Heart Failure With Preserved Ejection Fraction Group Research Articles

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.

Abstract 13532: Long-Term Survival of Different Heart Failure Categories in Patients Discharged Owing to Coronary Artery Disease With/Without Acute Coronary Syndrome

Background: Heart failure (HF) has been classified into distinct phenotypes based on left ventricular ejection fraction (LVEF). We conducted this retrospective cohort study to explore the long-term survival prognosis of different types of HF especially the HF with improved ejection fraction (HFimpEF) group. Methods: We collected patients who had ever been hospitalized owing to coronary artery disease or acute coronary syndrome between July 2006 and June 2017 at National Taiwan University Hospital (NTUH) and NTUH Hsin-Chu Branch. Patients were classified as (1) HF with reduced ejection fraction (HFrEF); (2) HFimpEF; (3) HF with mildly reduced ejection fraction (HFmrEF); (4) HF with preserved ejection fraction (HFpEF); according to echocardiography-derived LVEF during or after the index hospitalization. The date of the first echocardiography during or after the index hospitalization was defined as the index date. All patients were followed from their index date until death or the end of the study (December 31 2017), whichever occurred first. Results: Totally, 11549 patients were categorized into 4 groups (HFrEF group, n = 986; HFimpEF group, n = 461; HFmrEF group, n = 1454; and HFpEF group, n = 8648). The crude mortality rate during follow-up in HFrEF group, HFimpEF group, HFmrEF group, and HFpEF group was 60.4%, 28.0%, 36.6%, and 18.3%, respectively. Patients in HFimpEF group, HFmrEF group, and HFpEF group all possessed a significantly reduced risk of all-cause mortality compared with HFrEF group (adjusted hazard ratio [HR] 0.241, 95% confidence interval [CI] 0.199-0.292 for HFimpEF group; 0.443, 95% CI 0.393-0.500 for HFmrEF group; and 0.292, 95% CI 0.262-0.324 for HFpEF group). Using the time-varying Cox regression model to deal with the immortal time bias, we found a persistent lower risk of all-cause mortality in patients in HFimpEF group compared with patients in HFrEF group (adjusted HR 0.579, 95% CI 0.467-0.718). Conclusion: Patients in HFrEF group had the worst long-term survival prognosis and patient in HFpEF group had the best long-term survival prognosis. Patients in HFimpEF group represented a distinctive population with good survival prognosis than HFrEF group and HFmrEF group.

Abstract 14945: Left Bundle Branch Area Pacing Improves Right Ventricular Function in Heart Failure With Preserved Ejection Fraction: Evidence From PROPHET Trial

Introduction: 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. Hypothesis: LBBAP could improve cardiac function of 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 plane 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. Conclusions: 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.

Abstract 13886: Impaired Locomotor Muscle Blood Flow During Cycling Exercise in Heart Failure With Preserved Ejection Fraction

Introduction: Obesity and hypertension (HTN) are highly prevalent comorbid risk factors for heart failure with preserved ejection fraction (HFpEF). Obesity and HTN independently increase sympathetic nervous activity and impair muscle blood flow during exercise. Previous work has reported attenuated limb blood flow in patients with HFpEF; however, these findings were compared to controls with dissimilar comorbidities and during small muscle mass exercise. It is unclear if HFpEF alters muscle blood flow responses independent of the obesity- and HTN-mediated alterations. Hypothesis: We hypothesized the muscle blood flow response during cycling would be lower in HFpEF patients than age, sex, BMI, and HTN matched controls (CTL). Methods: HFpEF patients (n=14, 9M/5W, 71±7yrs, 32±4 kg/m 2 ) and CTL (n=12, 8M/4W, 69±7yrs, 31±4 kg/m 2 ) performed an incremental cycling test. Blood pressure was measured by manual sphygmomanometry, cardiac output (Q) by open-circuit acetylene wash-in technique, and systemic vascular resistance (SVR) was calculated. Vastus lateralis blood flow index (BFI) was measured by near-infrared spectroscopy and indocyanine green dye injections and venous norepinephrine concentration was measured. Changes from rest to 40 W of the incremental test are reported. Results: Resting Q, mean arterial pressure, SVR, and venous norepinephrine concentration were not statistically different between groups (p&gt;0.18). From rest to 40 W, the increases in Q (CTL: 3.9±0.8 vs. HFpEF: 3.6±0.7 L/min), mean arterial pressure (CTL: 5.7±2.7 vs. HFpEF: 6.6±6.1 mmHg), and SVR (CTL: -7.3±2.1 vs. HFpEF: -6.0±2.0 mmHg/L/min) were not statistically different between groups (all, p&gt;0.13). The HFpEF group had smaller increases in vastus lateralis BFI at 40 W compared to CTL (CTL: 7.2±3.6 vs. HFpEF: 4.2±2.6 fold-increase from rest) (p=0.02). The HFpEF group had greater increases in venous norepinephrine concentration from rest to 40 W than CTL (CTL: 164±216 vs. HFpEF: 377±247 pg/mL) (p=0.05). Conclusions: Our findings suggest that, compared to age, sex, BMI, and HTN matched controls, patients with HFpEF have an impaired locomotor muscle blood flow response during submaximal cycling exercise likely due to higher locomotor muscle vascular resistance.

Abstract 15926: Left Atrial Pressure and H 2 FPEF Score in Patients With Atrial Fibrillation Who Underwent Catheter Ablation

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a common comorbidity in atrial fibrillation (AF) patients and contributes to AF progression and stroke risk. Hypothesis: We explore the hemodynamic effects of left atrial pressure (LAP), which was directly measured during AF catheter ablation (AFCA), on HFpEF based on the H 2 FPEF score. Methods: We included 1,426 patients (73.3% male, median age, 61.0 [54.0-68.0] years; 45.7% persistent AF) who underwent AFCA, LAP measurements at both AF and sinus rhythm (SR), echocardiogram, and H 2 FPEF score, and excluded the patients with EF &lt;50%. We divided patients into low-risk (&lt; 6 points) and high-risk ( ≥ 6 points) HFpEF groups and measured LAP-mean depending on heart rates 90, 100, 110, and 120 bpm during right atrial pacing (Pace-HR) and isoproterenol (ISO-HR) infusion in all patients. Results: The LAP-mean was sequentially and significantly higher according to the H 2 FPEF score (p&lt;0.001) and had an independent association with the high-risk HFpEF group (OR 1.37 per 10mmHg increase [1.13-1.67], p=0.001). LAP-mean increased significantly with increasing Pace-HR (90-120 bpm, 10.4 to 11.6 mmHg, p&lt;0.001) but decreased with ISO-HR (90-120 bpm, 10.2 to 8.1 mmHg, p&lt;0.001). In patients with paroxysmal AF, LAP-mean[AF] was significantly higher than LAP-mean[SR] (p&lt;0.001), but not in those with non-paroxysmal AF (p=0.557). In patients with paroxysmal AF, ΔLAP-mean[Pace-HR, 120-90bpm] was significantly higher than that of non-paroxysmal AF (p&lt;0.001). Conclusions: LAP is independently associated with H 2 FPEF score and has inverse rate-dependent response depending on pacing or ISO infusion. Higher increase of LAP during AF or higher Pace-HR contributes to more severe symptoms in patients with paroxysmal AF than in non-paroxysmal AF.

Abstract 12425: Stim1 Deletion in Treg Cell Protects From HFpEF Pathogenesis

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a cardiovascular disease that remains untreatable in its pathogenesis. Therefore, there is a critical need to uncover the cellular and molecular mechanisms underlying HFpEF pathogenesis and identify potential targets for treatment that can enhance cardiac function and restrict disease progression. Previous studies have shown that Treg cells are crucial in hypertension-induced cardiovascular complications and metabolic dysregulation. Moreover, the function of Stromal interaction molecule 1 (STIM1) varies depending on the cell type. Hypothesis: We hypothesize that the deletion of STIM1 in Treg cells can protect against the development of HFpEF and its associated conditions. Methods: Male mice aged eight weeks (Stim1 flx/flx and Treg Stim1-/- ) were divided into four groups: control groups receiving a standard diet and water for five weeks, and HFpEF groups fed a high-fat diet (HFD) and N[w]-nitro-l-arginine methyl ester (L-NAME - 0.5g/L) in the drinking water for five weeks. Various measurements and assessments were conducted, including echocardiography, evaluations of metabolism and hypertension, analysis of heart and kidney injury markers, and assessment of vascular endothelial function. Results: After five weeks, Stim1 flx/flx mice subjected to HFD and L-NAME displayed evidence of HFpEF, including hypertension, metabolic disorders, cardiac hypertrophy with fibrosis, kidney injury with fibrosis, impaired exercise tolerance and vascular endothelial function, increased body weight and E/E' ratio, reduced cardiac index, and unchanged ejection fraction. Interestingly, Treg Stim1-/- mice were protected against HFD and L-NAME-induced HFpEF and its associated pathologies. Conclusions: These findings underscore the significance of targeting STIM1 in Treg cells to protect from the development and pathogenesis of HFpEF.

Abstract 12466: Targeted Quantitative Plasma Metabolomics Identifies Metabolite Signatures That Distinguish Heart Failure With Reduced and Preserved Ejection Fraction

Background: Despite recent advances, heart failure (HF) remains a high burden disease and is largely treated with a “one-size-fits-all” approach. Two phenotypes are recognized: HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). To develop HF disease-specific approaches to define and guide treatment, distinguishing biomarkers are needed. Methods: We conducted quantitative, targeted LC/MS plasma metabolomics on 787 samples collected by the Penn Medicine BioBank from patients with HFrEF (n=219), HFpEF (n=357), and matched non-failing Controls (n=211). Sample collection time from last meal was not controlled. A total of 97 metabolites were analyzed, comprising 30 amino acids, 8 organic acids, and 59 acylcarnitines classified by carbon length. Results: 3-hydroxybutyrate (3-HBA) was uniquely and significantly elevated in the HFrEF group [mean +/- SEM: HFpEF, 108.7(+/-7.15); HFrEF, 148.0(+/-12.4); Control, 86.29(+/-8.01); p &lt;.0001]. The 3-HBA metabolite C4-OH butyryl-carnitine also showed a similar HFrEF-specific pattern. Consistent with previous studies, long/very-long chain acylcarnitines were elevated in the HFrEF group to a much greater extent than the HFpEF group compared to Controls. Branched-chain amino acid (BCAA) levels were not different across the groups; however, acylcarnitine species indicative of BCAA degradation, including C04 Isobutyryl, C04-DC Methylmalonyl, C04-DC Succinyl, and C05 2-Methylbutyryl, were significantly elevated in both HF groups compared to Controls. Lastly, we found that the amino acid, asymmetric dimethylarginine, which promotes endothelial dysfunction and vasoconstriction, was uniquely elevated in the HFpEF cohort [mean +/- SEM: HFpEF, 1.236(+/- .019); HFrEF, 1.105(+/- .027); Control, 1.077(+/- .022); p &lt; .0001]. Conclusions: Taken together, these results identify plasma metabolite signatures that potentially distinguish between HFrEF and HFpEF and suggest patterns of metabolic re-programming in extra-cardiac tissue in the context of heart failure. Future studies will be necessary to define the utility of these metabolites as biosignatures to help guide therapeutics and to identify the underlying physiology responsible for these observations.

Pathological study on the relationship between nucleic acid oxidative stress and heart failure with preserved ejection fraction in patients aged over 85 years

Objective: To investigate the level of nucleic acid oxidation in myocardial tissue of patients aged over 85 with heart failure with preserved ejection fraction (HFpEF) and the correlation with myocardial amyloid deposition. Methods: This was a retrospective case-control study. Data of patients≥85 years old who underwent systematic pathological autopsy in Beijing Hospital from 2003 to 2017 were retrospectively collected. Twenty-six patients were included in the HFpEF group and 13 age-and sex-matched patients who had not been diagnosed with heart failure and died of non-cardiovascular diseases served as the control group. The left ventricular myocardium slices of both groups were semi-quantitatively analyzed using immunohistochemical staining of 8-oxidized guanine riboside (8-oxo-G) and 8-oxidized guanine deoxyriboside (8-oxo-dG) to evaluate the oxidation of RNA and DNA in cardiomyocytes. Using the median of the mean absorbance value of 8-oxo-G immunohistochemical staining as the cut-off value, patients were divided into high-absorbance group and low-absorbance group. Congo red staining was used to compare myocardial amyloid deposition between the two groups. Results: The mean age of patients in HFpEF group was (91.8±3.7) years, 24 (92.3%) were males. The mean age of patients in control group was (91.7±3.7) years old, 11 (84.6%) were males. The median mean optical absorbance value of 8-oxo-G immunohistochemical staining of myocardium was significantly higher in HFpEF patients than in control group (0.313 8 (0.302 2, 0.340 6) vs. 0.289 2 (0.276 7, 0.299 4), Z=-3.245, P=0.001). The median mean absorbance value of 8-oxo-dG immunohistochemical staining of myocardial tissue was similar between the two groups (0.300 0 (0.290 0, 0.322 5) vs. 0.300 0 (0.290 0, 0.320 0), Z=-0.454, P=0.661). Proportion of patients with moderate and severe cardiac amyloid deposition was significantly higher in the high-absorbance group than in the low-absorbance group ((85.0%, 17/20) vs. (31.6%, 6/19), P=0.001). Conclusion: The RNA oxidation degree of myocardium in HFpEF patients is higher than that in elderly people without heart failure. Degree of myocardial amyloid deposits is higher in patients with high levels of RNA oxidation.

Serum aldosterone in right ventricular failure versus left ventricular failure before and after mineralocorticoid receptor antagonists: case-control clinical trial

Background Heart failure (HF) is a global growing health threat. This case-control clinical trial aimed to detect the predictive value and difference in aldosterone level between right side heart failure, heart failure with decreased ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) and compare the efficacy and safety of adding mineralocorticoid receptor antagonist (MRA) for treatment. Patients and methods We recruited 151 participants, 135 HF patients divided equally into 45 patients in each group:(1) right side HF (2) HFrEF and (3) HFpEF and 16 healthy controls. Serum aldosterone, troponin and echocardiography were evaluated at the beginning of the study, three and six months after administration of MRA. Results Aldosterone level was significantly greater in HF patients relative to controls. Aldosterone level can detect HF with excellent accuracy. There were significantly lower levels of aldosterone in right side HF compared to left side HF. There was a significant decrease in right ventricle dimensions, pulmonary artery systolic pressure and pulmonary artery size and significant increase in tricuspid annular plane systolic excursion after treatment in patients with right side HF. In the HFrEF group, there was a significant decrease in left ventricular end diastolic dimension and a significant increase in left ventricular EF after treatment. In the HFpEF group, there was a significant decrease in E/A and E/e′ after treatment. Conclusions Aldosterone may have pathogenic role in HF. Measuring and follow-up of aldosterone levels should be considered in HF patients. MRA treatment gives a significant improvement in right side HF group.

Echocardiographic multiparameter assessment for patients with heart failure with preserved ejection fraction and atrial fibrillation.

We aimed to assess the echocardiographic parameters of cardiac structure and function in patients with heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF). Thirty-seven HFpEF patients with AF were selected, while 38 patients with simple HFpEF in the same period were selected as controls. Three-dimensional speckle-tracking echocardiography was performed on both groups and the parameters were compared. The early diastolic longitudinal peak strain rates [early diastolic longitudinal strain rate (LSRE), early diastolic circumferential strain rate (CSRE), early diastolic radial strain rate (RSRE) and early diastolic rotational strain rate (RotRE)], late diastolic longitudinal peak strain rates (LSRA, CSRA, RSRA and RotRA) and untwisting parameters [untwisting rate during isovolumic relaxation time (UTRIVR) and early peak untwisting rate (UTRE)] were all negatively correlated with the ratio of early diastolic transmitral velocity to early diastolic mitral annular velocity ( E/E') (p < 0.01). The cardiac event-free survival rate of the simple HFpEF group (92.11%) was significantly higher than that of the HFpEF + AF group (81.08%) (p < 0.0001). UTRIVR had a more significant correlation with E/E' ratio than the other indicators and could serve as a sensitive indicator for evaluating the diastolic function of patients with HFpEF + AF.

Contributions of anemia to exercise intolerance in heart failure with preserved ejection fraction-An exercise stress echocardiographic study.

Anemia is common in patients with heart failure with preserved ejection fraction (HFpEF) and is associated with exercise intolerance. However, there are limited data on how anemia contributes to reduced exercise capacity in patients with HFpEF. We aimed to characterize exercise capacity, cardiovascular and ventilatory reserve, and the oxygen (O2) pathway in anemic patients with HFpEF. A total of 238 patients with HFpEF and 248 dyspneic patients without HF underwent ergometry exercise stress echocardiography with simultaneous expired gas analysis. Patients with HFpEF were classified into two groups based on the presence of anemia (hemoglobin<13.0g/dL in men and<12.0g/dL in women). Anemic HFpEF patients (n=112) had worse nutritional status and renal function, lower iron levels, and greater left ventricular (LV) remodeling and plasma volume expansion than those without anemia (n=126). Exercise capacity, assessed by peak oxygen consumption, exercise intensity, and exercise duration, was lower in the anemic HFpEF group than in the other groups. Despite a similar cardiac output during exercise, anemic patients with HFpEF demonstrated limitations in arterial O2 delivery, lower arteriovenous O2 content difference, and ventilatory inefficiency (higher minute ventilation vs. carbon dioxide production slope) during peak exercise. Anemic HFpEF patients demonstrated unique pathophysiological features with greater LV remodeling and plasma volume expansion, limitations in arterial O2 delivery and peripheral O2 extraction, and ventilatory inefficiency, which may contribute to reduced exercise capacity. Further studies are needed to develop an optimal approach for treating anemia in patients with HFpEF.