessel model,whose parameters were adjusted to the measured hemodynamics.Results Measured LVEDPs of LS and HS rats were 4.9±3.4 mmHg and 13.2±5.4 mmHg(P-0.030 8),respectively.End-diastolic Cauchy stress along the fiber direction for LS rats was significantly lower than for HS rats(0.91±0.60 kPa vs 3.00±0.63 kPa,P=0.001 4)and there was a similar trend in end-diastolic Green Strain along the fiber direction(0.058±0.003 vs 0.072±0.010,P=0.012 8,Figure 1b),as well.There was no distinctive difference between end-systolic Cauchy stress along the fiber direction for LS rats and HS rats(17.2±4.3 kPa vs 17.2±5.5 kPa,P=0.991 9)but end-systolic Green Strain along the fiber direction for LS rats was significantly higher than for HS rats(-0. 108±0.017 vs-0.065±0.024,negative sign represents direction).Conclusions For rats with HFpEF,it is the elevated LVEDP that induces the increase in end-diastolic stress and strain,thereby leading to diastolic dysfunction.Because of the preserved ejection fraction,HFpEF has less effect on systolic function.

Increased index of microcirculatory resistance in older patients with heart failure with preserved ejection fraction

Objective To study the coronary microvascular function in older patients with heart failure with preserved ejection fraction (HFpEF) using an invasive pressure–temperature sensor guidewire. Methods Patients undergoing echocardiography and cardiac catheterization examinations for exertional dyspnea and a positive stress test were retrospectively enrolled from January 2014 to November 2017, and were allocated into the control group or HFpEF group. The HFpEF group was secondary divided into two groups according to the age of 65 years. Comparing the clinical features and values obtained in examinations between the three groups, multivariate regression analysis was used to analyze the predictors of left ventricle end diastolic pressure (LVEDP). Results There were 87 patients enrolled in this study. The older HFpEF patients (n = 32) were more likely to be female;and had the most comorbidities, such as diabetes mellitus, atrial fibrillation, and chronic kidney dysfunction (CKD) with a low estimated glomerular filtration rate (eGFR), and had a similar hypertensive prevalence as the adult HFpEF group (n = 24), whose mean LVEDP and index of microcirculatory resistance (IMR) were highest in comparison to the adult HFpEF patients and controls (n = 31). The coronary flow reserve (CFR) in the older HFpEF and adult HFpEF groups was similarly reduced. In the regression analysis, the IMR linearly correlated to LVEDP, and was the only independent predictor of LVEDP. Conclusions An increased IMR and reduced CFR were characteristics of microvascular dysfunction in older HFpEF patients. The IMR independently had a positive linear correlation with LVEDP. Microvascular rarefaction might be a subsequent pathological progression in the development of HFpEF.

Heart failure with preserved ejection fraction: A distinct heart failure phenotype?

The present work discusses the serious confusion resulting from the arbitrary nomenclature of heart failure with preserved ejection fraction(HFpEF),the presumed underlying pathophysiology,and the supposed features.A consequence of this misconception is that HFpEF trials have recruited patients with entirely different characteristics rendering the extrapolation of the results of one study to the other infeasible and dramatically affecting diagnosis and treatment.

Health-related quality of life among congestive heart failure patients with preserved and reduced ejection fraction

Objective:To determine factors that affect the health-related quality of life(HRQOL)of congestive heart failure(CHF)patients with preserved and reduced ejection fraction.Methods:A cross-sectional study design was used for this study.The stratified random sampling was applied for each subgroup.HRQOL was measured with the Minnesota Living with Hear t Failure Questionnaire.The data were analyzed using chi-square,Spearman's correlation analysis,and independent t-test.Results:A number of 67 respondents participated in the recent study.The total mean scores of HRQOL were significantly different(P=0.001)between heart failure(HF)patients with reduced and preserved ejection fractions,41.07±7.54 and 54.97±4.36,respectively.It related with the physical(mean±standard deviation[SD]=10.4±2.14;t=-10.08,95%CI=-12.46 to-8.34;P-value=0.001)and psychological(mean±SD=3.5±0.5;t=-6.68,95%CI=-4.55 to-2.45;P-value=0.001)domain.Strong correlation was found between age(r=-0.898,P<0.05),NYHA functional classes(r=-0.858,P<0.01),duration of HF(r=-0.807,P<0.01),family support(r=0.927,P<0.01),and quality of life(Qo L).Conclusions:HRQOL in HF patients with reduced ejection fraction was higher than in those with preserved ejection fraction.Family suppor t is a fur ther determinant factor that has a positive correlation to the Qo L.

Right ventricular-arterial uncoupling as an independent prognostic factor in acute heart failure with preserved ejection fraction accompanied with coronary artery disease

Background:Right ventricular(RV)-arterial uncoupling is a powerful independent predictor of prognosis in heart failure with preserved ejection fraction(HFpEF).Coronary artery disease(CAD)can contribute to the pathophysiological characteristics of HFpEF.This study aimed to evaluate the prognostic value of RV-arterial uncoupling in acute HFpEF patients with CAD.Methods:This prospective study included 250 consecutive acute HFpEF patients with CAD.Patients were divided into RV-arterial uncoupling and coupling groups by the optimal cutoff value,based on a receiver operating characteristic curve of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure(TAPSE/PASP).The primary endpoint was a composite of all-cause death,recurrent ischemic events,and HF hospitalizations.Results:TAPSE/PASP≤0.43 provided good accuracy in identifying patients with RV-arterial uncoupling(area under the curve,0.731;sensitivity,61.4%;and specificity,76.6%).Of the 250 patients,150 and 100 patients could be grouped into the RV-arterial coupling(TAPSE/PASP>0.43)and uncoupling(TAPSE/PASP≤0.43)groups,respectively.Revascularization strategies were slightly different between groups;the RV-arterial uncoupling group had a lower rate of complete revascularization(37.0%[37/100]vs.52.7%[79/150],P<0.001)and a higher rate of no revascularization(18.0%[18/100]vs.4.7%[7/150],P<0.001)compared to the RV-arterial coupling group.The cohort with TAPSE/PASP≤0.43 had a significantly worse prognosis than the cohort with TAPSE/PASP>0.43.Multivariate Cox analysis showed TAPSE/PASP≤0.43 as an independent associated factor for the primary endpoint,all-cause death,and recurrent HF hospitalization(hazard ratios[HR]:2.21,95%confidence interval[CI]:1.44-3.39,P<0.001;HR:3.32,95%CI:1.30-8.47,P=0.012;and HR:1.93,95%CI:1.10-3.37,P=0.021,respectively),but not for recurrent ischemic events(HR:1.48,95%CI:0.75-2.90,P=0.257).Conclusion:RV-arterial uncoupling,based on TAPSE/PASP,is independently associated with adverse outcomes in acute HFpEF patients with CAD.

Elevated level of high-sensitivity cardiac troponin I as a predictor of adverse cardiovascular events in patients with heart failure with preserved ejection fraction

Background:The relationship between the elevation of cardiac troponin and the increase of mortality and hospitalization rate in patients with heart failure with reduced ejection fraction is clear.This study investigated the association between the extent of elevated levels of high-sensitivity cardiac troponin I(hs-cTnI)and the prognosis in heart failure with preserved ejection fraction patients.Methods:A retrospective cohort study consecutively enrolled 470 patients with heart failure with preserved ejection fraction from September 2014 to August 2017.According to the level of hs-cTnI,the patients were divided into the elevated level group(hs-cTnI>0.034 ng/mL in male and hs-cTnI>0.016 ng/mL in female)and the normal level group.All of the patients were followed up once every 6 months.Adverse cardiovascular events were cardiogenic death and heart failure hospitalization.Results:The mean follow-up period was 36.2±7.9 months.Cardiogenic mortality(18.6%[26/140]vs.1.5%[5/330],P<0.001)and heart failure(HF)hospitalization rate(74.3%[104/140]vs.43.6%[144/330],P<0.001)were significantly higher in the elevated level group.The Cox regression analysis showed that the elevated level of hs-cTnI was a predictor of cardiogenic death(hazard ratio[HR]:5.578,95%confidence interval[CI]:2.995-10.386,P<0.001)and HF hospitalization(HR:3.254,95%CI:2.698-3.923,P<0.001).The receiver operating characteristic curve demonstrated that a sensitivity of 72.6%and specificity of 88.8%for correct prediction of adverse cardiovascular events when a level of hs-cTnI of 0.1305 ng/mL in male and a sensitivity of 70.6%and specificity of 90.2%when a level of hs-cTnI of 0.0755 ng/mL in female were used as the cut-off value.Conclusion:Significant elevation of hs-cTnI(≥0.1305 ng/mL in male and≥0.0755 ng/mL in female)is an effective indicator of the increased risk of cardiogenic death and HF hospitalization in heart failure with preserved ejection fraction patients.

Therapeutic Efficacy of Shexiang Baoxin Pill Combined with Exercise in Patients with Heart Failure with Preserved Ejection Fraction: A Single-Center, Double-Blind, Randomized Controlled Trial

Objective:To evaluate the therapeutic efficacy of Shexiang Baoxin Pill combined with exercise in heart failure patients with preserved ejection fraction(HFpEF).Methods:Sixty patients with HFpEF were randomly divided into group A(n=20),receiving Shexiang Baoxin Pill combined with home-based exercise training based on conventional drugs for 12 weeks;group B(n=20),receiving conventional drugs combined with home-based exercise training for 12 weeks;and group C(n=20),receiving conventional drug treatment only.Peak oxygen uptake(peakVO2),anaerobic threshold(AT),6-min walking test(6MWT),Pittsburgh Sleep Quality Index(PSQI),and SF-36 questionnaire(SF-36)results before and after treatment were compared among groups.Results:After the 12-week intervention,patients in group C showed significant declines in peakVO2,AT,6MWT,PSQI,and SF-36 compared with pre-treatment(P<0.01),while groups A and B both showed significant improvements in peakVO2,AT,6MWT,PSQI,and SF-36 results compared with pre-treatment(P<0.01).Compared with group C,patients in groups A and B showed significant improvements in peakVO2,AT,6MWT,PSQI,and SF-36(P<0.01).In addition,patients in group A showed more significant improvements in physical function,role-physical,vitality,and mental health scores on the SF-36 questionnaire,and PSQI scores than those in group B(P<0.01).Conclusions:Exercise training improved exercise tolerance,sleep quality and quality of life(QoL)in patients with HFpEF.Notably,Shexiang Baoxin Pill played an active role in sleep quality and QoL of patients with HFpEF.

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.

A Data Mining-Based Study on Medication Rules of Chinese Herbs to Treat Heart Failure with Preserved Ejection Fraction

Objective:To summarize the medication rules of Chinese herbs to treat heart failure with preserved ejection fraction(HFPEF)based on data mining and to provide references for clinical utilization.Methods:The China National Knowledge Infrastructure(CNKI),Wanfang database(Wanfang),VIP database(VIP),Chinese Biomedical Literature(CBM),PubMed,Embase,and Cochrane Library databases were searched from inception to October 2021 to identify relevant literature on treating HFPEF with Chinese herbs.Microsoft Excel 2019 was used to set up a database,and then,association rule analysis and hierarchical cluster analysis were performed by using apriori algorithm and hclust function respectively in R-Studio(Version 4.0.3).Results:A total of 182 qualified papers were included,involving a total of 92 prescriptions,130 Chinese herbs,and 872 individual herbs prescribed,with an average of 9.5 herbs per prescription.The six most frequently prescribed herbs were Astragali Radix(Huangqi),Salviae Miltiorrhizae Radix Et Rhizoma(Danshen),Poria(Fuling),Glycyrrhizae Radix Et Rhizoma(Gancao),Cinnamomi Ramulus(Guizhi),and Ginseng Radix Et Rhizoma(Renshen).There were 35 herbs used more than 5 times,involving 11 efficacy categories.The top three categories were deficiency-tonifying herbs,blood-activating and stasis-removing herbs,and dampnessdraining diuretic herbs.The most commonly used herbs were mainly warm and sweet.The primary meridian tropisms were Lung Meridian,Heart Meridian and Spleen Meridian.Association rule analysis yielded 26 association rules,such as Astragali Radix(Huangqi)&Salviae Miltiorrhizae Radix Et Rhizoma(Danshen),Poria(Fuling),Cinnamomi Ramulus(Guizhi)&Atractylodis Macrocephalae Rhizoma(Baizhu).Hierarchical cluster analysis yielded four herb classes,and their functions were mainly qi-replenishing and yang-warming,bloodactivating and diuresis-inducing.Conclusions:HFPEF is the syndrome of root vacuity and tip repletion,and its core pathogenesis is"deficiency","stasis",and"wafer",with"deficiency"being the most principal,which is closely related to Xin(heart),Fei(Lung),and Pi(Spleen).The treatment of this disease occurs by improving qi,warming yang,activating blood and inducing diuresis.Astragali Radix(Huangqi)with Salviae Miltiorrhizae Radix Et Rhizoma(Danshen)is the basic combination of herbs applied.

Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction:A randomized clinical trial

Objective To determine the effect of the phosphodiesterase-5 inhibitor sildenafil compared with placebo on exercise capacity and clinical status in HFPEF. Design Multicenter, double-blind, placebo-controlled, parallel-group, randomized clinical trial of 216 sta- ble outpatients with HF, ejection fraction ≥ 50%, elevated N-terminal brain-type natriuretic peptide or elevat- ed invasively measured filling pressures, and reduced exercise capacity. Participants were randomized from October 2008 through February 2012 at 26 centers in North America. Follow-up was through August 30, 2012.

Heart failure with preserved ejection fraction (HFpEF) in type 2 diabetes melitus: from pathophysiology to therapeutics

Type 2 diabetes mellitus(T2DM or T2D)is a devastating metabolic abnormality featured by insulin resistance,hyperglycemia,and hyperlipidemia.T2D provokes unique metabolic changes and compromises cardiovascular geometry and function.Meanwhile,T2D increases the overall risk for heart failure(HF)and acts independent of classical risk factors including coronary artery disease,hypertension,and valvular heart diseases.The incidence of HF is extremely high in patients with T2D and is manifested as HF with preserved,reduced,and midrange ejection fraction(HFpEF,HFrEF,and HFmrEF,respectively),all of which significantly worsen the prognosis for T2D.HFpEFis seen in approximately half of the HF cases and is defined as a heterogenous syndrome with discrete phenotypes,particularly in close association with metabolic syndrome.Nonetheless,management of HFpEF in T2D remains unclear,largely due to the poorly defined pathophysiology behind HFpEF.Here,in this review,we will summarize findings from multiple preclinical and clinical studies as well as recent clinical trials,mainly focusing on the pathophysiology,potential mechanisms,and therapies of HFpEF in T2D.

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.