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.

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.

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.

The role of device therapy in heart failure with reduced ejection fraction(HFrEF) : a narrative review

Heart failure has gained increasing notice due to its high prevalence and mortality rate. The management for heart failure has been emphasized on the role of device therapy. Implantable cardioverter defibrillator(ICD) and cardiac resynchronization therapy(CRT) were given strong recommendation for heart failure with reduced ejection fraction(HFrEF), considering their effectiveness on preventing sudden cardiac death(SCD), improving cardiac function and benefiting survival. In this review, we explained the underlying mechanisms of disease initiation and progression in HFrEF, in order to build the connection between the pathological basis of HFrEF and the rationality of ICD and CRT on terminating ventricular arrhythmia, improving cardiac function, decreasing the rate of adverse clinical outcomes and benefiting survival. In addition, we discussed the high-quality researches with significant values on the discovery of device therapy clinical benefits, and compared the class I recommendations for device therapy in HFr EF, suggested by American Heart Association and European Society of Cardiology.

A Brief Review of a Common Clinical Question: Intravenous Diltiazem or Metoprolol for Atrial Fibrillation with Rapid Ventricular Response?

Two classes of rate controlling medications—beta blockers (BBs) and non- dihydropyridine calcium channel blockers (CCBs)—are given to patients who present with atrial fibrillation (AF) with rapid ventricular response (RVR). Both are Class I recommendations from the American Heart Association (AHA), American College of Cardiology (ACC), and Heart Rhythm Society (HRS) for the management of AF with RVR. Multiple studies support the view that diltiazem is more effective than metoprolol, even though data from the AFFIRM trial suggests BBs are more frequently used. CCBs are generally avoided in AF with RVR patients who have concomitant heart failure with reduced ejection fraction (HFrEF) for concern of triggering decompensation. However, some recent studies indicate this idea may be unfounded. The aim of this article is to compare the efficacy of diltiazem and metoprolol for rate control in AF with RVR and examine the use of diltiazem in patients with both AF with RVR and HFrEF.

Research progress of sacubitril/valsartan in heart failure patients with preserved ejection fraction

With the launch of sacubitril/valsartan(ARNI),there are new options for the treatment of heart failure(HF).However,ARNI is currently only used in HF patients with reduced ejection fraction(HFrEF).No evidence shows that no modern treatment can reduce mortality in HF patients with preserved ejection fraction(HFpEF).Therefore,it is urgently necessary clarify whether ARNI can be used in the treatment of HFpEF.In the present study,we summarized the research progress of ARNI in the treatment of HFpEF.

Prognostic utility of NT-proBNP greater than 70,000 pg/mL in patients with end stage renal disease

Natriuretic peptides are synthesized in ventricular myocytes and released into the circulation in response to increased myocardial wall stress, Causes of myocardial wall stress include pulmonary hypertension, ventricular dilatation, as well as heart failure with reduced or preserved left ventricular function.

Association of frailty with in-hospital outcomes in elderly patients with heart failure

BACKGROUND Frailty is prevalent in elderly patients with cardiovascular diseases.However,the association between frailty and in-hospital outcomes for elderly patients with heart failure and reduced ejection(HFrEF)remains unknown.AIM To evaluate the predictive efficacy of frailty,compared with pre-frailty,for adverse events in these patients.METHODS Elderly patients(≥60 years)with HFrEF were assessed.Frailty was evaluated with the Fried phenotype criteria,and physical performance was evaluated based on handgrip strength and the short physical performance battery(SPPB).The composite incidence of adverse events,including all-cause death,multiple organ failure,cardiac shock,and malignant arrhythmia,during hospitalization was recorded.RESULTS Overall,252 elderly individuals with HFrEF[mean age:69.4±6.7 years,male:169(67.0%)]were included.One hundred and thirty-five(53.6%)patients were frail and 93(36.9%)were pre-frail.Frail patients were older,more likely to be female,to have a lower blood pressure,and to present with left ventricular thrombosis(P all<0.05).Frail patients with HFrEF had a higher incidence of in-hospital mortality(11.9%vs 4.3%,P=0.048).Multivariate analyses showed that female gender(OR=0.422),aging(OR=1.090),poor cardiac functional class(OR=2.167),frailty(OR=2.379),and lower handgrip strength(OR=1.106)were independent predictors of in-hospital adverse events(P all<0.05).CONCLUSION Frailty may be associated with poor in-hospital outcomes for elderly patients with HFrEF.The influence of frailty on long-term prognosis in these patients deserves further investigation.

Heart‘omicsin’AGEing (HOMAGE):design,research objectives and characteristics of the common database

Heart failure is common in older people and its prevalence is increasing.The Heart ＇omics＇ in AGEing（HOMAGE） project aims to provide a biomarker approach that will improve the early diagnosis of heart failure.A large clinical database,based on（1） prospective population studies or（2） cross-sectional,prospective studies or randomized controlled trials（RCTs） of patients at risk for or with overt cardiovascular disease will be constructed to determine most promising ＇omics＇-based biomarkers to identify the risk of developing heart failure and/or comorbidities.Population studies,patient cohorts and RCTs are eligible for inclusion in the common database,if they received ethical approval to obtain and share data and have baseline information on cardiovascular risk factors.Currently,the HOMAGE database includes 43,065 subjects,from 20 studies in eight European countries,including healthy subjects from three population studies in France,Belgium and Italy（n = 7,124）,patients with heart failure（n = 4,312） from four cohorts in the UK,Spain and Switzerland and patients at high risk for cardiovascular disease（n = 31,629） in 13 cohorts.It is anticipated that more partners will join the consortium and enlarge the pooled data.This large merged database will be a useful resource with which to identify candidate biomarkers that play a role in the mechanism underlying the onset and progression of heart failure.

The Effect of Sacubitril/Valsartan in a Dialysis Patient with Severe Heart Failure*

Heart failure (HF) is a major comorbidity in patients with end-stage renal disease (ESRD). The pathogenesis of HF in patients on renal replacement therapy represents the confluence of several traditional and nontraditional vascular risk factors, unique to the milieu of chronic kidney disease and the dialysis modality [1]. The purpose of this report is to describe the efficacy and safety of sacubitril/valsartan for an ESRD patient on hemodialysis therapy conmbined with heart failure with reduced ejection fraction (HFrEF). A 35-year-old woman was undergoing hemodialysis due to ESRD and suffering from heart failure with reduced ejection fraction. Because of worsening heart failure and hypertension, she was prescribed with sacubitril/valsartan at a dose of 50 mg twice a day, spironolactone at a dose of 20 mg three times a day and metoprolol at a dose of 23.75 mg once daily. There was a symptomatic improvement with the heart failure and reduction in NT-proBNP level, accompanied by a decrease of blood pressure after using sacubitric/valsartan. In conclusion, it is safe and effective to take sacubitril/valsartan in this hemodialysis patient with severe heart failure.

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.