Heart Failure With Reduced Ejection Fraction Group Research Articles

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.

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 efficacy and safety of cryoballoon atrial fibrillation ablation in patients with heart failure: A systematic review and meta-analysis

IntroductionWhile atrial fibrillation (AF) ablation has proven beneficial for heart failure (HF) patients, most reports were performed with radiofrequency ablation. We aimed to evaluate the efficacy and safety of cryoballoon AF ablation in patients with HFrEF. MethodWe comprehensively searched the databases of MEDLINE, EMBASE, and Cochrane database from inception to December 2022. Studies that reported the outcomes of freedom from atrial arrhythmia, complications, NYHA functional class (NYHA FC), and left ventricular ejection fraction (LVEF) after Cryoballoon AF ablation in HF patients were included. Data from each study were combined with a random-effects model. ResultA total of 9 studies observational studies with 1414 HF patients were included. Five studies had only HF with reduced ejection fraction (HFrEF), 1 study with HF with preserved ejection fraction (HFpEF), and others with mixed HF types. Freedom from AA in HFrEF at 12 months was 64% (95% CI 56–71%, I2 58%). There was a significant improvement of LVEF in these patients with a standard mean difference of 13% (95% CI 8.6–17.5%, I2 99% P < 0.001. The complication rate in HFrEF group was 6% (95% CI 4–10%, I2 0%). The risk of recurrence of atrial arrhythmia was not significantly different between HF and no HF patients (RR 1.34, 95% CI 0.8–2.23, I2 76%). ConclusionCryoballoon AF ablation is effective in HFrEF patients comparable to radiofrequency ablation. The complication rate was low.

Effects of High-Intensity Interval Training Using the 3/7 Resistance Training Method on Metabolic Stress in People with Heart Failure and Coronary Artery Disease: A Randomized Cross-Over Study.

The 3/7 resistance training (RT) method involves performing sets with increasing numbers of repetitions, and shorter rest periods than the 3x9 method. Therefore, it could induce more metabolic stress in people with heart failure with reduced ejection fraction (HFrEF) or coronary artery disease (CAD). This randomized cross-over study tested this hypothesis. Eleven individuals with HFrEF and thirteen with CAD performed high-intensity interval training (HIIT) for 30 min, followed by 3x9 or 3/7 RT according to group allocation. pH, HCO3-, lactate, and growth hormone were measured at baseline, after HIIT, and after RT. pH and HCO3- decreased, and lactate increased after both RT methods. In the CAD group, lactate increased more (6.99 ± 2.37 vs. 9.20 ± 3.57 mmol/L, p = 0.025), pH tended to decrease more (7.29 ± 0.06 vs. 7.33 ± 0.04, p = 0.060), and HCO3- decreased more (18.6 ± 3.1 vs. 21.1 ± 2.5 mmol/L, p = 0.004) after 3/7 than 3x9 RT. In the HFrEF group, lactate, pH, and HCO3- concentrations did not differ between RT methods (all p > 0.248). RT did not increase growth hormone in either patient group. In conclusion, the 3/7 RT method induced more metabolic stress than the 3x9 method in people with CAD but not HFrEF.

Left Ventricular End-Systolic Diameter May Predict Persistent Heart Failure with Reduced Ejection Fraction.

Patients with persistent heart failure (HF) with reduced ejection fraction (HFrEF) have a poorer prognosis than those with HF with improved ejection fraction (HFimpEF). However, data on the predictive value of echocardiographic parameters for persistent HFrEF are lacking. We retrospectively studied 443 patients who were diagnosed with HFrEF (EF ≤ 40%) during hospitalization and underwent echocardiography at the 1-year follow-up. We divided them into the 2 groups: HFimpEF (EF > 40%) and persistent HFrEF group at 1-year follow-up, and assessed the predictive value of echocardiographic parameters at discharge for persistent HFrEF. In total, 301/443 patients (68%) were diagnosed with persistent HFrEF and 142/443 (32%) with HFimpEF at the 1-year follow-up. Kaplan-Meier analysis revealed that the persistent HFrEF group had a poorer prognosis than the HFimpEF group (log-rank, P < 0.001). Receiver operating characteristic curve analysis revealed that left ventricular end-systolic diameter (LVESD) had the highest area under the curve (AUC) (0.70; 95% confidence interval [CI]: 0.64-0.75; cutoff value: 55 mm) among various echocardiographic parameters. LVESD was an independent predictor of persistent HFrEF at the 1-year follow-up (odds ratio: 1.07, 95%CI: 1.02-1.12) upon multivariable logistic regression analysis. The incidence of persistent HFrEF was higher in patients with an LVESD ≥ 55 mm than in those with an LVESD < 55 mm (81% versus 55%, Fisher's exact test, P < 0.001). In conclusion, an LVESD (≥ 55 mm) was associated with persistent HFrEF. Focusing on LVESD in daily practice may help clinicians with risk stratification for decision-making regarding management in patients with advanced HF refractory to guideline-directed medical therapy.

Abstract 12727: Liver Elasticity in Elderly Heart Failure Patient

Introduction: Liver elastography is a novel ultrasound technique assessing elasticity of liver tissue. Clinical indication of liver elastography remains unrevealed. Moreover, reports about relationship between liver stiffness and heart failure subtypes haven’t well been published. Hypothesis: We have investigated the cardio-hepatic interaction using liver elastography in heart failure subtypes. Methods: We prospectively enrolled 58 consecutive patients with heart failure admission from April 2022 to March 2023. Liver elastography, transthoracic echocardiography and blood sampling were done at the time of discharge from heart failure treatment. Results: Patients were divided into two groups according to the left ventricular ejection fraction (LVEF) of echocardiography: heart failure with reduced ejection fraction (HFrEF) group (EF ≦40%, n = 11) and non-HFrEF group (EF &gt;40%, n = 31). The mean age of all patients was 83 ± 11 years. The mean age and the prevalence of hypertension and diabetes mellitus was higher in non-HFrEF group than in HFrEF group. The prevalence of taking sodium glucose co-transporter 2 (SGLT2) inhibitors was lower in non-HFrEF group than in HFrEF group. LV end-diastolic diameter, LV end-systolic diameter was larger in HFrEF group than in non-HFrEF group. Tricuspid regurgitation pressure gradient (TRPG) was higher in non-HFrEF group than in HFrEF group. Inferior vena cava diameter was not different between two groups. The mean values of almost liver function tests of all patients were within the normal range. eGFR was lower in non-HFrEF group than in HFrEF group. Liver elasticity was higher in non-HFrEF group than in HFrEF group (7.1 ± 2.7 vs. 5.1 ± 1.5 hPa; P=0.008) indicating liver stiffness. Pearson’s correlation coefficient showed that liver elasticity was positively correlated with the prevalence of diabetes mellitus, LVEF, TRPG, serum creatinine, aspartate aminotransferase, γ-glutamyl transpeptidase and was negatively correlated with LV end-diastolic diameter, LV end-systolic diameter. Conclusions: Liver stiffness was elevated in EF-preserved heart failure patients. Liver elasticity was correlated with parameters of congestion (TRPG) and useful for the assessment of congestion in patients with heart failure.

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 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.

Abstract 18513: Causes and Predictors of 30-day Readmissions Following Covid-19 Hospitalizations and Co-Existing Acute Heart Failure: Insights From National Readmission Database 2020

Introduction: COVID-19 infection notably impacts the cardiovascular system, with evidence of higher in-hospital mortality in patients with acute heart failure (AHF) and COVID-19 infection. However, less is known about short-term outcomes following discharge. Therefore, we sought to analyze readmission data in COVID-19 hospitalizations with AHF from the National Readmission Database (NRD). Methods: NRD (2020) was queried to identify all COVID-19 hospitalizations and co-existing AHF using ICD-10 CM codes. The group was then stratified into heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). The outcomes were 30-day readmission rate, length of stay (LOS), total hospital charge (THC), and predictors of readmission. Multivariate/univariate logistic and linear regression analyses were used to analyze the outcomes and adjust for possible confounders. Results: A total of 53,337 COVID-19 admissions with co-existing AHF were identified, of which 38,401 were discharged alive. Within 30 days from discharge, 8,159 (21.26%) were readmitted. Upon stratification, 51% belonged to the HFrEF group and were found to have scarcely higher 30 days readmission rates than encounters with HFpEF (21.46% vs. 21.14%). Readmissions lead to an additional mean THC of $85,687 and a mean LOS of 7.8 days. The top five all-causes of readmissions were COVID-19 infection (24.8%), heart failure (16.2%), sepsis (15.4%), acute kidney injury (2.2%), and pneumonia (1.2%). Figure-1 shows a multivariate analysis of independent factors associated with readmissions. Conclusions: Our analysis showed a 21.26% 30-days readmission rate following acute heart failure during COVID-19 infection. Cirrhosis, anemia, diabetes mellitus, chronic lung diseases, and discharge against medical advice were significant readmission predictors. Optimizing these co-morbidities during index admission may reduce readmissions and overall financial burden.

Clinical, Echocardiographic, and Longitudinal Characteristics Associated With Heart Failure With Improved Ejection Fraction

Heart failure (HF) with improved ejection fraction (HFimpEF) has better outcomes than HF with reduced ejection fraction (HFrEF). However, factors contributing to HFimpEF remain unclear. This study aimed to evaluate clinical and longitudinal characteristics associated with subsequent HFimpEF. This was a single-center retrospective HFrEF cohort study. Data were collected from 2014 to 2022. Patients with HFrEF were identified using ICD codes, echocardiographic data, and natriuretic peptide levels. The main endpoints were HFimpEF (defined as ejection fraction >40% at ≥3 months with ≥10% increase) and mortality. Cox proportional hazards and mixed effects models were used for analyses. The study included 1307 HFrEF patients with a median follow-up of 16.3 months (IQR 8.0-30.6). The median age was 65 years; 68% were male while 57% were white. On follow-up, 38.7% (n=506) developed HFimpEF, while 61.3% (n=801) had persistent HFrEF. A multivariate Cox regression model identified sex, race comorbidities, echocardiographic, and natriuretic peptide as significant covariates of HFimpEF (p<0.05). The HFimpEF group had better survival compared to the persistent HFrEF group (p<0.001). Echocardiographic and laboratory trajectories differed between groups. In this HFrEF cohort, 38.7% transitioned to HFimpEF and approximately 50% met the definition within the first 12 months. In a HFimpEF model, sex, comorbidities, echocardiographic parameters, and natriuretic peptide were associated with subsequent HFimpEF. The model has the potential to identify patients at risk of subsequent persistent or improved HFrEF, thus informing the design and implementation of targeted quality-of-care improvement interventions.

The value of using left ventricular pressure-strain loops to evaluate myocardial work in predicting heart failure with improved ejection fraction

BackgroundThe ultrasound left ventricular pressure-strain loop (LV PSL) was applied to evaluate myocardial work in heart failure with improved ejection fraction (HFimpEF) versus patients with persistent heart failure with reduced ejection fraction (HFrEF) to investigate the value of myocardial work parameters in predicting HFimpEF. MethodsWe collected 120 patients with HFrEF and recorded clinical characteristics and echocardiographic parameters (PSL technique) of patients. Patients were divided into HFimpEF group or persistent HFrEF group according to the outcome of follow-up.Furthermore, differential clinical and echocardiographic parameters were determined by Student's t-test. We recognized the important echocardiographic parameters to predict whether patients would recover to HFimpEF using the univariate logistic regression analysis and ROC curves. In addition, the multivariate logistic regression models were constructed and evaluated using Delong test and decision curve analysis. ResultsFirstly, the HFimpEF group had a higher prevalence of hypertension and higher systolic blood pressure (P-values <0.05). In terms of echocardiographic parameters, HFimpEF group also had higher LVEF, LV GLS, GCW, GWE, and GWI and lower LVEDD (P-values <0.01). In particular, LVEF, LVEDD, GLS, GWI, and GCW were robust predictors of the conversion of HFrEF patients to HFimpEF (AUC >0.70, P-values <0.05). Finally, we determined that the predictive Model 4 (LVEF, LVEDD, GLS, and GCW) had the optimal diagnostic power. ConclusionThe model constructed by GCW with LVEF, LVEDD, and GLS has important predictive value for HFimpEF, which is an effective clinical decision-making tool for providing disease assessment.

Pre-discharge heart failure with reduced ejection fraction In elderly patients after myocardial infarction

Background: The prognosis of elderly people with myocardial infarction has improved over the past decade thanks to advances in treatment, but the rate of heart failure due to coronary heart disease continues to increase. Currently, little is known about heart failure with reduced ejection fraction (HFrEF) before discharge in older adults with myocardial infarction. Objective: To determine the rate of pre-discharge heart failure with reduced ejection fraction in elderly patients after myocardial infarction and related factors. Methods: Cross-sectional study involving older patients with myocardial infarction from September 2022 to March 2023 in the Interventional Cardiology Department, Thong Nhat Hospital and the Interventional Cardiology Department, University Medical Center at Ho Chi Minh city. Results: Of 326 ≥ 60 years old patients presented with myocardial infarction, 100 patients (30.7%) had HFrEF before discharge. Compared with the non-HFrEF group, the pre-discharge HFrEF was older and more frail, had a lower rate of coronary angiography and coronary intervention. There was no difference in the BCIS-JS scores between 2 groups, although the pre-discharge BCIS-JS ratio was lower in the HFrEF group. Conclusion: In elderly patients with myocardial nfarction, our study found that the rate of pre-discharge HFrEF was 30.7%. The HFrEF group had a higher number of frail patients, more likely to be medically treated alone, and there was no difference in BCIS-JS scores. Key words: elderly patients; frailty; myocardial infarction; heart failure after myocardial infarction; heart failure reduced ejection fraction.

[Similarities and differences of myocardial metabolic characteristics between HFpEF and HFrEF mice based on LC-MS/MS metabolomics].

Objective: To reveal the similarities and differences in myocardial metabolic characteristics between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) mice using metabolomics. Methods: The experimental mice were divided into 4 groups, including control, HFpEF, sham and HFrEF groups (10 mice in each group). High fat diet and Nω-nitroarginine methyl ester hydrochloride (L-NAME) were applied to construct a"two-hit"HFpEF mouse model. Transverse aortic constriction (TAC) surgery was used to construct the HFrEF mouse model. The differential expression of metabolites in the myocardium of HFpEF and HFrEF mice was detected by untargeted metabolomics (UHPLC-QE-MS). Variable importance in projection>1 and P<0.05 were used as criteria to screen and classify the differentially expressed metabolites between the mice models. KEGG functional enrichment and pathway impact analysis demonstrated significantly altered metabolic pathways in both HFpEF and HFrEF mice. Results: One hundred and nine differentially expressed metabolites were detected in HFpEF mice, and 270 differentially expressed metabolites were detected in HFrEF mice. Compared with the control group, the most significantly changed metabolite in HFpEF mice was glycerophospholipids, while HFrEF mice presented with the largest proportion of carboxylic acids and their derivatives. KEGG enrichment and pathway impact analysis showed that the differentially expressed metabolites in HFpEF mice were mainly enriched in pathways such as biosynthesis of unsaturated fatty acids, ether lipid metabolism, amino sugar and nucleotide sugar metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and arginine and proline metabolism. The differentially expressed metabolites in HFrEF mice were mainly enriched in arginine and proline metabolism, glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and arachidonic acid metabolism, etc. Conclusions: HFpEF mice have a significantly different myocardial metabolite expression profile compared with HFrEF mice. In addition, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, glycerophospholipid metabolism and arginine and proline metabolism are significantly altered in both HFpEF and HFrEF mice, suggesting that these metabolic pathways may play an important role in disease progression in both types of heart failure.

The E/e' ratio on echocardiography as an independent predictor of the improvement of left ventricular contraction in patients with heart failure with reduced ejection fraction.

Clinical feature of heart failure with improved ejection fraction (HFimpEF) remains to be fully elucidated. The present study investigated the association of clinical and echocardiographic parameters with the subsequent improvement of left ventricular ejection fraction (LVEF) in heart failure with reduced ejection fraction (HFrEF). From outpatients with a history of hospitalized for heart failure, 128 subjects diagnosed as HFrEF (LVEF <40%) on heart failure hospitalization were enrolled and longitudinally surveyed. During follow-up periods more than 1 year, 58 and 42 patients were identified as HFimpEF (improved LVEF to ≥40% and its increase of ≥10 points) and persistent HFrEF, respectively. There was no difference in age or sex between the two groups with HFimpEF and persistent HFrEF. The rate of ischemic heart disease was lower and that of tachyarrhythmia was higher in the HFimpEF group than in the persistent HFrEF group. At baseline (i.e., on heart failure hospitalization), LVEF did not differ between the two groups, but left ventricular systolic and diastolic diameters were already smaller and the ratio of early diastolic transmitral velocity to early diastolic tissue velocity (E/e') was lower in the HFimpEF group. A multiple logistic regression analysis revealed that lower baseline E/e' was a significant determinant of HFimpEF, independently of confounding factors such as ischemic heart disease, tachyarrhythmia, and baseline left ventricular dimension. Our findings indicate that the lower ratio of E/e' in the acute phase of heart failure onset is an independent predictor of the subsequent improvement of LVEF in HFrEF patients.

Muscle metaboreflex control of left ventricular systolic function in heart failure with reduced ejection fraction.

Heart failure with reduced ejection fraction (HFrEF) exhibits exaggerated sympathoexcitation and altered cardiac and vascular responses to muscle metaboreflex activation (MMA). However, left ventricular (LV) responses to MMA are not well studied in patients with HFrEF. The purpose of this study was to examine LV function during MMA using cardiac magnetic resonance imaging (MRI) in patients with HFrEF. Thirteen patients with HFrEF and 18 healthy age-matched controls underwent cardiac MRI during rest and MMA. MMA protocol included 6 min of isometric handgrip exercise followed by 6-min of brachial postexercise circulatory occlusion. LV stroke volume index (SVi), end-systolic volume index (ESVi), end-diastolic volume index (EDVi), and global longitudinal strain (GLS) were measured by two- and four-chamber cine images. Volumes were indexed to body surface area. Heart rate (via ECG) and brachial mean arterial pressure (MAP) were recorded. Cardiac output and total peripheral resistance (TPR) were calculated. SVi decreased during MMA in HFrEF (P = 0.037) but not in controls (P = 0.392). ESVi (P = 0.007) and heart rate (P < 0.001) increased during MMA in HFrEF but not controls (P ≥ 0.170). TPR (P = 0.021) and MAP (P < 0.001) increased during MMA in both groups. Cardiac output (P = 0.946), EDVi (P = 0.177), and GLS (P = 0.619) were maintained from rest to MMA in both groups. Despite similarly maintained cardiac output, LV strain, and increased TPR in HFrEF and control groups, SVi decreased, and heart rate increased during MMA in patients with HFrEF. These findings suggest an impaired contractility reserve in response to increased TPR during MMA in HFrEF.NEW & NOTEWORTHY Stroke volume decreases and end-systolic volume increases during muscle metaboreflex activation in patients with heart failure with reduced ejection fraction (HFrEF), suggesting impaired contractile reserve during muscle metaboreflex activation in patients with HFrEF. Total peripheral resistance increases similarly during muscle metaboreflex activation in patients with HFrEF compared to controls, indicating normal levels of peripheral vasoconstriction during muscle metaboreflex activation in patients with HFrEF.

PO-02-135 DOES LA SIZE PREDICT OUTCOMES IN AF AND SYSTOLIC HEART FAILURE?

Significant left atrial (LA) enlargement often accompanies heart failure with reduced ejection fraction (HFrEF) and may determine the success of AF ablation. However, the impact of LA size on long-term outcomes remains unclear. We aim to determine the relationship between LA size and AF recurrence in patients with normal LV function (NLV) and HFrEF following AF ablation. Consecutive patients undergoing index AF ablation across 11 centres were stratified according to baseline LVEF (<50% or >50%). The impact of baseline LA size on 12-month AF recurrence was determined utilising continuous remote rhythm monitoring to detect arrhythmia recurrence and quantify AF burden. 360 patients were included (NLV=237, HFrEF=123). The HFrEF group (mean LVEF 34.9±8.3%) were younger (62±10 vs 65 ± 9 years, p=0.020), with larger LA size (LAVI 54.6±16.5ml/m2 vs 45.4±14.1ml/m2, p<0.001). Despite differences in LA size, freedom from AF was similar in those with and without HF (56% vs 54% respectively, Log Rank p=0.621, figure 1a). Similarly, AF burden did not differ between groups (median burden HFrEF 0% (0-1.1); NLV 0 (0-2.5), p=0.195). An age-matched 1:1 comparison of NLV and HFrEF (N=246) demonstrated no impact of baseline LA size on arrhythmia recurrence (p=0.579), despite larger LA in those with HFrEF (LAVI 54.6±16.5 vs NLV 45.0±15.0, p=0.0002). LA enlargement did not predict arrhythmia recurrence (HR 1.400, 95% CI 0.952-2.057, p=0.086) regardless of HF status (figure 1b). At 12 months, LV function normalised in 80% (LVEF>50%) of those with HFrEF (ΔLVEF: +19±13%, p<0.001) with a significant reduction in LA size (54.6±16.5 to 44.7±14.6ml/m2, p<0.001), comparable in those with and without AF recurrence (p=0.819). Baseline LA enlargement did not influence AF recurrence in those with or without LV recovery (HR 1.622 95% CI 0.702-3.748, p=0.258). LA enlargement did not determine the outcome of AF ablation in those with and without HFrEF. LA size is less useful in guiding patient selection for AF ablation in HFrEF

Microvascular and structural analysis of the retina and choroid in heart failure patients with reduced ejection fraction

This cross-sectional study was designed to assess alterations of choroidal and retinal microvasculature in patients with Heart Failure with Reduced Ejection Fraction (HFrEF) and compare them with a normal age and sex-matched population. Fifty-two eyes of 26 patients with HFrEF (left ventricular ejection fraction [LVEF] < 40%) and 64 eyes of 32 healthy individuals were considered as the patient and the control groups, respectively. We found no statistically significant differences in age-adjusted mean central macular thickness (CMT), superficial or deep retinal capillary plexus vascular densities, and choriocapillaris flow (CC flow) density between the HFrEF group and the normal controls, with the exception of the parafoveal mean superficial capillary plexus vascular density (P = 0.023), which remained statistically significant after adjusting for age (P = 0.034). The patients with HFrEF had a significantly lower subfoveal choroidal thickness (SFCT) than the normal subjects (264 ± 82 vs 313 ± 72; P = 0.009), and the difference was still statistically significant after age adjustment (P = 0.026). Although choroidal vascularity index (CVI) was lower in the HFrEF group than in the control group, the difference was not statistically significant before and after age adjustment (73.45 ± 6.67 vs 75.77 ± 5.92; P = 0.118 and P = 0.096, respectively). In conclusion, in patients with HFrEF, we observed a reduction in parafoveal retinal VD in the superficial capillary plexus, as well as SFCT, but no significant change in CVI, CMT, or CC flow density.

Relationship between BUN/Cr and Prognosis of HF Across the Full Spectrum of Ejection Fraction.

In patients with heart failure (HF), due to the relative deficiency of blood volume, neurohormone system activation leads to renal vasoconstriction, which affects the content of blood urea nitrogen (BUN) and creatinine (Cr) in the body, while BUN and Cr are easily affected by other factors. Therefore, BUN/Cr can be used as another marker for the prognosis of HF. Explore the prognosis of adverse outcome of HF in the high BUN/Cr group compared with the low BUN/Cr group across the full spectrum of ejection fraction. From 2014 to 2016, symptomatic hospitalized HF patients were recruited and followed up to observe adverse cardiovascular outcomes. Logistic analysis and COX analysis were performed to determine significance. p-values <0.05 were considered statistically significant. In the univariate logistic regression analysis, the high BUN/Cr group had a higher risk of adverse outcome in heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Multivariate logistic regression analysis showed that the risk of cardiac death in the HFrEF group was higher than that in the low BUN/Cr group, while the risk of all-cause death was significant only in 3 months (p<0.05) (Central Illustration). The risk of all-cause death in the high BUN/Cr in the HFpEF group was significantly higher than that in the low BUN/Cr group at two years. The high BUN/Cr group is related to the risk of poor prognosis of HFpEF, and is not lower than the predictive value of left ventricular ejection fraction (LVEF).

Arterial stiffness and its associations with left ventricular diastolic function according to heart failure types

BackgroundLittle is known about the characteristics of arterial stiffness in heart failure (HF). This study was performed to compare the degree of arterial stiffness and its association with left ventricular (LV) diastolic function among three groups: control subjects, patients with HF with reduced ejection fraction (HFrEF), and patients with HF with preserved ejection fraction (HFpEF).MethodsA total of 83 patients with HFrEF, 68 patients with HFpEF, and 84 control subjects were analyzed. All HF patients had a history of hospitalization for HF treatment. Brachial-ankle pulse wave velocity (baPWV) measurement and transthoracic echocardiography were performed at the same day in a stable condition.ResultsThe baPWV was significantly higher in patients with both HFrEF and HFpEF compared to control subjects (1,661 ± 390, 1,909 ± 466, and 1,477 ± 296 cm/sec, respectively; P < 0.05 for each). After adjustment of age, baPWV values were similar between patients with HFrEF and HFpEF (P = 0.948). In the multiple linear regression analysis, baPWV was significantly associated with both septal e′ velocity (β = –0.360, P = 0.001) and E/e′ (β = 0.344, P = 0.001). However, baPWV was not associated with either of the diastolic indices in HFrEF group. The baPWV was associated only with septal e′ velocity (β = –0.429, P = 0.002) but not with E/e′ in the HFpEF group in the same multivariable analysis.ConclusionsAlthough arterial stiffness was increased, its association with LV diastolic function was attenuated in HF patients compared to control subjects. The degree of arterial stiffening was similar between HFrEF and HFpEF.