Factor In Heart Failure Research Articles

Impact of global longitudinal strain and anemia for predicting cardiovascular mortality in patients hospitalized for acute heart failure with atrial fibrillation

Abstract Background Iron deficiency is a prognostic factor in heart failure (HF) with reduced ejection fraction (EF). In patients with atrial fibrillation (AF) and HF, left ventricular EF (LVEF) measurements are imprecise due to irregular tachycardia, but it is unclear whether global longitudinal strain (GLS) and anemia assessment are prognostic. Purpose We examined whether GLS and anemia predict cardiovascular death (CD) in patients with acute HF complicated by AF. Methods We retrospectively enrolled patients aged 18 years or older with acute HF complicated by AF who were consecutively admitted to our hospital from January 2014 to December 2018. Exclusion criteria were acute coronary syndromes, no transthoracic echocardiogram performed within 30 days before or after admission, and missing data. All patients were followed up from admission to CD (due to myocardial infarction, HF, stroke or sudden death), or were censored at the date of last contact or 3 years. Anemia was defined as hemoglobin < 12 g/dL in females and hemoglobin < 13 g/dL in males. Patients were divided into four groups according to median GLS and anemia status. Results A total of 320 patients (mean age 79 ± 12 years, 163 females) were included in the analysis. The median duration of AF was 1.2 years; 11% (36/320) had paroxysmal AF. The median brain natriuretic peptide value was 623 pg/ml, and 52% of the patients (165/320) were in New York Heart Association functional class 4. During a median follow-up of 528 days, 24% (77/320) patients were observed with CDs: 2 myocardial infarctions, 51 HF-related deaths, 6 strokes, and 18 sudden cardiac deaths. At the 3-year follow-up, the survival rate by the Kaplan-Meier curve was 89% (95% confidence interval (CI) 76%-95%) in the no anemia group with high GLS (< -10%) and 40% (95% CI 25%-54%) in the anemia group with low GLS (≥ -10%) (p < 0.001, log-rank test). In multivariate Cox regression analysis, GLS (adjusted hazard ratio (aHR) 1.06, 95% CI 1.01-1.14, p = 0.017) and hemoglobin (aHR 0.85, 95% CI 0.76-0.96, p = 0.009) were independent factors for CD, with a significantly increased risk in the anemia group with low GLS compared to the no anemia group with high GLS (aHR 4.11, 95% CI 1.59-10.6, p = 0.004). The results were consistent with no interaction by gender or LVEF 50%. Conclusions Anemic patients with low GLS with AF and HF may have poor prognosis. Prospective studies are needed to determine whether iron supplementation improves prognosis in such patients.

The prognostic impact of renal dysfunction and anemia in japanese heart failure patients stratified by left ventricular ejection fraction

Abstract Background Renal dysfunction and anemia have been reported to be important prognostic factors in heart failure (HF) patients, but the differences in their effects stratified by left ventricular ejection fraction (LVEF) are not clear. Therefore, we investigated the prognostic impact of renal dysfunction and anemia in Japanese HF patients stratified by LVEF. Methods We combined two registry studies of acute HF patients in Japan and examined major events and associated factors during 2-year observation period. The primary endpoint was defined as all-cause mortality or HF hospitalization. Renal dysfunction was defined as eGFR <60 mL/min/1.73 m2, and anemia was defined as hemoglobin <13 g/dl in men and 12 g/dl in women. Two groups were also analyzed by LVEF (LVEF >50% and LVEF <49%). Results A total of 2142 patients were enrolled and analyzed. The mean observation period was 623±244 days. Mean age was 78.7 years. Forty-nine percent were male. Coronary artery disease and atrial fibrillation were present in 31% and 44% of patients, respectively. Medications included beta-blockers in 61% of patients and RAS inhibitors in 53%. Renal dysfunction was present in 1676 patients (74%) and anemia in 1523 patients (67%). Combination of both was observed in 1190 patients (53%). The primary endpoint was observed in 1015 patients, with 563 deaths and 737 HF hospitalizations. Multivariate analysis in a Cox proportional hazards model showed that renal dysfunction alone (HR: 1.39, 95%CI:1.06-1.81, p=0.02) and combination of renal dysfunction and anemia (HR 1.72, 95%CI:1.34-2.21, p<0.01) were independent prognostic factors in all patients. In patients with LVEF <49%, renal dysfunction alone (HR: 1.50, 95%CI:1.04-2.16, p=0.03) and combination of renal dysfunction and anemia (HR: 1.90, 95%CI:1.34-2.68, p<0.01) were predictive factors. On the other hand, in patients with LVEF >50%, only the combination of renal dysfunction and anemia were independent predictors (HR: 1.46, 95%CI:1.01-2.10, p=0.04). Conclusion We identified differences in the prognostic impact of anemia and renal dysfunction by LVEF.

Modulation of the Cardiovascular Risk in Type 1 Diabetic Rats by Endurance Training in Combination with the Prebiotic Xylooligosaccharide.

Diabetic cardiomyopathy is a major etiological factor in heart failure in diabetic patients, characterized by mitochondrial oxidative metabolism dysfunction, myocardial fibrosis, and marked glycogen elevation. The aim of the present study is to evaluate the effect of endurance training and prebiotic xylooligosaccharide (XOS) on the activity of key oxidative enzymes, myocardial collagen, and glycogen distribution as well as some serum biochemical risk markers in streptozotocin-induced type 1 diabetic rats. Male Wistar rats (n = 36) were divided into four diabetic groups (n = 9): sedentary diabetic rats on a normal diet (SDN), trained diabetic rats on a normal diet (TDN), trained diabetic rats on a normal diet with an XOS supplement (TD-XOS), and sedentary diabetic rats with an XOS supplement (SD-XOS). The results show that aerobic training managed to increase the enzyme activity of respiratory Complex I and II and the lactate dehydrogenase in the cardiomyocytes of the diabetic rats. Furthermore, the combination of exercise and XOS significantly decreased the collagen and glycogen content. No significant effects on blood pressure, heart rate or markers of inflammation were detected. These results demonstrate the beneficial effects of exercise, alone or in combination with XOS, on the cardiac mitochondrial enzymology and histopathology of diabetic rats.

Independent risk factors of left ventricular hypertrophy in non-diabetic individuals in Sierra Leone - a cross-sectional study

BackgroundLeft ventricular hypertrophy (LVH) is a critical factor in heart failure and cardiovascular event-related mortality. While the prevalence of LVH in diabetic patients is well-documented, its occurrence and risk factors in non-diabetic populations remain largely unexplored. This study addresses this issue by investigating the independent risk factors of LVH in non-diabetic individuals.MethodsThis cross-sectional study, conducted meticulously, utilized data from a robust and comprehensive source, DATADRYAD, in the Sierra Leone database, collected between October 2019 and October 2021, including LVH and various variables. All variables were described and screened using univariate analysis, Spearman correlation, and principal component analysis (PCA). The lipid profile, including total cholesterols (TC), triglycerides (TG), high-density lipoprotein (HDL-C), non-high-density lipoprotein (Non-HDL-C), and low-density lipoprotein cholesterol (LDL-C), TC/HDL-C ratio, TG/HDL-C ratio, Non-HDL-C /HDL-C ratio and LDL-C/HDL-C ratio, which quartiles were treated as categorical variables, with the lowest quartile serving as the reference category. Three adjusted models were constructed to mitigate the influence of other variables. To ensure the robustness of the model, receiver operating characteristic (ROC) curves were used to calculate the cutoff values by analyzing the ROC curves. A sensitivity analysis was performed to validate the findings further.ResultsThe dataset encompasses information from 2092 individuals. After adjusting for potential factors that could influence the results, we found that TC (OR = 2.773, 95%CI: 1.805–4.26), Non-HDL-C (OR = 2.74, 95%CI: 1.7723–4.236), TC/HDL-C ratio (OR = 2.237, 95%CI: 1.445–3.463), Non-HDL-C/HDL-C ratio (OR = 2.357, 95%CI: 1.548–3.588), TG/HDL-C ratio (OR = 1.513, 95%CI: 1.02–2.245) acts as independent risk factors of LVH. ROC curve analysis revealed the predictive ability of blood lipids for LVH, with Non-HDL-C exhibiting area under the curve (AUC = 0.6109), followed by TC (AUC = 0.6084).ConclusionsTC, non-HDL-C, TC/HDL-C ratio, Non-HDL-C/HDL-C ratio, and TG/HDL-C ratio were independent risk factors of LVH in non-diabetic people. Non-HDL-C and TC were found to be essential indicators for predicting the prevalence of LVH.

Identification of alternative splicing regulatory patterns and characteristic splicing factors in heart failure using RNA-seq data and machine learning

Heart failure (HF) represents the advanced stage of several cardiovascular disorders. This study aimed to build an alternative splicing regulatory network and identify potential splicing factors involved in HF utilizing RNA-seq data and machine learning algorithms. We performed bioinformatics analysis on RNA-seq datasets containing samples from HF patients and normal individuals to obtain gene expression matrices and identify differently regulated alternative splicing events in HF. By calculating percent spliced-in (PSI) value, we identified 4055 abnormal alternative splicing events of 3142 genes in HF. These genes were significantly enriched in PPAR signaling, regulation of actin cytoskeleton, and muscle contraction. Interestingly, based on abnormal alternative splicing events, two distinct clusters of HF patients with distinct molecular mechanisms and pathways were identified using unsupervised clustering. Additionally, we built a regulatory network consisting of heart failure-related alternative splicing and splicing factors. Subsequently, we identify 203 HF specific pairs between splicing factors and alternative splicing events. Four splicing factors (RBM5, ZRANB2, HnRNPF, and HnRNPA0) were found using LASSO and SVM-RFE algorithms, their expression patterns were confirmed in two other microarray datasets. Our study clarifies involvement of splicing factors and alternative splicing events in HF by thoroughly analyzing RNA-seq data with machine learning methods. The findings may advance our understanding of the regulatory systems underlying biological processes associated with heart failure by providing candidates for further investigation and markers for diagnostic and therapeutic purposes.

Recurrence of left ventricular systolic dysfunction and its risk factors in heart failure with improved ejection fraction patients receiving guideline-directed medical therapy: A trajectory analysis based on echocardiography

BackgroundDespite the better prognosis of heart failure (HF) with improved ejection fraction (HFimpEF), remnant cardiovascular risks, including cardiovascular death, rehospitalization, and future deterioration of left ventricular (LV) systolic function, remain in HFimpEF. However, for HFimpEF patients, especially for those receiving guideline-directed medical therapy (GDMT), the recurrent LV systolic dysfunction and its risk factors is still unclear. MethodsA total of 1098 HF patients under HF follow-up management system were initially screened. Echocardiography was re-evaluated at 3-, 6-, and 12-month follow-up. After exclusion, a total of 203 HFimpEF patients on GDMT were enrolled in our final analysis. Cox regression analysis was conducted to select risk factors. ResultsDuring the 1-year follow-up, a total of 28 (13.8%) patients had recurrent LV systolic dysfunction. The trajectory analysis of echocardiographic parameters illustrated that persistent decline of left ventricular ejection fraction (LVEF) and worsening LV remodeling was observed in patients with recurrent LV systolic dysfunction. Multivariable Cox regression analysis identified that ischemic cardiomyopathy, atrial fibrillation, higher left ventricular end-diastolic diameter index (LVEDDI), elevated serum potassium, and a lack of sodium-glucose co-transporter-2 inhibitors (SGLT2i) treatment were confirmed as independent risk factors for recurrent LV systolic dysfunction. Recurrent LV systolic dysfunction was associated with higher rehospitalization rate. ConclusionIn our longitudinal cohort study, almost 14% HFimpEF receiving GDMT suffered recurrent LV systolic dysfunction. Ischemic cardiomyopathy, atrial fibrillation, higher LVEDDI, higher serum potassium, and a lack of SGLT2i therapy were tightly associated with recurrence of LV systolic dysfunction. Relapse of LV systolic dysfunction correlated with poor prognosis.

Risk Factors and Preventive Measures for Cardiovascular Diseases.

Background: Cardiovascular diseases are the most frequent cause of death worldwide. The aim of this study was to identify and demonstrate correlations between mortality data and etiological factors in EU countries. The relationships presented could thus provide a better understanding of etiological factors and possible points for interventions to prevent cardiovascular diseases. The focus was on the following diseases: hypertensive heart disease, atrial flutter/atrial fibrillation, myocardial infarction, and ischemic heart disease, as well as heart failure. Methods: The data in this study come from WHO databases. Connections between the mortality rates and the possible influencing factors were analyzed. The significant factors from the correlation analysis were simultaneously evaluated using a stepwise multiple regression analysis. Results: Analysis of hypertensive heart disease in women reveals the following factors to be significant: drug expenses, health expenses on gross domestic product, and smoking. For men, population density, first admission to a drug treatment center, and drug expenses per person emerged as important factors. Admission to drug treatment centers and length of hospitalization were significant factors for atrial fibrillation and flutter. Fine dust pollution was the most important factor in heart failure. The most important influencing factor for myocardial infarction and ischemic heart disease is nitrogen dioxide concentration. For women, the second highest value is health expenses, followed by the number of outpatient contacts per year. For men, outpatient contacts are in second place. Conclusions: Prevention measures must be taken by the government. The extent to which population density has an influence on cardiovascular diseases should be examined in more detail. In order to reduce the number of initial admissions to drug treatment centers, behavioral prevention related to drug use could be improved.

Use of Statins in Heart Failure with Preserved Ejection Fraction: Current Evidence and Perspectives.

Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure (HF) with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties of statins, such as anti-inflammatory, antihypertrophic, antifibrotic, and antioxidant effects, are generally accepted and may be beneficial in HF, especially in HFpEF. Numerous observational clinical trials have consistently shown a beneficial prognostic effect of statins in patients with HFpEF, while the results of two larger trials in patients with HFrEF have been controversial. Such differences may be related to a more pronounced impact of the pleiotropic properties of statins on the pathophysiology of HFpEF and pro-inflammatory comorbidities (arterial hypertension, diabetes mellitus, obesity, chronic kidney disease) that are more common in HFpEF. This review discusses the potential mechanisms of statin action that may be beneficial for patients with HFpEF, as well as clinical trials that have evaluated the statin effects on left ventricular diastolic function and clinical outcomes in patients with HFpEF.

Role of NLRP3 inflammasome in heart failure and traditional Chinese medicine intervention: a review

Heart failure is characterized by high incidence and mortality rates, and the search for effective treatment strategies for heart failure and the improvement of clinical outcomes have always been important research directions. Imbalanced inflammation has been proven to be one of the critical pathological factors in heart failure, positively correlated with adverse events such as impaired cardiac function and myocardial fibrosis. In recent years, studies have confirmed that the activation of the NOD-like receptor thermal protein domain-associated protein 3(NLRP3) inflammasome plays a common regulatory role in the inflammation imbalance induced by various factors in heart failure. Moreover, certain traditional Chinese medicine(TCM) and active components can significantly inhibit the activation of the NLRP3 inflammasome, thereby improving heart failure. This article first overviewed the basic information about the NLRP3 inflammasome, summarized the regulatory mechanisms of the NLRP3 inflammasome in heart failure induced by various factors, introduced recent research progress on TCM and active components that inhibited the NLRP3 inflammasome to improve heart failure, aiming to provide references for innovative drug research in the field of integrated Chinese and western medicine for the prevention and treatment of heart failure.

Health-related quality of life and associated factors in heart failure with reduced ejection fraction patients at University of Gondar Hospital, Ethiopia.

Living with heart failure poses challenges due to its poor prognosis and impact on quality of life, making it crucial to assess how it affects patients for better patient-centered management. This study aimed to assess quality of life and associated factors in heart failure with reduced ejection fraction patients at University of Gondar Comprehensive Specialized Hospital in Ethiopia, 2023. An "institution-based" cross-sectional study was conducted at the University of Gondar Comprehensive Specialised Hospital. The data were collected using an interviewer-administered questionnaire. Health-related quality of life was measured using the Minnesota Living with Heart Failure Questionnaire. Sociodemographic, behavioral, clinical, biochemical, and echocardiographic characteristics were included in the questionnaire. The collected data were entered into EpiData version 4.6 and exported into SPSS version 25 for analysis. Multiple linear regression analysis (p < 0.05) was used to measure the degree of association between quality of life and independent variables. A total of 240 patients with heart failure and reduced ejection fraction participated in the study. The health-related quality of life scores for the physical, emotional, and total were 17.60 ± 10.33, 10.58 ± 6.33 and 46.12 ± 26.06, respectively. Health-related quality of life was significantly associated with age, marital status, occupation, income, heart failure duration, recent hospitalization, New York Heart Association functional class, heart failure etiology, atrial fibrillation comorbidity, systolic blood pressure, heart rate, heart failure medications, severe left ventricular systolic dysfunction, and severe or moderate pulmonary hypertension. This study found that patients with heart failure and reduced ejection fraction had poor health-related quality of life, influenced by identified factors. These findings aid professionals in assessing and identifying interventions that improve these patients' quality of life.

Sacubitril/Valsartan in Heart Failure with Hypertension Patients: Real-World Experiences on Different Ages, Drug Doses, and Renal Functions.

Hypertension is a significant risk factor in heart failure for worldwide patients. More than half of hypertensive patients suffer from heart failure. Recently, sacubitril/valsartan (sac/val) has been approved as an antihypertensive agent in China and Japan. Additionally, it is not approved for treating hypertension in Europe or the USA. To accumulate more real-world experiences to investigate the effectiveness and optimize clinical medication of sac/val in hypertensive patients with heart failure. We retrospectively enrolled adult patients diagnosed with hypertension (HTN) and heart failure (HF) and newly treated with sac/val. The baseline characteristics and clinical outcomes were retrospectively extracted from electronic medical records (EMR) in three centers. The efficacy and safety of sac/val were first analyzed in all enrolled patients. Stratified analyses were conducted in patients with different ages (≥ 65, < 65), maximum tolerated doses (≥ 200mg/days, < 200mg/days), and renal functions (e-GFR ≥ 60 ml/min/1.73 m2, < 60 ml/min/1.73 m2). Overall, 794 patients diagnosed with both HF and HTN were included in our study. During follow-up, significant reductions were found in blood pressure (BP) (SBP 12.8 ± 21.2 mmHg, P < 0.001, DBP 7.1 ± 16.5 mmHg, P < 0.001), and cardiac biomarkers (cardiac troponin 1.78 ± 19.1 ng/mL, P < 0.001, NT-proBNP 1403 ± 6937 pg/mL, P < 0.001) from baseline. In stratification analyses, the lower dosage group earned a higher BP control rate (83.4% vs. 75.6%, P = 0.025) and an overall improvement rate of cardiac indicators (61.3% vs. 48.0%, P = 0.002). The younger patients' group had significantly less cumulative hazard of recurrent cerebral-cardiovascular events than the elder group (log-rank P value < 0.001). Patients with renal dysfunction were observed with more AE incidences. Sac/val could reduce BP and improve cardiac structural and functional parameters in hypertensive patients with HF, even with less than target doses. However, more attention should be paid to older patients and renal dysfunction patients when using sac/val because of additional risks in adverse events.

A novel bioreactor platform to apply dynamic load to neonatal lamb living myocardial slices for the study of the regenerative properties of the heart

Abstract Background The inability of the myocardium to regenerate is a determining factor in heart failure (HF).Platforms that model cardiac disease require to approximate the in vivo environment and related factors.One such factor is mechanical load, and in vitro, application of this has been by static, isometric systems that mimic preload only.Application of both preload and afterload, however, better recapitulates the cardiac cycle.Mechanical load is relevant in neonatal tissue, where the perinatal period sees changes to the haemodynamics, and a loss to the CM's regenerative capacity.MyoLoop is a novel bioreactor that can apply dynamic loading conditions upon living myocardial slices (LMS) by using a 3-element Windkessel model, producing dynamically changing afterload, simulating pressure-volume (P/V) loops.Here we apply physiologically relevant pre- and afterload to neonatal lamb tissue and establish an in vitro method studying the effects of changing load on the regenerative properties of the heart. Hypothesis The aim of this study is to investigate the feasibility of the MyoLoop system to modulate contractility in neonatal LMS, in comparison to LMS under isometric preload. Methods 300 µm-thick LMS were obtained from the left ventricle of neonatal lambs (12-17hrs after birth). Mechanical load was applied isometrically by stretching LMS by 117.5% of their slack length, to recapitulate physiological preload. To reproduce dynamic afterload, LMS were placed in the MyoLoop and stretched at physiological preload (117.5%) but exposed to a dynamic physiological afterload, achieved by shortening of a linear actuator arm attached to the LMS. After 48 hours culture, maximum force produced by the slices under static preload was assessed using a force transducer and compared to the force production and P/V loop measurements recorded from the MyoLoop. Results Isometrically loaded slices at 0hrs demonstrated large force amplitude of 41±5.7mN/mm2(mean± SEM, n=6),compared to a lower range of force at 24 hrs(10.9±5.07mN/mm2; mean±SEM, n=5) and even weaker forces at 48hrs(2.42±0.84mN/mm2; n=8).There was a gradual decrease in time-to-peak (TTP) after 48hrs,from 264±0.01ms (mean±SEM, n=6) to 240±0.03ms (mean±SEM, n=8),with an shortening also seen in the relaxation parameters TT50% and TT90%. In contrast, LMS cultured in MyoLoop demonstrated an increase in force amplitude of 25.2% from 0-48hrs,and an increase in TTP and TT50% and TT90% decay(n=2).Additionally, LMS cultured within the MyoLoop system demonstrated viability at 72hrs, producing P/V loops and maintaining contractility at 12.6% above 0 hrs contraction. Conclusions The dynamic loading of neonatal LMS through the MyoLoop maintained LMS contractility over 48hrs, compared with isometrically loaded LMS. This highlights the importance of modelling both physiological pre-and afterload in vitro. Further work will elucidate the effects of changing dynamic mechanical load on the regenerative properties of the neonatal heart.

Peak VO2 and VE/VCO2 exhibit differential prognostic capacity for predicting cardiac events

Abstract Background Cardiopulmonary exercise testing (CPET) are commonly used to assess the functional capacity of patients with heart failure. While both peak oxygen uptake (VO2) and ventilatory efficiency (VE/CO2) are significant prognostic factors in heart failure, their values may not always be concordant. Methods This retrospective study included 688 patients who underwent both CPET and supine bicycle echocardiography (SBE) simultaneously. The primary endpoint of the study was defined as heart failure hospitalization or cardiac death. The patients were categorized into subgroups based on their VO2 and VE/VCO2 slope values. Results After median follow-up of 89 months, 111 (16.4%) patients developed cardiac events. The mean age and ejection fraction were 58 years and 59%. In multivariate analysis, both VO2 and VE/VCO2 remained powerful predictors of cardiac events after adjusting for age, ejection fraction, baseline or exercise E/e’, and peak TR velocity. Subgroup analysis revealed that Group III (VO2 &amp;gt;20 and VE/VCO2 &amp;gt;30) and IV (VO2 &amp;lt;20 and VE/VCO2 &amp;gt;30) had a significantly higher risk of cardiac events, with hazard ratios of 3.38 (CI 1.36-8.40) and 8.40 (CI 3.86-18.34), respectively, compared to Group I (VO2 &amp;gt;20 and VE/VCO2 &amp;lt;30). Group II (VO2 &amp;lt;20 and VE/VCO2 &amp;lt;30) had a non-significantly increased risk of cardiac events with a hazard ratio of 2.04 (CI 0.80-5.21) compared to Group I (Fig). Conclusion Both VO2 and VE/VCO2 slope were found to be excellent predictors of cardiac events in patients who underwent CPET and SBE. However, there is a slight difference between the two parameters, and poorer ventilatory inefficiency was found to be more associated with a worsened prognosis. The study suggests that the risk stratification using the VE/VCO2 slope and peak VO2 values can provide valuable information for clinicians in managing patients with heart failure.

Abstract 16064: Prognostication of Cardiopulmonary Exercise Testing in Heart Failure With Reduced Ejection Fraction on Optimized Guideline-Directed Medical Therapy

Introduction: Cardiopulmonary exercise testing (CPET) is a valuable tool for predicting outcomes in patients with heart failure. Peak oxygen consumption (VO2) and minute ventilation/carbon dioxide production (VE/VCO2) are important prognostic factors in heart failure with reduced ejection fraction (HFrEF). However, prior studies have not examined the impact of optimization of guideline-directed medical therapy (GDMT) on the utility of CPET in prognostication. Hypothesis: This study aims to investigate the prognostic value of CPET in a cohort of HFrEF patients who are compliant with all four GDMT components: beta-blockers (BB), ace-inhibitors (ACEi)/angiotensin II-receptor-blockers (ARB)/angiotensin-receptor-neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonist (MRA), and sodium-glucose cotransporter-2 (SGLT2). This will be compared to patients with HFrEF who are not fully optimized on GDMT to determine variation in the statistical significance of prognostic factors. Methods: We retrospectively analyzed data from 176 HFrEF patients who underwent CPET for prognostication purposes. The patients were followed for one year after. CPET testing was completed between January 2020 to June 2022. LVEF was evaluated by echocardiography, completed within 3 months of the CPET. From the data, 125 participants had an LVEF less than or equal to 40%. Of those, 71 were compliant with all four GDMT components, while 54 were not. Results: After one year, there were 16 events (MSR, transplant, or death) in the GDMT-optimized group comprised of 71 participants. Peak VO2 was higher in the no-event group and was notably the only statistically significant predictor of adverse event (p =0.0162). Similarly, of the 54 participants on less than four GDMT components, 13 adverse events occurred, and the strongest predictor was again peak VO2 (p=0.0027). In addition, VE/VCO2 slope were lower (p= 0.0234) and circulatory power were higher (p=0.0044) in the no-event group. Conclusions: In patients with HFrEF that are optimized on GDMT, peak VO2 is consistently the most robust and only statistically significant prognostication tool on CPET for MCS, transplantation, or death within one year.

Abstract 15158: Prognostic Impact of Right Ventricular-Pulmonary Arterial Coupling Ratio in Patients Undergoing Transcatheter Aortic Valve Replacement

Introduction: Right ventricular (RV) dysfunction is known as an important prognostic factor in heart failure. As reduced RV systolic reserve, RV contractility no longer increases against afterload, resulting in lower ratios of RV function to pulmonary artery (PA) pressure, known as RV-PA coupling ratios. Hypothesis: The assessment of RV-PA coupling ratios provides prognostic information for patients undergoing transcatheter aortic valve replacement (TAVR). Methods and Results: A total of 540 patients with TAVR (age, 84 ± 6 years; 186 men, 354 women) were included in this study. The RV-PA coupling ratio was calculated by dividing the tricuspid annular plane systolic excursion (TAPSE) by the PA systolic pressure (PASP) using transthoracic echocardiography before TAVR. Based on the median TAPSE/PASP (0.584 mm/mmHg), the patients were divided into two groups. Kaplan-Meier analysis demonstrated a higher incidence of adverse cardiac events (cardiac death and heart failure hospitalization) in the group with a low TAPSE/PASP ratio (log-rank test, P &lt;0.001). In multivariate Cox regression analysis, TAPSE/PASP was identified as an independent prognostic parameter (adjusted hazard ratio, 0.259; P = 0.028), whereas neither TAPSE alone nor PASP alone demonstrated any significant prognostic value. Conclusion: The RV-PA coupling ratio serves as a prognostic predictor for adverse cardiac events in patients undergoing TAVR.

Abstract 12042: Elevated Levels of Bicarbonate Predict Adverse Outcomes in Patients With Chronic Heart Failure

Background: The bicarbonate (HCO3 - ) buffer system plays a crucial role in maintaining acid-base homeostasis, and HCO3 - levels are affected by multiple factors in heart failure. Recently, a sub-analysis of the ADVOR trial for acute heart failure revealed that patients with elevated serum HCO3 - levels experienced beneficial effects of decongestion by acetazolamide. However, the significance of HCO3 - levels in chronic heart failure has not been fully understood. Aim: We sought to clarify whether HCO3 - levels have clinical relevance or prognostic impact in patients with chronic heart failure. Methods and Results: We conducted a prospective study involving hospitalized patients with stage C/D heart failure and measured HCO3 - levels in arterial blood gas samples prior to discharge. We enrolled a total of 718 patients (mean 68.3 years old and 62.1% male), with neutral pH ranging from 7.35 to 7.45, and found that 132 (18.4%) had HCO3 - levels exceeding 26 mmol/L. Patients with HCO3 - &gt; 26 mmol/L were more likely to be male and to use loop diuretics, and had higher serum sodium, as well as lower potassium levels, compared to those with HCO3 - &lt; 26 mmol/L, whereas there were no differences in B-type natriuretic peptide levels or left ventricular ejection fraction between the two groups. In a Kaplan-Meier analysis, patients with HCO3 - &gt; 26 mmol/L had lower event-free survival rates from cardiac deaths and decompensated heart failure as well as the composite of the cardiac events over a median follow-up period of 1540 days ( Figure ). In a multivariable Cox proportional hazard model after adjusting confounding variables, the presence of HCO3 - &gt; 26 mmol/L was independently associated with increased risks of the composite of cardiac events (hazard ratio, 1.64; P &lt; 0.01). Conclusion: Elevated HCO3 - levels may indicate enhanced proximal nephron activation and resistance to loop diuretics, which predicted adverse outcomes in patients with chronic heart failure, even within a normal pH range.

RBM25 binds to and regulates alternative splicing levels of Slc38a9, Csf1, and Coro6 to affect immune and inflammatory processes in H9c2 cells.

Alternative splicing (AS) is a biological process that allows genes to be translated into diverse proteins. However, aberrant AS can predispose cells to aberrations in biological mechanisms. RNA binding proteins (RBPs), closely affiliated with AS, have gained increased attention in recent years. Among these RBPs, RBM25 has been reported to participate in the cardiac pathological mechanism through regulating AS; however, the involvement of RBM25 as a splicing factor in heart failure remains unclarified. RBM25 was overexpressed in H9c2 cells to explore the target genes bound and regulated by RBM25 during heart failure. RNA sequencing (RNA-seq) was used to scrutinize the comprehensive transcriptional level before identifying AS events influenced by RBM25. Further, improved RNA immunoprecipitation sequencing (iRIP-seq) was employed to pinpoint RBM25-binding sites, and RT-qPCR was used to validate specific genes modulated by RBM25. RBM25 was found to upregulate the expression of genes pertinent to the inflammatory response and viral processes, as well as to mediate the AS of genes associated with cellular apoptosis and inflammation. Overlap analysis between RNA-seq and iRIP-seq suggested that RBM25 bound to and manipulated the AS of genes associated with inflammation in H9c2 cells. Moreover, qRT-PCR confirmed Slc38a9, Csf1, and Coro6 as the binding and AS regulatory targets of RBM25. Our research implies that RBM25 plays a contributory role in cardiac inflammatory responses via its ability to bind to and regulate the AS of related genes. This study offers preliminary evidence of the influence of RBM25 on inflammation in H9c2 cells.

Due Diligence of a Diastolic Index as a Prognostic Factor in Heart Failure with Preserved Ejection Fraction.

Of the existing non-invasive diastolic indices, none consider arterial load. This article reveals points of caution for determining the diastolic prognostic index using a novel index of vascular resistance-integrated diastolic function in old, real-world patients with heart failure with preserved ejection fraction (HFpEF) in Japan. This index represents the ratio of left ventricular diastolic elastance (Ed) to arterial elastance (Ea), where Ed/Ea = (E/e')/(0.9 × systolic blood pressure), showing a relative ratio of left atrial filling pressure to left ventricular end-systolic pressure. The role of hemodynamic prognostic factors related to diastolic function, such as Ed/Ea, may differ according to the clinical endpoint, follow-up duration, and sex. In HFpEF patients with heterogenous cardiac structure and function, an assessment using a serial echocardiographic diastolic index in clinical care can provide an accurate prognosis.

MiRNA-103-3p-Hlf regulates apoptosis and autophagy by targeting hepatic leukaemia factor in heart failure.

Cardiomyocyte apoptosis is an important factor leading to the occurrence and development of heart failure (HF), which is associated with high mortality of patients with cardiovascular diseases. This study aims to investigate the underlying mechanisms of HF in terms of expression and regulation patterns using bioinformatics and experimental validation. Two HF datasets were collected: a dataset GSE112056 downloaded from the GEO database (including mRNA and miRNA sequencing data) and another is the laboratory-owned mRNA dataset. Differential mRNAs and miRNAs in the two datasets were screened using the raw Bayesian approach method. Gene Ontology was used to perform functional enrichment analysis of the differential mRNAs and co-expression network analysis of the differential mRNAs, combined with nuclear transcription factors in the differential miRNAs and mRNAs for target gene prediction. A HF cell model was constructed using mouse cardiomyocytes (HL-1), and the role and mechanism of miRNA-103-3p-Hlf (hepatic leukaemia factor) in the process of HF was verified by cell transfection, luciferase reporter gene, WB, and qPCR. We found that Hlf gene expression was decreased in the HF model group and strongly correlated with FYCO1 (FYVE and coiled-coil domain-containing protein 1) gene, a phenomenon enriched in apoptotic autophagy-related pathways. MiR-103-3p expression was up-regulated in the HF model group, and its targeting correlation with Hlf was confirmed by luciferase activity assay. In the HL-1 cell model, miR-103-3p significantly promoted apoptosis and inhibited autophagy in HL-1 cells (all P<0.05), and overexpression of the Hlf gene reversed this phenomenon, inhibiting apoptosis and promoting autophagy in HL-1 cells (all P<0.05). MiR-103-3p affects myocardial cells apoptosis and autophagy by targeting Hlf, playing as a potential therapeutic biomarker for HF progression.

"&lt;i&gt;Primum non nocere&lt;/i&gt; (First, do no harm)". Case report

Diastolic myocardial dysfunction is the most important pathogenetic factor in heart failure and makes a significant contribution to hemodynamic disorders, which leads to a significant deterioration in the quality of life and prognosis of patients. This article presents a case of a patient with hypertrophic cardiomyopathy with paroxysmal atrial fibrillation and repeated pulmonary edema due to impaired diastolic function, a significant increase in mitral regurgitation and pulmonary hypertension. Given the ineffectiveness of antiarrhythmic therapy and the predicted failure of catheter ablation of the arrhythmogenic focus, the patient was scheduled for atrioventricular destruction. However, the strategy was revised to optimize the heart failure therapy, against which the tachysystole paroxysmal atrial fibrillation did not recur over the following time.