Heart Failure With Mid-range Ejection Fraction Patients Research Articles

Prevalence, treatment, and 1-year outcomes of heart failure with mid-range ejection fraction

Background: The prevalence of patients with heart failure with mid-range ejection fraction (HFmrEF) remains unchanged regardless of healthcare strategies. HFmrEF has mixed characteristics of heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). The treatment of HFmrEF was recommended to be similar to the treatment of HFpEF in the 2016 guidelines of the European Society of Cardiology (ESC) but was changed to those of HFrEF in the 2021 version. Objective: To describe the clinical characteristics of inpatients with HFmrEF with a focus on treatment practices. Methods: A prospective study was conducted on patients diagnosed with HFmrEF who were admitted to the cardiology department of Nhan Dan Gia Dinh hospital from July 2019 to July 2020. Rehospitalization and mortality were followed up by telephone after 1 year. Results: Of a total of 529 heart failure cases admitted to the hospital during the study period, there were 73 patients (13.8%) with HFmrEF. The mean age was 68 years and males comprised 53%. The average hospitalization stay length was 6.7 days. The most common precipitating factors of heart failure were non-adherence (42.5%) and infection (39.7%) followed by hypertensive crisis (8.2%), anemia (6.8%), acute myocardial infarction (5.5%), arrhythmia (4.1%), and hyperthyroidism (2.7%). Ischemic heart disease was the leading cause (61.6%) of HFmrEF, followed by hypertension (12.3%). The rates of HFmrEF patients treated with beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and aldosterone receptor antagonists were 76.1%, 76.71%, 37.73%, and 47.95%, respectively. There were no statistically significant differences in the guideline-directed medical therapy (GDMT) medications administered between HFmrEF due to ischemic and non-ischemic causes. After 1-year follow-up, the combined outcome of rehospitalization and mortality in HFmrEF was 24.7%. Conclusion: The treatment of HFmrEF was similar to that of HFrEF between 2019 and 2020 at Nhan Dan Gia Dinh hospital and was in accordance with the 2021 ESC guidelines.

Mild and moderate to severe early acute kidney injury following cardiac surgery among patients with heart failure and preserved vs. mid-range vs. reduced ejection fraction: A retrospective cohort study.

Patients with heart failure who undergo cardiac surgery have increased long-term mortality in which acute kidney injury (AKI) plays a role. However, little is known about whether the incidence of AKI differs according to stratified left ventricular ejection fraction (LVEF). To assess the risks of mild AKI and moderate to severe AKI postcardiac surgery among patients with heart failure. Retrospective cohort analysis of patient data. Ejection fractions were categorised as LVEF less than 40%, heart failure with reduced ejection fraction (HFrEF); LVEF 40 to 49%, heart failure with mid-range ejection fraction (HFmrEF); and LVEF at least 50%, heart failure with preserved ejection fraction (HFpEF). Patients who underwent cardiac surgery from 2012 to 2019 in Fuwai Hospital, Beijing, China, were consecutively enrolled. The primary endpoint was postoperative AKI staged either as mild AKI or moderate to severe AKI. The secondary outcome was the peri-operative composite adverse event of dialysis support, tracheotomy, intrasurgical and postsurgical mechanical cardiac support and in-hospital mortality. This study also assessed chronic renal dysfunction at follow-up. Of the 54 696 included patients, 18.9% presented with heart failure. Among these with HFpEF, HFmrEF and HFrEF, the incidence of postoperative mild AKI was 37.0, 33.4 and 37.6%, respectively. Patients with HFpEF and HFmrEF were characterised by numerically greater prevalence of moderate to severe AKI than HFrEF (8.5 vs. 9.1 vs. 5.8%). HFrEF and HFmrEF patients had comparable risks for mild AKI relative to HFpEF patients, odds ratio (OR) 0.885; 95% confidence interval CI 0.763 to 1.027 for HFmrEF vs. HFpEF; OR 1.083; 95% CI 0.933 to 1.256 for HFrEF vs. HFpEF. Patients with HFmrEF were more at risk for moderate to severe AKI than patients with HFpEF (OR, 1.368; 95% CI 1.066 to 1.742), but HFrEF and HFpEF did not differ significantly (OR 1.012; 95% CI 0.752 to 1.346). An increasing number of noncardiac comorbidities led to a higher risk of mild AKI and moderate to severe AKI in patients with heart failure; and its effect on AKI was almost equal among the three heart failure strata. The incidence of postoperative composite adverse outcome increased in a graded manner from HFpEF to HFmrEF to HFrEF. Information on the creatine concentrations at 3 months postoperatively and longer were retained for 5200 out of 10 347 (50.6%) heart failure patients in our charts.The AKI severity and the presence of HFmrEF contributed substantially to the development of renal dysfunction over a median [IQR] follow-up of 10 months [4.0 to 21.0]. Initiative programmes aimed at patients with HFrEF to prevent moderate to severe AKI and chronic kidney dysfunction should also include patients with HFmrEF.

Left atrial function in patients with heart failure with mid-range and preserved ejection fraction

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Little is known about the left atrial (LA) function in patients with heart failure with mid-range and preserved ejection fraction (EF). We explored LA function in patients with heart failure with mid-range ejection fraction (HFmrEF) and compared to that in patients heart failure with preserved ejection fraction (HFpEF). Methods A total of 66 HF patients (35 HFpEF and 31 HFmrEF) were included in the study. Left venticular EF, global longitudinal strain (GLS) and the mitral E/e" ratio were measured in all patients. LA function was assesed by measuring phasic changes in LA volume - maximal LA volume, pre-atrial contraction volume and minimal LA volume. All volumes were indexed to body surface area before calculating the indices of LA function: LA total emtying fraction (reservoir function), LA passive emptying fraction (conduit function) and LA active emptying fraction (pump function). Peak LA strain during ventricular systole (S-LAs) and peak LA strain during atrial systole (S-LAa) were measured also as LA functional parameters (reservoir and pump function). Conduit function of LA was derived as difference of S-LAs and S-LAa. LA deformation was also assessed by strain rate at different phases of the cardiac cycle. Strain rate analysis was used to measure peak LA strain rate during ventricular systole (SR-LAs), during early LV filling (SR-LAe) and during atrial contraction (SR-LAa). Results There were no significant differences in GLS and the mitral E/e’ between patients with HFmrEF and HFpEF (p > 0.05 for all). Significantly lower values of LA total emptyng fraction (47.6 ± 13.0 vs 38.9 ± 11.8, p = 0.006), LA passive emptyng fraction (26.6 ± 13,2 vs 20.9 ± 9.4, p = 0.049) and LA active emptyng fraction (33.0 ± 10.0 vs. 26.0 ± 9.7, p = 0.005) were observed in HFmrEF tham HFpEF patients, respectively. Significantly lower values of S-LAs (27,3 ± 5,8 vs 22,3 ± 8,0, p = 0,004), S-LAa (12,8 ± 4,0 vs 10,3 ± 3,7, p = 0,01) (Figure 1), SR-LAs (1,40 ± 0,42 vs 1,18 ± 0,43, p = 0,045), SR-Lae (-1,47 ± 0,56 vs -1,13 ± 0,51, p = 0,012) and SR-LAa (-1,90 ± 0,50 vs -1,64 ± 0,55, p = 0,044) were obtained in group of HFmrEF patients. Conclusions All components of left atrial function were worse in patients with HFmrEF than in those with HFpEF, despite similar GLS and mitral E/e" ratio. Clinical and prognostic implications of these observations warrant futher research. Abstract Figure.

Angiotensin-Converting Enzyme Inhibitor Therapy Effects in Patients With Heart Failure With Preserved and Mid-Range Ejection Fraction.

BackgroundThere is hypothesis that endothelial function enhancement is strongly associated with better outcome and functional class improvement in heart failure with preserved ejection fraction (HFpEF) and heart failure with mid-range ejection fraction (HFmrEF) patients. Perindopril is the only angiotensin-converting enzyme inhibitor (ACEI) drug with proven positive effect on the endothelium in coronary artery disease (CAD) patients. In patients with HFpEF and HFmrEF, its impact is still unknown. The aim of this study was to assess perindopril’s influence on endothelial dysfunction markers in these groups of patients.MethodsWe included 60 patients with HFpEF and HFmrEF. At the baseline, endothelial dysfunction biomarkers were measured by IFA and echocardiographic parameters (left atrial volume index (LAVI), ejection fraction (EF), left ventricular mass index (LVMI), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-diastolic volume (LVEDV)) were studied. In patients with no history of previous ACEI or angiotensin II receptor blockers (ARBs) therapy, perindopril was prescribed for 12 months. If patient was treated with ARB or ACEI drug other than perindopril before the study, after 48-h withdrawal period, previous drug was replaced by perindopril.ResultsAfter 12-month therapy with perindopril, E-selectin decreased from 57.25 to 46.05 ng/mL and from 56.55 to 47.6 ng/mL in HFpEF and HFmrEF patients, respectively (P < 0.05). Significant reductions from 0.99 to 0.76 pg/mL (P < 0.05) and from 1.08 to 0.97 pg/mL (P < 0.05) in endothelin-1 level were shown in patients with HFpEF and HFmrEF.ConclusionThe 12-month therapy with perindopril leads to LAVI reduction in HFmrEF patients and potential endothelial dysfunction markers decrease in HFpEF and HFmrEF patients.

Angiotensin-Converting Enzyme Inhibitor Therapy Effects in Patients With Heart Failure With Preserved and Mid-Range Ejection Fraction

Background: There is hypothesis that endothelial function enhancement is strongly associated with better outcome and functional class improvement in heart failure with preserved ejection fraction (HFpEF) and heart failure with mid-range ejection fraction (HFmrEF) patients. Perindopril is the only angiotensin-converting enzyme inhibitor (ACEI) drug with proven positive effect on the endothelium in coronary artery disease (CAD) patients. In patients with HFpEF and HFmrEF, its impact is still unknown. The aim of this study was to assess perindopril’s influence on endothelial dysfunction markers in these groups of patients. Methods: We included 60 patients with HFpEF and HFmrEF. At the baseline, endothelial dysfunction biomarkers were measured by IFA and echocardiographic parameters (left atrial volume index (LAVI), ejection fraction (EF), left ventricular mass index (LVMI), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-diastolic volume (LVEDV)) were studied. In patients with no history of previous ACEI or angiotensin II receptor blockers (ARBs) therapy, perindopril was prescribed for 12 months. If patient was treated with ARB or ACEI drug other than perindopril before the study, after 48-h withdrawal period, previous drug was replaced by perindopril. Results: After 12-month therapy with perindopril, E-selectin decreased from 57.25 to 46.05 ng/mL and from 56.55 to 47.6 ng/mL in HFpEF and HFmrEF patients, respectively (P < 0.05). Significant reductions from 0.99 to 0.76 pg/mL (P < 0.05) and from 1.08 to 0.97 pg/mL (P < 0.05) in endothelin-1 level were shown in patients with HFpEF and HFmrEF. Conclusion: The 12-month therapy with perindopril leads to LAVI reduction in HFmrEF patients and potential endothelial dysfunction markers decrease in HFpEF and HFmrEF patients. Cardiol Res. 2021;000(000):000-000 doi: https://doi.org/10.14740/cr1322

Risk stratification and survival in patients with HFmrEF: the role of cardiopulmonary exercise testing

Abstract Background The prognostic value of cardiopulmonary exercise testing (CPET) is established for risk stratification in patients with heart failure (HF) and reduced ejection fraction (HFrEF). Since the introduction of HF with mid-range ejection fraction (HFmrEF) as an additional category in 2016, optimal management strategy and risk stratification for these patients is a field of ongoing research. Purpose Left ventricular ejection fraction (LVEF) is only one part of the picture when planning treatment and estimating long time risk for patients with HF. We planned to investigate the predictive long-term value of exercise intolerance as measured by CPET in patients with HFmrEF in comparison to HFrEF. Methods We performed a single-center retrospective cohort study of ambulatory consecutive patients that showed signs of heart failure (NYHA functional class II or III) and had a LVEF of 49% or below as measured by echocardiography at the time of CPET. All patients underwent CPET evaluation with an upright bicycle between 2015–2017. The primary endpoint of all-cause mortality as well as the secondary composite endpoint of all-cause mortality or heart transplant/ventricular assist device implantation (transplant/VAD free survival) were assessed. Results For the primary analysis, 253 patients (mean age 61.2±13.0 years, 82.6% male) were included. 68 patients showed an LVEF between 40 and 49% (HFmrEF) whereas 185 patients had an LVEF of below 40% (HFrEF). HF etiology was in 31.3% ischemic. Mean BNP values were 788±1061 pg/ml while HFmrEF patients had on average lower values than HFrEF (322±676 vs. 945±1121, p&amp;lt;0.001). Patients were followed up for a median of 4.2 years (IQR: 3.5–5.0 years). Over this period, the primary and secondary end-point occurred in 22.5%/30.8% of patients. Patients in the HFmrEF group showed a higher mean peak oxygen uptake compared to HFrEF (pVO2; 17.3±4.6 vs 14.2±3.7 ml/min/kg, p&amp;lt;0.001), peak exercise power (Pmax; 111±49 vs 91±38 Watt, p=0.02) and peak oxygen pulse (pO2/HR; 12.6±4.2 vs 10.4±4.1 ml/min/kg, p&amp;lt;0.001). The Kaplan-Meier-Estimate showed a significant difference in survival for both HFmrEF and HFrEF who had pVO2 below 14 ml/min/kg (Log Rank: Chi2: 4.45, p=0.035 and Chi2: 10.05, p=0.02). In univariate Cox regression, pVO2 was predictive of the primary endpoint (HR per +1 mL/kg/min: 0.81; CI: 0.71–0.93; p=0.002 and HR per +1 mL/kg/min: 0.84; CI: 0.77–0.92; p&amp;lt;0.001) in both groups as was Pmax and pO2/HR (p&amp;lt;0.05 for both variables in both groups). Conclusion As in HFrEF, CPET is a useful tool to stratify risk in HFmrEF as well. Our findings support the prognostic role of pVO2 as well as pO2/HR and Pmax in HF with mid-range LVEF. Using a cut off of pVO2 14 ml/min/kg selected patients at risk with similar long-term prognosis as in the HFrEF cohort. Further research to identify subgroups at risk within the heterogeneous group of HFmrEF is warranted for optimal risk stratification. Funding Acknowledgement Type of funding sources: None.

Similarities and Differences Between HFmrEF and HFpEF.

The new guidelines classify heart failure (HF) into three subgroups based on the ejection fraction (EF): HF with reduced EF (HFrEF), HF with mid-range EF (HFmrEF), and HF with preserved EF (HFpEF). The new guidelines regarding the declaration of HFmrEF as a unique phenotype have achieved the goal of stimulating research on the basic characteristics, pathophysiology, and treatment of HF patients with a left ventricular EF of 40–49%. Patients with HFmrEF have more often been described as an intermediate population between HFrEF and HFpEF patients; however, with regard to etiology and clinical indicators, they are more similar to the HFrEF population. Concerning clinical prognosis, they are closer to HFpEF because both populations have a good prognosis and quality of life. Meanwhile, growing evidence indicates that HFmrEF and HFpEF show heterogeneity in presentation and pathophysiology, and the emergence of this heterogeneity often plays a crucial role in the prognosis and treatment of the disease. To date, the exact mechanisms and effective treatment strategies of HFmrEF and HFpEF are still poorly understood, but some of the current evidence, from observational studies and post-hoc analyses of randomized controlled trials, have shown that patients with HFmrEF may benefit more from HFrEF treatment strategies, such as beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and sacubitril/valsartan. This review summarizes available data from current clinical practice and mechanistic studies in terms of epidemiology, etiology, clinical indicators, mechanisms, and treatments to discuss the potential association between HFmrEF and HFpEF patients.

Heart Failure With Midrange Ejection Fraction: Prior Left Ventricular Ejection Fraction and Prognosis.

Aims: Evidence-based guidelines for heart failure management depend mainly on current left ventricular ejection fraction (LVEF). However, fewer studies have examined the impact of prior LVEF. Patients may enter the heart failure with midrange ejection fraction (HFmrEF) category when heart failure with preserved ejection fraction (HFpEF) deteriorates or heart failure with reduced ejection fraction (HFrEF) improves. In this study, we examined the association between change in LVEF and adverse outcomes.Methods: HFmrEF patients with at least two or more echocardiograms 3 months apart at the First Affiliated Hospital of Dalian Medical University between September 1, 2015 and November 30, 2019 were identified. According to the prior LVEF, the subjects were divided into improved group (prior LVEF < 40%), stable group (prior LVEF between 40 and 50%), and deteriorated group (prior LVEF ≥ 50%). The primary outcomes were cardiovascular death, all-cause mortality, hospitalization for worsening heart failure, and composite event of all-cause mortality or all-cause hospitalization.Results: A total of 1,168 HFmrEF patients (67.04% male, mean age 63.60 ± 12.18 years) were included. The percentages of improved, stable, and deteriorated group were 310 (26.54%), 334 (28.60%), and 524 (44.86%), respectively. After a period of follow-up, 208 patients (17.81%) died and 500 patients met the composite endpoint. The rates of all-cause mortality were 35 (11.29%), 55 (16.47%), and 118 (22.52%), and the composite outcome was 102 (32.90%), 145 (43.41%), and 253 (48.28%) for the improved, stable, and deteriorated groups, respectively. Cox regression analysis showed that the deterioration group had higher risk of cardiovascular death (HR: 1.707, 95% CI: 1.064–2.739, P = 0.027), all-cause death (HR 1.948, 95% CI 1.335–2.840, P = 0.001), and composite outcome (HR 1.379, 95% CI 1.096–1.736, P = 0.006) compared to the improvement group. The association still remained significant after fully adjusted for both all-cause mortality (HR = 1.899, 95% CI 1.247–2.893, P = 0.003) and composite outcome (HR: 1.324, 95% CI: 1.020–1.718, P = 0.035).Conclusion: HFmrEF patients are heterogeneous with three different subsets identified, each with different outcomes. Strategies for managing HFmrEF should include previously measured LVEF to allow stratification based on direction changes in LVEF to better optimize treatment.

Heart failure with mid-range ejection fraction and the effect of β-blockers after acute myocardial infarction.

There is currently an ongoing debate about the 'grey area' of heart failure with mid-range ejection fraction (HFmrEF). We evaluated characteristics, prognosis, and the effect of β-blockers on clinical outcomes in patients with HFmrEF after acute myocardial infarction (AMI). We included a total of 10,785 patients and divided them into three groups: EF 40-49% (HFmrEF; n = 2717; reference); EF < 40% (reduced EF [HFrEF]; n = 1194); and EF ≥ 50% (preserved EF [HFpEF]; n = 6874). The primary outcome was 2-year all-cause mortality. HFmrEF was intermediate between HFrEF and HFpEF for baseline characteristics. The risk of all-cause mortality was lower for HFmrEF patients compared to HFrEF patients (adjusted hazard ratio [HR] 0.710; 95% confidence interval [CI] 0.544-0.927; P = 0.012). However, HFmrEF patients tended to be at higher risk for 2-year all-cause mortality than HFpEF patients (adjusted HR 1.235; 95% CI 0.989-1.511; P = 0.090). β-blockers were associated with reductions in all-cause mortality for the entire cohort (adjusted HR 0.760; 95% CI 0.592-0.975; P = 0.031). β-blockers were effective in patients with HFrEF (adjusted HR 0.667; 95% CI 0.471-0.944; P = 0.022), tended to be effective in patients with HFmrEF (adjusted HR 0.665; 95% CI 0.426-1.038; P = 0.072), but not effective in patients with HFpEF (adjusted HR 0.852; 95% CI 0.548-1.326; P = 0.478; interaction P = 0.026). In conclusion, clinical profiles and prognosis of patients with post-AMI HFmrEF are largely intermediate between HFrEF and HFpEF. β-blockers reduced or tended to reduce 2-year all-cause mortality in patients with HFrEF or HFmrEF, respectively, but not those with HFpEF after AMI.

Effects of sacubitril/valsartan on clinical symptoms, echocardiographic parameters, and outcomes in HFrEF and HFmrEF patients with coronary heart disease and chronic kidney disease

Objective To compare the effects of Angiotensin Receptor-Neprilysin inhibitor (ARNI) on the clinical symptoms, echocardiographic parameters, and outcomes (cardiovascular death and hospitalization) in heart failure with reduced ejection fraction (HFrEF) and heart failure with mid-range ejection fraction (HFmrEF) patients with coronary heart disease and chronic kidney disease. Method A retrospective observational study was conducted from January 2018 to May 2019, with a follow-up period of 95.4 ± 57.8 days (8 months). Data from 127 patients were included. Results A statistically significant increase of 68.8% was observed in left ventricular ejection fraction (LVEF) in HFrEF patients compared to that in HFmrEF patients, with an increase of 27.2% at 8 months of follow-up. Sacubitril/valsartan significantly reduced left ventricular end-systolic volumes (LVESV) in HFrEF patients unlike in HFmrEF patients. The decrease in LVESV was 28.8% in HFrEF patients and 17.1% in HFmrEF patients. A significant reduction in the prevalence of severe secondary mitral regurgitation (EROA > 0.4 cm2) was observed in HFrEF compared to that in HFmrEF patients with the use of sacubitril/valsartan. A reduction of 15.6% was observed in HFrEF patients, whereas a reduction of 7.1% was observed in HFmrEF patients. Improvement in functional classification (NYHA) was observed during follow-up. The prevalence of (NYHA III) reduced from 50% to 15.7% in HFrEF patients, whereas a reduction from 21.1% to 8.8% was observed in HFmrEF patients. There was a significant reduction in NT-proBNP in HFrEF patients compared to that in HFmrEF patients. A reduction of 52% was observed in HFrEF patients, whereas a reduction of 28.7% was observed in HFmrEF pateints. Sacubitril/valsartan reduced primary endpoint events in both groups. The prevalence of HF-related hospitalization was higher in HFrEF than in HFmrEF patients: 12.1% vs 7.5%, respectively. The prevalence of CV death in HFrEF vs HFmrEF patients was 3.7% vs 0.5%, respectively. Cardiovascular (CV) death was higher in patients with atrial fibrillation in both groups. Conclusion Sacubitril/valsartan significantly improved morphofunctional remodeling parameters and clinical symptoms in HFrEF patients than in HFmrEF patients.

Association Between Physical Status and the Effects of Combination Therapy With Renin-Angiotensin System Inhibitors and β-Blockers in Patients With Acute Heart Failure.

Background: This study investigated whether combination therapy (CT) with renin-angiotensin system inhibitors and β-blockers improved endpoints in acute heart failure (AHF).Methods and Results: AHF patients were recruited to this prospective multicenter cohort study between April 2015 and August 2017. Patients were divided into 3 categories based on ejection fraction (EF), namely heart failure (HF) with reduced EF (HFrEF), HF with midrange EF (HFmrEF), and HF with preserved EF (HFpEF), and a further into 2 groups according to physical status (those who could walk independently outdoors and those who could not). The composite endpoint included all-cause mortality and hospitalization for HF. Data at the 1-year follow-up were available for 1,018 patients. The incidence of the composite endpoint was significantly lower in the CT than non-CT group for HFrEF patients, but not among HFmrEF and HFpEF patients. For patients who could walk independently outdoors, a significantly lower rate of the composite endpoint was recorded only in the HFrEF group. The differences were maintained even after adjustment for comorbidities and prescriptions, with hazard ratios (95% confidence intervals) of 0.39 (0.20–0.76) and 0.48 (0.22–0.99), respectively.Conclusions: In this study, CT was associated with the prevention of adverse outcomes in patients with HFrEF. Moreover, CT prevented adverse events only among patients without a physical disorder, not among those with a physical disorder.

MORNING SURGE IN BLOOD PRESSURE AS A PREDICTOR OF WORSENING HEART FAILURE IN HEART FAILURE WITH REDUCED EJECTION FRACTION

Objective: Abnormal circadian blood pressure (BP) rhythm is observed in heart failure (HF) patients. Rising BP in the morning known as the morning surge (MS) is one of the abnormal circadian BP rhythm, and a cardiovascular risk factor in hypertensives. However, the significance of MS is not established in patients with HF. Design and method: We performed a prospective, observational cohort study of hospitalized HF patients who underwent ambulatory BP monitoring (ABPM). Four hundred fifty seven hospitalized HF patients (age, 68 ± 13 yrs; 63.9% males [n = 292] and 36.1% females [n = 165]) were followed up for 20.0 (median) months. Results: HF with reduced ejection fraction (HFrEF) was 197 (43.1%), HF with mid-range ejection fraction (HFmrEF) was 101 (22.1%), and HF with preserved ejection fraction (HFpEF) was 159 (34.8%). The composite outcome consisting of all-cause mortality and worsening HF was observed in 143 patients. In a Kaplan-Meier analysis, the MS group had a significantly higher incidence of the composite outcome than the non-MS group in HFrEF and HFmrEF patients.(figure) However, in multivariate Cox regression analysis, MS was a significant predictor for adverse outcomes only in HFrEF patients (HR 2.63, 95%CI 1.11–6.25, p = 0.03). Conclusions: The MS was found to be a novel predictor of worsening HF in patients with HFrEF.

β-blocker and 1-year outcomes among patients hospitalized for heart failure with mid-range ejection fraction.

AimsThe beneficial effect of β-blocker on heart failure with reduced ejection fraction is well established. However, its effect on the 1-year outcome of heart failure with mid-range ejection fraction (HFmrEF) remains unclear.Methods and resultsWe analysed the data of the patients with left ventricular ejection fraction (LVEF) between 40% and 49% in China Patient-centred Evaluative Assessment of Cardiac Events Prospective Heart Failure Study (China PEACE 5p-HF Study), in which patients hospitalized for heart failure from 52 Chinese hospitals were recruited from 2016 to 2018. Two primary outcomes were all-cause death and all-cause hospitalization. The associations between β-blocker use at discharge and outcomes were assessed by inverse probability of treatment weighting (IPTW)-weighted Cox regression analyses. To assess consistency, IPTW adjusting medications analyses, multivariable analyses and dose-effect analyses were performed. A total of 1035 HFmrEF patients were included in the analysis. The mean age was 65.5 ± 12.7 years and 377 (36.4%) were female. The median (interquartile range) of LVEF was 44% (42–47%). Six hundred and sixty-one (63.8%) were treated with β-blocker. Patients using β-blocker were younger with better cardiac function, and more likely to use renin–angiotensin system inhibitor and mineralocorticoid receptor antagonist. During the 1-year follow-up, death occurred in 84 (12.7%) treated and 85 (22.7%) untreated patients (P < 0.0001); all-cause hospitalization occurred in 298 (45.1%) treated and 188 (50.3%) untreated patients (P = 0.04). After IPTW-weighted adjustment, β-blocker use was significantly associated with lower risk of all-cause death [hazard ratio (HR): 0.70; 95% confidence interval (CI): 0.51–0.96, P = 0.03], but not with lower all-cause hospitalization (HR, 0.92, 95% CI, 0.76–1.10, P = 0.36). Consistency analyses showed consistent favourable effect of β-blocker on all-cause death, but not on all-cause hospitalization.ConclusionsAmong patients with HFmrEF, β-blocker use was associated with lower risk of all-cause death, but not with lower risk of all-cause hospitalization.

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.

Special prognostic phenomenon for patients with mid-range ejection fraction heart failure: a systematic review and meta-analysis.

Background:Clinical features and outcomes of heart failure (HF) with mid-range ejection fraction (HFmrEF) remain controversial. Thus, we systematically reviewed literatures of clinical research to assess and analyze characteristics and prognosis of patients with HFmrEF.Methods:PubMed, Embase, and Web of Science were searched for cohort studies up to April 23, 2019. Clinical features and multivariate adjusted hazard ratios (HRs) of endpoints of short-term all-cause mortality (SAM), long-term all-cause mortality (LAM), long-term cardiovascular death (LCD) and long-term HF rehospitalization (LHR) among patients with HFmrEF and HF with preserved ejection fraction (HFpEF), HF with reduced ejection fraction (HFrEF) were well addressed. The primary outcome was LAM.Results:Totally 19 studies were included in this study with 164,678 patients enrolled. The follow-up time of LAM was 3.6 ± 2.5 years. HRs of LAM, SAM, LCD, LHR indicated that the risks of patients with HFmrEF were higher than HFpEF patients but lower than HFrEF patients, as for LAM, HFmrEF:HFpEF (reference) HR: 1.07, 95% confidence interval (CI): 1.00–1.15 (I2 = 63%, P = 0.0005); HFmrEF:HFrEF (reference) HR: 0.80, 95% CI: 0.73–0.88 (I2 = 70%, P < 0.0001). However, HFmrEF patients had the lowest rate in LAM (30.94%), SAM (2.73%), LCD (17.45%), LHR (26.36%) compared with the other two groups.Conclusions:This systematic review and meta-analysis compared features and prognosis between patients with HFmrEF and HFpEF, HFrEF by HRs. There appeared a special “separation phenomenon” showing rates of endpoints were inconsistent with their hazards in patients with HFmrEF compared with HFpEF patients.

Spironolactone use is associated with improved outcomes in heart failure with mid-range ejection fraction.

AimsSpironolactone has been shown to improve outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). We investigated whether the discharge use of spironolactone could be associated with better long‐term outcomes among patients with HF with mid‐range EF (HFmrEF).Methods and resultsWe analysed HFmrEF (left ventricular EF 40–49%) patients enrolled in the Japanese Cardiac Registry of Heart Failure in Cardiology, which prospectively studied the clinical characteristics, treatments, and long‐term outcomes of patients hospitalized due to HF. Patients were divided into two groups according to the use of spironolactone at discharge. The primary outcome was a composite of all‐cause death or HF rehospitalization. A total of 457 patients had HFmrEF. The mean age was 69.3 years and 286 (62.6%) were male. Among them, spironolactone was prescribed at discharge in 158 patients (34.6%). Chronic kidney disease (7.6% vs. 16.8%, P = 0.007) was less prevalent and loop diuretics (89.2% vs. 70.2%, P < 0.001) were more often prescribed in patients with spironolactone. During a mean follow‐up of 2.2 years, patients with spironolactone had a lower incidence rate of the primary outcome than those without it (171.5 vs. 278.8 primary outcome per 1000 patient‐years, incidence rate ratio 0.61, 95% confidence interval 0.44–0.86; P = 0.004). After multivariable adjustment, spironolactone use at discharge was associated with a significant reduction in the composite of all‐cause death or HF rehospitalization (adjusted hazard ratio 0.63, 95% confidence interval 0.44–0.90, P = 0.010).ConclusionsAmong patients with HF hospitalized for HFmrEF, spironolactone use at discharge was associated with better long‐term outcomes.

Heart Failure With Mid-range Ejection Fraction.

To describe the epidemiology, pathophysiology, management, and prognosis of patients with heart failure with mid-range ejection fraction (HFmrEF). In 2013, The American Heart Association (AHA)/American College of Cardiology (ACC) assigned an ejection fraction (EF) range to heart failure with reduced ejection fraction (HFrEF, EF ≤ 40%) and heart failure with preserved ejection fraction (HFpEF, EF ≥50%). This classification created a "gray zone" of patients with EFs between 41% and 49% that ultimately came to be known as heart failure with borderline or mid-range ejection fraction. HFmrEF patients represent a group with heterogeneous clinical characteristics that at times resembles HFrEF, at others HFpEF, and at others still a unique phenotype altogether. No randomized controlled trials exist in those with HFmrEF, though HFrEF and HFpEF studies that include overlap suggest some potential benefit of beta blockers, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and angiotensin receptor-neprilysin inhibitors. Mortality rates among the HFmrEF population are significant, and are similar to those in patients with HFrEF and HFpEF. HFmrEF is a complex disorder that remains poorly understood. Future research is needed to better elucidate the pathophysiology, management, and prognosis of this condition.

Comparison of clinical features and conventional echocardiographic characteristics of patients with heart failure with mid-range ejection fraction with and without interatrial block

Heart failure with mid-range ejection fraction (HFmrEF) has been proposed as a distinct heart failure (HF) phenotype. Interatrial block (IAB) is a conduction delay between the atria and is associated with cardiovascular disease. Although there are several studies examining the effect of IAB in patients with HF with reduced ejection fraction and HF with preserved ejection fraction, a literature review did not reveal any study investigating the clinical importance of the presence of IAB in patients with HFmrEF. Thus, the aim of this research was to evaluate clinical characteristics of HFmrEF with and without IAB.A total of 520 consecutive patients with HFmrEF in sinus rhythm who were examined at outpatient clinics were enrolled in the study (244 patients with IAB and 276 patients without IAB). Surface 12-lead standard electrocardiograms (ECGs) were recorded. Clinical characteristics, echocardiographic examination results, and laboratory values of the patients were recorded.The mean age of the patients was 67.4±11.1 years, and 76.1% were male. The patients with IAB had more comorbidities, including hypertension, diabetes mellitus, and stroke/transient ischemic attack. A statistically significant, strong, positive linear correlation was observed between P-wave duration and age, systolic blood pressure, and left atrial volume index (r=0.718, p<0.001; r=0.704, p<0.001; and r=0.725, p<0.001, respectively).To the best of our knowledge, the present study is the first to evaluate the clinical relevance of IAB in HFmrEF. Adding this simple ECG marker to the clinical evaluation could add significantly to the management of HFmrEF. IAB can be used to identify high-risk HFmrEF patients, as well as to guide follow-up and appropriate treatment.

P6330Obesity paradox in heart failure with mid-range ejection fraction

Abstract Background Obesity is identified as an independent risk factor for developing congestive heart failure (HF). Paradoxically it has been reported that obesity is associated with improved survival in different cohorts of HF patients. Nevertheless, the presence of obesity paradox in HF with mid-range ejection fraction (HFmrEF) is not completely elucidated. Objective To analyse the relationship between body mass index (BMI) and mortality in a HFmrEF ambulatory cohort of different aetiologies followed in a HF unit, with especial focus on the role of obesity in prognosis. Methods Baseline BMI was analysed as continuous variable and categorized in 4 groups based on 2009 WHO classification: low weight (BMI &lt;20.5 kg/m2), normal weight (BMI 20.5 to &lt;25.5 kg/m2), overweight (BMI 25.5 to &lt;30 kg/m2) and obesity (BMI ≥30 kg/m2). All-cause mortality was the primary end-point of the study. Cox regression analyses adjusted by age, sex and NYHA functional class were performed and survival curves plotted. Results Three-hundred thirty patients were included in the study (age 65.9±13.2 years, 68% men). The main aetiology was ischemic heart disease (52%, followed by dilated cardiomyopathy (11%) and hypertensive cardiomyopathy (11%). The majority of patients were in NYHA class II (65%) and III (26%). Mean ejection fraction was 43.2% ± 2.7. During a mean follow-up of 5.3±4.6 years 142 patients (42%) died. BMI showed a protective effect on survival in Cox regression analysis (HR 0.96 [95% CI 0.92–0.99], p=0.01). When categorized groups of BMI were analysed, obese patients showed a trend towards lower mortality than normal weight patients (reference): adjusted HR 0.65 [95% CI 0.40–1.03], p=0.07. Survival curves adjusted by age, sex and NYHA functional class according to BMI category are depicted in the figure. As a significant interaction (p=0.02) was found between BMI and ischemic aetiology of HF, separate analyses were performed for BMI categories for ischemic and non-ischemic patients, with remarkably different results: ischemic aetiology: HR 0.97 [95% CI 0.52–1.79], p=0.91; non-ischemic aetiology HR 0.28 [95% CI 0.13–0.64], p=0.003. Conclusions A greater BMI was associated with lower mortality rates in patients with HFmrEF during a mean follow-up of five years. Obesity showed a protective effect in HFmrEF patients, which remarkable in patients from non-ischemic aetiology and was absent in patients from ischemic aetiology.

P326Characteristic of sympathetic nerve activity in two subgroups of patients with heart failure (HFrEF and HFmrEF)

Abstract Introduction Sympathetic overactivity is a well documented in severe heart failure (HF) with reduced ejection fraction (HFrEF). The European Society of Cardiology has recently introduced a new HF category, i.e. HF with mid-range ejection fraction (HFmrEF), characterized by left ventricular EF of 40–49%. The sympathetic regulation in this new category has not been thoroughly described. Aims Characterization of the sympathetic regulation in patients with HFmrEF compared with data obtained from HFrEF patients and healthy volunteers. Method 14 HFrEF patients, 22 HFmrEF patients and 10 control subjects were enrolled (Table 1). Muscle sympathetic nerve activity, (MSNA) was recorded in the superficial peroneal nerve by microneurography, and processed by the Nerve Traffic Analyzer System (Model 662C-3, Iowa). Continuous ECG and non-invasive blood pressure (Finapres 2300) were digitized online (500 Hz/channel). Sympathetic burst frequency (bursts/minute) and burst incidence (bursts/100 heartbeats) were determined. The 6 min walking distances (6MWD) and NT proBNP levels in the HF subgroups were also assessed. Results Both burst frequency and incidence were significantly elevated in the HF subgroups compared to controls, and significant differences were also seen between the HFrEF and HFmrEF groups. The sympathetic burst activity in the HF populations significantly correlated with the NT proBNP level (R=0.53, p=0.003) and inversely correlated with the ejection fraction (R=−0.38, p=0.03). Table 1. Results EF &lt;40% EF: 40–49% Healthy control group (HC) p p p (n=14) (n=22) (n=10) EF &lt;40% vs. EF: 40–49% EF &lt;40% vs. HC EF: 40–49% vs. HC NYHA I–II 8 21 − − − − III–IV 6 1 − − − − Age 58.36±12.31 62.23±9.74 52.44±10.41 0.302 0.247 0.019 BMI 29.65±3.77 29.84±4.19 − 0.895 − − NT proBNP [ng/L] 1574.75±1415.06 300.20±247.35 − 0.002 − − 6MWT [m] 476.88±63.53 496.53±76.59 − 0.503 − − EF [%] 44.47±3.34 26.78±8.58 − − − − Baseline burst/min 59.29±14.18 39.55±9.48 25.78±8.47 &lt;0.001 &lt;0.001 0.001 burst/100 84.64±12.63 65.68±15.48 35.78±11.27 0.001 &lt;0.001 &lt;0.001 Conclusion Sympathetic activity is elevated in heart failure as compared to healthy controls. In patients with HFrEF both parameters of sympathetic activity were significantly higher as compared to patients with HFmrEF. Acknowledgement/Funding The work is supported by the GINOP-2.3.2-15-2016-00043 project. The project is co-financed by the EU and the European Regional Development Fund