Decompensated Heart Failure Research Articles

Comparing de novo heart failure and acute decompensated heart failure using a proteomic approach

Abstract Background Acute heart failure (HF) is defined as new or worsening symptoms of HF and stands as the most common cause of unscheduled hospital admission in patients above the age of 65. Acute HF can be classified into de novo HF (DNHF), defined as no previous history of HF, and acutely decompensated HF (ADHF), defined as worsening symptoms of HF in individuals with a prior diagnosis of HF. Clinically, it is relevant to distinguish ADHF from DNHF as they differ regarding aetiology, comorbidities, mortality, and morbidity. The aim of this study was to compare DNHF and ADHF using a proteomic approach. Method Using a proximity extension assay in a Swedish HF cohort, a total of 324 individuals hospitalized for acute HF underwent proteomic analysis of 92 proteins. The population was categorized into DNHF and ADHF, subsequently comparing normally distributed proteins using an independent samples t-test. Non-normally distributed proteins were compared using the Mann-Whitey U-test. To adjust for multiple testing, Benjamini Hochberg method was applied with a false discovery rate of 5%. Fold change was calculated by subtracting the mean or median protein concentration in ADHF from DNHF. As protein concentrations are expressed on a log2-scale, the difference between the groups equals the fold change. Proteins were considered differentially expressed at a fold change threshold of 1.15. The proteins that met a cut-off, were thereafter analysed with a pathway enrichment analysis using Reactome (only a corrected p-value ≤0.05 was considered significant). Results Complete data was available for n=317 (30.3% women; mean age 74.6) individuals (Table 1). After FDR adjustment, differential protein expression analysis yielded 56 differentially expressed proteins. After applying the fold change threshold, 51 proteins were significantly up regulated in ADHF compared to DNHF and one (Paraoxonase 3) was significantly downregulated. The most prominently up-regulated protein was fatty acid binding protein-4 (FABP4) (fold change 1.68, p <0.001). The largest number of proteins were related to neutrophil degranulation (Figure 1). Conclusion In patients hospitalized for acute HF, we identified several common pathways of the proteins differentially expressed in DNHF compared with ADHF. Neutrophil degranulation was related to the largest number of proteins. The most prominently up regulated protein was FABP4. These findings may inspire future investigation into the different underlying molecular mechanisms in ADHF and DNHF and reveal potentially different targets of treatment between the two conditions.Figure 1.Pathway enrichment analysis

The role of malnutrition and dependence on outside help in hospitalized elderly patients with decompensated heart failure

Abstract Introduction Despite recent achievement in the diagnosis and treatment of heart failure, the prognosis for disease remains unfavorable especially in elderly patients. It has been recently actively proposed to introduce a comprehensive geriatric assessment to determine the group of adverse outcome and frailty, however the assessment of geriatric syndromes in acute decompensated heart failure (ADHF) among hospitalized patients is poor. Aim To assess the prognostic role of malnutrition and dependence on outside help in hospitalized elderly patients with ADHF. Materials and methods The study included 60 patients over 75 years old who were hospitalized for ADHF. The median [IQR] age was 83.0 [77.0-87.0] years, 41.7% (n=25) were men. The preserved left ventricular ejection fraction (LVEF) prevailed – 51.2% (n=22), moderately reduced and low LVEF – 23.3% (n=10) and 25.6% (n=11), respectively. Total/severe dependence on outside help was determined with Barthel Index of ≤60 points, malnutrition – with a Mini Nutritional Assessment Scale of <17 points, sarcopenia with SARC-F ≥4 points. At discharge, all patients underwent bioimpedance analysis of body composition (BIA). The primary endpoint was hospital mortality. Results 48.3% (n=29) of hospitalized elderly patients with ADHF had total/severe dependence on outside help. This group of patients had a higher risk of malnutrition (OP 2.01, 95% CI 1.49-2.83, p=0.04) and sarcopenia (OP 8.25, 95% CI 1.55-44.02, p=0.01). Elderly patients with ADHF and malnutrition had a more severe functional class (NYHA III-IV) than patients without malnutrition (97.1% vs. 66.7%, respectively, p=0.02). There were no differences in ADHF phenotypes depending on the presence of malnutrition. The ability to self-serve according to Barthel Index has positively correlated with the BIA Index (r=0.483, p=0.04). The risk of sarcopenia on the SARC-F scale has negatively correlated with fat, lean and active cell mass according to BIA (r=-0.538, r=-0.599 and r=-0.532, respectively, p<0.05). Elderly patients with ADHF and a combination of total/severe dependence on outside help and malnutrition (27.9%, n=12) had higher inflammation level (neutrophil-lymphocytic index 5.6 [2.6-7.7] vs. 3.9 [2.0-6.0], p=0.03, respectively) and the need for longer intravenous diuretic therapy (OP 4.38, 95% CI 1.21-15.81, p=0.03) compared with patients without these disorders (72.1%, n=31), The primary endpoint was reached by 4 patients, in 100% of cases there was a combination of total/severe dependence on outside help and malnutrition. Conclusion The combination of total/severe dependence on outside help and malnutrition is an unfavorable prognostic marker of hospital mortality in hospitalized elderly patients with ADHF. A comprehensive geriatric assessment and determination of body composition can identify a risk group for an adverse outcome.

Acetazolamide for patients with acute decompensated heart failure: a systematic review and meta-analysis of randomised controlled trials

Abstract Background The role of acetazolamide as an adjunct to standard loop diuretic therapy in patients with acute decompensated heart failure (ADHF) remains uncertain. Purpose We undertook a systematic review and meta-analysis to ascertain the efficacy and safety of acetazolamide plus standard of care (SOC) in patients with ADHF. Methods In January 2024, we systematically searched PubMed, Embase, and Cochrane for randomised controlled trials (RCTs) comparing acetazolamide plus SOC versus SOC alone in patients with ADHF. Effective decongestion was defined as per the definition of each individual study. We pooled risk ratios (RR) and standardized mean difference (SMD) with 95% confidence intervals (CI) for binary and continuous outcomes, respectively. Statistical analyses were performed using Review Manager version 5.4.1. Results We included 4 RCTs comprising 634 patients, of whom 318 (50.1%) were randomised to acetazolamide plus SOC. The mean age was 77.1 years and 64.2% were male. Nearly half of the patients (n=320; 50.5%) had impaired left ventricular ejection fraction at baseline. Most patients had a New York Heart Association functional class III or higher, ranging from 75 to 91% in each study. In the pooled analysis, acetazolamide plus SOC significantly increased the proportion of patients with clinical decongestion at day 3 compared with SOC alone (RR 1.36; 95% CI 1.10 to 1.68; p=0.005; Figure 1A). There was no significant difference between groups in natriuresis at day 1 (SMD 0.46; 95% CI -0.01 to 0.94; p=0.06; Figure 1B) or worsening renal function (RR 1.71; 95% CI 0.73 to 3.98; p=0.22; Figure 1C). Conclusion In this meta-analysis of RCTs among patients admitted with ADHF, acetazolamide plus SOC significantly improved the proportion of patients with clinical decongestion at day 3 relative to SOC alone, without significantly affecting renal function or natriuresis.Figure 1

ICARUS registry: findings from the first 1595 cases of acute decompensated heart failure in a single center in a latin american country

Abstract Introduction Institutional aCute decompensAted HeaRt FailUre RegiStry (ICARUS) will provide information on clinical characteristics, medical practice, patterns of treatment, and outcomes of patients hospitalized with Acute Decompensated Heart Failure (ADHF) in a hospital in a middle-income country. Objective Describe the methodological aspects, sociodemographic, and clinical characteristics of patients hospitalized with ADHF and their short-term outcomes. Method Prospective cohort of patients with ADHF from the emergency service of a cardiovascular center. Descriptive statistics were used to synthesize sociodemographic characteristics, clinical characteristics during hospitalization, and outcomes. Results 1595 patients with ADHF. The median age was 68 years (Q1=58; Q3=76), and 69.28% were men. The median hospital stay was six days (Q1=4; Q3=11), with an accumulative incidence (AI) for rehospitalization at 30 days of 8.70 % (95% CI 7.18 to 10.40%), in-hospital mortality AI of 4.33% (95% CI 3.38 to 5.44%), and a median change in the quality-of-life score like Minnesota Living with Heart Failure Questionnaire (MLHFQ) at 30 days of -20 points (Q1=-37; Q3=-5). At discharge, all patients had a percentage greater than 70% of the use of quadruple neurohormonal blockade therapy. Conclusions ICARUS is one of the first registries in Latin America since the indication of the use of SGLT2 inhibitors, evaluating the clinical and sociodemographic characteristics, treatment patterns, and outcomes of a preliminary cohort of 1595 patients hospitalized for ADHF. The results indicate that, at discharge, up to 82.79% of patients were receiving quadruple neurohormonal blockade therapy, which is considerably challenging to achieve in Latin America. Considering the results of the Safety, tolerability and efficacy of up-titration of Guideline-Directed Medical therapies for acute heart failure (STRONG-HF study), our study reinforces the benefit of discharge with Guideline-Directed Medical Therapy (GDMT) for heart failure from hospitalization. The use of GDMT for heart failure may have influenced our positive outcomes in terms of in-hospital mortality, improvement in quality of life, and the percentage of short-term rehospitalizations compared to similar cohorts.Proportion of HF drug group

Telehealth-aided outpatient management of acute heart failure in a specialist virtual ward compared to standard care

Abstract Background/Introduction Acute decompensated heart failure (ADHF) leads to hospitalisations, frequent re-hospitalisations and mortality. The safety and efficacy of telehealth-guided outpatient ADHF management (virtual ward-VW) as an alternative to hospitalisation has not been assessed previously. Aim The aim of this study was to assess the safety and outcomes of our acute heart failure virtual ward (HFVW) pathway (Figure 1) when compared to hospitalised ADHF patients. Methods This cohort study (May 2022-October 2023) assessed the outcomes of telehealth-guided outpatient ADHF management using bolus intravenous furosemide in a HF-specialist VW. We compared baseline patient characteristics, NTproBNP, ejection fraction, NYHA Class, clinical risk score (Get With the Guidelines-Heart Failure-GWTG-HF), comorbidities (Charlson Co-morbidity Index-CCI), frailty (Rockwood Clinical Frailty Score-CFS), HF therapies and measured clinical outcomes at 1, 3, 6 and 12 months (re-hospitalisations, mortality) in the HFVW cohort versus standard care (ADHF patients managed without telehealth in 2021). Results 554 HFVW ADHF patients (age 73.1±10.9 years; 46% female) were compared with 402 ADHF patients (74.2±11.8; p=0.15 and 49% female) in the standard care cohort (SC). Despite similar baseline patient characteristics, GWTG-HF score, CCI and CFS, re-hospitalisations were significantly lower in the HFVW compared to standard care (1 month - 11.6% vs. 21%, p=0.002; 3 months - 20.4% vs. 30%, p=0.001; 6 months -29.3% vs 41%, p=0.02 and 12 months-48% vs. 57%,p=0.03) whereas mortality was lower at 1 month (6% vs. 14%; p<0.001), 3 months (10.5% vs. 15%; p=0.02) and 6 months (15.5% vs. 21%; p=0.04) (Figure 2). Multivariate logistic regression analysis showed that an increased daily step count whilst on HFVW independently predicted reduced odds of re-hospitalisations at 1 month (OR 0.85; 95% CI 0.7-0.9; p=0.005), 3 months [OR 0.95 (0.93-0.98); p=0.003] and 1 month mortality [OR 0.85 (0.7-0.95), p=0.01]. Whereas CCI predicted adverse 12-month outcomes [OR 1.2 (1.1-1.4), p=0.03]. Higher GWTG-HF score independently predicted increased odds of re-hospitalisation [1-month OR 1.2 (1.1-1.3), p=0.01; 12-month OR 1.1, 1.05-1.2, p=0.03) as well as mortality [1-month OR 1.2 (1.1-1.4), p=0.01; 12-month OR 1.3 (1.1-1.7), p=0.02]. Similarly higher CFS also independently predicted increased odds of re-hospitalisations [1-month OR 1.5 (1.1-2.2), p=0.03; 12-month OR 1.9 (1.2-3, p=0.01] and mortality [1-month OR 2 (1.1-3.5), p=0.02; 12-month OR 2.6 (1.6-10); p=0.02] throughout the follow-up period. Conclusions A telehealth-guided specialist HFVW management strategy for ADHF may offer a safe and efficacious alternative to hospitalisation in suitable patients. Daily step count, GWTG, CCI and CFS can play a vital role in assessing suitability for VW and in predicting risk of adverse clinical outcomes.Heart Failure Virtual Ward PathwayMortality & Re-hospitalisations outcomes

The mortality implications of increasing and decreasing sST2 levels during acute decompensated heart failure

Abstract Introduction Soluble Suppressor of Tumorigenicity (sST2), a marker of cardiac remodelling and fibrosis, has demonstrated promises in prognostication of heart failure (HF) and therefore recommended as an additional test for risk stratification of HF in the 2017 ACC/AHA/HFSA guidance. It is well investigated as single measurements in acute and ambulatory settings. Data regarding sST2 level changes during acute decompensated heart failure (ADHF) and its potential in providing additional prognostic information is however sparse. We therefore sought to evaluate changes in sST2 and its prognostic implications in hospitalized patients during ADHF. Methods Between December 2019 and February 2022, consecutive patients with ADHF and reduced ejection fraction (EF<50%) presenting to our University Hospital were recruited as part of the Investigating the soluble ST2 biomarker in addition to Natriuretic peptides in managing patients with Heart Failure and a Reduced Ejection Fraction (INST2ANT-HF) study (REC Reference: 19/EE/0269). Serum samples were taken at clinician determined decompensation and recompensation in all participants, who were then followed up for one year post discharge. The study primary end point was all-cause mortality at one year. A 2x2 contingency table was constructed to display the relationship between the frequency of unchanged/increased or decreased sST2 levels at recompensation and the frequency of mortality at one year (Table 1). A Kaplan-Meier curve was plotted to display the survival probability of the two groups during one-year follow up (Figure 1), and log-rank test applied to evaluate for significant difference in the survival distributions. Results In 169 patients with paired sST2 samples, median age (IQR) was 72 (62-80.8), 39 (23.2%) were female and 160 (95.2%) were ethnically white. 158 (94.1%) presented with NYHA class II-IV and the median (IQR) EF was 26% (17.5-32.5). Median (IQR) length of stay in hospital was 8 days (5-13). Median (IQR) sST2 level at decompensation and recompensation were 60ng/ml (40-93.3) and 39.5ng/ml (24-64.8) respectively. At clinician determined recompensation, sST2 level decreased in 136 (81%) patients while 32 (19%) had unchanged/increased sST2 levels. One-year mortality was 37.5% in patients with unchanged or increasing sST2 levels during ADHF, compared to 16.2% in those with decreased sST2 levels. The mean (SE) survival time was 332 (7) days for patients with unchanged/increasing sST2, and 274 (22.5) days for patients with decreasing sST2 at HF recompensation (p=0.003). Conclusion Our data demonstrates that there was a downward trend in sST2 in most patients during recovery from an ADHF episode. Importantly, a static or increasing sST2 level from HF decompensation to recompensation was associated with a significantly higher risk of mortality at one year. Further research may ascertain if the mortality risk is also dependent on the percentage changes in sST2 concentrations.Table 1:2x2 contingency tableFigure 1:Kaplan-Meier curve

VExUS score improvement is associated with better outcomes in acute decompensated heart failure

Abstract Background Venous Excess Ultrasound Score (VExUS) has recently emerged as a non-invasive tool for venous congestion assessment in acute decompensated heart failure (ADHF). Although VExUS is associated with cardiorenal syndrome, the prognostic role regarding hard outcomes in ADHF is still unknown. Purpose To evaluate whether dynamic changes in VExUS within 72 hours after Cardiovascular Intensive Care Unit (CICU) admission is associated with in-hospital mortality in ADHF patients. Methods Prospective cohort study enrolling consecutive patients with ADHF admitted to CICU of a tertiary public hospital. VExUS evaluations ranging from 0 (no congestion) and 3 (severe congestion) and assessing the inferior vena cava, hepatic, and portal veins flow, were initially performed within 24 hours of admission and re-evaluated at 72 hours (third day) after treatment initiation. Changes in VExUS scores were compared between these two time points. Mann-Whitney test and logistic regression was performed to evaluate VExUS improvement association with mortality. Results Between October 2022 and January 2024, 81 patients were admitted to the CICU due to ADHF. Following the exclusion of 10 patients who were not assessed within the first 24 hours, 71 patients were included in the final analysis. Mean age was 65 ± 13.3 years, with 66.7% being male. Ischemic etiology was identified in 40.7%, and atrial fibrillation was present in 34.6%. Mean left ventricular ejection fraction was 27.4% ± 12.2, and 64.2% had right ventricular dysfunction. Upon admission, 73.2% were classified as B and 23.9% as C hemodynamic profiles. Overall in-hospital mortality was 25.9%. In-hospital mortality across VExUS categories assessed in the third day was 16.7%, 12.5%, 28.6% e 40%, for VExUS 0-3, respectively. The median VExUS variation between the two time points was greater in patients who survived [-1 vs. 0; p=0.030] and VExUS improvement at 72 hours was associated with a 46% decrease in hospital mortality for each class reduction (OR=0.536; 95% CI 0.29-0-81; p=0.043 - Figure 1). Conclusion Improvement in VExUS score between admission and 72 hours is associated with reduced in-hospital mortality. This finding highlights the potential role of dynamic VExUS monitoring for identifying delayed treatment response patients. Thus, changes in VExUS emerged as a prognostic tool offering a pathway to potentially intensify treatment strategies for high-risk patients with ADHF.VExUS score changes within 72 hours

Increased risk of cardiovascular events in the weeks following hospitalised COPD exacerbations: the EXACOS-CV French nationwide case-crossover study

Abstract Introduction Previous studies indicate that in people living with chronic obstructive pulmonary disease (COPD), the risk of myocardial infarction (MI), heart failure (HF) decompensation, arrhythmias and ischemic stroke increases following a COPD exacerbation. This association has not been explored for detailed types of cardiovascular events (CVE), namely for different types of myocardial infarction. Objective To quantify the risk of CVE following a COPD exacerbation overall, and by detailed type of CVE. Methods A case-crossover study was conducted using the French national hospital discharge database (Programme de Médicalisation des Systèmes d'Information, PMSI). Case-patients: (i) were aged≥40 years with a COPD diagnosis; (ii) hospitalised in 2018-2019 for CVE; (iii) experienced the CVE within 24 weeks of a hospitalised exacerbation of COPD. Hospitalisation date for CVE was index date. Conditional logistic regression models estimated the association between a hospitalised exacerbation and CVE (overall and by type of CVE) – expressed as odds ratios (OR) – comparing the odds of a hospitalised COPD exacerbation during the risk period (4 weeks prior to index date) versus control periods (9-24 weeks prior to index date). Results Among 122,172 patients with COPD hospitalised for a severe CVE in 2018-2019, 9,840 (8%) had a hospitalised exacerbation of COPD in the prior 24 weeks and qualified as case-patients. Mean age was 76.8 years (SD 10.7); 6,496 (66%) were male. The most frequent CVE were decompensated heart failure (n=5,888, 60%) and acute coronary syndrome (n=1,070, 11%); in-hospital death in the 24 weeks following an exacerbation of COPD occurred in 950 (10%) patients. Median time elapsed between hospitalised exacerbation and CVE (any type) was 43 days (Figure 1); the shortest delays were observed for non-STEMI (24 days) and resuscitated cardiac arrest (28 days). Risk of CVE in the 4 weeks following a hospitalised COPD exacerbation was 3-times the risk in the 9-24 weeks post-exacerbation (OR 3.0; 95%CI 2.9-3.2 – Figure 2). This increase in risk was observed for each individual type of CVE. The highest effect size was observed for non-STEMI (OR 5.3; 95%CI 4.5-6.3). Conclusion The risk of CVE substantially increases following a hospitalised exacerbation of COPD overall and for all types of CVE (acute ischemic events, arrhythmias, and heart failure decompensation). The first month following a hospitalised exacerbation is a period of vulnerability for people living with COPD, with some variability in the magnitude and temporality of risk increase according to the type of CVE. These results stress the need for immediate and sustained monitoring of exacerbating COPD patients to prevent a subsequent severe cardiac event. In addition, exacerbations prevention is an essential target of COPD treatment.

Prognostic impact of systemic immune-inflammation index in patients with acute decompensated heart failure with preserved ejection fraction -PURSUIT-HFpEF Registry-

Abstract Background Systemic inflammation has been implicated in the pathophysiology of heart failure with preserved ejection fraction. Several studies have shown that systemic immune-inflammation index (SII), a novel index based on platelets, neutrophils, and lymphocytes, predicts poor prognosis in patients with cardiovascular disease. However, it remains to be elucidated whether SII could have predictive value in patients with acute decompensated heart failure with preserved ejection fraction (ADHF-HFpEF). Purpose This study is designed to investigate the association of SII at admission or discharge with poor clinical outcome in patients with ADHF-HFpEF. Methods Patients’ data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study, which is a prospective multicenter observational registry for ADHF-HFpEF in a city. Laboratory data and body weight measurements were performed just before discharge. We analyzed 966 patients (mean age: 81 years old, male: 45%) after exclusion of patients on dialysis, missing follow-up data, or missing data to calculate SII. SII was calculated as follows: SII = platelet count × neutrophil count / lymphocyte count on admission and at discharge. The primary endpoint was the composite of all-cause death and rehospitalization for worsening heart failure. Results During a mean follow-up period of 1.8±1.3 years, the primary endpoint was observed in 435 patients (259 patients died and 176 patients underwent rehospitalization for worsening heart failure). In multivariate Cox analysis, high SII at discharge (> 536×109 determined by receiver operating characteristic curve analysis (AUC: 0.564 [0.526-0.602]) was significantly independently associated with not only the primary endpoint (hazard ratio 1.28 [1.04-1.57], p=0.020) but also all-cause death ((hazard ratio 1.39 [1.06-1.81], p=0.018) after adjustment for major confounders such as age, gender, body mass index, NYHA class, systolic blood pressure, heart rate and laboratory data including NT-proBNP and CRP. However, high SII on admission was not significantly associated with primary endpoint after multivariate adjustment. Kaplan-Meier analysis revealed that patients with high SII at discharge had significantly greater risk of both the primary endpoint (56% vs 43%, p<0.001) and all-cause mortality than those with low SII (36% vs 24%, p<0.001). Conclusion Systemic immune-inflammation index at discharge, but not on admission, would be associated with post-discharge poor outcome in patients with acute decompensated heart failure with preserved ejection fraction.

Randomized trial assessing worsening renal function with dapagliflozin addition in acute decompensated heart failure: ROAD-ADHF trial

Abstract Background Dapagliflozin (DAPA), a sodium-glucose co-transporter 2 inhibitor, has shown to reduce cardiovascular mortality in patients with chronic heart failure.1) In addition, DAPA can enhance diuresis in patients with acute decompensated heart failure (ADHF).2) However, there is little known how early initiation of DAPA might impact the worsening renal function (WRF) when combined with standard decongestive therapy for ADHF. Purpose We aimed to evaluate the impact of initiating DAPA within 24 hours after ADHF admission on WRF, compared to standard decongestive therapy with loop diuretics alone. Methods We enrolled consecutive ADHF patients with a left ventricular ejection fraction (LVEF) less than 50%. The patients were prospectively randomized to either the DAPA group who received DAPA at a dose of 10 mg once daily within 24 hours of admission or the conventional therapy group (CON group) who received loop diuretics alone. Furosemide, loop diuretic, dosage was adjusted by increase or decrease of 10 mg to maintain urine output between a 1-2 mL/kg/hour.3) The primary endpoint was the incidence of WRF, which was defined as an increase in the serum creatinine of ≥ 0.3 mg/dL from baseline within 7 days of admission.4) Additionally, right heart catheterization (RHC) was performed before discharge if the consent was obtained. Results From May 2021 to May 2023, we analyzed a total of 114 patients (56 in the DAPA group and 58 in the CON group). The mean age was 73 years, 35% were female, and the mean LVEF was 32.5%. There was no significant difference in the incidence of WRF between two groups (16.1% in the DAPA group vs. 12.1% in the CON group, P=0.54, Figure 1). The cumulative loop diuretics dose over 7 days was lower in the DAPA group than CON group (184 ± 9.64 mg vs. 214 ± 9.81 mg, P=0.03, Figure 2). RHC before discharge was performed in 54 patients (96.4%) in the DAPA group and in 54 (93.1%) in the CON group. There were no significant differences in the pulmonary artery wedge pressure, pulmonary artery pressure, right atrial pressure, and cardiac index by the thermodilution method or the Fick method between two groups. Conclusion This randomized prospective trial revealed the early initiation of DAPA within 24 hours of admission for ADHF reduced loop diuretic demand without inducing WRF compared to standard decongestive therapy.Figure 1Figure 2

Residual congestion in acute decompensated heart failure: A novel approach through microvascular imaging of renal circulation

Abstract Background In patients admitted for acute decompensated heart failure (ADHF), residual congestion at discharge is associated with adverse clinical outcomes. Traditionally, the extent of congestion has been inferred from central venous pressure, but it has also been highlighted that this is insufficient for a comprehensive evaluation of residual congestion. On the other hand, renal congestion is an important finding of organ congestion, and Superb Microvascular Imaging (SMI), a technique that reveals minute flow details, is promising for assessing renal circulation. We hypothesized that in patients with ADHF, assessment of renal circulation using SMI may be superior to conventional methods in assessing residual congestion. Methods In this prospective study, we enrolled 45 consecutive patients admitted with ADHF. We performed comprehensive evaluations including blood tests, echocardiography, and renal ultrasonography using SMI. The vascular index (VI), as measured by SMI, was calculated as the percentage of blood flow signal area in the region of interest. Subsequently, we calculated the intra-renal perfusion index (IRPI), representing cyclic variation in VI, as (maximum VI - minimum VI) within one cardiac cycle, divided by the maximum VI (Figure). Brain Natriuretic Peptide (BNP) levels were utilized to evaluate the state of decongestion. Results At discharge, the mean IRPI was 0.61±0.04, while the median BNP levels were 204.9 pg/ml (interquartile range: 102.7, 428.2). Patients exhibiting elevated log BNP levels at discharge (>2.31, based on median value) displayed significantly higher IRPI values [0.61(0.49, 0.86) vs 0.53(0.35, 0.59), p=0.02] and were older (80.8±8.5 vs 70.3±14.9 years, p=0.010). However, no significant differences were observed regarding laboratory parameters including hematocrit and creatinine levels, as well as echocardiographic parameters such as ejection fraction, E/e' ratio, and estimated right atrial pressure (RAP). Moreover, at discharge, creatinine levels (p=0.56) and estimated RAP (p=0.06) exhibited no significant correlation with IRPI. Conclusion Renal circulation evaluated by SMI may serve as a useful indicator of the extent of residual congestion at discharge compared to blood tests and echocardiographic estimates of right atrial pressure in patients admitted for ADHF.

Association of renal circulation at acute phase with decongestion level at discharge in patients admitted for acute decompensated heart failure

Abstract Background In patients admitted with acute decompensated heart failure (ADHF), renal hemodynamics may play an important role in the clinical course during hospitalization based on the close cardio-renal relationship. Superb Microvascular Imaging (SMI), distinguished by its advanced clutter suppression capabilities to reveal microflow details, holds promise for evaluating renal circulation. Consequently, our study aims to explore the association between renal circulation as assessed by SMI and the levels of brain natriuretic peptide (BNP) at discharge as an indicator of decongestion status. Methods In a prospective design, 45 ADHF patients were sequentially examined via renal ultrasound with SMI at discharge. The vascular index (VI) by SMI was calculated as the percentage of blood flow signal area in the region of interest. Then, the intra-renal perfusion index (IRPI) as an index of cyclic variation in VI, was calculated as the maximum VI minus the minimum VI within one cardiac cycle in the ROI divided by the Max.VI (Figure A). Results The values of IRPI were as follows: at 12h, 0.70±0.04; at 48h, 0.58±0.05; at 1W, 0.50±0.04; and at discharge, 0.61±0.04. The IRPI measured at 48h showed a stronger correlation with BNP at discharge (r = 0.57, p<0.001) than those at the other three points (Figure B). Patients with higher log BNP at discharge (> 2.31: determined by the median value) had significantly higher IRPI and age, and lower hemoglobin levels at 48h, however, there were no significant differences in estimated glomerular filtration rate, ejection fraction, or systolic pulmonary artery pressure at 48h. The area under the curve of IRPI at 48h for higher log BNP at discharge > 2.31 at discharge was 0.746 (sensitivity 100%, specificity 48%). Conclusion Early assessment of renal circulation by SMI around 48 hours after ADHF admission may predict congestion resolution at discharge. This underscores the potential utility of SMI in guiding more aggressive decongestive treatment strategies earlier in ADHF.

Feasibility and efficacy of acetazolamide in the treatment of acute decompensated heart failure

Abstract Background The ADOVAR trial showed that the addition of acetazolamide to loop diuretics could be expected to result in more rapid diuresis and shorter hospital stays in patients with acute decompensated heart failure (ADHF). However, tolvaptan and SGLTII inhibitors are often added for patients with ADHF in Japan. Method An inception cohort of patients with ADHF admitted between January 2022 and June 2023 was assessed. We studied baseline characteristics and divided the patients into "acetazolamide-use" and "no-use" groups. After three days of admission, the endpoint was the reduction rate of body weight, urine output, and the Congestion Score Index (CSI) improvement rate. Results A total of 222 patients were included (73 of the use group and 149 of the no-use group). Baseline characteristics showed the use of catecholamines, PDE III inhibitors, and SGLTII inhibitors were higher in the use group (30.1% vs. 14.8%; P<0.05, 37.0% vs. 8.1%; P<0.05, and 75.3% vs. 38.3%; P<0.05). The reduction rate of body weight, the amount of urine output, and the CSI improvement rate were higher in the use group (6.5% vs. 4.1%; P<0.05, 2745.8ml/day vs. 2004.8ml/day; P<0.05, and 27.8% vs. 19.2%; P<0.05). A hierarchical multiple regression analysis showed the use of acetazolamide and SGLT II inhibitors were the factors that contributed to the reduction of body weight, the amount of urine output, and the improvement of the CSI (P<0.05). Conclusion The addition of acetazolamide to daily medical therapy in patients with ADHF in Japan resulted in a greater incidence of successful decongestion.

Increased frailty is associated with risk of hospital-acquired infections and death during heart failure hospital admissions

Abstract Background Frailty is common in patients admitted with acute decompensation of heart failure (ADHF) and it is unclear how the frailty syndrome affects heart failure (HF) patients during their acute hospital admission. Understanding the interplay between frailty, impaired renal function, hospital-acquired infections (HAI), and death may be useful in optimising patient care and prognosis. Purpose The aim of this analysis was to explore the relationship between admission frailty levels and the incidence of HAI, acute kidney injury (AKI), and mortality in acute HF hospital admissions. Methods This is a retrospective analysis of data submitted from a single centre to the National HF audit between January and June 2023. Additional frailty and baseline renal function data was retrospectively collected from electronic patient health records. Patients were categorised into three groups according to their Rockwood Clinical Frailty Scale (CSF) (1): no/mild frailty (CFS 1-3), moderate frailty (CFS 4-6) and severe frailty (CFS 7-9). AKI was defined based on baseline and admission creatinine, as per KDIGO guidelines (2). Chi-squared and t-tests were used to compare baseline characteristics between frailty groups. Chi-squared tests were used to compare frailty groups in terms of: HAI, AKI, mortality. Results Between 1st January and 22nd June 2023, there were 344 acute HF hospital admissions in our centre. Most patients had moderate frailty on admission (n=256, 74.4%). Frail patients were significantly older, had a lower admission mean haemoglobin and more were female, compared to non-frail patients (Figure 1A). Patients who were more frail were more likely to experience HAI during their admission; p=0.035 (figure 1B). Furthermore, patients with HAI had a greater risk of mortality, at a median follow-up of 171 (IQR 100.25) days after admission, compared to those without HAI (p>0.001). 41.9% of acute HF admissions were associated with an AKI, and although numerically more frail patients had an AKI, this did not achieve statistical significance (p=0.084). Patients who were more frail were more likely to die, both during hospital admission and at 3 months following discharge; p<0.001 (Figure 1B). Furthermore, this trend persisted after follow-up; p<0.001 (Figure 2). Conclusions Patients with moderate or severe frailty are at greater risk of adverse events (HAI, death) during an acute HF hospital admission, than patients with no or mild frailty. It is imperative to consider the frailty status of all patients with ADHF, to be aware of the frailty-associated risks, and act proactively with targeted interventions (screen for infections, daily bloods, early conversations with patients and their families about treatment escalation plans and patient priorities) to improve outcomes and enhance the quality of care for this vulnerable patient population. Further research is warranted to explore potential interventions to address frailty-related risks in HF management.

Heart failure and advanced chronic kidney disease: differences in characteristics, treatment and outcomes in patients with glomerular filtration rate greater or less than 30 ml/minute/m2

Abstract Introduction Heart failure (HF) is a serious health problem and continues to have a high mortality and incidence of decompensation, despite advances in its management. Chronic kidney disease (CKD) is very prevalent in patients with HF, hinders their treatment and worsens their prognosis, especially when it is advanced CKD (glomerular filtration rate-GFR <30 ml(min/m2). It is important to know the differential characteristics of these patients to improve their management. Purpose To analyze in a contemporary registry of HF patients followed in specialized HF units in Spain the differences in clinical characteristics and treatment between patients with HF and advanced CKD. Methods We analyzed data from the registry of the SEC-Excelente-IC quality accreditation program of the Spanish Society of Cardiology, with 1716 patients with HF included between 2019 and 2021 by 45 specialized HF units accredited by the SEC. Patients were included consecutively in two 1-month cutoffs (March and October) in that period. The clinical and demographic characteristics and comorbidities of the patients were compared according to GFR < or > 30ml/min/m2. Results Of the 1,716 patients, 11.1% had a GFR<30 and 88.9% >30 mL/min/m2. Figure 1 shows the main clinical characteristics and comorbidities of the 2 groups. Median LVEF was similar in both groups: 42 (30-58) vs 38% (29-54). The group with advanced CKD was older (77±9.6 vs 70.5±12.6 years; p<0.001), had greater HF severity (more admissions for HF in the last year, worse NYHA functional class and longer evolution time), and a higher prevalence of coronary heart disease, hypertension, diabetes mellitus, cognitive impairment, anemia, iron deficiency and hyponatremia. There were no differences in sex, BMI, serum potassium or other comorbidities (Figure 1). Figure 2 shows the treatment received in each group. Patients with GFR <30 received in a significantly lower proportion all drugs for HF (p<0.001), except diuretics and potassium binders (ACEI/ARA, sacubitril-valsartan, MRA, beta-blockers, digoxin and SLGT2 inhibitors), and less cardiac rehabilitation (5.2 vs 10.4%; p=0.029). Incidence of one-year mortality was significantly higher in patients with GFR<30 ml/min/m2 (37.2 vs 14.4 per 100 persons-year, p<0.001), as were HF hospitalizations (61.3 vs 33.0; p<0.001) and HF decompensations without hospitalization (24.1 vs 11; p<0.001). Conclusions In our contemporary cohort of real-life HF patients, the prevalence of advanced CKD was 11.1%. These patients had a higher severity of HF, despite which, the utilization of HF drugs, including SGLT2 inhibitors was much lower than in those with GFR >30 ml/min/m2. One-year mortality, HF hospitalization and HF decompensations were almost 3-times higher. This treatment trend needs to be modified to improve the prognosis of these patients.

Daily Subcutaneous injections of Relaxin is a therapy for heart failure with preserved ejection fraction

Abstract Background and Significance: Relaxin (RLX), a hormone of pregnancy has engendered a great deal of excitement as a therapy for cardiovascular diseases. Clinical trials treated patients with acute decompensated Heart Failure (HF) with RLX (i.v. 30µg/kg/day-2 days) and reported a 37% decrease in mortality during a 6-months follow up. This led the FDA to declare RLX a ‘break-through’ therapy. However, a larger trial failed to meet the sought-after end points. Here, we propose that periodic subQ RLX pulses are more effective. We measured the pharmacokinetics of serum RLX following subQ injections of RLX in Sprague Dawley rats. Further, we treated rats with confirmed HFpEF with daily subQ RLX (2-weeks) to reverse the diastolic dysfunction (DD), arrhythmia and fibrotic profile. Methods Sprague-Dawley (250 g, n=20, either sex) received 2-subQ injections 12 hrs apart of RLX (from Relaxera) or the vehicle. Serial blood samples were drawn following each injection to measure [RLX]. ZSF1 rats (9-weeks old, either sex) were placed on a high fat diet (HFD) and serial echos tracked the DD. Once severe DD was established (25-35 weeks of HFD), rats received daily subQ injections of RLX (100µg/kg) or vehicle. After 2-weeks, hearts were perfused to optically map action potentials and Ca2+ transients, and analyze the arrhythmia profile. IF and Westerns were used to measure changes in fibrosis (collagen 1), Nav1.5, connexin 43, Wnt1 and β-catenin. Results After an injection, RLX reached a peak in ~60 min, fell to 50% in 5-6 hours. Injections of 0, 30, 100 or 500 µg/kg yielded peak levels of 0, 11.26±3.52, 58.33±16.10, and 209.42±29.04 ng/ml and residual levels after 24-hrs of 0, 4.9, 45.1 and 156 pg/ml, respectively. The 30µg/kg injections had no effect and 100 µg/kg increased Nav1.5 (25%), Cx43 (30%) and β-catenin (90%). The 500 µg/kg injections increased Nav1.5 and Cx43 but upregulated β-catenin, only slightly. In ZSF1 HFpEF rats that received the vehicle (n=12), a premature stimulus (at 30 ms) elicited arrhythmia in 67% of the hearts. RLX injections reversed DD, suppressed sustained atrial and ventricular arrhythmias (n=0/12) but not self-terminating arrhythmias, lasting < 10sec. RLX improved the conduction velocity (CV), particularly at fast rates (100ms) from 0.74 to 0.9 m/s (p<0.001, n=12). RLX significantly increased Cx43 expression, Nav1.5 and β-catenin at intercalated disks. RLX reduced collagen deposition in HFpEF rats, to normal levels and increased Wnt1 compared to control HFpEF rats. Conclusions The ZSF1 diabetic rat on a HFD recapitulates human HFpEF, high blood pressure, fibrosis, DD, AF and VF. SubQ RLX injections reversed DD i.e. enlarged Left Atrium, E/e’ ratio, fibrosis, and the arrhythmia vulnerability by increasing CV, Cx43, and Nav1.5. Daily subQ RLX injections were highly effective as a therapy for HFpEF.Echo parameterHFpEF + RLX

Transferrin saturation is a superior prognostic biomarker for iron deficiency after acute decompensated heart failure: a retrospective clinical real-world cohort study

Abstract Background Iron deficiency (ID) is the most common extracardiac comorbidity in heart failure (HF) and associated with worse outcomes. While a uniform definition of ID in HF remains lacking, several biomarkers for ID, including ferritin and transferrin saturation (TSAT), are used in both clinical trials and clinical practice. However, which biomarker is a superior prognostic predictor for ID in HF remains unsettled. In addition, real-world clinical data on ID screening and intravenous (IV) iron treatment is largely missing. Purpose To determine which biomarker is a superior prognostic predictor for the composite endpoint of HF rehospitalisation (HHF) and all-cause mortality in a real-world cohort of patients with HF and coexisting ID, and to investigate frequency and predictors of ID screening and IV iron treatment. Methods In this retrospective cohort study, all patients aged 18-85 years hospitalised at a tertiary university hospital with new onset HF with reduced ejection fraction (HFrEF) in 2016-2020 were consecutively included from medical records by ICD-10 code I50.0-I50.9 and followed until 31 December 2021. Patient characteristics, comorbidities, medications, laboratory results and data on follow-up, including if ID was tested for, IV iron administration, HHF and all-cause mortality was collected. First available iron status after admission for index hospitalisation was used. Predictors for ID screening and IV iron use were identified with univariate logistic regression. The association between ID markers and the composite endpoint was analysed with Cox regression adjusted for age, sex, baseline anemia, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and N-terminal pro-B type natriuretic peptide (NT-proBNP) below median value with median ferritin and TSAT values set as references respectively. Results In all, 753 patients were included (66.5 ± 12.7 years, 508 (67.5%) men, ejection fraction 29.5 ± 6.9% and mean NT-proBNP 6241 ± 7183 ng/L). Of these, 484 (64.3%) were screened for ID and 235 (48.6%) fulfilled criteria for ID. Of these, 94 (40.0%) received IV iron. Of screened patients, 28.6% had ID with anemia and 20.8% ID without anemia (Table 1). Factors associated with screening for ID were follow-up at hospital, anemia, eGFR <30 mL/min/1.73 m2 and ischemic heart disease, and for IV iron additionally chronic kidney disease and peripheral artery disease. Median ferritin was 140 µg/L and TSAT 0.2. Both ferritin and TSAT displayed an inversely linear association with outcomes, while TSAT <0.2 showed a stronger association with increased risk of HHF and all-cause mortality compared to median values (Figure 1-2). Conclusions In a real-world clinical setting, TSAT was a superior prognostic biomarker for worse outcomes compared to ferritin in patients hospitalised for acute HF. While both ID screening and IV iron use remained greatly underutilised in clinical practice, identification of a reliable biomarker for ID is critical.

Effect of nutritional guidance on mortality and composite endpoints in patients with acute myocardial infarction: a single center retrospective cohort study

Abstract Background/Introduction Acute myocardial infarction (AMI) stands as a major global cause of mortality. Various intervention strategies, such as pre-hospital care, reperfusion therapies, pharmacological interventions, dietary modifications, and exercise therapies, have been researched to improve patient prognosis (1,2). While reports suggest the efficacy of the Mediterranean diet, there remains a lack of evidence regarding the impact of nutritionist-led dietary guidance on the prognosis of AMI patients. Purpose This study aimed to elucidate whether nutritional guidance by nutritionists who have national qualifications would improve the mortality and the primary composite endpoint (including acute decompensated heart failure, stroke, and acute coronary syndrome) of patients following an acute myocardial infarction. Methods A retrospective cohort study was conducted, enrolling 446 consecutive AMI patients who underwent emergency coronary angiography and percutaneous coronary interventions between September 1, 2015, and October 31, 2023. Patients meeting the universal definition of myocardial infarction were included (3). After excluding 37 in-hospital deaths, evaluations for all-cause mortality, cardiovascular mortality, and composite endpoints were performed during follow-up in 409 patients. Nutritionists guided 223 patients (54.5%) during hospitalization in this study. The nutritional guidance used in our study was also based on the definition of adequate caloric intake of 25–30 kcal per ideal body weight (kg). Under an appropriate total energy intake, a fat energy ratio of 20–25% and a carbohydrate energy ratio of 50–60% are recommended, with protein and lipid restrictions depending on the disease state. Results During a median follow-up of 39 months, 24 cases of all-cause mortality (5.9%) and 6 cases of cardiovascular mortality (1.5%) were recorded. Additionally, 15 cases of nonfatal stroke (3.7%), 17 cases of nonfatal acute coronary syndrome (4.2%), and 20 cases of hospitalizations for acute decompensated heart failure (4.9%) were observed. Kaplan–Meier curves demonstrated significantly higher incidence rates of death and primary composite endpoints among patients without nutritional guidance. The multivariate Cox regression model incorporated all variables exhibiting statistically significant associations with long-term mortality, and the primary composite endpoints. The multivariate Cox regression model revealed nutritional guidance as a significant predictor for long-term mortality but not for primary composite endpoints. Conclusion Nutritional guidance for AMI patients may improve overall mortality. Further research is warranted to explore the physiological impacts of improved diets resulting from such guidance and their effects on enhancing prognosis.

Multiple comorbidities are associated with poor prognosis in patients with ADHF-HFpEF and non-frailty or mild frailty but not moderate-severe frailty -PURSUIT-HFpEF Registry-

Abstract Background A variety of comorbidities are frequently observed and represent a major problem in the management of patients with heart failure. Frailty is a strong predictor of poor clinical outcome in patients with heart failure, which may be partially attributable to the presence of multiple comorbidities. However, it remains to be clarified whether frailty is prognostically useful in relation to multiple comorbidities in patients with acute decompensated heart failure and preserved ejection fraction (ADHF-HFpEF). Purpose The purpose of this study is to investigate the relationship between frailty, multiple comorbidities and prognosis in patients with ADHF-HFpEF. Methods We prospectively studied 1028 patients with ADHF-HFpEF. Frailty was assessed using Clinical Frailty Scale (CFS). Multiple comorbidities were defined as the presence of 4 or more factors from the following 11 groups: diabetes, obesity, lung disease, anemia, renal dysfunction, electrolyte disorder, dyslipidemia, depression, hypertension, stroke and cancer. The primary outcome of this study was the composite endpoint of all-cause mortality and rehospitalization for worsening heart failure. Results During a mean follow-up period of 1.6±1.3 years, 454 patients underwent primary outcome. CFS (p<0.001) and the number of comorbidities (p=0.006) were significantly independently associated with primary outcome after multivariate adjustment. Kaplan-Meier analysis revealed that patients with multiple comorbidities had significantly higher risk for primary outcome than those without multiple comorbidities in the group with non-frailty (defined as CFS of 1 or 2, p=0.019) and mild frailty (CFS of 3 or 4, p=0.036). However, there was no significant difference in the group with moderate or greater frailty (CFS of 5 or more) in patients with ADHF-HFpEF. Conclusion(s) Multiple comorbidities would be associated with poor prognosis in patients with ADHF-HFpEF and non-frailty or mild frailty but not in patients with moderate or greater frailty.Multiple comorbidities and MACE risk

Prognostic impact of left atrial reverse remodeling in patients with ADHF-HFpEF regardless of atrial fibrillation -PURSUIT-HFpEF Registry-

Abstract Background Left atrial (LA) dilatation is associated with increased mortality in patients with cardiovascular disease including heart failure (HF) and LA reverse remodeling (LARR) was reported to be associated with favorable outcomes in patients with HF. However, it remains to be clarified whether LARR could have prognostic value in patients with HF with preserved ejection fraction (HFpEF). Purpose The purpose of this study is to elucidate whether LARR is associated with clinical outcome in patients with HFpEF in relation to the presence of atrial fibrillation (AF). Methods We prospectively studied 492 patients with acute decompensated heart failure with preserved ejection fraction (ADHF-HFpEF) without the poor outcome during the first year postdischarge. Echocardiography was performed just before discharge and at 1 year after discharge. LARR was defined as the reduction of 15% or more in left atrial end-systolic volume (LAV). The primary outcome was rehospitalization for worsening heart failure. Results All study patients were divided into 2 groups according to the presence of AF at discharge (AF group, n=182 and non-AF group, n=310). During a mean follow-up period of 1.4±1.2 years, 78 patients were rehospitalized for worsening heart failure (37 patients in AF group and 41 in non-AF group). ΔLAV, the degree of reduction in LAV during the first year postdischarge, was significantly independently associated with primary outcome after multivariable adjustment both in AF group (p=0.033, HR 0.992 [0.984-0.999]) and non-AF group (p=0.021, HR 0.986 [0.974-0.998]). Kaplan-Meier analysis revealed that patients with LARR had significantly lower risk for primary outcome than those without LARR not only in the whole study patients (8% vs 20%, p=0.001) but also both in AF group (9% vs 24% p=0.013) and in non-AF group (8% vs 16% p=0.043). Among clinical characteristics during the index hospitalization, the presence of AF and prior HF hospitalization were significantly independently associated with LARR at multivariate Cox logistic regression analysis (p=0.006, OR 0.554 [0.364-0.843] and p=0.007, OR 0.491 [0.292-0.826], respectively). Conclusion(s) The left atrial reverse remodeling could have the prognostic impact in patients with ADHF-HFpEF regardless of the presence of atrial fibrillation.Kaplan-Meier curves in AF and non-AF