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.     

Associations With and Prognostic and Discriminatory Role of N-Terminal Pro–B-Type Natriuretic Peptide in Heart Failure With Preserved Versus Mid-range Versus Reduced Ejection Fraction

Background

The aim of this study was to characterize N-terminal pro–B-type natriuretic peptide (NT-proBNP) in terms of determinants of levels and of its prognostic and discriminatory role in heart failure with mid-range (HFmrEF) versus preserved (HFpEF) and reduced (HFrEF) ejection fraction.

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.     

Epidemiology and clinical characteristics of hospitalized elderly patients for heart failure with reduced,mid-range and preserved ejection fraction

Introduction: Elderly patients hospitalized with heart failure (HF) have high mortality rates and requires specific evidence based theraphy, however there are few studies which have focused on patients older than 80 years hospitalized with HF. The aim of the present study is to evaluate the overall clinical characteristics, management, and in-hospital outcomes of elderly patients hospitalized with HF.Methods: Journey-HF study was conducted in 37 different centers in Turkey and recruited 1606 patients who were hospitalized with HF between September 2015 and September 2016. In this study, clinical profile of patients ≥ 80 years old and 65-79 years old hospitalized with HF were described and compared based on EF-related classification: HFrEF (HF with reduced ejection fraction), HFmrEF (HF with mid-range ejection fraction) and HFpEF (HF with preserved ejection fraction).Results: A total of 1034 elder patients (71.6% 65–79 years old and 28.4% ≥80 years old) were recruited. Of the 65–79 years old patients 67.4% had HFrEF, 16.2% had HFmrEF and 16.3% had HFpEF. Among patients ≥80 years old 61.6% had HFrEF, 15.6% had HmrEF and 22.8% had HFpEF.When compared with patients with HFrEF and HFmrEF, patients ≥80 years old with HFpEF were more likely to be older, have atrial fibrilation (AF), and less likely to have diabetes mellitus (DM), coronary artery disease (CAD) or to be recieving an angiotensin-converting enzyme inhibitor (ACEi) or beta blocker theraphy. When compared to patients 65–79 years old with HFpEF, patients ≥80 years with HFpEF had a higher rate of AF and less likely DM. Acute coronary syndrome was the most common precipitant factor for hospitalization in both age groups with HFrEF group. Arrhythmia was a major precipitant factor for hospitalization of patients ≥80 years old with HFpEF. Non-compliance with theraphy was a major problem of patients ≥80 years old with HFrEF.Conclusion: Elderly patients with HFrEF, HFmrEF and HFpEF each had characterized unique patient profiles and the guideline recommended medications were less likely to be used in these patient populations. In hospital mortality rate is worrisome and reflects a need for more specific tretment strategy.     

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.     

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.

     

Rationale,Design and Baseline Characteristics of the PARAGLIDE-HF Trial: Sacubitril/Valsartan vs Valsartan in HFmrEF and HFpEF With a Worsening Heart Failure Event

BackgroundThe PARAGON-HF trial studied the effect of sacubitril/valsartan (Sac/Val) compared with valsartan (Val) on clinical outcomes in patients with chronic heart failure with preserved ejection fraction (HFpEF) or mildly reduced EF (HFmrEF). Further data are needed regarding the use of Sac/Val in these groups with EF and with recent worsening heart failure (WHF) events and in key populations not broadly represented in the PARAGON-HF trial, including those with de novo HF, the severely obese and Black patients.MethodsThe PARAGLIDE-HF trial is a multicenter, double-blind, randomized, controlled trial of Sac/Val vs Val that enrolled patients at 100 sites. Medically stable patients ≥ 18 years old with EF > 40%, amino terminal-pro B-type natriuretic peptide (NT-proBNP) levels ≥ 500 pg/mL and within 30 days of a WHF event were eligible for participation. Patients were randomly assigned 1:1 to Sac/Val vs Val. The primary efficacy endpoint is time-averaged proportional change in NT-proBNP from baseline through Weeks 4 and 8. Secondary endpoints include clinical outcomes during follow-up and additional biomarker assessments. Safety endpoints include symptomatic hypotension, worsening renal function and hyperkalemia.ResultsThe trial enrolled 467 participants from June 2019 through October 2022 (52% women, 22% Black, age 70 ± 12 years, median (IQR) BMI 33 (27–40) kg/m²). The median (IQR) EF was 55% (50%–60%), 23% with HFmrEF (LVEF 41%–49%), 24% with EF > 60% and 33% with de novo HFpEF. Median screening NT-proBNP was 2009 (1291–3813) pg/mL, and 69% were enrolled in the hospital.ConclusionsThe PARAGLIDE-HF trial enrolled a broad and diverse range of patients with heart failure with mildly reduced or preserved ejection fraction and will inform clinical practice by providing evidence about the safety, tolerability and efficacy of Sac/Val vs Val in those with a recent WHF event.     

Clinical Characteristics,Comorbidities and Prognosis in Patients With Heart Failure With Mid-Range Ejection Fraction

BackgroundPatients with left ventricular ejection fractions between 40% and 49% either discovered de novo, having declined from ≥50%, or improved from <40% have been described as heart failure (HF) with mid-range ejection fraction (HFmrEF). Though clinical signs and symptoms are similar to other phenotypes, possible prognostic differences and therapeutic responses reinforce the need for further understanding of patients’ characteristics especially in a rural community based population. The purpose of this study is to evaluate the clinical characteristics, comorbidities and prognosis of a rural patient population with HFmrEF.Materials and MethodsWe queried the electronic medical record from a community based university practice for all patients with a HF diagnosis. We included only those patients with >3 months follow-up and interpretable Doppler echocardiograms. We recorded demographic, Doppler-echo, and outcome variables (up to 2,083 days).ResultsThere were 633 HF patients: 42.4% with preserved ejection fraction (HFpEF, EF ≥50%), 36.4% with HFmrEF, and 21.0% with reduced ejection fraction (HFrEF, EF <40%). HFmrEF patients were older, had greater coronary disease prevalence, lower systolic blood pressure, elevated brain natriuretic peptide, lower hemoglobin, and higher creatinine than HFpEF. All-cause mortality was intermediate between HFrEF and HFpEF but was not significantly different. Landmark analysis revealed a trend toward greater second readmission in HFmrEF as compared to HFpEF (hazard ratio: 1.43 [0.96-2.14],P = 0.0767).ConclusionsRural patients with HFmrEF without an ambulatory HF clinic represent a higher percentage of HF patients than previously reported with greater coronary disease prevalence with comparable readmission rates and nonsignificantly different all-cause mortality.     

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.     

Red blood cell distribution width and its relation to cardiac function and biomarkers in a prospective hospital cohort referred for echocardiography

BackgroundRed blood cell distribution width (RDW), a measure of anisocytosis, is a prognostic biomarker for heart failure (HF). However it is still unclear how RDW is associated with heart function and established cardiac biomarkers.Methods and resultsIn a prospective hospital cohort of 296 patients referred for echocardiography because of suspected HF, blood sampling and clinical examination were performed within 24 h after echocardiography. The patients were divided into four HF groups, including one group where the HF diagnosis was uncertain (gray zone). In the patients the mean age was 70 ± 11 years, 44% with systolic HF (SHF), 18% with heart failure with normal ejection fraction (HFNEF), 17% with gray zone and 21% without HF (non-HF). RDW was higher among patients with SHF and HFNEF, compared with gray zone and non-HF patients. The distribution of different variables over the RDW quartiles showed an inverse correlation between RDW levels and LVEF and a positive correlation between RDW and NT-proBNP levels. Further analysis with stepwise multiple linear regression demonstrated that NT-proBNP levels, but not LVEF, were independently correlated with RDW.ConclusionIn patients referred for echocardiography because of suspected HF, RDW levels were higher in patients with SHF and HFNEF. Moreover, NT-proBNP levels were independently linked with elevated RDW.     

Empagliflozin in Heart Failure With Predicted Preserved Versus Reduced Ejection Fraction: Data From the EMPA-REG OUTCOME Trial

BackgroundIn the EMPA-REG OUTCOME trial, ejection fraction (EF) data were not collected. In the subpopulation with heart failure (HF), we applied a new predictive model for EF to determine the effects of empagliflozin in HF with predicted reduced (HFrEF) vs preserved (HFpEF) EF vs no HF.Methods and ResultsWe applied a validated EF predictive model based on patient baseline characteristics and treatments to categorize patients with HF as being likely to have HF with mid-range EF (HFmrEF)/HFrEF (EF <50%) or HFpEF (EF ≥50%). Cox regression was used to assess the effect of empagliflozin vs placebo on cardiovascular death/HF hospitalization (HHF), cardiovascular and all-cause mortality, and HHF in patients with predicted HFpEF, HFmrEF/HFrEF and no HF. Of 7001 EMPA-REG OUTCOME patients with data available for this analysis, 6314 (90%) had no history of HF. Of the 687 with history of HF, 479 (69.7%) were predicted to have HFmrEF/HFrEF and 208 (30.3%) to have HFpEF. Empagliflozin's treatment effect was consistent in predicted HFpEF, HFmrEF/HFrEF and no-HF for each outcome (HR [95% CI] for the primary outcome 0.60 [0.31–1.17], 0.79 [0.51–1.23], and 0.63 [0.50–0.78], respectively; P interaction = 0.62).ConclusionsIn EMPA-REG OUTCOME, one-third of the patients with HF had predicted HFpEF. The benefits of empagliflozin on HF and mortality outcomes were consistent in nonHF, predicted HFpEF and HFmrEF/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.     

Quantitative Metabolomics Reveals Heart Failure With Midrange Ejection Fraction as a Distinct Phenotype of Heart Failure

BackgroundHeart failure with midrange ejection fraction (HFmrEF) has been recently acknowledged as a separate phenotype, but metabolomics evaluation of this subtype remains largely unexamined.MethodsA quantitative metabolomics study on amino acids and acylcarnitines was performed to characterize different states of heart failure (HF) in 628 participants. Both multivariate orthogonal partial least squares- discriminant analysis and univariate Mann-Whitney U test were used to explore reliable metabolic profiles associated with different HF states. The resulting metabolites were further refined to obtain diagnostic metabolite scores (DMSs) with the use of ordinal logistic regression. Lasso-penalized regression was applied to produce a survival-associated prognostic metabolite score (PMS). The Cox proportional hazards model, Kaplan-Meier curves, and time-dependent receiver operating characteristics were used for a comprehensive assessment of prognostic value using PMS versus traditional clinical biomarkers.ResultsThe optimized models identified a panel of 15 differential metabolites that were shared across different HF states, whereas some metabolites were associated with a specific state. PMS consisting of 9 metabolites demonstrated an appreciably better prognostic value (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.25-2.1) vs the natural logarithm of N-terminal pro–B-type natriuretic peptide (Ln[NT-proBNP]; HR 1.23, 95% CI 0.94-1.61; P < 0.001). The overall area under the receiver operating characteristic curve value of PMS was superior to that of Ln(NT-proBNP) in risk prediction for patients with HFmrEF and HF with reduced ejection fraction (HFrEF) subtypes (P < 0.001).ConclusionsTargeted metabolomics has provided a novel understanding of the molecular mechanism underlying HF. Both DMS and PMS clearly demonstrated HFmrEF as a distinct phenotype between a mild HF with preserved ejection fraction state and a severe HFrEF state. PMS exhibited superior prognostic value than Ln(NT-proBNP). Further investigation is needed with independent large-scale validation.     

射血分数中间值的心力衰竭患者的临床特征及预后研究

背景射血分数中间值的心力衰竭(HFmrEF)作为心力衰竭新增分型,其病理生理机制、群体特征、合并症及临床特征与射血分数降低的心力衰竭(HFr EF)患者不尽相同。目的探讨HFmr EF患者的临床特征及预后,以期为HFmr EF患者的临床诊治提供一定参考。方法本研究为回顾性研究。选取2016年6月—2019年6月在石河子大学医学院第一附属医院血管内科住院治疗的心力衰竭患者654例作为研究对象,根据左心室射血分数(LVEF)分为HFr EF组(LVEF <40%,n=299)、HFmr EF组(40≤LVEF <50%,n=153)和射血分数保留的心力衰竭(HFp EF)组(LVEF≥50%,n=202)。收集三组患者基线资料、入院24 h内实验室检查指标及超声心动图检查指标。所有患者均随访1年,记录患者全因死亡情况和全因死亡时间、因心力衰竭再入院情况和因心力衰竭再入院时间。结果HFmr EF组与HFr EF组患者年龄小于HFp EF组,HFr EF组患者年龄小于HFmr EF组(P <0.05);HFr EF组患者女性占比低于HFmr EF组与HFp EF组(P <0.05);HFmr EF组与HFr EF组患者心率大于HFp EF组,纽约心脏病协会(NYHA)分级优于HFp EF组,有糖尿病病史、陈旧性心肌梗死病史者所占比例高于HFp EF组,有心房颤动病史、慢性阻塞性肺疾病(COPD)病史者所占比例低于HFp EF组(P <0.05)。HFmr EF组与HFr EF组患者血肌酐、血尿酸、空腹血糖、中性粒细胞与淋巴细胞比值(NLR)及氨基末端脑钠肽前体(NT-pro BNP)高于HFp EF组,高密度脂蛋白低于HFp EF组(P <0.05);HFr EF组患者血肌酐、血尿酸、空腹血糖、NLR及NT-pro BNP高于HFmr EF组,高密度脂蛋白低于HFmr EF组(P <0.05)。HFmr EF组和HFr EF组患者左心房内径和左心室舒张末期内径(LVEDD)大于HFp EF组,HFr EF组患者左心房内径和LVEDD大于HFmr EF组(P <0.05)。Spearman秩相关分析结果显示,心力衰竭分型与血肌酐(r=0.110)、血尿酸(r=0.264)、空腹血糖(r=0.139)、NLR(r=0.415)、NT-pro BNP(r=0.571)、左心房内径(r=0.246)及LVEDD(r=0.607)呈正相关,与高密度脂蛋白(r=-0.144)呈负相关(P <0.05)。本组患者随访过程中失访18例,失访率为2.7%,平均随访(12.0±1.6)个月。生存曲线分析结果显示,HFr EF组患者1年累积生存率和1年累积无心力衰竭再入院率低于HFp EF组和HFmr EF组,HFmr EF组患者1年累积无心力衰竭再入院率低于HFp EF组(P <0.05)。结论 HFmr EF患者的临床特征与HFr EF相似,其心力衰竭严重程度及左心室重构程度介于HFr EF与HFp EF之间,其1年累积生存率与HFp EF患者相似,均优于HFr EF患者,但其1年累积无心力衰竭再入院率低于HFpEF患者。     

Microalbuminúria e seu Significado Prognóstico em Pacientes com Insuficiência Cardíaca Aguda com Fração de Ejeção Preservada,Intermediária e Reduzida

BackgroundThe prevalence and significance of microalbuminuria have not been well studied in patients with different heart failure subtypes.ObjectiveThe prevalence and significance of microalbuminuria have not been well studied in patients with different heart failure subtypes. Therefore, we aimed to investigate the frequency and prognostic value of microalbuminuria in patients hospitalized for acute heart failure (AHF) with preserved ejection fraction (HFpEF), mid-range ejection fraction (HFmrEF), and reduced ejection fraction (HFrEF).MethodsAll consecutive adult patients referred to the hospital due to AHF between June 2016 and June 2019 were enrolled. Microalbuminuria is defined as urinary albumin to creatinine ratio (UACR) level in the range of 30–300 mg/g. Hospital mortality was the endpoint of this studyResultsOf the 426 AHF patients (mean age 70.64 ± 10.03 years, 53.3 % female), 50% had HFrEF, 38.3% had HFpEF, and 11.7% had HFmrEF at presentation.The prevalence of microalbuminuria was 35.2%, 28.8%, and 28.0% in HFrEF, HFpEF, and HFmrEF, respectively. A total of 19 (4.5%) patients died during the in-hospital course, and in-hospital mortality was higher in HFrEF patients (6.6%) compared to patients with HFpEF (2.5%) and HFmrEF (2.0%). Multivariate analysis showed that the presence of microalbuminuria predicted in-hospital mortality in patients with HFrEF and HFmrEF but not in HFpEF.ConclusionAlthough microalbuminuria was common in all subgroups of AHF patients, it has been found to predict prognosis only in patients with HFrEF and HFmrEF.     

Prevalence,characteristics and prognostic impact of aortic valve disease in patients with heart failure and reduced,mildly reduced,and preserved ejection fraction: An analysis of the ESC Heart Failure Long-Term Registry

Aims

To assess the prevalence, clinical characteristics, and outcomes of patients with heart failure (HF) with or without moderate to severe aortic valve disease (AVD) (aortic stenosis [AS], aortic regurgitation [AR], mixed AVD [MAVD]).

Methods and results

Data from the prospective ESC HFA EORP HF Long-Term Registry including both chronic and acute HF were analysed. Of 15 216 patients with HF (62.5% with reduced ejection fraction, HFrEF; 14.0% with mildly reduced ejection fraction, HFmrEF; 23.5% with preserved ejection fraction, HFpEF), 706 patients (4.6%) had AR, 648 (4.3%) AS and 234 (1.5%) MAVD. The prevalence of AS, AR and MAVD was 6%, 8%, and 3% in HFpEF, 6%, 3%, and 2% in HFmrEF and 4%, 3%, and 1% in HFrEF. The strongest associations were observed for age and HFpEF with AS, and for left ventricular end-diastolic diameter with AR. AS (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.23–1.67), and MAVD (adjusted HR 1.37, 95% CI 1.07–1.74) but not AR (adjusted HR 1.13, 95% CI 0.96–1.33) were independently associated with the 12-month composite outcome of cardiovascular death and HF hospitalization. The associations between AS and the composite outcome were observed regardless of ejection fraction category.

Conclusions

In the ESC HFA EORP HF Long-Term Registry, one in 10 patients with HF had AVD, with AS and MAVD being especially common in HFpEF and AR being similarly distributed across all ejection fraction categories. AS and MAVD, but not AR, were independently associated with increased risk of in-hospital mortality and 12-month composite outcome, regardless of ejection fraction category.     

左心室射血分数保留性心力衰竭患者预后相关生物靶向标志物的表达特征

目的分析射血分数下降的心力衰竭(heart failure with reduced ejection fraction,HFrEF)和射血分数保留(或正常)的心力衰竭(heart failure with preserved ejection fraction,HFpEF)患者生物靶向标志物表达差异情况。评估生物靶向标志物对HFpEF识别与预后判断价值。方法连续选择2015年1月至2016年5月香港大学深圳医院100例HFpEF(左心室射血分数≥50%)及310例HFrEF(左心室射血分数<50%)患者,收集患者基本临床治疗与相关生物靶向标志物,以12个月不良事件为研究终点。结果HFpEF患者中,氨基末端脑钠肽前体(N-terminal pro-brain natriuretic peptide,NT-proBNP)浓度[1911(877~4130)pg/mL vs.3001(1498~6120)pg/mL,P<0.05]、高敏肌钙蛋白T(high-sensitivity troponin T,hsTnT)浓度[21.1(15.9~41)pg/mL vs.31.2(18.1~52.7)pg/mL,P<0.05]、高敏C-反应蛋白(high-sensitivity C-reactive protein,hs-CRP)浓度[3.6(1.7~6.9)mg/L vs.2.1(0.9~4.8)mg/L,P<0.05]明显低于HFrEF患者,而胱抑素C浓度高于HFrEF患者[1.7(1.3~2.2)mg/L vs.1.4(1.0~2.0)mg/L,P<0.05],差异有统计学意义。而且在HFpEF组中白细胞介素-6,hsTnT和尿素氮与终点事件有关,NT-proBNP对HFpEF患者远期预后无统计学意义。结论生物标志物在HFpEF与HFrEF患者中存在差异性表达情况。在HFpEF患者中,预后相关的预测因子可能进一步提高临床对于HFpEF诊断、风险评估与治疗。     

Tecido Adiposo Epicárdico nos Fenótipos de Insuficiência Cardíaca – Uma Metanálise

BackgroundEpicardial adipose tissue (EAT) is increased in comorbidities common in heart failure (HF). In this sense, EAT could potentially mediate effects that lead to an impaired cardiac function.ObjectivesThis meta-analysis aims to investigate if the amount of EAT in all-types of HF and each HF phenotype is significantly different from control patients.MethodsThis meta-analysis followed the Meta-analysis Of Observational Studies in Epidemiology guidelines. The search was performed in the MEDLINE, Embase, and Lilacs databases until November 2020. Two authors performed screening, data extraction, and quality assessment. A p-value <0.05 was defined as statistically significant.ResultsEight observational studies were included, comprehending 1,248 patients in total, from which 574 were controls, 415 had HF with reduced ejection fraction (HFrEF) and 259 had HF with mid-range or preserved ejection fraction (HFmrEF or HFpEF). The amount of EAT was not different between all types of HF and the control group (SMD = -0.66, 95% CI: -1.54 to 0.23, p =0.14). Analyzing each HF phenotype separately, patients with HFrEF had a reduced EAT when compared to the controls (SMD= -1.27, 95% CI: - 1.87 to -0.67, p <0.0001), while patients with HFmrEF or HFpEF showed an increased EAT when compared to controls (SMD= 1.24, 95% CI: 0.99 to 1.50, p <0.0001).ConclusionThe amount of EAT was not significantly different between all types of HF and the control group. In patients with HFrEF, the EAT volume was reduced, whereas in HFpEF and HFmrEF, the amount of EAT was significantly increased. PROSPERO registration number: CRD42019134441.     

Mortalidade por Insuficiência Cardíaca com Fração de Ejeção Intermediária

Background The prognostic importance of the classification ‘heart failure (HF) with mid-range ejection fraction (EF)’ remains uncertain.Objective To analyze the clinical characteristics, comorbidities, complications, and in-hospital and late mortality of patients classified as having HF with mid-range EF (HFmrEF – EF: 40%-49%), and to compare them to those of patients with HF with preserved EF (HFpEF – EF > 50%) and with HF with reduced EF (HFrEF – EF < 40%) on admission for decompensated HF.Methods Ambispective cohort of patients admitted to the cardiac intensive care unit due to decompensated HF. Clinical characteristics, comorbidities, complications, and in-hospital and late mortality were assessed. The software R was used, with a 5% significance, for the tests chi-square, analysis of variance, Cox multivariate, and Kaplan-Meier survival curve, in addition to machine-learning techniques (Elastic Net and survival tree).Results 519 individuals were included between September 2011 and June 2019 (mean age, 74.87 ± 13.56 years; 57.6% were men). The frequencies of HFpEF, HFmrEF and HFrEF were 25.4%, 27% and 47.6%, respectively. Previous infarction was more frequent in HFmrEF. The mean follow-up time was 2.94 ± 2.55 years, with no statistical difference in mortality between the groups (53.8%, 52.1%, 57.9%). In the survival curve, there was difference between neither the HFpEF and HFmrEF groups, nor the HFpEF and HFrEF groups, but between the HFmrEF and HFrEF groups. Age over 77 years, previous HF, history of readmission, dementia and need for vasopressors were associated with higher late mortality in the survival tree.Conclusion The EF was not selected as a variable associated with mortality in patients with decompensated HF.     

Heart Failure With Midrange Ejection Fraction—What Is It,If Anything?

The patient cohort with left ventricular ejection fractions (LVEFs) of 41%-49%, which has been defined as heart failure with midrange ejection fraction (HFmrEF), represent a significant proportion of the heart failure (HF) population. Despite the clear cutoffs established by different society guidelines, confusion remains regarding the exact significance of midrange LVEF within the HF syndrome. Patients with LVEF 41%-49% represent a heterogeneous group of patients sharing pathophysiologic mechanisms, biomarker profiles, comorbidities, and clinical characteristics with patients with preserved and reduced LVEF. In this clinical review, we discuss the underlying pathophysiologic mechanisms that culminate in the clinical syndrome of HF and contribute to the disparities observed between HFpEF, HFrEF, and HFmrEF. We highlight differences and similarities in clinical characteristics and imaging features between HFpEF and HFrEF in an effort to disentangle the heterogeneous group of patients with midrange LVEF, but ultimately we conclude that LVEF should be seen as simply one important element of a continuum throughout the HF syndrome, and that although is useful, it is an oversimplification, because HF syndrome is more of a continuum. The underlying pathophysiology, etiology, and comorbidities of patients presenting with HF is becoming ever more important as the limitations of a classification solely based on LVEF are being better recognised, and as patient-specific personalisation of care is becoming ever more important.