Effect of vericiguat on left ventricular structure and function in patients with heart failure with reduced ejection fraction: The VICTORIA echocardiographic substudy

Aim

Vericiguat significantly reduced the primary composite outcome of heart failure (HF) hospitalization or cardiovascular death in the VICTORIA trial. It is unknown if these outcome benefits are related to reverse left ventricular (LV) remodelling with vericiguat in patients with HF with reduced ejection fraction (HFrEF). The aim of this study was to compare the effects of vericiguat versus placebo on LV structure and function after 8 months of therapy in patients with HFrEF.

Methods and results

Standardized transthoracic echocardiography (TTE) was performed at baseline and after 8 months of therapy in a subset of HFrEF patients in VICTORIA. The co-primary endpoints were changes in LV end-systolic volume index (LVESVI) and LV ejection fraction (LVEF). Quality assurance and central reading were performed by an echocardiographic core laboratory blinded to treatment assignment. A total of 419 patients (208 vericiguat, 211 placebo) with high-quality paired TTE at baseline and 8 months were included. Baseline clinical characteristics were well balanced between treatment groups and echocardiographic characteristics were representative of patients with HFrEF. LVESVI significantly declined (60.7 ± 26.8 to 56.8 ± 30.4 ml/m²; p < 0.01) and LVEF significantly increased (33.0 ± 9.4% to 36.1 ± 10.2%; p < 0.01) in the vericiguat group, but similarly in the placebo group (absolute changes for vericiguat vs. placebo: LVESVI −3.8 ± 15.4 vs. −7.1 ± 20.5 ml/m²; p = 0.07 and LVEF +3.2 ± 8.0% vs. +2.4 ± 7.6%; p = 0.31). The absolute rate per 100 patient-years of the primary composite endpoint at 8 months tended to be lower in the vericiguat group (19.8) than the placebo group (29.6) (p = 0.07).

Conclusions

In this pre-specified echocardiographic study, significant improvements in LV structure and function occurred over 8 months in both vericiguat and placebo in a high-risk HFrEF population with recent worsening HF. Further studies are warranted to define the mechanisms of vericiguat's benefit in HFrEF.     

Outcomes and Predictors of Mortality Among Cardiac Intensive Care Unit Patients With Heart Failure

BackgroundLittle is known regarding the causes of critical illness and determinants of prognosis of patients with heart failure (HF) admitted to the modern cardiac intensive care unit (CICU). We sought to describe the epidemiology and outcomes of patients with HF admitted to the contemporary CICU.Methods and ResultsRetrospective cohort analysis of Mayo Clinic CICU patients admitted with HF from 2007 to 2018 who had left ventricular ejection fraction (LVEF) data. HF with reduced LVEF (HFrEF) was defined as a LVEF of less than 50%, and HF with preserved LVEF (HFpEF) as a LVEF of 50% or greater. In-hospital mortality was analyzed using multivariable logistic regression. Survival to 1 year was analyzed using a Kaplan–Meier analysis. We included 4012 patients, including 67.8% with HFrEF and 32.2% with HFpEF. Patients with HFrEF and HFpEF were comparable and had equivalent severity of illness. Critical care therapies were used in 59.4%, with a slight preponderance in patients with HFrEF. In-hospital mortality occurred in 12.5% of patients and was similar in HFrEF vs HFpEF. Shock and cardiac arrest were the strongest predictors of adjusted in-hospital mortality, followed by Braden skin score and serum chloride level; patients with HFrEF and HFpEF had similar adjusted mortality rates. The 1-year survival after hospital discharge was 74.5% and was slightly lower for patients with HFpEF. All-cause rehospitalization occurred in 36.6%, and 52.8% of hospital survivors died or were readmitted within 1 year.ConclusionsCICU patients with HF have a substantial burden of critical illness, high use of critical care therapies, and poor outcomes regardless of LVEF. This finding emphasizes the potential unmet care needs in this cohort.Lay summaryPatients with heart failure who require admission to the cardiac intensive care unit have high severity of illness and are at significant risk of death during and after hospitalization. These patients often require specialized critical care therapies to treat manifestations of critical illness. Patients who are admitted with cardiac arrest or shock, including those who require mechanical ventilation or vasopressors, are at particularly high risk of death. Patients’ left ventricular ejection fraction is not strongly associated with the risk of death when accounting for other major predictors including frailty and laboratory abnormalities.     

Sympathetic activation and outcomes in chronic heart failure: Does the neurohormonal hypothesis apply to mid-range and preserved ejection fraction patients?

BackgroundSympathetic activity (SA) is increased in patients with heart failure and reduced ejection fraction (HFrEF) and is associated with poor outcomes. However, its clinical implications are less understood in HF with mid-range (HFmrEF) and preserved ejection fraction (HFpEF). We aimed to study SA across left ventricle ejection fraction (LVEF) groups and its association with clinical outcomes.Methods and ResultsSA estimated by norepinephrine (NE) levels was determined in 742 consecutive outpatients with chronic HF: 348 (47%) with HFrEF, 116 (16%) HFmrEF, and 278 (37%) HFpEF. After a mean follow-up of 15 months, 17% died. Adjusted analyses showed that patients with HFpEF and HFmrEF had lower estimated marginal means of NE levels compared to HFrEF (278 and 116 pg/mL, respectively, vs. 348 pg/mL; p-value=0.005). Adjusted Cox regression analyses showed that high norepinephrine levels independently predicted all-cause mortality (ACM) in all 3 groups. The strongest associations between high NE levels and cardiovascular mortality (CVM) were observed in HFmrEF (HR: 4.7 [1.33–16.68]), while the weakest association was in HFpEF (HR: 2.62 [1.08–6.35]).ConclusionsAdjusted analyses showed that HFpEF and HFmrEF were associated with lower SA compared to HFrEF. Nevertheless, increasing NE levels were independently associated with ACM and CVM in all three LVEF groups. The strongest association between high NE levels and CVM was present in HFmrEF patients, while the weakest was seen in HFpEF. These findings could explain why the response to neurohormonal therapies in patients with HFmrEF is similar to that of patients with HFrEF rather than with HFpEF.     

Changes in the Left Ventricular Ejection Fraction and Outcomes in Hospitalized Heart Failure Patients with Mid-range Ejection Fraction: A Prospective Observational Study

Objective Current clinical guidelines have proposed heart failure (HF) with mid-range ejection fraction (HFmrEF), defined as a left ventricular ejection fraction (LVEF) of 40-49%, but the proportion and prognosis of patients transitioning toward HF with a reduced LVEF (LVEF <40%, HFrEF) or HF with a preserved LVEF (LVEF ≥50%, HFpEF) are not fully clear. The present study prospectively evaluated the changes in the LVEF one year after discharge and the outcomes of hospitalized patients with HFmrEF. Methods We prospectively studied 259 hospitalized patients with HFmrEF who were discharged alive at our institutions between 2015 and 2019. Among them, 202 patients with HFmrEF who underwent echocardiography at the one-year follow-up were included in this study. Patient characteristics, echocardiographic data and all-cause death were collected. Results Eighty-seven (43%) patients transitioned to HFpEF (improved group), and 35 (17%) transitioned to HFrEF (worsened group). During a median follow-up of 33 months, 27 (13%) patients died. After adjustment, patients in the worsened group had an increased risk of all-cause mortality compared with those in the improved group [hazard ratio 7.02, 95% confidence interval (CI) 1.13-43.48]. The baseline LVEF (per 1% decrease) and tricuspid annular plane systolic excursion (per 1 mm decrease) were independent predictors of the worsened LVEF category (odds ratio 2.13, 95% CI 1.25-3.63 and odds ratio 1.31, 95% CI 1.01-1.70, respectively). Conclusion Our study showed that a worsened LVEF one year after discharge was associated with a poor prognosis in hospitalized patients with HFmrEF.     

Representativeness of the VICTORIA Trial Population in Clinical Practice: Analysis of the PINNACLE Registry

BackgroundIn the VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial, vericiguat reduced the risk of mortality due to cardiovascular problems and of hospitalization due to heart failure (HF) among patients with HF with reduced ejection fraction (HFrEF) and recent worsening HF events (WHFEs). The representativeness of the VICTORIA population of patients with WHFE in clinical practice is unknown.Methods and ResultsPatients with HF and ejection fraction <45% were identified in the Practice Innovation And Clinical Excellence (PINNACLE) registry and were stratified by the occurrence of WHFEs. Characteristics and outcomes of patients in the PINNACLE registry with and without WHFEs were compared to the VICTORIA population. Of the 14,180 PINNACLE patients identified with HFrEF, 26.5% had had a WHFE. The VICTORIA population was similar to PINNACLE patients with WHFEs in mean age (67.3 vs 66.7), ejection fraction (28.9% vs 28.3%), body mass index (26.8 vs 27.6), and comorbidity burden. The rate of hospitalization because of HF at 1 year was 29.6% in the placebo group of VICTORIA, compared to 35.8% in PINNACLE patients with WHFEs and 13.3% in patients without WHFEs.ConclusionsThe PINNACLE patients with WHFEs meeting the VICTORIA definition resembled the VICTORIA population in characteristics and outcomes, suggesting that VICTORIA's population may be generalizable to patients with WHFEs in clinical practice.     

Características e Tendências na Mortalidade em Diferentes Fenótipos de Insuficiência Cardíaca na Atenção Primária

Background:The classification of heart failure (HF) by phenotypes has a great relevance in clinical practice.Objective:The study aimed to analyze the prevalence, clinical characteristics, and outcomes between HF phenotypes in the primary care setting.Methods:This is an analysis of a cohort study including 560 individuals, aged ≥ 45 years, who were randomly selected in a primary care program. All participants underwent clinical evaluations, b-type natriuretic peptide (BNP) measurements, electrocardiogram, and echocardiography in a single day. HF with left ventricular ejection fraction (LVEF) < 40% was classified as HF with reduced ejection fraction (HFrEF), LVEF 40% to 49% as HF with mid-range ejection fraction (HFmrEF) and LVEF ≥ 50% as HF with preserved ejection fraction (HFpEF). After 5 years, the patients were reassessed as to the occurrence of the composite outcome of death from any cause or hospitalization for cardiovascular disease.Results:Of the 560 patients included, 51 patients had HF (9.1%), 11 of whom had HFrEF (21.6%), 10 had HFmrEF (19.6%) and 30 had HFpEF (58.8%). HFmrEF was similar to HFpEF in BNP levels (p < 0.001), left ventricular mass index (p = 0.037), and left atrial volume index (p < 0.001). The HFmrEF phenotype was similar to HFrEF regarding coronary artery disease (p = 0.009). After 5 years, patients with HFmrEF had a better prognosis when compared to patients with HFpEF and HFrEF (p < 0.001).Conclusion:The prevalence of ICFEI was similar to that observed in previous studies. ICFEI presented characteristics similar to ICFEP in this study. Our data show that ICFEi had a better prognosis compared to the other two phenotypes.     

Fração de Ejeção do Ventrículo Esquerdo Aumentada,Diminuída ou Estável ao Longo do Tempo em uma Série de 626 Pacientes com Insuficiência Cardíaca que Receberam Tratamento Médico

Background:Ejection fraction (EF) has been used in phenotype analyses and to make treatment decisions regarding heart failure (HF). Thus, EF has become a fundamental part of daily clinical practice.Objective:This study aims to investigate the characteristics, predictors, and outcomes associated with EF changes in patients with different types of severe HF.Methods:A total of 626 severe HF patients with New York Heart Association (NYHA) class III–IV were enrolled in this study. The patients were classified into three groups according to EF changes, namely, increased EF (EF-I), defined as an EF increase ≥10%, decreased EF (EF-D), defined as an EF decrease ≥10%, and stable EF (EF-S), defined as an EF change <10%. A p-value lower than 0.05 was considered significant.Results:Out of 377 severe HF patients, 23.3% presented EF-I, 59.5% presented EF-S, and 17.2% presented EF-D. The results further showed 68.2% of heart failure with reduced ejection fraction (HFrEF) in the EF-I group and 64.6% of heart failure with preserved ejection fraction (HFpEF) in the EF-D group. The predictors of EF-I included younger age, absence of diabetes, and lower left ventricular ejection fraction (LVEF). The predictors of EF-D were absence of atrial fibrillation, lower uric acid level, and higher LVEF. Within a median follow-up of 40 months, 44.8% of patients suffered from all-cause death.Conclusion:In severe HF, HFrEF presented the highest percentage in the EF-I group, and HFpEF was most common in the EF-D group.     

Time to Triple Therapy in Patients With de Novo Heart Failure With Reduced Ejection Fraction: a Population-Based Study

BackgroundQuadruple therapy is recommended for the management of patients with heart failure (HF) and reduced ejection fraction (HFrEF). In order to provide background and identify barriers to quadruple therapy, in this study, the aim was to explore the time to initiation of triple therapy in a population-based cohort of patients with de novo HF.MethodsAdult patients with de novo hospital or emergency department (ED) diagnosis of HF between April 1, 2008, and March 31, 2018, in Alberta, Canada, were included and were linked to echocardiography data to identify patients with HFrEF (EF ≤ 40%). Any treatment with angiotensin-converting enzyme inhibitors/ angiotensin receptor blockers/ angiotensin receptor neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists was captured if prescribed for ≥ 28 days and filled at least once during the 12 months after the index episode.ResultsAmong 14,092 patients with de novo HF and available echocardiography data, 54.9% had HFrEF. By 1 year after diagnosis, of those in the HFrEF cohort, 9.5% had received no therapy, 27.5% monotherapy, 41.6% dual therapy, and 21.4% triple therapy. The median (interquartile range) of time to mono-, dual- and triple therapy in patients with HFrEF were 1 (0, 26), 8 (0, 44), and 14 (0, 52) days, respectively. Patients who received triple therapy were younger, more likely to be male and to have higher frequencies of coronary artery disease, higher glomerular filtration rates and lower left ventricular ejection fraction levels compared to their counterparts. Patients with triple therapy had lower rates of clinical outcomes compared to those on no, mono or dual therapy (adjusted hazard ratio 0.15, 95% confidence interval 0.13, 0.17 for the composite outcome of death, hospitalization due to HF, or ED visit due to HF).ConclusionDespite guideline recommendations, triple therapy is underused and is slowly deployed in patients with HFrEF, even after hospitalization and ED presentation.     

Eligibility for vericiguat in a real-world heart failure population according to trial,guideline and label criteria: Data from the Swedish Heart Failure Registry

Aim

We investigated the eligibility for vericiguat in a real-world heart failure (HF) population based on trial, guideline and label criteria.

Methods and results

From the Swedish HF registry, 23 573 patients with HF with reduced ejection fraction (HFrEF) enrolled between 2000 and 2018, with a HF duration ≥6 months, were considered. Eligibility for vericiguat was calculated based on criteria from (i) the Vericiguat Global Study in Subjects with Heart Failure and Reduced Ejection Fraction (VICTORIA) trial; (ii) European and American guidelines on HF; (iii) product labelling according to the Food and Drug Administration and European Medicines Agency. Estimated eligibility for vericiguat in the trial, guidelines, and label scenarios was 21.4%, 47.4%, and 47.4%, respectively. Prior HF hospitalization within 6 months was the criterion limiting eligibility the most in all scenarios (met by 49.1% of the population). In the trial scenario, other criteria meaningfully limiting eligibility were elevated N-terminal pro-B-type natriuretic peptide levels and nitrate use. In all scenarios, eligibility was higher among patients hospitalized for HF at baseline (44.3% vs. 21.4% [trial scenario] and 97.3% vs. 47.4% [guideline/label scenarios] for hospitalized vs. non-hospitalized patients). Overall, eligible patients were older, had more severe HF, more comorbidities, and consequently higher cardiovascular mortality and HF hospitalization rates compared with ineligible patients across all scenarios.

Conclusion

In a large and contemporary real-world HFrEF cohort, we estimated that 21.4% of patients would be eligible for vericiguat according to the VICTORIA trial selection criteria, 47.4% based on guidelines and labelling. Eligibility for vericiguat translated into the selection of a population at high risk of morbidity/mortality.     

Clinical significance of reactive oxidative metabolites in patients with heart failure with reduced left ventricular ejection fraction

BackgroundWe investigated the clinical significance of the derivative of reactive oxygen metabolites (DROM), a new marker of reactive oxygen species (ROS), in patients with heart failure (HF) with reduced left ventricular ejection fraction (LVEF) (HFrEF).Methods and ResultsSerum DROM concentrations were measured in 201 consecutive patients with HFrEF (EF < 50%) in stable condition. DROM values were significantly higher in patients with HFrEF than in risk-matched patients without HF (P < 0.01). They also correlated significantly with high-sensitivity C-reactive protein and B-type natriuretic peptide. Kaplan-Meier analysis demonstrated significantly higher probabilities of HF-related events in the high-DROM group than in the low-DROM group (log-rank test, P < 0.01). Multivariable Cox hazard analysis revealed that DROM were independent and significant predictors of cardiovascular events. In a subgroup analysis, DROM levels were also measured at the aortic root and coronary sinus in 49 patients. The transcardiac gradient of DROM values was significantly higher in patients with HFrEF than in patients without HF (P = 0.04), indicating an association between DROM production in the coronary circulation and HFrEF development. Changes in DROM following optimal therapy were significantly associated with LVEF improvement (r = 0.34, P = 0.04).ConclusionsThe higher levels of DROM and their association with cardiovascular events suggest the clinical benefit of DROM measurements in the risk stratification of patients with HFrEF.     

Serum uric acid and outcomes in patients with chronic heart failure through the whole spectrum of ejection fraction phenotypes: Analysis of the ESC-EORP Heart Failure Long-Term (HF LT) Registry

BackgroundRetrospective analyses of clinical trials indicate that elevated serum uric acid (sUA) predicts poor outcome in heart failure (HF). Uric acid can contribute to inflammation and microvascular dysfunction, which may differently affect different left ventricular ejection fraction (LVEF) phenotypes. However, role of sUA across LVEF phenotypes is unknown.ObjectivesWe investigated sUA association with outcome in a prospective cohort of HF patients stratified according to LVEF.MethodsThrough the Heart Failure Long-Term Registry of the European Society of Cardiology (ESC-EORP-HF-LT), 4,438 outpatients were identified and classified into: reduced (<40% HFrEF), mid-range (40–49% HFmrEF), and preserved (≥50% HFpEF) LVEF. Endpoints were the composite of cardiovascular death/HF hospitalization, and individual components.ResultsMedian sUA was 6.72 (IQ:5.48-8.20) mg/dl in HFrEF, 6.41 (5.02-7.77) in HFmrEF, and 6.30 (5.20-7.70) in HFpEF. At a median 372-day follow-up, the composite endpoint occurred in 648 (13.1%) patients, with 176 (3.6%) deaths and 538 (10.9%) HF hospitalizations. Compared with lowest sUA quartile (Q), Q-III and Q-IV were significantly associated with the composite endpoint (adjusted HR 1.68: 95% CI 1.11–2.54; 2.46: 95% CI 1.66–3.64, respectively). By univariable analyses, HFrEF and HFmrEF patients in Q-III and Q-IV, and HFpEF patients in Q-IV, showed increased risk for the composite endpoint (P<0.05 for all); after model-adjustment, significant association of sUA with outcome persisted among HFrEF in Q-IV, and HFpEF in Q-III-IV.ConclusionsIn a large, contemporary-treated cohort of HF outpatients, sUA is an independent prognosticator of adverse outcome, which can be appreciated in HErEF and HFpEF patients.     

Effect of digoxin in patients with heart failure and mid‐range (borderline) left ventricular ejection fraction

Aims

To evaluate the effects of digoxin in patients with the newly described phenotype of heart failure (HF) and mid‐range ejection fraction (HFmrEF), attributed to mild left ventricular systolic dysfunction.

Methods and results

We carried out a retrospective analysis of the Digitalis Investigation Group (DIG) trial which had 7788 patients available for analysis with a left ventricular ejection fraction (LVEF) ranging between 3% and 85%. We compared the effect of digoxin to placebo in three mutually exclusive groups of patients defined by LVEF category: <40% (HF with reduced LVEF, HFrEF, n = 5874), 40–49% (HFmrEF, n = 1195) and ≥50% (HF with preserved LVEF, HFpEF, n = 719). The primary outcome was the composite of cardiovascular death or HF hospitalisation. Patients with HFmrEF resembled patients with HFrEF, more than those with HFpEF, with respect to age, sex and aetiology but were more like HFpEF patients with respect to blood pressure and the prevalence of hypertension. Event rates in patients with HFmrEF were similar to those in HFpEF and much lower than in HFrEF. Digoxin reduced the primary endpoint in patients with HFrEF, mainly due to reduced HF hospitalisation: the digoxin/placebo hazard ratio (HR) for HF hospitalisation was 0.71 [95% confidence interval (CI) 0.65–0.77]. The digoxin/placebo HR for HF hospitalisation in patients with HFmrEF was 0.80 (95% CI 0.63–1.03) and 0.85 (95% CI 0.62–1.17) in those with HFpEF. The digoxin/placebo HR for the composite of HF death or HF hospitalisation was 0.74 (95% CI 0.68–0.81) in HFrEF, 0.83 (95% CI 0.66–1.05) in HFmrEF and 0.88 (95% CI 0.65–1.19) in HFpEF.

Conclusions

In this study, event rates in patients with HFmrEF were closer to those in HFpEF than HFrEF. Digoxin had most effect on HF hospitalisation in patients with HFrEF, an intermediate effect in HFmrEF, and the smallest effect in HFpEF.

     

Current concept in the diagnosis,treatment and rehabilitation of patients with congestive heart failure

Heart failure(HF) is a major public health problem with a prevalence of 1%-2% in developed countries. The underlying pathophysiology of HF is complex and as a clinical syndrome is characterized by various symptoms and signs. HF is classified according to left ventricular ejection fraction(LVEF) and falls into three groups: LVEF ≥ 50%-HF with preserved ejection fraction(HFpEF), LVEF 40%-HF with reduced ejection fraction(HFrEF), LVEF 40%-49%-HF with mid-range ejection fraction. Diagnosing HF is primarily a clinical approach and it is based on anamnesis, physical examination, echocardiogram, radiological findings of the heart and lungs and laboratory tests, including a specific markers of HF-brain natriuretic peptide or N-terminal pro-B-type natriuretic peptide as well as other diagnostic tests in order to elucidate possible etiologies. Updated diagnostic algorithms for HFpEF have been recommended(H2 FPEF, HFA-PEFF). New therapeutic options improve clinical outcomes as well as functional status in patients with HFrEF(e.g., sodium-glucose cotransporter-2-SGLT2 inhibitors) and such progress in treatment of HFrEF patients resulted in new working definition of the term "HF with recovered left ventricular ejection fraction". In line with rapid development of HF treatment, cardiac rehabilitation becomes an increasingly important part of overall approach to patients with chronic HF for it has been proven that exercise training can relieve symptoms, improve exercise capacity and quality of life as well as reduce disability and hospitalization rates. We gave an overview of latest insights in HF diagnosis and treatment with special emphasize on the important role of cardiac rehabilitation in such patients.     

The Optimal Timing of Primary Prevention Implantable Cardioverter-Defibrillator Referral in the Rapidly Changing Medical Landscape

The use of implantable cardioverter-defibrillators (ICDs) significantly reduces the risk of mortality in patients with heart failure with reduced ejection fraction (HFrEF). Current guidelines, which are based on seminal clinical trials published nearly 2 decades ago, recommend that patients be on optimal medical therapy for HF for a minimum of 3 months before referral for prophylactic ICD. This waiting period allows for left ventricular reverse remodelling and improvement in HF symptoms, which may render primary prevention ICD implantation unnecessary. However, medical therapy for HFrEF has significantly evolved since the publication of these landmark trials. Given the plethora of medical therapy options now available for HFrEF, it is appropriate to reassess the duration of this waiting period. In the present review, we examine the landmark randomised trials in primary prevention of sudden cardiac death in patients with HFrEF, summarise the novel medical therapies (sacubitril-valsartan, sodium-glucose cotransporter 2 inhibitors, ivabradine, vericiguat, and omecamtiv mecarbil) that have emerged since the publication of those trials, discuss the optimal timing of ICD referral, and review subtypes of nonischemic cardiomyopathy where timing of ICD insertion is guided by alternative criteria. With the steps now needed to optimise medical therapy for HFrEF, in terms of both classes of drugs and doses of each agent, it can easily take up to 6 months to achieve optimisation. Following that, waiting periods of 3 months for ischemic cardiomyopathy and 6 months for nonischemic cardiomyopathy may be required to allow adequate reverse remodelling before reevaluating for ICD implantation.     

New Drugs and Devices in the Pipeline for Heart Failure with Reduced Ejection Fraction Versus Heart Failure with Preserved Ejection Fraction

Heart failure (HF) is a growing problem in the USA and other industrialized nations. HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) each make up approximately half of the overall HF burden. Although a variety of medical and surgical therapies exist for the treatment of patients with HFrEF, morbidity and mortality remain high, and cardiac transplantation, considered the current gold standard for patients with HFrEF and severe symptoms, is reserved for relatively few eligible patients. Patients with HFpEF have more limited therapeutic options, because no medical therapy to date has been shown to improve survival in these patients. With the rising prevalence of HF and its increasing role in health care expenditure, there is a substantial need for new drug and device therapies for HFrEF and, in particular, HFpEF. This forms the topic of the current review.     

Functional variants in the promoter region of macrophage migration inhibitory factor rs755622 gene (MIF G173C) among patients with heart failure: Association with echocardiographic indices and disease severity

BackgroundHeart failure (HF) is a serious public health concern resulting in death. An individual predisposition to HF is determined by relationship between genetic and environmental variables. The macrophage migration inhibitory factor (MIF) is a significant mediator that involved in a variety of inflammatory and cardiovascular diseases. To reveal contribution of MIF rs755622 G173C gene variants in the promoter region towards HF pathogenesis and investigate association between recognized genotype and clinical characteristics.Patients and methodsWe recruited 90 patients with HF, 63 with preserved ejection fraction (HFpEF) and 27 with reduced ejection fraction (HFrEF), and 60 age- and sex- matched controls. MIF rs755622 (G>C) single-nucleotide polymorphism was genotyped by PCR-RFLP method.ResultsThe GG genotype of MIF rs755622 gene polymorphism was more frequent in HF patients than in controls which increased the risk of HF by about 4.25 times (p<0.05). The distribution of the GG, GC and CC genotypes of MIF were 42%, 21% and 0.0% among HFrEF, and 33.3%, 55.6% and 11.1% among HFpEF respectively. Higher frequency of MIF rs755622 G allele among HFrEF (100%) compared to HFpEF (88.9%) (p = 0.007). MIF-GG genotype variant had significantly lower LVEF. In multivariate analysis, MIF-GG genotype was independent risk predictor among HF (OR 4.6).ConclusionMIF rs755622 (GG) could be considered as a probable genotypic risk factor for HF, especially in those with HFrEF which increases the possibility that MIF contribute to HF progression. MIF genotype assay may serve as early predictor and help to recognize those at great risk of developing HF.     

Epidemiología y tratamiento de la insuficiencia cardiaca en España: estudio PATHWAYS-HF

Introduction and objectivesTo describe the epidemiology and treatment of a large contemporary cohort of patients with heart failure (HF).MethodsObservational, retrospective, population-based study using the BIG-PAC database, which includes people aged ≥ 18 years seeking care for HF between 2017 and 2019. The main variables were the prevalence/annual incidence rate, comorbidities, clinical variables, and medication administered.ResultsWe identified 19 762 patients with HF from a total of 1 189 003 persons seeking medical attention from 2017 to 2019 (2019: mean age, 78.3 years; 53.0% men). Distribution by type of left ventricular ejection fraction (LVEF) was as follows: 51.7% reduced, 40.2% preserved, and 8.1% mid-range. In 2019, the prevalence was 1.89% (95%CI, 1.70-2.08), with an incidence rate of 2.78 new cases per 1000 persons/y. No statistically significant differences were observed in prevalence and/or incidence from 2017 to 2019. Among patients with HF with reduced ejection fraction (HFrEF), 64% received beta-blockers, 80.5% angiotensin-converting enzyme inhibitor/angiotensin receptor blockers or sacubitril-valsartan, and 29.8% an aldosterone antagonist. In addition, from the diagnosis (baseline) to 24 months of follow-up, there was discreet treatment optimization, which was notable in the first 3 to 6 months.ConclusionsEpidemiological data on HF remained stable during the study period, with a lower prevalence than that reported in non–population-based studies. There is wide room for improvement in the optimization of medical treatment of HFrEF.     

The predictive value of global longitudinal strain in patients with heart failure mid-range ejection fraction

BackgroundHeart failure (HF) with mid-range ejection fraction (HFmrEF) is defined as HF with a left ventricular (LV) ejection fraction (LVEF) of 41–49%. However, the change in LV function and the subsequent prognosis in these patients remain unclear. We aimed to investigate whether LV global longitudinal strain (LV GLS) could differentiate the changes in LVEF and predict the clinical outcomes in patients with HFmrEF.MethodsAccording to the changes in LVEF on follow-up echocardiography, 273 outpatients with HFmrEF were divided into 3 groups: HFwEF (HF with worse EF: <40%), HFsEF (HF with similar EF: 40–49%), and HFrecEF (HF with recovered EF: >50%). Further, the LV GLS at diagnosis was evaluated.ResultsThe average follow-up duration was 31 months. Among patients with HFmrEF, the more impaired the LV GLS at baseline, the higher probability of HFwEF development. In comparison with patients with HFwEF and HFsEF, those with HFrecEF had a lower risk of hospitalization for HF. At a cut-off value of ?11%, LV GLS differentiated the subsequent risk of cardiovascular death in patients with HFmrEF. In Cox regression, patients with LV GLS >?11% had a high risk of cardiovascular death.ConclusionIn patients with HFmrEF, LV GLS is associated with LVEF changes and subsequent cardiovascular death. Patients with HFrecEF had a lower risk of hospitalization for HF.