Heart Failure With Preserved Ejection Fraction Group Research Articles

Empagliflozin protects against heart failure with preserved ejection fraction partly by inhibiting the senescence-associated STAT1–STING axis

Heart failure with preserved ejection fraction (HFpEF) is a mortal clinical syndrome without effective therapies. Empagliflozin (EMPA) improves cardiovascular outcomes in HFpEF patients, but the underlying mechanism remains elusive. Here, mice were fed a high-fat diet (HFD) supplemented with L-NAME for 12 weeks and subsequently intraperitoneally injected with EMPA for another 4 weeks. A 4D-DIA proteomic assay was performed to detect protein changes in the failing hearts. We identified 310 differentially expressed proteins (DEPs) (ctrl vs. HFpEF group) and 173 DEPs (HFpEF vs. EMPA group). The regulation of immune system processes was enriched in all groups and the interferon response genes (STAT1, Ifit1, Ifi35 and Ifi47) were upregulated in HFpEF mice but downregulated after EMPA administration. In addition, EMPA treatment suppressed the increase in the levels of aging markers (p16 and p21) in HFpEF hearts. Further bioinformatics analysis verified STAT1 as the hub transcription factor during pathological changes in HFpEF mice. We next treated H9C2 cells with IFN-γ, a primary agonist of STAT1 phosphorylation, to investigate whether EMPA plays a beneficial role by blocking STAT1 activation. Our results showed that IFN-γ treatment caused cardiomyocyte senescence and STAT1 activation, which were inhibited by EMPA administration. Notably, STAT1 inhibition significantly reduced cellular senescence possibly by regulating STING expression. Our findings revealed that EMPA mitigates cardiac inflammation and aging in HFpEF mice by inhibiting STAT1 activation. The STAT1–STING axis may act as a pivotal mechanism in the pathogenesis of HFpEF, especially under inflammatory and aging conditions.Graphical abstractThe schematic figure depicts a mechanism model of the STAT1–STING axis in HFpEF (this figure was drawn using FigDraw software).

Prognostic impact of beta-blocker use by N-terminal pro-brain natriuretic peptide level in acute heart failure patients.

Both patients with heart failure (HF) with reduced ejection fraction (HFrEF) and those with HF with preserved ejection fraction (HFpEF) present with elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) and have multiple comorbidities; consequently, the prognostic effect of NT-proBNP according to beta-blocker (BB) use is unknown. This retrospective study evaluated patients admitted for acute HF between January 2012 and December 2017 at Ulsan University Hospital. Clinical, echocardiographic, laboratory and drug prescription data, including BB data, were collected from the hospital database. Information on mortality was collected by reviewing medical records or using national death data. Of the 472 patients evaluated, 216 (45.8%) and 256 (54.2%) patients were and were not prescribed BB at discharge, respectively. A total of 224 (47.5%) patients died within a median follow-up duration of 44months. The Kaplan-Meier analysis showed reduced all-cause mortality with BB in HFrEF (ejection fraction≤40%) but not in HFpEF (ejection fraction>40%). In the multivariate Cox regression analysis, transmitral to tissue Doppler imaging, early diastolic velocity ratio (E/E'), NT-proBNP and BB use were independent predictors of all-cause mortality in HFrEF. Meanwhile, haemoglobin and NT-proBNP levels were independent predictors of HFpEF. The NT-proBNP cut-off value for determining all-cause mortality was set to 4800pg/mL. Among HFrEF patients with NT-proBNP<4800pg/mL, the survival rate was higher for patients with BB use than those with no BB use (log-rank P<0.001). However, in the HFpEF group, the survival rate associated with BB use did not differ according to the NT-proBNP levels. Both HFrEF and HFpEF patients with NT-proBNP levels of ≥4800pg/mL presented with multiple comorbidities, including lower body mass index and haemoglobin levels and higher creatinine levels, NT-proBNP levels and E/E'. In patients with acute HF, BB use is associated with reduced all-cause mortality in those with HFrEF but not in those with HFpEF. HFrEF patients with NT-proBNP levels of <4800pg/mL treated with BB have a higher survival rate than those not treated with BB. However, this benefit is not seen in HFrEF patients with NT-proBNP levels of ≥4800pg/mL or in all HFpEF patients, regardless of the NT-proBNP level. NT-proBNP levels are elevated in multiple comorbid conditions, and these comorbidities may contribute to the attenuated effects of BB on all-cause mortality.

Comparative Analysis of Heart Failure with Preserved Vs Reduced Ejection Fraction: Patient Characteristics, Outcomes, Mortality Prediction, and Machine Learning Model Development in the JoHFR.

Heart failure (HF) is a global health challenge affecting millions, with significant variations in patient characteristics and outcomes based on ejection fraction. This study aimed to differentiate between HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) with respect to patient characteristics, risk factors, comorbidities, and clinical outcomes, incorporating advanced machine learning models for mortality prediction. The study included 1861 HF patients from 21 centers in Jordan, categorized into HFrEF (EF <40%) and HFpEF (EF ≥ 50%) groups. Data were collected from 2021 to 2023, and machine learning models were employed for mortality prediction. Among the participants, 29.7% had HFpEF and 70.3% HFrEF. Significant differences were noted in demographics and comorbidities, with a higher prevalence of males, younger age, smoking, and familial history of premature ASCVD in the HFrEF group. HFpEF patients were typically older, with higher rates of diabetes, hypertension, and obesity. Machine learning analysis, mainly using the Random Forest Classifier, demonstrated significant predictive capability for mortality with an accuracy of 0.9002 and an AUC of 0.7556. Other models, including Logistic Regression, SVM, and XGBoost, also showed promising results. Length of hospital stay, need for mechanical ventilation, and number of hospital admissions were the top predictors of mortality in our study. The study underscores the heterogeneity in patient profiles between HFrEF and HFpEF. Integrating machine learning models offers valuable insights into mortality risk prediction in HF patients, highlighting the potential of advanced analytics in improving patient care and outcomes.

Artificial intelligence-assisted automated heart failure detection and classification from electronic health records.

Electronic health records (EHR) linked to Digital Imaging and Communications in Medicine (DICOM), biological specimens, and deep learning (DL) algorithms could potentially improve patient care through automated case detection and surveillance. We hypothesized that by applying keyword searches to routinely stored EHR, in conjunction with AI-powered automated reading of DICOM echocardiography images and analysing biomarkers from routinely stored plasma samples, we were able to identify heart failure (HF) patients. We used EHR data between 1993 and 2021 from Tayside and Fife (~20% of the Scottish population). We implemented a keyword search strategy complemented by filtering based on International Classification of Diseases (ICD) codes and prescription data to EHR data set. We then applied DL for the automated interpretation of echocardiographic DICOM images. These methods were then integrated with the analysis of routinely stored plasma samples to identify and categorize patients into HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), and controls without HF. The final diagnosis was verified through a manual review of medical records, measured natriuretic peptides in stored blood samples, and by comparing clinical outcomes among groups. In our study, we selected the patient cohort through an algorithmic workflow. This process started with 60850 EHR data and resulted in a final cohort of 578 patients, divided into 186 controls, 236 with HFpEF, and 156 with HFrEF, after excluding individuals with mismatched data or significant valvular heart disease. The analysis of baseline characteristics revealed that compared with controls, patients with HFrEF and HFpEF were generally older, had higher BMI, and showed a greater prevalence of co-morbidities such as diabetes, COPD, and CKD. Echocardiographic analysis, enhanced by DL, provided high coverage, and detailed insights into cardiac function, showing significant differences in parameters such as left ventricular diameter, ejection fraction, and myocardial strain among the groups. Clinical outcomes highlighted a higher risk of hospitalization and mortality for HF patients compared with controls, with particularly elevated risk ratios for both HFrEF and HFpEF groups. The concordance between the algorithmic selection of patients and manual validation demonstrated high accuracy, supporting the effectiveness of our approach in identifying and classifying HF subtypes, which could significantly impact future HF diagnosis and management strategies. Our study highlights the feasibility of combining keyword searches in EHR, DL automated echocardiographic interpretation, and biobank resources to identify HF subtypes.

Atrial Fibrillation Ablation in Heart Failure With Reduced vs Preserved Ejection Fraction

Catheter ablation is associated with reduced heart failure (HF) hospitalization and death in select patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF). However, the benefit in patients with HF with preserved ejection fraction (HFpEF) is uncertain. To investigate whether catheter ablation for AF is associated with reduced HF-related outcomes according to HF phenotype. A systematic search of MEDLINE, Embase, and Cochrane Central was conducted among studies published from inception to September 2023. Parallel-group randomized clinical trials (RCTs) comparing catheter ablation with conventional rate or rhythm control therapies in patients with HF, New York Heart Association functional class II or greater, and a history of paroxysmal or persistent AF were included. Pairs of independent reviewers screened 7531 titles and abstracts, of which 12 RCTs and 4 substudies met selection criteria. Data were abstracted in duplicate according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Pooled effect estimates were calculated using random-effects Mantel-Haenszel models. Interaction P values were used to test for subgroup differences. The primary outcome was HF events, defined as HF hospitalization, clinically significant worsening of HF, or unscheduled visits to a clinician for treatment intensification. Secondary outcomes included cardiovascular and all-cause mortality. A total of 12 RCTs with 2465 participants (mean [SD] age, 65.3 [9.7] years; 658 females [26.7%]) were included; there were 1552 participants with HFrEF and 913 participants with HFpEF. Compared with conventional rate or rhythm control, catheter ablation was associated with reduced risk of HF events in HFrEF (risk ratio [RR], 0.59; 95% CI, 0.48-0.72), while there was no benefit in patients with HFpEF (RR, 0.93; 95% CI, 0.65-1.32) (P for interaction = .03). Catheter ablation was associated with reduced risk of cardiovascular death compared with conventional therapies in HFrEF (RR, 0.49; 95% CI, 0.34-0.70) but a differential association was not detected in HFpEF (RR, 0.91; 95% CI, 0.46-1.79) (P for interaction = .12). Similarly, no difference in the association of catheter ablation with all-cause mortality was found between HFrEF (RR vs conventional therapies, 0.63; 95% CI, 0.47-0.86) and HFpEF (RR vs conventional therapies, 0.95; 95% CI, 0.39-2.30) groups (P for interaction = .39). This study found that catheter ablation for AF was associated with reduced risk of HF events in patients with HFrEF but had limited or no benefit in HFpEF. Results from ongoing trials may further elucidate the role of catheter ablation for AF in HFpEF.

Applicability of H2FPEF and HFA-PEFF Scores in Chinese Patients Suffering From Heart Failure With Preserved Ejection Fraction and Heart Failure With Preserved Ejection Fraction Complicated With Atrial Fibrillation

Objective To analyze the diagnostic values of H2FPEF and HFA-PEFF scores for heart failure with preserved ejection fraction (HFpEF) and HFpEF complicated with atrial fibrillation (HFpEF-AF) in Chinese patients and explore the related factors. Methods A cross-sectional study was conducted.A total of 835 consecutive HFpEF patients treated in the Department of Geriatric Cardiology,the First Hospital of Lanzhou University from 2009 to 2020 were selected and assigned to a HFpEF-AF group (n=267) and a HFpEF group (n=568) according to the presence of AF or not.HFA-PEFF and H2FPEF scores were used for retrospective diagnosis and the diagnostic consistency of the two scores was assessed.One hundred and thirty-six healthy volunteers with age and sex matching the patients during the same period were selected as healthy controls.The receiver operating characteristic (ROC) curves were established for H2FPEF and HFA-PEFF scores in diagnosing HFpEF-AF and HFpEF,on the basis of which the diagnostic performance of the two scores was evaluated. Results There was no difference in the HFA-PEFF score between the two groups (P=0.070).However,the HFpEF-AF group had higher mean H2FPEF score and higher proportion of patients with the score no less than 6 than the HFpEF group (P<0.001).According to the ROC curves,HFA-PEFF and H2FPEF scores demonstrated high performance in diagnosing all HFpEF patients,with the area under the curve (AUC) of 0.892 and 0.922 and the optimal cut-offs of 4 and 4,respectively.The HFA-PEFF score showed similar performance in diagnosing HFpEF and HFpEF-AF,with the AUC of 0.899 and 0.911,respectively.The H2FPEF score had higher performance in diagnosing HFpEF-AF (AUC of approximately 1.000) and low performance in diagnosing HFpEF (AUC of 0.885). Conclusions The HFA-PEFF score is applicable in the diagnosis of both HFpEF and HFpEF-AF.The H2FPEF score may underestimate HFpEF in Chinese patients,and its applicability in the Chinese patients with HFpEF alone remains to be investigated.

Risk factors for pregnancy-associated heart failure with preserved ejection fraction and adverse pregnancy outcomes: a cross-sectional study.

Although pregnancy-associated heart failure with preserved ejection fraction (HFpEF) is increasing and contributing to maternal morbidity, little is known about its impact on pregnancy. We examined the risk factors for and adverse pregnancy outcomes of HFpEF in pregnant women. We conducted a cross-sectional analysis of pregnancy-related hospitalizations from 2009 to 2020 using the perinatal database of seven multicenters. Cases of HFpEF were identified using the International Classification of Diseases and echocardiography findings. The patients were categorized into the HFpEF and control groups. Risk factors were evaluated using multivariate logistic regression analysis to generate odds ratios (OR) and 95% confidence intervals (CI). Furthermore, adjusted associations between HFpEF and adverse pregnancy outcomes were determined. Risk scores for the stratification of women at a high risk of HFpEF were calculated using a statistical scoring model. Of the 34,392 women identified, 258 (0.76%) were included in the HFpEF group. In multivariate analysis, HFpEF was significantly associated with old maternal age (OR, 1.04; 95% CI 1.02-1.07), multiple pregnancy (OR, 2.22; 95% CI 1.53-3.23), rheumatic disease (OR, 2.56; 95% CI 1.54-4.26), pregnancy induce hypertension (OR 6.02; 95% CI 3.61-10.05), preeclampsia (OR 24.66; 95% CI 18.61-32.66), eclampsia or superimposed preeclampsia (OR 32.74; 95% CI 21.60-49.64) and transfusion in previous pregnancy (OR 3.89; 95% CI 1.89-8.01). A scoring model to predict HFpEF with those factors achieved an area under the curve of 0.78 at cutoff value of 3. Women with HFpEF also had increased odds ratios of intensive care unit admission during the perinatal period (odds ratio, 5.98; 95% confidence interval, 4.36-8.21) and of postpartum hemorrhage (odds ratio, 5.98; 95% confidence interval, 2.02-3.64). Pregnancy-associated HFpEF is associated with adverse pregnancy outcomes. A scoring model may contribute to screening HFpEF using echocardiography and preparing adverse pregnancy outcomes.

HBI-8000 improves heart failure with preserved ejection fraction via the TGF-β1/MAPK signalling pathway.

Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of total heart failure patients and is characterized by peripheral circulation, cardiac remodelling and comorbidities (such as advanced age, obesity, hypertension and diabetes) with limited treatment options. Chidamide (HBI-8000) is a domestically produced benzamide-based histone deacetylase isoform-selective inhibitor used for the treatment of relapsed refractory peripheral T-cell lymphomas. Based on our invivo studies, we propose that HBI-8000 exerts its therapeutic effects by inhibiting myocardial fibrosis and myocardial hypertrophy in HFpEF patients. At the cellular level, we found that HBI-8000 inhibits AngII-induced proliferation and activation of CFs and downregulates the expression of fibrosis-related factors. In addition, we observed that the HFpEF group and AngII stimulation significantly increased the expression of TGF-β1 as well as phosphorylated p38MAPK, JNK and ERK, whereas the expression of the above factors was significantly reduced after HBI-8000 treatment. Activation of the TGF-β1/MAPK pathway promotes the development of fibrotic remodelling, and pretreatment with SB203580 (p38MAPK inhibitor) reverses this pathological change. In conclusion, our data suggest that HBI-8000 inhibits fibrosis by modulating the TGF-β1/MAPK pathway thereby improving HFpEF. Therefore, HBI-8000 may become a new hope for the treatment of HFpEF patients.

Identification of molecular signatures in epicardial adipose tissue in heart failure with preserved ejection fraction.

The molecular signatures in epicardial adipose tissue (EAT) that contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF) are poorly characterized. In this study, we sought to elucidate molecular signatures including genetic transcripts and long non-coding RNAs (lncRNAs) in EAT that might modulate HFpEF development. RNA sequencing (RNA-seq) was performed to identify differentially expressed lncRNAs and mRNAs in EAT samples from patients with HFpEF (n=5) and without HF (control, n=5) who underwent coronary artery bypass grafting. The sequencing results were validated using quantitative real-time PCR (qRT-PCR). Bioinformatics analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) of differentially expressed RNAs was performed to predict enriched functions. HFpEF patients had higher EAT thickness and NT-proBNP levels than the control group. A total of 64471 transcripts were detected including 35395 protein-coding sequences, corresponding to 16854 genes in EAT. RNA-seq identified a total of 741 dysregulated mRNA transcripts (394 up-regulated and 347 down-regulated) and 334 differentially expressed lncRNA transcripts (222 up-regulated and 112 down-regulated) in the HFpEF group compared with the control group (P<0.05). qRT-PCR analysis confirmed that two lncRNAs ENST00000561775 (P=0.0194) and ENST00000519093 (P=0.027) and an mRNA POSTN (P=0.003) were differentially expressed. Functional enrichment analysis of the differentially expressed mRNAs suggested their potential roles in immune response involving cytokine interaction and chemokine signalling. We are the first group to report on the lncRNA and mRNA landscape in EAT in HFpEF patients. Our study suggests the possible role of lncRNAs in EAT.

Diabetes mellitus does not alter mortality or hospitalisation risk in patients with newly diagnosed heart failure with preserved ejection fraction: Time to rethink pathophysiological models of disease progression.

Type 2 diabetes is a common and adverse prognostic co-morbidity for patients with heart failure with reduced ejection fraction (HFrEF). The effect of diabetes on long-term outcomes for heart failure with preserved ejection fraction (HFpEF) is less established. Prospective cohort study of patients referred to a regional HF clinic with newly diagnosed with HFrEF and HFpEF according to the 2016 European Society of Cardiology guidelines. The association between diabetes, all-cause mortality and hospitalisation was quantified using Kaplan-Meier or Cox regression analysis. Between 1st May 2012 and 1st May 2013, of 960 unselected consecutive patients referred with suspected HF, 464 and 314 patients met the criteria for HFpEF and HFrEF respectively. Within HFpEF and HFrEF groups, patients with diabetes were more frequently male and in both groups patients with diabetes were more likely to be treated with β-adrenoceptor antagonists and angiotensin converting enzyme inhibitors. After adjustment for age, sex, medical therapy and co-morbidities, diabetes was associated with increased mortality in individuals with HFrEF (HR 1.46 95% CI: 1.05-2.02; p = .023), but not in those with HFpEF (HR 1.26 95% CI 0.92-1.72; p = .146). In unselected patients with newly diagnosed HF, diabetes is not an adverse prognostic marker in patients with HFpEF, but is in HFrEF.

The value of speckle-tracking stratified strain combined with myocardial work measurement in evaluating left ventricular function in patients with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent progressive disease accompanied by poor quality of life, high utilization of medical resources, morbidity, and mortality. However, the role of left ventricular (LV) systolic dysfunction has yet to be well elaborated despite the preservation of the LV ejection fraction. This study aimed to explore the diagnostic value of speckle-tracking stratified strain combined with myocardial work (MW) measurement in evaluating LV systolic dysfunction in patients with HFpEF. A total of 125 study consecutive individuals, 64 HFpEF patients, and 61 controls were prospectively enrolled in the Fourth Affiliated Hospital of Harbin Medical University. In addition to the conventional echocardiographic parameters, LV stratified strain and MW parameters were statistically compared between the HFpEF and control groups. The global longitudinal strain (GLS) of the subendocardium, myocardium, and subepicardium (GLSendo, GLSmyo, and GLSepi); the transmural gradient (ΔGLS); the global myocardial work index (GWI), global myocardial work efficiency (GWE), global myocardial constructive work (GCW), and the global myocardial wasted work (GWW) were included. Area under the receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of these univariate and multivariable logistic models in detecting impaired LV systolic function in HFpEF. Ten-fold cross-validation was used to evaluate the generalizability of the predictive model. Stratified strains values showed a gradient decline from GLSendo to GLSepi in both control and HFpEF patients. Compared with the control group, HFpEF patients had a significantly reduced GLSepi, GLSmyo, GLSendo, ΔGLS, GWI, GWE, and GCW and a significantly increased GWW (all P<0.001). In the derivation set, the optimal logistic model (combined stratified strain and MW variables) demonstrated the highest performance in predicting LV systolic function impairment in HFpEF patients. The best-performing model with a mean area under the curve (AUC) of 0.966 [95% confidence interval (CI): 0.88 to 1] accessed by 10-fold cross-validation. In the validation set, the AUC of the optimal logistic model was 0.933 (95% CI: 0.85 to 1), the sensitivity was 87%, and the specificity was 93%. Both speck-tracking stratified strain and MW measurement may sensitively detect impairment of LV myocardial function at an early stage for patients with HFpEF. Combining the two techniques may improve the quality of HFpEF diagnosis and may provide a reference value for the early diagnosis of HFpEF in the future.

A non-invasive nomogram for predicting heart failure with preserved ejection fraction in taiwanese outpatients with unexplained dyspnea and fatigue

BackgroundWhile Reddy proposed the H2FPEF diagnostic algorithm to aid in diagnosing heart failure with preserved ejection fraction (HFpEF), certain parameters like age and obesity are not suitable for Asian population, especially given the increasing incidence of HFpEF in younger individuals. Therefore, this study aimed to develop an easy-to-use nomogram with non-invasive indices that can be used in outpatient clinics in Taiwan to quickly estimate the probability of HFpEF and help decide whether further invasive cardiopulmonary exercise test (CPET) is needed. MethodsOutpatients with unexplained dyspnea and fatigue were recruited divided into HFpEF (n = 64) and non-HFpEF (n = 34) groups based on invasive CPET and echocardiography. Multivariate logistic regression analyses identified independent noninvasive variables for developing an HFpEF nomogram. The nomogram's performance was assessed and validated using the concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis. ResultsMultivariate logistic regression analyses identified five independent noninvasive variables for developing an HFpEF nomogram, including dyslipidemia (OR = 5.264, p = 0.010), diabetes (OR = 3.929, p = 0.050), left atrial area (OR = 1.130, p = 0.046), hemoglobin <13 g/dL (OR = 5.372, p = 0.010), and NT-proBNP ≥245 pg/mL (OR = 5.108, p = 0.027). The nomogram showed good discriminatory ability (C-index = 0.842) and calibration performance (p = 0.873) and high net benefit (0.1−0.95). Notably, the HFpEF nomogram showed better diagnostic accuracy than the H2FPEF score model in predicting Taiwanese HFpEF patients (AUC: 0.873 vs. 0.608, p = 0.0006). ConclusionThe noninvasive HFpEF nomogram provides a preliminary estimation of the probability of HFpEF in Taiwanese outpatients with unexplained dyspnea and fatigue, which may help the decision-making on further invasive CPET.

Distinguishing heart failure subtypes: the diagnostic power of different cardiac magnetic resonance imaging parameters.

The aim of this retrospective study was to explore the diagnostic potential of various cardiac parameters in differentiating between heart failure with preserved ejection fraction (HFpEF) and heart failure with mid-ranged and reduced ejection fraction (HFm + rEF), and to discern their relationship with normal cardiac function. This research encompassed a comparative analysis of heart failure subtypes based on multiple indicators. Participants were categorized into HFm + rEF, HFpEF, and control groups. For each participant, we investigated indicators of left ventricular function (LVEDVi, LVESVi, and LVEF) and myocardial strain parameters (GLS, GCS, GRS). Additionally, quantitative tissue evaluation parameters including native T1, enhanced T1, and extracellular volume (ECV) were examined.For comprehensive diagnostic performance analysis, receiver operating characteristic (ROC) curve evaluations for each parameters were conducted. HFm + rEF patients exhibited elevated LVEDVi and LVESVi and decreased LVEF compared to both HFpEF and control groups. Myocardial strain revealed significant reductions in GLS, GCS, and GRS for HFm + rEF patients compared to the other groups. HFpEF patients showed strain reductions relative to the control group. In cardiac magnetic resonance imaging (CMR) evaluations, HFm + rEF patients demonstrated heightened native T1 times and ECV fractions. Native T1 was particularly effective in distinguishing HFpEF from healthy subjects. Native T1, ECV, and myocardial strain parameters have substantial diagnostic value in identifying HFpEF. Among them, native T1 displayed superior diagnostic efficiency relative to ECV, offering critical insights into early-stage HFpEF. These findings can play a pivotal role in refining clinical management and treatment strategies for heart failure patients.

High-Sensitivity C-Reactive Protein Is Associated With Heart Failure Hospitalization in Patients With Metabolic Dysfunction-Associated Fatty Liver Disease and Normal Left Ventricular Ejection Fraction Undergoing Coronary Angiography.

Systemic chronic inflammation plays a role in the pathophysiology of both heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated fatty liver disease. This study aimed to investigate whether serum hs-CRP (high-sensitivity C-reactive protein) levels were associated with the future risk of heart failure (HF) hospitalization in patients with metabolic dysfunction-associated fatty liver disease and a normal left ventricular ejection fraction. The study enrolled consecutive individuals with metabolic dysfunction-associated fatty liver disease and normal left ventricular ejection fraction who underwent coronary angiography for suspected coronary heart disease. The study population was subdivided into non-HF, pre-HFpEF, and HFpEF groups at baseline. The study outcome was time to the first hospitalization for HF. In 10 019 middle-aged individuals (mean age, 63.3±10.6 years; 38.5% women), the prevalence rates of HFpEF and pre-HFpEF were 34.2% and 34.5%, with a median serum hs-CRP level of 4.5 mg/L (interquartile range, 1.9-10 mg/L) and 5.0 mg/L (interquartile range, 2.1-10.1 mg/L), respectively. Serum hs-CRP levels were significantly higher in the pre-HFpEF and HFpEF groups than in the non-HF group. HF hospitalizations occurred in 1942 (19.4%) patients over a median of 3.2 years, with rates of 3.7% in non-HF, 20.8% in pre-HFpEF, and 32.1% in HFpEF, respectively. Cox regression analyses showed that patients in the highest hs-CRP quartile had a ≈4.5-fold increased risk of being hospitalized for HF compared with those in the lowest hs-CRP quartile (adjusted-hazard ratio, 4.42 [95% CI, 3.72-5.25]). There was a high prevalence of baseline pre-HFpEF and HFpEF in patients with metabolic dysfunction-associated fatty liver disease and suspected coronary heart disease. There was an increased risk of HF hospitalization in those with elevated hs-CRP levels.

An altered plasma lipidome-phenome network characterizes heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a multifactorial, multisystemic syndrome that involves alterations in lipid metabolism. This study aimed to test whether distinct plasma lipid profiles or lipid entities or both are associated with clinical and functional echocardiographic parameters in HFpEF. We examined the human plasma lipidome in HFpEF patients (n=18) with left ventricular ejection fraction ≥50% and N-terminal pro-brain natriuretic peptide (NT-proBNP) >125pg/mL and control subjects (n=12) using mass spectrometry-based shotgun lipidomics. The cohort included 8 women and 22 men with average age of 67.8±8.6 SD. The control and disease groups were not significantly different with respect to age, body mass index, systolic and diastolic blood pressure, and waist-to-hip ratio. The disease group experienced more fatigue (P<0.001), had more often coronary artery disease (P=0.04), and received more medications (beta-blockers, P<0.001). The disease group had significantly different levels of HFpEF-relevant parameters, including NT-proBNP (P<0.001), left ventricular mass index (P=0.005), left atrial volume index (P=0.001), and left ventricular filling index (P<0.001), and lower left ventricular end-diastolic diameter (P=0.014), with no difference in left ventricular ejection fraction. Significant differences in lipid profiles between HFpEF patients and controls could not be detected, including no significant differences in abundance of circulating lipids binned by carbon chain length or by double bonds, nor at the level of individual lipid species. However, there was a striking correlation between selected lipids with smoking status that was independent of disease status, as well as between specific lipids and hyperlipidaemia [with corresponding significance of either false discovery rate (FDR) <0.1 or FDR<0.01]. In an exploratory network analysis of correlations, we observed significantly stronger correlations within the HFpEF group between individual lipids from the cholesterol ester and phosphatidylcholine (PC) classes and clinical/echocardiographic parameters such as left atrial volume index, left ventricular end-diastolic diameters, and heart rate (FDR<0.1). In contrast, the control group showed significantly stronger negative correlations (FDR<0.1) between individual species from the PC and sphingomyelin classes and left ventricular mass index or systolic blood pressure. We did not find significant direct associations between plasma lipidomic parameters and HFpEF and therefore could not conclude that any specific lipids are biomarkers of HFpEF. The validation in larger cohort is needed to confidently conclude the absence of first-order associations.

Unveiling the vulnerability of C57BL/6J female mice to HFpEF and its related complications

IntroductionThe impact of female biological sex on the development of heart failure with preserved ejection fraction (HFpEF) and its associated kidney disease and vascular endothelial dysfunction is still controversial. Whether females are protected from HFpEF and associated complications is not well established. Previous studies report conflicting prevalence between genders. We hypothesize that female mice are unprotected from HFpEF and its associated kidney disease and vascular endothelial dysfunction. MethodsEight-week-old female mice were divided into four groups: control groups receiving a standard diet and water for either 5 or 16 weeks, and HFpEF groups fed a high-fat diet (HFD, Rodent Diet With 60 kcal% Fat) and N[w]-nitro-l-arginine methyl ester (L-NAME - 0.5 g/L) in the drinking water for 5 or 16 weeks. Various measurements and assessments were performed, including echocardiography, metabolic and hypertensive evaluations, markers of heart and kidney injury, and assessment of vascular endothelial function. ResultsFemale mice with HFD and L-NAME developed HFpEF at 5 weeks, evidenced by increased E/E' ratio, reduced cardiac index, left ventricular mass, and unchanged ejection fraction. After 16 weeks, HFpEF worsened. Metabolic disorders, hypertension, lung wet/kidney weight increase, exercise intolerance, and cardiac/renal injury markers were observed. Vascular endothelial dysfunction was associated with ER stress and fibrosis induction. ConclusionsWe found that female mice are susceptible to the development of HFpEF and its associated kidney disease and vascular endothelial dysfunction. Our data support the concept that the female sex does not protect from HFpEF and its associated kidney disease and vascular endothelial dysfunction when disease risk factors are present.

Association of HFA-PEFF score with clinical outcomes after catheter ablation for atrial fibrillation

BackgroundThe Heart Failure Association Pretest assessment, echocardiography and natriuretic peptide, functional testing and final aetiology (HFA-PEFF) score has been developed for diagnosing heart failure with preserved ejection fraction (HFpEF), which...

Diagnostic potential of energy metabolism-related genes in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is associated with changes in cardiac metabolism that affect energy supply in the heart. However, there is limited research on energy metabolism-related genes (EMRGs) in HFpEF. The HFpEF mouse dataset (GSE180065, containing heart tissues from 10 HFpEF and five control samples) was sourced from the Gene Expression Omnibus database. Gene expression profiles in HFpEF and control groups were compared to identify differentially expressed EMRGs (DE-EMRGs), and the diagnostic biomarkers with diagnostic value were screened using machine learning algorithms. Meanwhile, we constructed a biomarker-based nomogram model for its predictive power, and functionality of diagnostic biomarkers were conducted using single-gene gene set enrichment analysis, drug prediction, and regulatory network analysis. Additionally, consensus clustering analysis based on the expression of diagnostic biomarkers was utilized to identify differential HFpEF-related genes (HFpEF-RGs). Immune microenvironment analysis in HFpEF and subtypes were performed for analyzing correlations between immune cells and diagnostic biomarkers as well as HFpEF-RGs. Finally, qRT-PCR analysis on the HFpEF mouse model was used to validate the expression levels of diagnostic biomarkers. We selected 5 biomarkers (Chrna2, Gnb3, Gng7, Ddit4l, and Prss55) that showed excellent diagnostic performance. The nomogram model we constructed demonstrated high predictive power. Single-gene gene set enrichment analysis revealed enrichment in aerobic respiration and energy derivation. Further, various miRNAs and TFs were predicted by Gng7, such as Gng7-mmu-miR-6921-5p, ETS1-Gng7. A lot of potential therapeutic targets were predicted as well. Consensus clustering identified two distinct subtypes of HFpEF. Functional enrichment analysis highlighted the involvement of DEGs-cluster in protein amino acid modification and so on. Additionally, we identified five HFpEF-RGs (Kcnt1, Acot1, Kcnc4, Scn3a, and Gpam). Immune analysis revealed correlations between Macrophage M2, T cell CD4+ Th1 and diagnostic biomarkers, as well as an association between Macrophage and HFpEF-RGs. We further validated the expression trends of the selected biomarkers through experimental validation. Our study identified 5 diagnostic biomarkers and provided insights into the prediction and treatment of HFpEF through drug predictions and network analysis. These findings contribute to a better understanding of HFpEF and may guide future research and therapy development.

Left bundle branch area pacing improves right ventricular function in heart failure with preserved ejection fraction: evidence from PROPHET trial

Abstract Background Left bundle branch area pacing (LBBAP) has emerged as a promising pacing strategy, especially for patients with heart failure. However, the impact of LBBAP on hemodynamics and cardiac function in heart failure with preserved ejection fraction (HFpEF) has not been investigated yet. Aim To investigate the hemodynamic response and change of cardiac function of LBBAP in patients with HFpEF. Methods This prospective cohort study enrolled patients with preserved left ventricular ejection fraction who were receiving LBBAP, and two cohorts (non-HFpEF cohort and HFpEF cohort) were built based on diagnosis of HFpEF. Hemodynamics before and after LBBAP were measured using right heart catheterization (RHC). And the changes of cardiac function were evaluated by transthoracic speckle tracking echocardiography (STE). Results 30 consecutive patients were included in the study, with 17 patients in the non-HFpEF group and 13 patients in the HFpEF group. Preprocedural STE showed worsened right ventricular function in the HFpEF group indicated by global longitudinal strain rate, free-wall strain rate, fractional area change, Tricuspid annular pulmonary systolic excursion and Tei index. And RHC showed elevated right ventricular stroke work index (RVSWI, 8.6±4.1 non-HFpEF vs 15.0±5.6 HFpEF, P = 0.170). While post-LBBAP evaluation showed a more significant reduction in RVSWI in the HFpEF group (6.7±2.5 (reduction 22.1%) non-HFpEF vs 8.0±1.0 (reduction 46.7%) HFpEF, P = 0.043). Besides, post-LBBAP STE showed improvement of right ventricular function, despite no significant difference in the extent of improvement was found between groups. Conclusion LBBAP might be more beneficial to patients with HFpEF as it could improve right ventricular function by alleviating the workload of right ventricle. Long-term benefit of LBBAP in HFpEF requires further investigation.

Association between omentin-1 and heart failure with preserved ejection fraction in Chinese elderly patients.

Omentin-1 is a novel adipokine and is associated with chronic inflammation and cardiovascular diseases. However, it remains unclear whether omentin-1 levels are associated with diagnostic significance in elderly patients with heart failure with preserved ejection fraction (HFpEF). This study aimed to investigate the correlation between omentin-1 and HFpEF in Chinese elderly patients. Omentin-1 may be invovled in HFpEF and there may be a difference of omentin-1 levels between HFpEF and control. 217 subjects were selected, including 115 patients with HFpEF and 102 control subjects. Enzyme-linked immuno sorbent assay (ELISA) was used to detect plasma levels of omentin-1, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The receiver operating characteristics (ROC) curve was used to examine the diagnostic performance of omentin-1 in HFpEF. The levels of omentin-1 decreased significantly in the HFpEF group (14.02 ± 8.35 vs. 19.74 ± 8.45 ng/mL, p < .001), while NT-proBNP, IL-6, and TNF-α levels were significantly increased in the HFpEF group compared with the control group. Spearman correlation analysis showed that omentin-1 levels were negatively correlated with E/e' (r = -.340, p < .001). The multivariate logistic regression analysis indicated that omentin-1 was an independent protective factor for HFpEF (odd ratio = 0.948, 95% confidence interval [CI] 0.905-0.993, p = .025). Omentin-1 levels were negatively correlated with NT-proBNP (r = -.273, p < .001) and TNF-α (r = -.221, p = .001). Diagnostic efficiency by ROC curve analysis in the patients with HFpEF showed that the area under the curve (AUC) for omentin-1 was equivalent to NT-proBNP (AUC: 0.734, 95%CI 0.667-0.802; AUC: 0.800, 95%CI 0.738-0.861). Subgroup analysis showed that in the patients between the age of 70 and 80, the predictive capability of omentin-1 was stronger than NT-proBNP (AUC: 0.809, 95%CI 0.680-0.937; AUC: 0.674, 95%CI 0.514-0.833). Omentin-1 levels which were associated with inflammation, were decreased in the HFpEF patients. It could be regarded as a valuable biomarker for the occurrence and development of HFpEF in elderly patients.