Prognosis In Heart Failure Patients Research Articles

HEART FAILURE PATIENTS WITH IMPROVED EJECTION FRACTION: INSIGHTS FROM THE MECKI SCORE DATABASE

Abstract Aims Improvement of left ventricular ejection fraction is a major goal of heart failure (HF) treatment. However, data on clinical characteristics, exercise performance and prognosis in HF patients who improved ejection fraction (HFimpEF) are scarce. The study aimed to determine whether HFimpEF patients have a distinct clinical phenotype, biology and prognosis than HF patients with persistently reduced ejection fraction (pHFrEF). Methods 7948 patients enrolled in the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database were evaluated (median follow–up of 1490 days). We analyzed clinical, laboratory, ECG, echocardiographic, exercise, and survival data from HFimpEF (n=1504) and pHFrEF (n=6017) patients. The primary endpoint of the study was the composite of cardiovascular death, left ventricular assist device implantation, and urgent heart transplantation. Results Main results are shown in Figure 1. HFimpEF patients had lower HF severity: LVEF 44.0[41.0–47.0] vs. 29.7[24.1–34.5]%, BNP 122[65–296] vs. 373[152–888] pg/mL, hemoglobin 13.5[12.2–14.6] vs. 13.7[12.5–14.7] g/dL, renal function by MDRD 72.0[56.7– 89.3] vs. 70.4[54.5–85.3] mL/min, peakVO2 62.2[50.7–74.1] vs. 52.6[41.8–64.3]%pred, VE/VCO2 slope 30.0[26.9–34.4] vs. 32.1[28.0–38.0] in HFimpEF and pHFrEF, respectively (p<0.001 for all). Cardiovascular mortality rates were 26.6 and 46.9 per 1000 person–years for HFimpEF and pHFrEF, respectively (p<0.001). Kaplan–Meier analysis (Fig.2) showed that HFimpEF had better a long–term prognosis compared with pHFrEF patients. After adjustment for variables differentiating HFimpEF from pHFrEF, except echocardiographic parameters, the Kaplan–Meier curves showed the same prognosis. Conclusions HFimpEF represents a peculiar group of HF patients whose clinical, laboratory, ECG, echocardiographic, and exercise characteristics parallel the recovery of systolic function. Nonetheless, these patients remain at risk for adverse outcome.

Role of Vascular Function in the Prognosis of Heart Failure Patients.

Background: Blood vessels have the Windkessel effect and are involved in blood circulation. The breakdown of this mechanism is also involved in the pathogenesis of heart failure (HF); however, the relationship between vascular dysfunction and HF prognosis is not fully understood. Methods: We evaluated 214 patients hospitalized for HF at our institution who underwent a cardio-ankle vascular index (CAVI), which evaluates vascular function, between January 2012 and July 2018. To investigate factors (including CAVI) associated with major adverse cardiac events (MACE) during 1 year after patients with HF were discharged, we evaluated clinical profiles, blood tests, chest X-P, 12-lead electrocardiography, and transthoracic echocardiographic findings. MACE was defined as cardiovascular death or readmission for HF. Results: The severity of HF between the MACE and non-MACE was not significantly different. Previous HF and chronic kidney disease were significantly more common in the MACE group. CAVI and % mean atrial pressure in the MACE group were statistically higher than those in the non-MACE group. The cardiac shadow as shown by chest X-P and left ventricular size in the MACE group were significantly bigger, and HF preserved ejection fraction (EF) (EF > 50%) was significantly more common in the MACE group. In multivariate analysis, CAVI was an independent predictive factor for the occurrence of MACE (model 1; hazard ratio (HR): 1.33, 95% confidence interval (CI): 1.05-1.68, p = 0.018; model 2; HR: 1.31, 95% CI: 1.07-1.60, p = 0.009). Conclusions: Because high CAVI is associated with poor prognosis of HF, these patients require more careful treatment.

MiR-200b-3p relieved inflammation in patients with heart failure by regulating ZEB1 expression

BackgroundMicroRNA-200b-3p (miR-200b-3p) plays a pivotal role in inflammatory responses and is implicated in various inflammatory disorders. In this study, we aim to explore the role of miR-200b-3p in the inflammatory response in heart failure (HF).MethodsPatients diagnosed with heart failure and age-matched healthy controls were studied. Peripheral blood samples from participants were collected for RNA-seq analysis to explore the expression profile of miR-200b-3p. The predictive value of miR-200b-3p and ZEB1 in the prognosis of heart failure was evaluated by analyzing the receiver operating characteristic (ROC) curve. Bioinformatics analysis and double luciferase reporter gene analysis were used to confirm the interaction between miR-200b-3p and ZEB1. Real-time quantitative polymerase chain reaction (QRT-PCR) was used to detect the expression levels of miR-200b-3p and ZEB1 in cardiopulmonary bypass. Additionally, the effects of miR-200b-3p on myocardial cell line (H9c2) injury were evaluated by enzyme-linked immunosorbent assay (ELISA).ResultsIn the extracardiac circulation of HF patients, miR-200b-3p expression was significantly reduced, while ZEB1 levels were notably elevated. Analysis of the ROC curve revealed that miR-200b-3p and ZEB1 have predictive value in the prognosis of HF patients. The double luciferase reporter experiment demonstrated that miR-200b-3p binds to ZEB1 and inhibits its expression. Overexpression of miR-200b-3p demonstrated a remarkable ability to alleviate inflammation and inhibit the damage to myocardial cells in vivo.ConclusionMiR-200b-3p can target and inhibit ZEB1, reducing the inflammatory reaction of myocardial cells. The miR-200b-3p/ZEB1 network may be helpful in preventing and treating HF.

Prognostic Value of Body Surface Area-Adjusted Oxygen Uptake Efficiency Slope in Heart Failure Patients.

COVID-19 has been associated with a higher risk of developing heart failure (HF). Among the parameters derived from cardiopulmonary exercise testing (CPET), oxygen uptake efficiency slope (OUES) has become one of the most important parameters for predicting the prognosis of HF patients. However, the clinical utilization of OUES is limited owing to its variation with patient height and weight. This study aimed to evaluate the prognostic value of body surface area-adjusted OUES (OUES/BSA) in adults with HF. Thirty-six HF patients (mean age, 57 ± 12 years; 30 men) undergoing CPET between July 2019 and May 2020 who were followed up for 12 months were enrolled. The endpoints were major cardiovascular (CV) events, including hospitalization due to acute decompensated HF, left ventricular assist device implantation, heart transplantation, and cardiovascular-related death. We analyzed the correlations between clinical/CPET variables and major CV events. Among the analyzed CPET variables, OUES/BSA had better correlation with maximal oxygen uptake (VO2max) than other variables. In univariate Cox proportional analysis, OUES/BSA and peak VO2 were both significant independent prognostic factors. The cutoff value of OUES/BSA was 595 ml/min/m2 with an area under the curve of 0.929. The patients with OUES/BSA < 595 ml/min/m2 had a lower CV event-free survival rate at 12 months of follow-up compared with the other group (33.3% and 100%, respectively; log-rank test, p < 0.001). BSA-adjusted OUES is an effective independent predictor for prognosis in HF patients and can be an alternative to peak VO2 for risk stratification in HF patients, regardless of exercise intensity. However, further large-scale studies are required to validate our findings.

The COVID-19 Pandemic Was Associated with a Change in Therapeutic Management and Mortality in Heart Failure Patients.

Background: Heart failure (HF)-related mortality has been exacerbated by the COVID-19 pandemic; however, it is unclear how healthcare reassessment has contributed to the excess mortality versus SARS-CoV-2 infection itself. We aimed to assess how the pandemic affected the therapeutic management and prognosis of HF patients. Methods: We retrospectively reviewed the healthcare utilization databases of the Lombardy region (Italy) to identify all newly-diagnosed HF patients from January 2018 to December 2021. Outcomes were the utilization of HF therapies (Sacubitril/Valsartan; cardiac resynchronization therapy [CRT] and/or implantable cardioverter-defibrillator [ICD]; mechanical circulatory support [MCS]; heart transplantation [HTX]) and mortality. Cox regression models were fitted to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with the pandemic. Results: 36,130 and 17,263 patients were identified in the pre-pandemic and pandemic eras, respectively. The pandemic reduced Sacubitril/Valsartan utilization (HR = 0.77, 95% CI: 0.65-0.91) and CRT/ICD implantation (HR = 0.85, 95% CI: 0.78-0.92), but not MCS (HR = 1.11, 95% CI: 0.86-1.43) and HTX (HR = 0.88, 95% CI: 0.70-1.09). An increased mortality risk was observed during the pandemic (HR = 1.19, 95% CI: 1.15-1.23), which was attributable to SARS-CoV-2 infection (HR for non-COVID-19-related mortality = 1.01, 95% CI: 0.97-1.04). Conclusions: The COVID-19 pandemic was associated with a reduction in medical and interventional therapies for HF and an increase in mortality for HF patients.

Implication of geriatric nutritional risk index on treatment response and long-term prognosis in patients with cardiac resynchronization therapy

PurposeGeriatric Nutritional Risk Index (GNRI) is a simple tool for assessing the nutritional status of the aging population. This study aims to explore the clinical implication of GNRI on treatment response and long-term clinical outcomes in heart failure (HF) patients receiving cardiac resynchronization therapy (CRT). MethodsPatients who underwent CRT implantation or upgrade at our hospital were retrospectively included. The association of GNRI and its tertiles with the echocardiographic response, all-cause mortality or heart transplantation, and the first hospitalization due to HF were investigated. ResultsTotally, 647 patients were enrolled, with a median age of 60 [Interquartile Range (IQR): 52–67] years and mean score of GNRI at 107.9 ± 23.7. Super-response rates increased significantly among the GNRI T1, T2, and T3 groups (25.1%, 29.8% vs. 41.1%, P = 0.002). Patients with higher GNRI were more likely to have better LVEF improvement after multiple adjustments (OR = 1.13, 95% CI: 1.04–1.23, P = 0.010). Higher GNRI was independently associated with a lower risk of all-cause mortality or heart implantation (HR = 0.95, 95% CI: 0.93–0.96, P < 0.001) and HF hospitalization (HR = 0.96, 95% CI: 0.95–0.98, P < 0.001). The inclusion of GNRI enhanced the predictability of all-cause mortality based on traditional model, including sex, New York Heart Association functional class, left bundle branch block, QRS reduction, and N-terminal pro-B-type natriuretic peptide level (C statistics improved from 0.785 to 0.813, P = 0.007). ConclusionHigher GNRI was associated with better treatment response and long-term prognosis in HF patients with CRT. Evaluation of nutritional status among CRT population is necessary for individualized choice of potential responders.

Single cell RNA-seq identifies a FOS/JUN-related monocyte signature associated with clinical response of heart failure patients with mesenchymal stem cell therapy.

Heart failure (HF) is a serious global health issue that demands innovative treatment approaches. In this study, we collected samples from 4 HF patients before and after MSC therapy and performed scRNA-seq. After the MSC therapy, the proportion of CD14+ monocytes decreased significantly in both the treatment response and non-response groups, with a more pronounced decrease in the treatment response group. The therapy-response and non-response group were clearly separated in the UMAP plot, while the CD14+ monocytes in the therapy-response group before and after MSC therapy were very similar, but there were significant differences in the non-response group. By further performing NMF analysis, we identified 11 subsets of CD14+ monocytes. More importantly, we identified a therapy-related CD14+ monocyte subpopulation. The predictive model based on CD14+ monocytes constructed by machine learning algorithms showed good performance. Moreover, genes such as FOS were highly enriched in the therapy-related CD14+ monocytes. The SCENIC analysis revealed potential regulatory factors for this treatment-responsive CD14+ monocytes, and FOS/JUN were identified as potential core indicators/regulators. Finally, HF patients were divided into three groups by NMF analysis, and the therapy-responsive CD14+ monocyte characteristics were differentially activated among the three groups. Together, this study identifies treatment-responsive CD14+ monocytes as a crucial biomarker for assessing the suitability of MSC therapy and determining which HF patients could benefit from it. This provides new clues for further investigating the therapeutic mechanisms of MSC therapy, offering beneficial insights for personalized treatment and improving prognosis in HF patients.

Systematic review and meta-analysis of the screening and identification of key genes in gastric cancer using DNA microarray database

OBJECTIVE: A comprehensive evaluation of studies using DNA microarray datasets for screening and identifying key genes in gastric cancer is the goal of this systematic review and meta-analysis. To better understand the molecular environment associated with stomach cancer, this study aims to provide a quantitative synthesis of findings. PURPOSE: Using DNA microarray databases in a systematic manner, this study aims to analyze gastric cancer (GC) screening and gene identification efforts. Through a literature review spanning 2002–2022, this research aims to identify key genes associated with GC and develop strategies for screening and prognosis based on these findings. METHODS: The following databases were searched extensively: Science Direct, NCKI, Web of Science, Springer, and PubMed. Fifteen studies met the inclusion and exclusion criteria; 10,134 tissues served as controls and 11,724 as GCs. The levels of critical genes, including COL1A1, COL1A2, THBS2, SPP1, SPARC, COL6A3, and COL3A1, were compared in normal and GC tissues. Rev Man 5.3 was used to do the meta-analysis. While applying models with fixed or random effects, 95% confidence intervals and weighted mean differences were computed. RESULTS According to the meta-analysis, GC tissues exhibited substantially elevated levels of important genes when contrasted with the control group. In particular, there were statistically significant increases in COL1A1 (MD = 2.43, 95% CI: 1.84–3.02), COL1A2 (MD = 2.75, 95% CI: 1.09–4.41), THBS2 (MD = 2.54, 95% CI: 1.66–3.41), SPP1 (MD = 3.64, 95% CI: 3.40–3.88), SPARC (MD = 1.57, 95% CI: 0.37–2.77), COL6A3 (MD = 2.31, 95% CI: 2.02–2.60), and COL3A1 (MD = 2.21, 95% CI: 1.59–2.82). CONCLUSIONS: The COL1A1, THBS2, SPP1, COL6A3, and COL3A1 genes were shown to have potential use in germ cell cancer screening and prognosis, according to this research. Clinical assessment and prognosis of heart failure patients may be theoretically supported by the results of this study.

Impact of nurse-led interprofessional work in older patients with heart failure and multimorbidity: A retrospective cohort study

BackgroundThe number of patients with multimorbidity has increased due to the aging of the global population. Although the World Health Organization has indicated that multimorbidity will be a major medical problem in the future, the appropriate interventions for patients with multimorbidity are currently unknown. This study aimed to investigate whether nurse-led interprofessional work is associated with improved prognosis in heart failure patients with multimorbidity aged ≥65 years who were admitted in an acute care hospital. MethodsPatients who were admitted to the cardiovascular medicine ward of an acute care hospital in Osaka, Japan, and underwent nurse-led interprofessional work from April 1, 2017 to March 31, 2020, and from April 1, 2014 to March 31, 2016, were included in this retrospective cohort study. The patients were matched by age, sex, and New York Heart Association classification. The nurse-led interprofessional work was based on a three-step model that incorporates recommendations from international guidelines for multimorbidity. The primary outcome was all-cause mortality. ResultsThe mean age of the participants was 80 years, and 62 % were men. The nurse-led interprofessional work group showed a significant difference in all-cause mortality compared with the usual care group (hazard ratio, 0.45; 95 % confidence interval [CI], 0.29–0.69; P < 0.001). Compared with the usual care group, the nurse-led interprofessional work group exhibited a 7 % difference in mortality rate at 1-year post-discharge (P < 0.001). ConclusionsNurse-led interprofessional work may reduce the all-cause mortality in older patients with heart failure and multimorbidity.

Effect of short-term cardiac function changes after cardiac resynchronization therapy on long-term prognosis in heart failure patients with and without diabetes.

The relationship between short-term cardiac function changes and long-term outcomes in heart failure (HF) patients undergoing cardiac resynchronization therapy (CRT) remains uncertain, especially when stratified by diabetes status. This study aims to assess the association between short-term cardiac function changes and outcomes such as all-cause mortality and HF hospitalization in patients undergoing CRT, stratified by diabetes status. This is a cohort longitudinal retrospective study. A total of 666 HF patients, treated with CRT between March 2007 and March 2019, were included in this study. Among them, 166 patients (24.9%) were diagnosed with diabetes. Cardiac function was assessed at baseline and again at 6 months, incorporating evaluations of left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left atrial diameter (LAD), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and QRS duration. The QRS duration represents the time required for a stimulus to spread through the ventricles (ventricular depolarization). The primary endpoints of the study were all-cause mortality and HF-related hospitalization. During a median follow-up of 2.51 years, 172 (25.8%) patients died and 197 (29.6%) were hospitalized for HF. Changes in LVEF, LVEDD, and LAD within 6 months had similar effects on adverse outcomes in both diabetic and nondiabetic patients. However, the presence of diabetes significantly modified the association between changes in NT-proBNP and QRS duration and adverse outcomes. Short-term changes in NT-proBNP and QRS duration were positively associated with all-cause mortality and HF hospitalization in patients without diabetes. However, the relationship between short-term changes in NT-proBNP and QRS duration and adverse outcomes was non-linear in diabetic patients. Improvement of cardiac function after CRT implantation can reduce long-term risk of all-cause mortality and HF hospitalization in HF patients. However, the presence of diabetes may affect the association between short-term changes in NT-proBNP and QRS duration and adverse outcomes.

Role of vericiguat in management of patients with heart failure with reduced ejection fraction after worsening episode.

Worsening heart failure (HF) is a vulnerable period in which the patient has a markedly high risk of death or HF hospitalization (up to 10% and 30%, respectively, within the first weeks after episode). The prognosis of HF patients can be improved through a comprehensive approach that considers the different neurohormonal systems, with the early introduction and optimization of the quadruple therapy with sacubitril-valsartan, beta-blockers, mineralocorticoid receptor antagonists, and inhibitors. Despite that, there is a residual risk that is not targeted with these therapies. Currently, it is recognized that the cyclic guanosine monophosphate deficiency has a negative direct impact on the pathogenesis of HF, and vericiguat, an oral stimulator of soluble guanylate cyclase, can restore this pathway. The effect of vericiguat has been explored in the VICTORIA study, the largest chronic HF clinical trial that has mainly focused on patients with recent worsening HF, evidencing a significant 10% risk reduction of the primary composite endpoint of cardiovascular death or HF hospitalization (number needed to treat 24), after adding vericiguat to standard therapy. This benefit was independent of background HF therapy. Therefore, optimization of treatment should be performed as earlier as possible, particularly within vulnerable periods, considering also the use of vericiguat.

Usefulness of a scoring evaluation for practical introduction of the guideline-directed medical therapy (GDMT) in heart failure patients

Abstract Backgrounds Guideline-directed medical therapy (GDMT) has been recommended for heart failure (HF) with reduced EF (HFrEF) based on the accumulating clinical evidence. However, it is difficult to introduce all the trial-proven drugs to every patient in a real-world setting. Purpose We developed a simple GDMT score consisting of RAS (renin-angiotensin system) inhibitor, beta-blocker, MRA (mineralocorticoid receptor antagonist), and SGLT2 (sodium-glucose cotransporter 2) inhibitor, which is a modification of the previously proposed GDMT score, and investigated whether this score is related to the prognosis of HF patients and how this score can be used in daily clinical practice. Methods We retrospectively analyzed 1782 consecutive patients with ADHF at our hospital from April 2015 to March 2022. One thousand fifty-four patients with HFrEF and HFmrEF (HF with mildly reduced EF) were extracted, excluding 61 patients who died in hospital, 53 patients with dialysis, and 614 patients with HFpEF. First, we calculated the simple GDMT score in these patients. Then, the association with clinical outcomes (composite outcome: HF readmission or all-cause death, HF readmission, all-cause death) was examined. Results The cut-off value for the association between the composite outcome and the simple GDMT score was 4 points (AUC = 0.607, 95%CI = 0.57-0.64) using the receiver operating characteristic (ROC) curve. Multivariate analysis showed that high simple GDMT score (more than 5 points) was strongly associated with the composite outcome (HR = 0.606, 95%CI = 0.403-0.912, p = 0.016), HF readmission (HR = 0.207, 95%CI = 0.077-0.558, p = 0.001) and all-cause death (HR = 0.250, 95%CI = 0.093-0.669, p = 0.005). The Kaplan-Meier curve showed that events were less frequent in the group with a high simple GDMT score group. Furthermore, a simple GDMT score of 5 or higher was associated with a good prognosis in both subgroups. Conclusions The designed GDMT score was associated with prognosis in HFrEF and HFmrEF patients. Even if for some reason all four drugs cannot be introduced, a regimen with the simple GDMT score ≧ 5 may improve the prognosis in HF patients.

Continuous measurement of percutaneous oxygen saturation during 6-minute walk test is useful for stratification of the prognostic risk in patients with heart failure

Abstract Background The 6-minute walk test (6MWT) is an established test to assess the functional exercise performance and the 6-minute walk distance is strongly correlated with the functional capacity and the prognosis in patients with heart failure (HF). Also, the hypoxia during 6MWT is reported to be associated with severity of pulmonary diseases. However, no study has reported the clinical implication of sequential changes in percutaneous oxygen saturation (SpO2) during 6MWT was not investigated in HF patients. Purpose To prospectively clarify the association between sequential changes in SpO2 during 6MWT and prognosis in patients with HF. Methods In this prospective observational study, 50 patients admitted to our hospital with acute heart failure were enrolled. The 6MWT was performed at the time before discharge, after hemodynamic stability was confirmed. The average of SpO2 was calculated from data obtained at rest (3 minutes just before the test) and during 6MWT by employing the wearable pulse-oximeter which are designed to record and store the SpO2 value every seconds. Alternations in SpO2 (Δ SpO2) were analyzed by subtracting the average during 6MWT from that at rest. Patients were followed 1 year for composite outcome of heart failure-hospitalization and death). Results The mean age of participants was 78.8 years, and 23 (46%) were female. The mean EF was 46.1% and the number of the patients with EF≧50, 50&amp;gt;EF&amp;gt;40, 40≧EF were 22, 6, and 22, respectively. Mean NT-proBNP was 4374.5pg/ml. The mean walk distance was 250 ± 112m and the mean Δ SpO2 was 2.88 ± 4.3%. All cases were classified by walk distance and Δ SpO2; long- (&amp;gt;220m) vs. short-distance group (≦220m) and low- (&amp;lt;3.5%) vs. high-ΔSpO2 group (≧3.5%). There were no significant differences in cardiac parameters and respiratory function between long- and short-distance group as well as between low- and high-ΔSpO2 group. Kaplan-Meier analysis revealed that cardiac event rate was higher in the short-distance group than in the long-distance group (HR = 2.89, CI = 1.24-6.71, p = 0.014), and higher in the high-Δ SpO2 group than in the low-ΔSpO2 group (HR = 3.49, CI = 1.55-7.83, p = 0.002) (Figure 1A and 1B). When these classifications were combined, the patients with short-distance and low-ΔSpO2 showed remarkably high event rate of 91% (Figure 2). Conclusions This study showed that, compared to walk distance, ΔSpO2 was more predictive of prognosis of heart failure patients, and that the combination of ΔSpO2 and walk distance may identify the highest risk group. The elucidation of the usefulness of continuous SpO2monitoring during 6MWT as the marker for severity of heart failure and treatment effect warrants further investigation.Figure1Figure 2

Redox state of human serum albumin predicts 1-year prognosis in patients with heart failure: a single center prospective cohort study

Abstract Background As chronic inflammation would be a fundamental underlying mechanism in the pathogenesis in patients with heart failure (HF), oxidative stress has a possibility to closely associate with the prognosis. However, little is known about the association of oxidative stress with the prognosis in HF patients. Purpose In this study, we assessed the association of the fraction of human mercapto-albumin [f(HMA)], an index of the redox state of human serum albumin, with prognosis in patients hospitalized for HF with the aim to find the possible biomarker available on the prediction for adverse events in HF patients. Methods A single-center prospective cohort study was conducted. In the cohort, 290 ambulate patients admitted for acute HF or exacerbation of chronic HF were registered. Of these, 182 who were successfully followed-up patients were analyzed (median age: 79 years, men: 68.3%. median follow-up: 365 days). The primary outcome was a composite of HF rehospitalization and all-cause mortality. The high-performance liquid chromatography postcolumn bromocresol green method was used to part human serum albumin into human nonmercaptalbumin (oxidized form) and human mercaptalbumin (HMA, reduced form). We divided patients into two groups by median f(HMA) level. Kaplan-Meier Curve and the Cox proportional hazards model was used to examine the significance of f(HMA) as a prognostic indicator of HF patients, adjusting for potential confounding factors. Results Median level of f(HMA) was 57.2%. During 50,965 person-days of follow-up, 52 patients (28.6%) were re-hospitalized due to HF exacerbation, and 25 patients (13.7%) died due to cardiac or noncardiac reasons. Log-rank analysis showed that a high f(HMA) group reduced adverse events (Fig. 1). In the Cox proportional hazards model, a high level of f(HMA) was associated with a reduced risk of composite outcomes (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.39-1.07). In the subgroup analysis, high f(HMA) showed an event-reducing effect in HF rehospitalizations (HR 0.53; 95% CI 0.30-0.94), but not in all-cause mortality (HR 0.61; 95%CI 0.27-1.38). Conclusion The findings of this study support that f(HMA) could be a novel prognostic biomarker for HF patients.Fig. 1

The beneficial effects of adherence to outpatient telecare intervention on clinical outcomes after an episode of acute heart failure: insights from the prospective randomised controlled AMULET trial

Abstract Background The prevention of hospitalisations and deaths is a major therapeutic aim in patients with heart failure (HF). In our previously published prospective randomised controlled trial, we demonstrated that an outpatient intervention comprising nurse-led non-invasive assessments, telemedicine support and remote cardiologist decision-making (AMULET telecare) reduced the risk of HF hospitalisation or cardiovascular death by 31% during the 12-month follow-up in HF patients after an episode of acute HF. Purpose To present the results of the prespecified per-protocol analysis of the AMULET trial that reveal the impact of AMULET telecare adherence on the prognosis of patients. Methods Patients with HF and left ventricular ejection fraction (LVEF) ≤49% and who experienced an episode of acute HF in the past 6 months were randomly assigned to receive either AMULET telecare (n=298) or standard care (n=305). Those who completed the predefined schedule of AMULET telecare (n=190) and all standard care patients were included in the per-protocol population. Results In this per-protocol analysis, when compared to standard care, the implementation of AMULET telecare reduced the risk of the primary outcome, a composite of unplanned HF hospitalisation or cardiovascular death (by 51%), and the following secondary outcomes: first unplanned HF hospitalisation, first unplanned cardiovascular hospitalisation, first all-cause unplanned hospitalisation, total unplanned HF hospitalisations and the number of days lost due to HF hospitalisations or death. There was no statistically significant difference in cardiovascular mortality, mortality due to HF and overall mortality between the study groups (Table). Conclusions Adherence to AMULET telecare enhances the positive effects of this intervention on the prognosis of HF patients with an LVEF≤49% after an episode of acute HF.

Abstract 16404: Symptom Perception Predicts Short-Term Prognosis in Patients With Heart Failure

Background: The type and severity of symptoms perceived by heart failure (HF) patients may be a useful prognostic predictor, but the impact of symptom perception on clinical events among HF patients has not been fully tested. Aim: To assess the symptoms perceived by HF patients using the Heart Failure Somatic Perception Scale (HFSPS) and to test whether symptom perception predicts short-term prognosis in HF patients. Methods: Using the prospective observational design, we collected data from 315 outpatients with HF (mean age 73 ± 13 years, 72% male). Data included sample characteristics, BMI, BNP, comorbidities, ADL, depressive symptoms, symptom perception assessed by HFSPS at baseline, and clinical composite outcomes (readmission, all-cause death, and emergency department visits) at three months. HFSPS is a scale that assesses the degree to which 18 physical symptoms perceived by HF patients are bothersome in daily life. The study subjects were classified into low, medium, and high HFSPS total score groups. The impact of HFSPS on clinical composite outcomes was analyzed using the Cox proportional hazard model, considering the influence of covariates. Results: The mean overall HFSPS score was 11.7 ± 12.3 points, with 87 patients (28%) in the low HFSPS group, 151 (48%) in the medium group, and 77 (24%) in the high group. Symptoms reported were nocturia (74.6%), shortness of breath (58.4%), fatigue (54.6%), malaise (44.5%), and cough (42.9%). Three-month composite event rate was 25.7%, with statistically significant differences between the HFSPS groups (16.1% in the low group, 23.2% in the medium group, and 41.6% in the high group (p=0.001). The results of analysis using the Cox proportional Hazard model using age, gender, BMI, BNP, comorbidities, depression, and ADL as covariates, the high HFSPS group had a significantly higher incidence of clinical composite. The incidence of clinical composite outcomes at three months was significantly higher in the high HFSPS group than in the other groups (HR=2.090 (95% CI=1.067-4.096), p=0.032). Conclusions: Symptom perception, which can be regarded as a patient-reported outcome, is a promising predictor of short-term prognosis in HF patients.

Abstract 11667: Red Cell Indices and Long-Term Prognosis of Heart Failure Patients

Introduction: It has been demonstrated that some properties of red blood cells also play a role in the etiology of cardiovascular diseases and their complications. Hypothesis: We determined to what extent red blood cell indices observed during hospitalization for heart failure (HF) affect the long-term prognosis of these patients. Methods: We followed 3697 patients [mean age 71.4 years (±SD10.1), 59.1% males] hospitalized for decompensated HF between 2010-20. In the multivariate model, we assessed the five-year all-cause mortality risk associated with red cell distribution width (RDW), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and hemoglobin concentration (dichotomized by tertiles). Results: Kaplan-Meier survival curves comparing the tertiles of red cell indices are in Figure. Patients with RDW in the top tertile showed roughly two-fold higher 5-year mortality risk than those in the bottom tertile; increased risk we also observed in the middle tertile of RDW. This association remained significant even after complex adjustments for individual characteristics (age, gender, ejection fraction, HF etiology, history of malignancy, revascularization, hypertension, diabetes, LDL, atrial fibrillation, and glomerular filtration) as well as treatments (furosemide, beta-blockers, RAS blockers, MRA′s, statins). [HRR 1.83 (95% CIs: 1.53-2.18), p&lt;0.0001, 3 rd versus 1 st ; 1.42 (95%CIs: 1.19-1.68), p&lt;0.0001, 2 nd versus 1 st ] Similarly, we observed increased mortality risk in the bottom tertile of MCHC [HRR 1.34 (95%CIs:1.14-1.59), p=0.001, 1 st versus 3 rd ( fully adjusted)] or hemoglobin [HRR 1.37 (95%CIs: 1.15-1.62), p&lt;0.0001]. In contrast, MCV did not show any additive mortality risk. Conclusions: High degree of anisocytosis and low red cell status of hemoglobin represents independent indicators of poor prognosis in heart failure patients, even long-term after an acute manifestation.

Abstract 14276: Using Artificial Intelligence and Natural Language Processing on Electronic Health Records of Heart Failure Patients to Examine the Impact of Estimated Glomerular Filtration Rate Trend on Mortality

Introduction and Hypothesis: Heart failure (HF) often leads to an imbalance between heart and kidney function, with a poor prognosis in HF patients linked to dynamic changes in renal function as well as chronic kidney disease (CKD). This study aimed to determine the incidence of reduced renal function upon HF diagnosis and to explore the potential for dynamic changes in kidney function to predict short- and long-term outcomes in a real-world cohort of HF patients. Methods: Clinical data of patients with a diagnosis of HF (index event) were gathered retrospectively using natural language processing. Patients were classified as having CKD based on their eGFR (&lt;60 mL/min/1.73m2) and a history of CKD and/or dialysis. eGFR trajectories were analyzed using linear mixed effects models. Cox proportional hazard models were used to analyze the relationship between baseline variables and mortality. Joint modeling was employed to assess the relationship between the eGFR trend and mortality. Results: There were 1986 patients in the study population, with a mean (SD) age of 74.8 ± 11.7 years and 58% of males. At the index event, 58% (n = 1156) had CKD, and 17% (n = 339) had HF with preserved ejection fraction (HFpEF). Median follow-up was 3.16 years. After 2 years, 10% (n = 198) of the patients had passed away. The proportion of CKD at index was considerably lower in the 2-year survivors group (55% vs 76%, p &lt; 0.001) in this group. The calculated mean annual eGFR reduction was 4.2 mL/min/1.73m 2 . Age, CVA, diastolic blood pressure, hemoglobin, HDL, potassium, and NT-proBNP levels in blood serum were found to be the primary predictors of mortality in multivariate Cox PH model. Joint modeling revealed that a current eGFR value that was 10 mL/min/1.73m 2 lower between patients corresponded with a higher mortality hazard of 1.22 ± 0.05 (p &lt; 0.001). In addition, a drop in eGFR of 10 mL/min/1.73m 2 over the previous year showed an the elevated mortality hazard of 1.97 ± 0.16 (p &lt; 0.001). Conclusions: We show that the prevalence of CKD is significant in a real-world population of HF patients, and CKD is a standalone predictor of mortality. Current eGFR value and the eGFR slope from the previous year have a potential to be used for individual mortality hazard assessment in the clinical follow-up of HF patients.

Abstract 11590: Body Mass-Corrected Estimated Plasma Volume at Discharge Predicts Mortality of Heart Failure Patients With Non-Normal and Normal Left Ventricular Ejection Fraction

Introduction: Estimated plasma volume(ePV) is a parameter of body fluid volume and an indicator for residual congestion. Even in the era of novel cardioprotective drugs, achieving adequate body fluid volume with heart failure is sometimes challenging. We investigated the prognosis of heart failure patients with a one-time evaluation of ePV at discharge corrected by body mass index (BMI). Since current heart failure treatment algorithms follow different paths with left ventricular ejection fraction (LVEF), we also examined whether these groups have a difference in prognosis prediction. Methods: This is a single-center, prospective observational study. A total of 1427 consecutive heart failure hospitalizations, excluding acute coronary syndromes, were included from January 2018 to June 2022. We evaluated 858 patients, excluding repeat hospitalizations of the same patient, in-hospital deaths, transfers for cardiac surgery and forced discharges, and missing data. A prognosis investigation was conducted for all patients. BMI and ePV (ml, Hakim's formula) was calculated from height, weight, and hematocrit at discharge. Survival analysis was performed with ePV divided by BMI (ePV/BMI). The primary endpoint was all-cause death. Results: Median of 527 days of post-discharge observation, 286 deaths occurred. BMI and ePV at discharge show a positive significant correlation in both normal (≧50%) and non-normal LVEF (&lt;50%) groups. Among the mortality group during follow-up, ePV/BMI at discharge was significantly higher than the non-mortality group. Survival analysis with Kaplan-Meier curve by ePV/BMI three tertiles (Low, Medium, High) in normal (66.8% vs 50.1% vs 44.0%, Logrank P&lt;0.001), non-normal LVEF (72.2% vs 69.3% vs 49.6%, Logrank P&lt;0.001) and overall (70.6% vs 55.5% vs 47.4%, Logrank P&lt;0.001) population had a significantly worse three-year prognosis in the high ePV/BMI group. Multivariable Cox proportional hazard model with covariant univariable predictive factors shows higher ePV/BMI tertile, as well as a continuous variable of ePV/BMI, was predictive factor of death in normal, non-normal LVEF and overall population. Conclusions: Even after therapeutic intervention, ePV/BMI at discharge is a useful predictor of heart failure prognosis.

Abstract 12748: Continuous Measurement of Percutaneous Oxygen Saturation During 6-Minute Walk Test is Useful for Predicting the Prognostic Risk in Patients With Heart Failure

Background: The 6-minute walk test (6MWT) is an established test to assess functional exercise performance and the 6-minute walk distance (6MWD) is strongly correlated with the functional capacity and the prognosis in patients with heart failure (HF). However, the clinical implication of sequential changes in percutaneous oxygen saturation (SpO2) during 6MWT has not been investigated in HF patients. Purpose: To prospectively clarify the association between sequential changes in SpO2 during 6MWT and prognosis in patients with HF. Methods: Fifty patients admitted with acute heart failure were enrolled. The 6MWT was performed at the time before discharge, after hemodynamic stability was confirmed. The average of SpO2 was calculated from data obtained at rest and during 6MWT by employing the wearable pulse-oximeter which is designed to record the SpO2 value every second. Alternations in SpO2 (ΔSpO2) were obtained by subtracting the average during 6MWT from that at rest. Patients were followed up to 9 months for the composite outcome of heart failure-hospitalization and death. Results: The mean age of participants was 78.8 years, and 23 (46%) were female. The mean EF was 46.1% and the number of patients with EF ≦40 was 22. The 6MWD was 250 ± 112m and the ΔSpO2 was 2.88 ± 4.3%. All cases were classified by walk distance and ΔSpO2; long- (&gt;220m) vs. short-distance group (≦220m) and low- (&lt;3.5%) vs. high-ΔSpO2 group (≧3.5%). There were no significant differences in cardiac parameters and respiratory function between long- and short-distance group as well as between low- and high-ΔSpO2 group. Kaplan-Meier analysis revealed that higher ΔSpO2 showed a more strong and statistically significant impact on cardiovascular outcome compared to longer 6MWD (HR=3.25, CI=1.40-7.51, p=0.006, HR=2.24, CI=0.94-5.32, p=0.067, respectively). Conclusions: This study showed that, compared to walk distance, ΔSpO2 during 6MWT was more predictive of the prognosis of heart failure patients.