Chronic Heart Failure With Preserved Ejection Fraction Research Articles

Threonine In Different Phenotypes Of Chronic Heart Failure With Preserved Ejection Fraction

Background — Chronic heart failure with preserved ejection fraction (CHFpEF) develops as a result of many diseases that lead to significant metabolic disorders. Given the heterogeneity of this group of patients, therapeutic options for this syndrome are extremely limited. In this regard, it seems promising to study the metabolomic profile in patients with CHFpEF to identify biomarkers, examine their roles in the pathogenesis of the syndrome, and search for potential targets for targeted therapy. Objective — The study aimed at testing the correlation between the threonine level and the features of the clinical course of CHFpEF. Methods — The study included a total of 154 patients: 82 with CHFpEF, 45 with hypertension and/or coronary artery disease (comparison group), and 27 healthy volunteers (control group). Threonine levels were assessed using high-performance liquid chromatography-mass spectrometry. Results — The threonine concentration was significantly reduced in patients with CHFpEF (1) vs. comparison group (2) and control group (3): p<0.001; p1-3<0.001; p2-3=0.037). A reduction in the threonine level was characteristic for patients with diabetes mellitus vs. patients without it (p=0.029). Conclusion — Given the importance of threonine in energy metabolism and significant changes in its level in various pathophysiological processes, it should be considered as an additional diagnostic and prognostic criterion for CHFpEF. Additional studies are needed to better understand the role of threonine in the pathophysiology of cardiovascular diseases.

Inflammatory Biomarkers in Patients With Type 2 Diabetes Mellitus and Heart Failure With Preserved Ejection Faction.

To verify the relationship between gene polymorphisms of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) with inflammation markers and codependent metabolic variables in patients with type 2 diabetes mellitus and chronic heart failure (CHF). This study included 154 patients (mean age, 69.1±3.2 years). The control group consisted of 47 patients with metabolic syndrome (MS) without CHF; the 2nd group included 56 patients with CHF with preserved ejection fraction (CHFpEF); and the 3rd group consisted of 51 patients with CHF with reduced ejection fraction (CHFrEF). The rs1800629 polymorphism of the TNF-α gene (TNF-α: G308A) was studied in real time by the polymerase chain reaction (PCR) method and the rs1800795 polymorphism of the IL-6 gene (IL-6: 174 G>C) was studied by PCR with the electrophoretic detection. The frequencies of polymorphic alleles were compared with the clinical blood test results, plasma concentrations of C-reactive protein (CRP), TNF-α, leptin, and fibrinogen. Differences between the groups were determined using the F test. Relationships between individual studied parameters were identified using the regression analysis. In most patients, the occurrence of gene polymorphisms was eident as increased plasma concentrations of biomarkers. An association was found between the TNF-α gene polymorphism (G308A) and an increase in plasma TNF-α and between the IL-6 gene polymorphism (174 C>G) and an increase in plasma CRP. In the CHFpEF group, the rs1800629 gene polymorphism was observed in 55% of patients, among whom 93% had increased TNF-α. The rs1800795 gene polymorphism was observed in 82% of CHFpEF patients, among whom 21% had increased CRP. In the CHFrEF group, the G308A transition in the TNF-α gene was observed in 53% of patients; an increase in the respective cytokine was noted in 67% of patients; the IL-6 gene polymorphism 174 C>G was found in 78%, however, only 14% of patients with this polymorphism had also increased CRP. In the control group, the TNF-α G308A gene polymorphism was found in 30% of patients, while an increase in free TNF-α was associated with this polymorphism in 50% of patients; the IL-6 174 C>G gene polymorphism was detected in 78%, while no increase in the CRP level was observed in this group. This demonstrates a high probability of the TNF-α G308A gene polymorphism occurrence in patients with CHF. Inflammatory markers are important predictors of CHF. The most significant predictor was the TNF-α G308A gene polymorphism, which was observed in more than 50% of patients, the majority of whom had an increase in plasma TNF-α.

Heart failure with preserved ejection fraction management: a systematic review of clinical practice guidelines and recommendations.

Multiple guidelines exist for the diagnosis and management of heart failure with preserved ejection fraction (HFpEF). We systematically reviewed current guidelines and recommendations, developed by national and international medical organizations, on the management of HFpEF in adults to aid clinical decision-making. We searched MEDLINE and EMBASE on 28 February 2024 for publications over the last 10 years as well as websites of organizations relevant to guideline development. Of the ten guidelines and recommendations retrieved, seven showed considerable rigour of development and were subsequently retained for analysis. There was consensus on the definition of HFpEF and the diagnostic role of serum natriuretic peptides and resting transthoracic echocardiography. Discrepancies were identified in the thresholds of serum natriuretic peptides and transthoracic echocardiography parameters used to diagnose HFpEF. There was agreement on the general pharmacological and supportive management of acute and chronic HFpEF. However, differences exist in strategies to identify and address specific phenotypes. Contemporary guidelines for HFpEF management agree on measures to avoid its development and the consideration of cardiac transplantation in advanced disease. There were discrepancies in recommended frequency of surveillance for patients with HFpEF and sparse recommendations on screening for HFpEF in the general population, use of diagnostic scoring systems, and the role of newly emerging therapies.

The level of highly sensitive C-reactive protein and mortality within a year after discharge from the hospital in patients with chronic heart failure with preserved ejection fraction

Background. In recent years, there has been a steady trend in the form of an increase in the number of polymorbid patients with chronic heart failure with preserved ejection fraction (CHFpEF) and an increase in the frequency of its decompensation, which leads to an increased risk of adverse outcomes and increased mortality rates.Objective: to study the mortality structure in patients with CHFpEF within 1 year from the moment of discharge after initial hospitalization for decompensation of heart failure, as well as the level of highly sensitive C-reactive protein (hs-CRP) and clinical and laboratory characteristics of patients depending on the outcome.Methods. The data of patients with CHFpEF were retrospectively analyzed within 1 year from the moment of discharge after hospitalization due to decompensation of heart failure (n=372; median age 72.6 [63.3; 82.8] years, women – 44.4 %, NYHA class III and IV chronic heart failure, respectively, had 79.3 % and 15.9 % of patients). The concentration of hs-CRP in serum was determined in all patients during the first 24 hours after admission to the hospital.Results. During the follow-up, 65 deaths were registered (17.5 % of the included patients), of which 56 (86.2 % of all deaths) were caused by cardiovascular and cerebrovascular events – acute myocardial infarction (30 cases, 46.2 %), postinfarction cardiosclerosis (11 cases, 16.9 %), ischemic stroke (10 cases, 15.4 %), and rupture of an aortic aneurysm (1 case, 1.5 %). The level of hs-CRP compared with the surviving patients (4.84 [3.78; 5.88] mg/l) was statistically significantly higher both in the group of deaths from cardiovascular causes (5.22 [4.53; 6.21] mg/l, p=0.029) and in the group of deaths from all causes (5.33[4.49; 6.19] mg/l, p=0.020). A comparative analysis of patient characteristics revealed that patients who died from cardiovascular causes, compared with survivors, had a statistically significantly lower body mass index (p=0.046), higher total cholesterol (p=0.002), and aspartate aminotransferase (p=0.025). When comparing patients who died from all causes with patients without a fatal outcome, statistically significant differences in similar indicators were obtained.Conclusion. In patients with CHFpEF, both cardiovascular mortality and all-cause mortality within 1 year after hospitalization for decompensation of heart failure may be associated with sluggish inflammation, as well as an initially lower body mass index, higher total cholesterol and indirect signs of more pronounced myocardial damage.

Impact of Ayurveda-based lifestyle modification, diet, and panchakarma on the hemodynamic parameters in heart failure patients with preserved ejection fraction

Abstract Background: Heart failure (HF) with preserved ejection fraction (HFpEF) is a medical problem with a growing prevalence that requires sophisticated management techniques. New management strategies for HF have constantly been called for by researchers, which has drawn our attention to Ayurveda, the traditional alternative medicine practiced extensively in India. One such treatment used to treat heart failure is Heart Failure Reversal Therapy (HFRT), which combines herbal therapies including Snehan, Swedan, Basti (per rectal drug administration), and Hridaydhara. Objective: The study is aimed to evaluate the effects of HFRT and Ayurveda Dinacharya on known chronic HFpEF patients. Materials and Methods: This observational study was conducted between May 2021 and October 2021, wherein patients (both genders) with HF (New York Heart Association, NYHA Class I, II, and III) having a left ventricular ejection fraction of more than 40 and aged between 18 and 60 years were identified. The effect of study therapy, HFRT, and Ayurveda Dinacharya over 7 days in 14 sittings was observed. A total of 73 patients with HFpEF underwent study therapy for 7 days. Data related to patient demographics on Cardiac Output (CO), Diastolic Blood Pressure (DBP), Heart Rate (HR), Left Ventricular (LV), Systolic Blood Pressure (SBP), Systemic Vascular Resistance (SVR), Systolic (SYS), End-diastolic volume (EDV), Ejection factor (EF), etc. were analyzed pre- and post-study. Results: There was a remarkable improvement in the mean values of SVR from day 1 to day 7. The mean value of SVR on day 1 was 2271.39 ± 509.66, and on day 7 was 1876.18 ± 315.21. Reduced SVR values mean the amount of LV force needed to open the aortic valve is also reduced. This causes more efficient pumping action in the left ventricle, reflected by increased CO and increased VO2 max, thus improving the quality of life. Conclusion: The HFRT therapy and Ayurveda Dinacharya for seven days demonstrated a significant change in the hemodynamics of HFpEF patients, thus improving the quality of life.

Impact of different types of heart failure on coronavirus disease 2019 infection outcomes

Abstract Background Pre-existing cardiovascular disease has been associated with increased mortality in patients with coronavirus disease 2019 (COVID-19). However, the impact of different types of heart failure in unvaccinated patients with COVID-19 infection has been understudied. Purpose In this study, we compare the in-hospital outcomes of patients with COVID-19 and chronic heart failure with reduced ejection fraction (HFrEF) against patients with COVID-19 and chronic heart failure with preserved ejection fraction (HFpEF). Methods This was a retrospective cohort study done by utilizing the 2020 National Inpatient Sample database. We identified patients admitted to the hospital with a principal diagnosis of COVID-19 infection and a secondary diagnosis of either chronic HFrEF or HFpEF. We conducted propensity score matching using a greedy nearest neighbor 1:1 model. Multivariable logistic regression, adjusted for age, sex, hospital characteristics (bed size, location, region), health insurance and comorbidities was used to compare mortality. The comorbidities adjusted for included atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease, coronary artery disease, hypertension, obesity, prior myocardial infarction and type 2 diabetes mellitus. The categorical and continuous variables were analyzed by Pearson’s chi-squared and Student t-test respectively. Results 12,518 patients met our inclusion criteria. Patients with COVID-19 infection and chronic HFrEF had 1.11 times higher odds of suffering in-hospital mortality compared to patients with COVID-19 infection and chronic HFpEF (aOR 1.11, 95% CI: 1.01-1.21; p = 0.03). When separated by race, there was no difference in mortality between our two cohorts (Figure 1). Patients with COVID-19 infection and chronic HFrEF were more likely to have acute hepatic failure (1.2% vs 0.6%, p < 0.001), ventricular tachycardia (6.7% vs 3.1%, p < 0.001) and ventricular fibrillation (0.6% vs 0.2%, p < 0.001), but less likely to have acute respiratory distress syndrome (5.0% vs 6.6%, p < 0.001, Table 1). In terms of comorbidities, patients with both COVID-19 and chronic HFrEF were more likely to have atrial fibrillation (22.8% vs 21.3%, p = 0.03) coronary artery disease (39.5% vs 35.1%, p < 0.001) and prior myocardial infarction (8.8% vs 6.4%, p < 0.001, Table 1). These patients also had shorter hospital stays (8.4 days vs 9.0 days, p < 0.001), but there was no difference in mean total hospital charges ($87,975.84 vs $88,715.96, p = 0.75, Table 1). Conclusion Patients with COVID-19 and chronic HFrEF had higher odds of suffering in-hospital mortality compared to patients with COVID-19 and chronic HFpEF. These patients were also more likely to have acute hepatic failure, ventricular tachycardia and ventricular fibrillation. Further studies should investigate how COVID-19 vaccination status influences the outcomes of this vulnerable population.

Abstract 13847: Biomarker-Based Phenomapping in Chronic Stable HFpEF and Exercise Capacity: An Analysis of the RELAX Trial

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a heterogenous disease associated with low exercise capacity. Hypothesis: Unsupervised clustering of biomarker data can identify subgroups of individuals with HFpEF and differences in exercise capacity. Methods: The study included participants with chronic, stable HFpEF from the RELAX trial with available serum biomarker data. We used unsupervised hierarchical clustering analysis of 9 serum biomarkers to derive phenogroups of participants with HFpEF. Adjusted linear regression was used to assess the association between cluster membership with peak oxygen consumption (VO2), maximum exercise watts, and VO2 anaerobic threshold. Results: Among 211 participants in the RELAX trial, 3 phenogroups were identified based on the gain in within-inertia. No significant differences were observed in age, sex, or race across phenogroups. Phenogroup 1 (n=136) participants had the lowest burden of CV (cardiovascular) risk factors, including diabetes, anemia, and kidney disease as well as the lowest overall biomarkers levels ( Fig. A ). Phenogroup 2 (n=61) consisted of participants who were older with a higher burden of CV risk factors and fibrosis biomarkers, including galectin-3, collagen-I, and troponin-I levels. Phenogroup 3 (n=14) participants were younger with high burden of CV risk factors and inflammatory biomarkers including aldosterone, CRP, and uric acid. Compared with phenogroup 1, phenogroup 2 and 3 had significantly lower peak VO2, adjusted for traditional CV risk factors [estimate (95% CI): -1.99 (-2.83, -1.16) and -2.31 (-3.66, -0.95), respectively] (Fig. B ). Additionally, phenogroup 3 vs. 1 had lower exercise watts and VO2 anaerobic threshold. Conclusion: Using serum biomarkers, we identified 3 unique phenogroups of patients with chronic, stable HFpEF and significant differences in CV risk factor burden and exercise capacity.

Skeletal Muscle Mitochondrial Respiration and Exercise Intolerance in Patients With Heart Failure With Preserved Ejection Fraction

The pathophysiology of exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF) remains incompletely understood. Multiple lines of evidence suggest that abnormal skeletal muscle metabolism is a key contributor, but the mechanisms underlying metabolic dysfunction remain unresolved. To evaluate the associations of skeletal muscle mitochondrial function using respirometric analysis of biopsied muscle fiber bundles from patients with HFpEF with exercise performance. In this cross-sectional study, muscle fiber bundles prepared from fresh vastus lateralis biopsies were analyzed by high-resolution respirometry to provide detailed analyses of mitochondrial oxidative phosphorylation, including maximal capacity and the individual contributions of complex I-linked and complex II-linked respiration. These bioenergetic data were compared between patients with stable chronic HFpEF older than 60 years and age-matched healthy control (HC) participants and analyzed for intergroup differences and associations with exercise performance. All participants were treated at a university referral center, were clinically stable, and were not undergoing regular exercise or diet programs. Data were collected from March 2016 to December 2017, and data were analyzed from November 2020 to May 2021. Skeletal muscle mitochondrial function, including maximal capacity and respiration linked to complex I and complex II. Exercise performance was assessed by peak exercise oxygen consumption, 6-minute walk distance, and the Short Physical Performance Battery. Of 72 included patients, 50 (69%) were women, and the mean (SD) age was 69.6 (6.1) years. Skeletal muscle mitochondrial function measures were all markedly lower in skeletal muscle fibers obtained from patients with HFpEF compared with HCs, even when adjusting for age, sex, and body mass index. Maximal capacity was strongly and significantly correlated with peak exercise oxygen consumption (R = 0.69; P < .001), 6-minute walk distance (R = 0.70; P < .001), and Short Physical Performance Battery score (R = 0.46; P < .001). In this study, patients with HFpEF had marked abnormalities in skeletal muscle mitochondrial function. Severely reduced maximal capacity and complex I-linked and complex II-linked respiration were associated with exercise intolerance and represent promising therapeutic targets.

Supervised Exercise Training for Chronic Heart Failure With Preserved Ejection Fraction: A Scientific Statement From the American Heart Association and American College of Cardiology.

Heart failure with preserved ejection fraction (HFpEF) is one of the most common forms of heart failure; its prevalence is increasing, and outcomes are worsening. Affected patients often experience severe exertional dyspnea and debilitating fatigue, as well as poor quality of life, frequent hospitalizations, and a high mortality rate. Until recently, most pharmacological intervention trials for HFpEF yielded neutral primary outcomes. In contrast, trials of exercise-based interventions have consistently demonstrated large, significant, clinically meaningful improvements in symptoms, objectively determined exercise capacity, and usually quality of life. This success may be attributed, at least in part, to the pleiotropic effects of exercise, which may favorably affect the full range of abnormalities-peripheral vascular, skeletal muscle, and cardiovascular-that contribute to exercise intolerance in HFpEF. Accordingly, this scientific statement critically examines the currently available literature on the effects of exercise-based therapies for chronic stable HFpEF, potential mechanisms for improvement of exercise capacity and symptoms, and how these data compare with exercise therapy for other cardiovascular conditions. Specifically, data reviewed herein demonstrate a comparable or larger magnitude of improvement in exercise capacity from supervised exercise training in patients with chronic HFpEF compared with those with heart failure with reduced ejection fraction, although Medicare reimbursement is available only for the latter group. Finally, critical gaps in implementation of exercise-based therapies for patients with HFpEF, including exercise setting, training modalities, combinations with other strategies such as diet and medications, long-term adherence, incorporation of innovative and more accessible delivery methods, and management of recently hospitalized patients are highlighted to provide guidance for future research.

Risk Assessment of Adverse Outcomes in Symptomatic Patients With Arterial Hypertension and Chronic Heart Failure With Preserved Ejection Fraction Using THE HFA-PEFF Algorithm

Aim To study the incidence of heart failure (HF) in patients with arterial hypertension (AH), symptoms of HF, and left ventricular ejection fraction (LV EF) ≥50 % using a novel, modified HFA-PEFF diagnostic algorithm and to evaluate the liver hydration status and density depending on the established HF profiles and the prognostic significance of this algorithm.Material and methods This study included 180 patients (median age, 72 years) with AH, symptoms of HF, and LV EF ≥50 %. The incidence of chronic HF with preserved ejection fraction (CHFpEF) was studied with the stepwise, modified HFA-PEFF diagnostic algorithm, and long-term outcomes were assessed at 3, 6, and 12 months of follow-up. The hydration status was determined by a bioimpedance vector analysis, and the liver density was measured by indirect fibroelastometry. The following tests were performed for all patients: standard, general clinical and laboratory examination with evaluation of CH symptoms (including N-terminal pro-brain natriuretic peptide test); extended echocardiography with assessment of structural and functional parameters of the heart; a KCCQ questionnaire was used for evaluation of patients' condition and quality of life (QoL). Long-term outcomes were studied by phone calls at 3, 6, and 12 months following discharge from the hospital/visit (worsened QoL, repeated hospitalization for cardiovascular causes, cardiovascular death or all-cause death).Results The following profiles were determined by the HFA-PEFF algorithm: with CHFpEF, with intermediate probability of HF, and without HF (58.9, 31.1, and 10 %, respectively). The study showed that patients with CHFpEF compared to patients of the intermediate group and without HF, had higher levels of brain natriuretic peptide, more pronounced signs of congestion according to results of the bioimpedance vector analysis and a higher liver density according to results of indirect fibroelastometry of the liver, which allowed identification of a group of patients with a high probability of CHFpEF. The diagnosis of HF by HFA-PEFF had an adverse prognostic significance with respect of worsened QoL according to the KCCQ questionnaire, and of repeated admission for HF during a year.Conclusion In AH patients with symptoms of HF and LV EF ≥50 %, CHFpEF was detected with the HFA-PEFF algorithm in 58.9 % of cases. Patients with AH and verified CHFpEF had a high incidence of hyperhydration and increased liver density. A diagnosis of CHFpEF by the HFA-PEFF algorithm had an adverse prognostic significance with respect of long-term outcomes.

FK506-Binding Protein like (FKBPL) Has an Important Role in Heart Failure with Preserved Ejection Fraction Pathogenesis with Potential Diagnostic Utility.

Heart failure (HF) is the leading cause of hospitalisations worldwide, with only 35% of patients surviving the first 5 years after diagnosis. The pathogenesis of HF with preserved ejection fraction (HFpEF) is still unclear, impeding the implementation of effective treatments. FK506-binding protein like (FKBPL) and its therapeutic peptide mimetic, AD-01, are critical mediators of angiogenesis and inflammation. Thus, in this study, we investigated-for the first time-FKBPL's role in the pathogenesis and as a biomarker of HFpEF. In vitro models of cardiac hypertrophy following exposure to a hypertensive stimulus, angiotensin-II (Ang-II, 100 nM), and/or AD-01 (100 nM), for 24 and 48 h were employed as well as human plasma samples from people with different forms of HFpEF and controls. Whilst the FKBPL peptide mimetic, AD-01, induced cardiomyocyte hypertrophy in a similar manner to Ang-II (p < 0.0001), when AD-01 and Ang-II were combined together, this process was abrogated (p < 0.01-0.0001). This mechanism appears to involve a negative feedback loop related to FKBPL (p < 0.05). In human plasma samples, FKBPL concentration was increased in HFpEF compared to controls (p < 0.01); however, similar to NT-proBNP and Gal-3, it was unable to stratify between different forms of HFpEF: acute HFpEF, chronic HFpEF and hypertrophic cardiomyopathy (HCM). FKBPL may be explored for its biomarker and therapeutic target potential in HFpEF.

Хроническая сердечная недостаточность с сохраненной фракцией выброса на фоне предиабета и абдоминального ожирения: компартменты жировых депо и кардиометаболические маркеры

Aim: to assess the fat depot compartments and some cardiometabolic risk markers in patients with chronic heart failure with preserved ejection fraction (CHFpEF), prediabetes and abdominal obesity. Patients and Methods: this randomized open single-center study was carried out in the Research Institute for Therapy and Preventive Medicine — Branch of the Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the RAS and included 64 subjects (32 of them were males) with CHFpEF, prediabetes and abdominal obesity. The standard general clinical examination and laboratory tests, measurements of NT-proBNP and high-sensitivity C-reactive protein (CRP) in blood plasma, as well as ultrasonography for imaging epicardial and preperitoneal fat depots (lipometry) were used to evaluate patients. Results: median age of the studied male patients was 58.00 [54.25; 60.00] years, female patients — 58.00 [56.00; 59.00] years. Males had a higher body weight as compared to females (р=0.036). The level of NT-proBNP in women was lower than in men (p=0.036), just as the glomerular filtration rate (р=0.034). The thickness of the epicardial and preperitoneal fat layers were similar in men and women, while the subcutaneous fat layer was thicker in women (р=0.001). Male patients with grade 3 obesity had the lowest NT-proBNP concentration in blood plasma. In women with grade 2 and 3 obesity the concentration of high-sensitivity C-reactive protein (CRP) in blood plasma was higher than in women with overweight and grade 1 obesity (р=0.047). A moderate linear relationship between NT-proBNP and high-sensitivity CRP levels was found in female patients (r=0.375, p=0.034). Conclusion: body weight measurements, glomerular filtration rates and NT-proBNP concentrations in blood plasma were higher in the studied sample of men as compared to those in women. Male patients with grade 3 obesity had the minimal NT-proBNP level (just slightly above the diagnostic limit). The highest high-sensitivity CRP measurements were reported in women with grade 2 and 3 obesity which underscores their proinflammatory status. No significant differences in the visceral epicardial and preperitoneal fat compartments were found between male and female patients. KEYWORDS: chronic heart failure with preserved ejection fraction, prediabetes, obesity, NT-proBNP, C-reactive protein, epicardial fat, premesenteric fat, subcutaneous fat, males, females. FOR CITATION: Tsygankova O.V., Evdokimova N.E., Latyntseva L.D. Chronic heart failure with preserved ejection fraction amid prediabetes and abdominal obesity: fat depot compartments and cardiometabolic risk markers. Russian Medical Inquiry. 2023;7(1):22–29 (in Russ.). DOI: 10.32364/2587-6821-2023-7-1-22-29.

Abstract 11247: Impact of Pre-Existing Heart Failure on Non-St Segment Elevation Myocardial Infarction Outcomes

Introduction: There is limited data examining how pre-existing heart failure impacts patients with a non-ST segment elevation myocardial infarction (NSTEMI). In this study, we compare the in-hospital outcomes of NSTEMI patients with chronic heart failure with reduced ejection fraction (HFrEF) against NSTEMI patients with chronic heart failure with preserved ejection fraction (HFpEF). Methods: We queried the National Inpatient Sample database (2016-2019) to identify patients admitted with a principal diagnosis of NSTEMI and a secondary diagnosis of chronic heart failure. We conducted propensity score matching using a greedy nearest neighbor 1:1 model. Multivariable logistic regression was used to compare mortality. Results: 51,564 patients met our inclusion criteria. Patients with a NSTEMI and chronic HFrEF had 1.71 times higher odds of suffering in-hospital mortality compared to NSTEMI patients with chronic HFpEF (aOR 1.71, 95% CI: 1.55-1.90; p &lt; 0.001). When separated by race, NSTEMI patients with HFrEF had a higher mortality rate amongst White patients (5.7% vs 4.4%, p &lt; 0.001, Figure 1). These patients also had higher rates of coronary artery disease, hypertension and prior myocardial infarction (Table 1). There was no difference in percutaneous coronary intervention (21.7% vs 21.5%, p = 0.60, Table 1) or postoperative cardiac arrest, cerebral infarction and hemorrhage between our two cohorts. Conclusions: Patients with a NSTEMI and chronic HFrEF had higher odds of suffering in-hospital mortality compared to NSTEMI patients with chronic HFpEF. Further studies should explore the interventions providers may undertake to better support this vulnerable population.

Systemic Biomarkers and Unique Pathways in Different Phenotypes of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) accounts for around 50% of all heart failure cases. It is a heterogeneous condition with poorly understood pathogenesis. Here, we aimed to identify unique pathogenic mechanisms in acute and chronic HFpEF and hypertrophic cardiomyopathy (HCM). We performed unbiased, comprehensive proteomic analyses of plasma samples from gender- and BMI-matched patients with acute HFpEF (n = 8), chronic HFpEF (n = 9) and HCM (n = 14) using liquid chromatography–mass spectrometry. Distinct molecular signatures were observed in different HFpEF forms. Clusters of biomarkers differentially abundant between HFpEF forms were predominantly associated with microvascular inflammation. New candidate protein markers were also identified, including leucine-rich alpha-2-glycoprotein 1 (LRG1), serum amyloid A1 (SAA1) and inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3). Our study is the first to apply systematic, quantitative proteomic screening of plasma samples from patients with different subtypes of HFpEF and identify candidate biomarkers for improved management of acute and chronic HFpEF and HCM.

Biomarker-driven prognostic models in chronic heart failure with preserved ejection fraction: the EMPEROR-Preserved trial.

Biomarker-driven prognostic models incorporating N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) in heart failure (HF) with preserved ejection fraction (HFpEF) are lacking. We aimed to generate a biomarker-driven prognostic tool for patients with chronic HFpEF enrolled in EMPEROR-Preserved. Multivariable Cox regression models were created for (i) the primary composite outcome of HF hospitalization or cardiovascular death, (ii) all-cause death, (iii) cardiovascular death, and (iv) HF hospitalization. PARAGON-HF was used as a validation cohort. NT-proBNP and hs-cTnT were the dominant predictors of the primary outcome, and in addition, a shorter time since last hospitalization, New York Heart Association (NYHA) class III or IV, history of chronic obstructive pulmonary disease (COPD), insulin-treated diabetes, low haemoglobin, and a longer time since HF diagnosis were key predictors (eight variables, all p< 0.001). The consequent primary outcome risk score discriminated well (c-statistic=0.75) with patients in the top 10th of risk having an event rate >22× higher than those in the bottom 10th. A model for HF hospitalization alone had even better discrimination (c= 0.79). Empagliflozin reduced the risk of cardiovascular death or hospitalization for HF in patients across all risk levels. NT-proBNP and hs-cTnT were also the dominant predictors of all-cause and cardiovascular mortality followed by history of COPD, low albumin, older age, left ventricular ejection fraction ≥50%, NYHA class III or IV and insulin-treated diabetes (eight variables, all p< 0.001). The mortality risk model had similar discrimination for all-cause and cardiovascular mortality (c-statistic=0.72 for both). External validation provided c-statistics of 0.71, 0.71, 0.72, and 0.72 for the primary outcome, HF hospitalization alone, all-cause death, and cardiovascular death, respectively. The combination of NT-proBNP and hs-cTnT along with a few readily available clinical variables provides effective risk discrimination both for morbidity and mortality in patients with HFpEF. A predictive tool-kit facilitates the ready implementation of these risk models in routine clinical practice.

Relaxin-2, pathophysiological insights and outcomes in heart failure with preserved ejection fraction: Findings from the NETDiamond cohort

AimsThe role of relaxin-2 as a circulating marker in heart failure (HF) with preserved ejection fraction (HFpEF) is poorly understood. We aimed to characterize relaxin-2 circulating levels in a population of chronic HFpEF patients and their association with long-term prognosis. MethodsRelaxin-2 serum levels were measured in 85 chronic HFpEF patients from a prospective cohort study (NETDiamond). Clinical, imaging, and analytical data were compared across relaxin-2 tertiles. The primary outcome was a composite of cardiovascular death, HF hospitalisation, acute HF episode or diuretic intensification and the secondary outcome a composite of cardiovascular death and total HF hospitalisations. Cox regression and negative binomial models were used to assess the relation between relaxin-2 and the outcomes. ResultsRelaxin-2 levels were positively associated with left atrial volume, left ventricular mass and peripheral oedema, and negatively associated with ischemic heart disease and statin use. Higher relaxin-2 levels were associated with an increased risk of primary outcome, even after adjustment for age, B-type natriuretic peptide (BNP) and glomerular filtration rate (eGFR) (adjusted HR = 2.80, 95%CI 1.4–7.3, p = 0.034 for tertile 3). They were also associated with the occurrence of the secondary outcome (Incidence Rate Ratio = 5.28, 95%CI 1.2–23.2, p = 0.027), but this significance was lost when simultaneously adjusted for BNP and eGFR. ConclusionIn chronic HFpEF patients, higher relaxin-2 circulating levels were associated with left chambers remodelling, congestion, and adverse prognosis. These findings support a potential role for relaxin-2 as a pathophysiological agent and as a circulating biomarker in HFpEF.

Unsupervised Machine Learning To Define Acute Hfpef Phenotypes: Findings From Ascend-hf

Introduction : Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous condition with distinct phenotypes. Prior studies have used cluster analysis to group patients with chronic ambulatory HFpEF by shared characteristics. Data are limited regarding different HFpEF phenotypes in the hospitalized setting. Hypothesis We hypothesized that distinct clusters of patients hospitalized for HFpEF would have unique baseline characteristics and distinct clinical outcomes. Methods : We applied an unsupervised machine learning analysis to group patients hospitalized with HFpEF in the ASCEND-HF trial into distinct phenotypes. Groups were made via hierarchical clustering after variable reduction on a set of 39 baseline variables including demographics, medical comorbidities, and clinical data at the time of admission. Cox regression models were used to evaluate the association between HFpEF phenotypes and 180-day mortality. Results : Overall, 812 patients with EF >40% were included. Hierarchical clustering identified 4 phenotypes that had distinct baseline characteristics and outcomes (Figure). Cluster 1 was older, predominantly White/Asian, female, and had high rates of atrial fibrillation. Cluster 2 had high rates of hypertension, the highest systolic blood pressure, and lowest heart rate. Cluster 3 was the youngest, predominantly male, had a high proportion of Black patients, and had the highest BMI and diabetes prevalence. Cluster 4 had a high the lowest systolic blood pressure, a high heart rate, and high natriuretic peptide concentrations. Cluster 4 (chosen as the reference group) demonstrated the highest 180-day mortality, followed by Cluster 1 (HR= 0.68 [95% CI: 0.42-1.09]), Cluster 2 (HR=0.45 [95% CI: 0.25-0.79]), and Cluster 3 (HR=0.31 [95% CI: 0.16-0.59]) (Overall p-value =0.007). Conclusions : In this clinical trial cohort of patients hospitalized for HFpEF, cluster analysis incorporating demographic, vital sign, laboratory, and comorbidity data demonstrated distinct patient phenotypes with differing clinical profiles and outcomes. These clusters may inform patient selection for future clinical trials and may facilitate matching investigational therapies to patients more likely to benefit. : Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous condition with distinct phenotypes. Prior studies have used cluster analysis to group patients with chronic ambulatory HFpEF by shared characteristics. Data are limited regarding different HFpEF phenotypes in the hospitalized setting. We hypothesized that distinct clusters of patients hospitalized for HFpEF would have unique baseline characteristics and distinct clinical outcomes. : We applied an unsupervised machine learning analysis to group patients hospitalized with HFpEF in the ASCEND-HF trial into distinct phenotypes. Groups were made via hierarchical clustering after variable reduction on a set of 39 baseline variables including demographics, medical comorbidities, and clinical data at the time of admission. Cox regression models were used to evaluate the association between HFpEF phenotypes and 180-day mortality. : Overall, 812 patients with EF >40% were included. Hierarchical clustering identified 4 phenotypes that had distinct baseline characteristics and outcomes (Figure). Cluster 1 was older, predominantly White/Asian, female, and had high rates of atrial fibrillation. Cluster 2 had high rates of hypertension, the highest systolic blood pressure, and lowest heart rate. Cluster 3 was the youngest, predominantly male, had a high proportion of Black patients, and had the highest BMI and diabetes prevalence. Cluster 4 had a high the lowest systolic blood pressure, a high heart rate, and high natriuretic peptide concentrations. Cluster 4 (chosen as the reference group) demonstrated the highest 180-day mortality, followed by Cluster 1 (HR= 0.68 [95% CI: 0.42-1.09]), Cluster 2 (HR=0.45 [95% CI: 0.25-0.79]), and Cluster 3 (HR=0.31 [95% CI: 0.16-0.59]) (Overall p-value =0.007). : In this clinical trial cohort of patients hospitalized for HFpEF, cluster analysis incorporating demographic, vital sign, laboratory, and comorbidity data demonstrated distinct patient phenotypes with differing clinical profiles and outcomes. These clusters may inform patient selection for future clinical trials and may facilitate matching investigational therapies to patients more likely to benefit.

Evaluation of a blood-based geroscience biomarker index in a randomized trial of caloric restriction and exercise in older adults with heart failure with preserved ejection fraction.

Intermediate endpoints are needed to evaluate the effect of interventions targeting the biology of aging in clinical trials. A working group identified five blood-based biomarkers that may serve such a purpose as an integrated index. We evaluated the responsiveness of the panel to caloric restriction or aerobic exercise in the context of a randomized clinical trial conducted in patients with heart failure with preserved ejection fraction (HFpEF) with obese phenotype who were predominantly female. Obese HFpEF is highly prevalent in women, and is a geriatric syndrome whose disease pathology is driven by non-cardiac factors and shared drivers of aging. We measured serum Interleukin-6, TNF-α-receptor-I, growth differentiating factor-15, cystatin C, and N-terminal pro-b-type natriuretic peptide at baseline and after 20weeks in older participants with stable obese HFpEF participating in a randomized, controlled, 2 × 2 factorial trial of caloric restriction and/or aerobic exercise. We calculated a composite biomarker index, summing baseline quintile scores for each biomarker, and analyzed the effect of the interventions on the index and individual biomarkers and their associations with changes in physical performance. This post hoc analysis included 88 randomized participants (71 women [81%]). The mean ± SD age was 66.6 ± 5.3years, and body mass index (BMI) was 39.3 ± 6.3kg/m2. Using mixed models, mean values of the biomarker index improved over 20weeks with caloric restriction (- 0.82 [Formula: see text] 0.58 points, p = 0.05), but not with exercise (- 0.28 [Formula: see text] 0.59 points, p = [Formula: see text]), with no evidence of an interaction effect of CR [Formula: see text] EX [Formula: see text] time (p = 0.80) with adjustment for age, gender, and BMI. At baseline, the biomarker index was inversely correlated with 6-min walk distance, scores on the short physical performance battery, treadmill test peak workload and exercise time to exhaustion (all [Formula: see text] s = between - 0.21 and - 0.24). A reduction in the biomarker index was also associated with increased 4-m usual walk speed ([Formula: see text] s = - 0.31). Among older patients with chronic obese HFpEF, caloric restriction improved a biomarker index designed to reflect biological aging. Moreover, the index was associated with physical performance and exercise tolerance.

A year in heart failure: an update of recent findings.

Major changes have occurred in these last years in heart failure (HF) management. Landmark trials and the 2021 European Society of Cardiology guidelines for the diagnosis and treatment of HF have established four classes of drugs for treatment of HF with reduced ejection fraction: angiotensin‐converting enzyme inhibitors or an angiotensin receptor‐neprilysin inhibitor, beta‐blockers, mineralocorticoid receptor antagonists, and sodium‐glucose co‐transporter 2 inhibitors, namely, dapagliflozin or empagliflozin. These drugs consistently showed benefits on mortality, HF hospitalizations, and quality of life. Correction of iron deficiency is indicated to improve symptoms and reduce HF hospitalizations. AFFIRM‐AHF showed 26% reduction in total HF hospitalizations with ferric carboxymaltose vs. placebo in patients hospitalized for acute HF (P = 0.013). The guanylate cyclase activator vericiguat and the myosin activator omecamtiv mecarbil improved outcomes in randomized placebo‐controlled trials, and vericiguat is now approved for clinical practice. Treatment of HF with preserved ejection fraction (HFpEF) was a major unmet clinical need until this year when the results of EMPEROR‐Preserved (EMPagliflozin outcomE tRial in Patients With chrOnic HFpEF) were issued. Compared with placebo, empagliflozin reduced by 21% (hazard ratio, 0.79; 95% confidence interval, 0.69 to 0.90; P < 0.001), the primary outcome of cardiovascular death or HF hospitalization. Advances in the treatment of specific phenotypes of HF, including atrial fibrillation, valvular heart disease, cardiomyopathies, cardiac amyloidosis, and cancer‐related HF, also occurred. Coronavirus disease 2019 (COVID‐19) pandemic still plays a major role in HF epidemiology and management. All these aspects are highlighted in this review.

Evaluation of the diagnostic accuracy of current biomarkers in heart failure with preserved ejection fraction: A systematic review and meta-analysis

A number of circulating biomarkers are currently utilized for the diagnosis of chronic heart failure with preserved ejection fraction (HFpEF). However, due to HFpEF heterogeneity, the accuracy of these biomarkers remains unclear. This study aimed to systematically determine the diagnostic accuracy of currently available biomarkers for chronic HFpEF. PubMed, Web of Science, MEDLINE and SCOPUS databases were searched systematically to identify studies assessing the diagnostic accuracy of biomarkers of chronic HFpEF with left ventricular ejection fraction (LVEF) ≥50%. All included studies were independently assessed for quality and relevant information was extracted. Random-effects models were used to estimate the pooled diagnostic accuracy of HFpEF biomarkers. The search identified 6145 studies, of which 19 were included. Four biomarkers were available for meta-analysis. The pooled sensitivity of B-type natriuretic peptide (BNP) (0.787, 95% confidence interval [CI] 0.719-0.842) was higher than that of N-terminal pro-BNP (NT-proBNP) (0.696, 95% CI 0.599-0.779) in chronic HFpEF diagnosis. However, NT-proBNP showed improved specificity (0.882, 95% CI 0.778-0.941) compared to BNP (\0.796, 95% CI 0.672-0.882). Galectin-3 (Gal-3) exhibited a reliable diagnostic adequacy for HFpEF (sensitivity 0.760, 95% CI 0.631-0.855; specificity 0.803, 95% CI 0.667-0.893). However, suppression of tumorigenesis-2 (ST2) displayed limited diagnostic performance for chronic HFpEF diagnosis (sensitivity 0.636, 95% CI 0.465-0.779; specificity 0.595, 95% CI 0.427-0.743). NT-proBNP and BNP appear to be the most reliable biomarkers in chronic HFpEF with NT-proBNP showing higher specificity and BNP showing higher sensitivity. Although Gal-3 appears more reliable than ST2 in HFpEF diagnosis, the conclusions are limited as only three studies were included in this meta-analysis.