Glomerular Filtration Research Articles

Evaluation of concordance and association with clinical outcomes across eGFR values calculated with eight different formulas in a large cohort of european patients with atrial fibrillation

Abstract Background In randomized clinical trials of Direct Oral Anticoagulants (DOACs), the assessment of renal function impairment glomerular filtration rate (eGFR) in patients with Atrial Fibrillation (AF) has predominantly utilized the Cockroft-Gault (CG) formula for estimating Creatinine clearance (CrCl). However, in clinical practice, several other formulas for estimating glomerular filtration rate (eGFR) are employed. Limited data exist regarding the evaluation and comparison of eGFR/CrCl in AF patients. Objectives This study aimed to assess the concordance in the categorisation of renal function in in 6 classes taking into account eight different formulas for eGFR/CrCl (CG, CKD-EPI, CG/body surface area [BSA], BIS1, LMK, EKFC, FAS, MDRD) and their associations with a composite outcome (Major Adverse Cardiovascular Events [MACE] and all-cause death) in AF patients. Methods A contemporary European AF patient registry was utilized, and eGFR/CrCl were calculated using CG, CKD-EPI, CG/BSA, BIS1, LMK, EKFC, FAS, and MDRD formulas. eGFR was categorized according to KDIGO classes, with CKD patients defined as having eGFR/CrCl <60 ml/min/m2. Concordance was estimated using weighted Cohen’s kappa. Associations were evaluated through adjusted Cox regression analyses for the composite outcome, and results were plotted as spline curves. Results: A total of 8516 patients were included in the analysis (Median [IQR] age: 70 [63-77] years; 3518 women, 41.3%). Among the formulas, EKFC exhibited the highest median values of eGFR and the lowest prevalence of CKD patients, while BIS1 had the lowest median eGFR values, and the FAS formula led to the highest prevalence of CKD patients [Figure 1]. In the concordance analysis, CKD-EPI demonstrated the highest concordance with all other formulas, even if Cohen’s kappa for measuring the degree of concordance ranged from 0.61 to 0.88 [Figure 1]. In adjusted Cox regression analyses, all formulas were associated with an increased risk for the composite outcome, progressively as eGFR decreased. When plotted as spline curves, the associations with the composite outcome visually showed a similar behaviour of risks across eGFR values in all formulas compared to the CG spline [Figure 2]. Conclusions Among AF patients, the CKD-EPI formula exhibited variable, but substantially good concordance with CG, CG/BSA, BIS1, LMK, EKFC, FAS, and MDRD formulas. All calculated eGFR values showed a strong association with the composite outcomes, similarly to the CG formula, with higher risk when renal function decreased.FIGURE 1FIGURE 2

Interleukin-6 and suPAR are associated with diastolic function in type 1 diabetes: The Thousand & 1 Study

Abstract Background Heart failure (HF) is a common complication in individuals with type 1 diabetes (T1D). Inflammation is an important contributor to the pathogenesis and progression of both T1D and HF – especially HF with preserved ejection fraction (HFpEF). Diastolic dysfunction is a hallmark of HFpEF. Despite this, the association between diastolic function and inflammatory biomarkers is not well-known in individuals with T1D. Methods The Thousand & 1 study of individuals with T1D without known heart disease was studied. Diastolic parameters, including E/e’, was obtained by echocardiography and associated with Interleukin-6 (IL-6), soluble urokinase-type plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein (hsCRP). These inflammatory biomarkers were analysed as continuous variables and dichotomized in above/below 3 pg/mL (IL-6), 4 ng/mL (suPAR), and 4 mg/L (hsCRP). In multivariable regression analysis, adjustments were made for age, gender, body mass index, duration of diabetes, HbA1c, systolic blood pressure, left ventricular ejection fraction, glomerular filtration rate, albuminuria status, use of statins, tobacco use and physical activity levels. In an additional analyse, we also adjusted for N-terminal pro–B-type natriuretic peptide (NT-proBNP). Results We included 1,014 individuals (52% male, mean age 50±15). IL-6 was elevated in 207 individuals, suPAR in 182 individuals, and hsCRP in 863 individuals. Mean E/e’ was 7.6 and mean left ventricular ejection fraction was 58±5%. In fully adjusted models, inflammatory biomarkers were significantly associated with diastolic function. Thus, individuals with IL-6 > 3 pg/mL had 0.6 (95% confidence intervals: 0.2 to 1.0), P=0.001) higher E/e’ compared to individuals with IL-6 < 3 pg/mL. For every doubling of suPAR levels, E/e’ increased by 0.5 (0.2 to 0.9, P=0.003). For every doubling of hsCRP levels, E/e’ increased by 0.1 (0.02 to 0.2, P=0.022). Individuals with elevated levels of all three biomarkers had 1.9 (0.5 to 3.2, P=0.006) higher E/e’ compared to low levels of all three biomarkers. Including NTproBNP to the model did essentially not change the estimates. Conclusions Firstly, in T1D, elevated levels of IL-6, suPAR and hsCRP are associated with diastolic function assessed by E/e’, independent of traditional risk factors including NT-proBNP. Secondly, IL-6, suPAR and hsCRP may contain information about diastolic function in T1D which is not detected by NT-proBNP.Figure 1Figure 2

Long-term outcome of diabetic patients after unprotected left main percutaneous coronary interventions

Abstract Background Diabetes mellitus (DM) represents an elevated risk in terms of percutaneous coronary intervention (PCI), especially in patients with significant left main (LM) disease. Purpose Our aims were to investigate the 60-month mortality and event-free survival of consecutive patients with DM undergoing unprotected LM PCI at our centre and sought to determine the independent predictors of event-free survival. Methods We included all patients undergoing unprotected LM PCI at our tertiary care centre between 1 January 2007 and 31 December 2014. The primary endpoint was the composite of all-cause mortality, myocardial infarction, and target lesion revascularization at 60 months. Survival curves were constructed using the Kaplan-Meier non-parametric estimator. ROC analysis was used to investigate the predictive power of conventional risk scores (SYNTAX, SYNTAX II, EuroSCORE II, additive and logistic EuroSCORE, ACEF, GRACE 2). Independent predictors were determined by univariate and multivariate analysis. Results A total of 513 patients (mean age 68 ± 12 years, 64% male) underwent unprotected LM PCI during this period, among these 310 (60%) were non-diabetic (non-DM) and 203 (40%) were diabetic (DM). In terms of indication, 157 (31%) elective and 356 (69%) acute LM PCI were performed. There was no significant difference between the non-DM and DM groups in terms of acute indication (218 (70%) vs. 138 (68%), p=0.574). Within the DM group, 135 (67%) were treated with oral antidiabetics (OAD) and 68 (33%) were treated with insulin (IDM). The mean survival (34.6 vs. 39.7 vs. 43.1 months, p=0.003) and event-free survival (29.3 vs. 34.7 vs. 39.3 months, p=0.001) were significantly lower in the IDM and OAD groups compared to non-DM, respectively. Of the risk scores, the SYNTAX score was the most predictive in diabetic patients (AUC=0.767). Based on the SYNTAX score, diabetic patients with a low SYNTAX score (<23) had less events (59% vs. 66%, p=0.043) than those having a moderate/high SYNTAX score (≥23). LVEF (HR 0.976; 95% CI, 0.965-0.987, p<0.001), right coronary artery occlusion (HR 2.031; 95% CI, 1.346-3.064, p=0.001), acute coronary syndrome (HR 1.861; 95% CI, 1.252-2.767, p=0.002), use of FFR (HR 0.481; 95% CI, 0.265-0.871, p=0.016), true bifurcation lesion (HR 1.559; 95% CI, 1.068-2.277, p=0.021) and newer DES generation (HR 0.706; 95% CI, 0.568-0.877, p=0.002) were predictors of event-free survival in diabetics by univariate analysis. Glomerular filtration rate (HR 0.982; 95% CI, 0.973-0.991, p<0.001) emerged as an independent predictor according to multivariate analysis. Conclusion Consecutive diabetic patients with significant unprotected LM stenosis have poor long-term outcome after LM PCI. Anatomical complexity of the lesions is a significant predictor of event-free survival. Careful intervention planning and the use of appropriate tools can improve the outcome in this high-risk population.

Characterization and progression of heart failure with preserved ejection fraction in SDT fatty rats

Abstract Background Heart failure with preserved ejection fraction (HFpEF) is a complex clinical phenotype associated with the presence of multiple comorbidities including diabetes, obesity, and metabolic syndrome. A major challenge in the search of new therapies for HFpEF is the development of relevant animal models. The Spontaneously Diabetic Torii (SDT) fatty rat is a well-established type2 diabetic model with multiple diabetes-related comorbidities such as nephropathy, neuropathy, and retinopathy. However, the onset and spontaneous progression of cardiac dysfunction is not yet reported in this model. Purpose To validate the SDT fatty rat as a type2 diabetes related HFpEF model, we assessed the natural evolution, i.e., without any diet or surgical intervention, of cardiac function in SDT fatty at different ages starting at 7-week of age. Methods The cardiovascular phenotyping of male SDT fatty rats was assessed by echocardiography at 7, 12 and 17-week of age and invasive left intraventricular and blood pressure measurements at 17-week of age. Vascular function of isolated thoracic aortas was also evaluated at 17-week of age. Renal function was investigated by measuring the Glomerular Filtration Rate (GFR) and urine parameters at 7, 12 and 17-week of age. A group of Sprague Dawley (SD) rats was included as a negative control. Results Compared to SD rats, echocardiography in SDT fatty showed cardiac remodeling starting at 7 weeks and persistent with age. Systolic function and ejection fraction were preserved, while diastolic function was impaired as early as 7-week of age and worsened with time. E/A was comparable in SDT fatty and SD rats at 7-week of age and then increased with age to reach 1.8±0.1 vs 1.2±0.05 in SD (p<0.001) at 17 weeks, while E’/A’ was already inverted at 7 weeks (0.9± 0.02 vs 1.3±0.03 in SD, p<0.001), and lasted with age which is a sign of relaxation default and suggestive of a restrictive filling pattern. E/E’ was significantly higher at 7-week of age (16.1± 0.9 vs 12.1±0.6 in SD, p<0.01) and further increased at 17 weeks (23.1± 0.8 vs 12.1±0.8 in SD, p<0.001) indicating higher filling pressure. Intraventricular and arterial pressure were also increased (p<0.05). As well, SDT fatty rats showed altered endothelium vasodilating properties. As expected, SDT fatty rats were hyperglycemic and showed renal impairment expressed by higher proteinuria, urine albumin/creatinine ratio, KIM-1 and cystatin-C levels and a hyperfiltration state (80% higher GFR, p<0.05). Conclusions The present data demonstrate that the SDT fatty rats developed diastolic dysfunction characterized by a restrictive profile combining compliance and relaxation impairments as well as higher filling pressure along with hypertension. This type2 diabetic model seems as a very promising model to translate the hypertension/kidney dysfunction and cardiometabolic clinical HFpEF phenogroups and is consequently a relevant model to evaluate drugs targeting HFpEF.

Machine-learning based calculator for personalized risk following ST-elevation myocardial infarction

Abstract Background Despite recent advancements in the management of patients with ST-elevation myocardial infarction (STEMI), a high risk for adverse events remains during the first year following the event. There are several risk scores which estimate the risk of major adverse cardiac events (MACE) following STEMI. However, the most established risk scores are not contemporary, their diagnostic accuracy ranges across populations, and they are far from being personalized. Purpose We aimed to develop a machine learning (ML)-based calculator to provide patients and physicians with a personalized prognostic tool based on modern-world data to determine outcomes for patients following STEMI. Our goal was to predict mortality within 1-year post-STEMI and contribute personalized recommendations to reduce the risk of events. Additionally, we aimed to have the calculator provide a personalized risk assessment for each independent variable. Methods We included patients from two large tertiary care centers in Israel and Italy. 2888 patients who suffered STEMI between the years of 2000 – 2020 were included in our training model. Our calculator leveraged CatBoost for supervised machine learning, utilizing gradient boosting on decision trees. The model was subsequently tested on 321 patients from the Israeli center and 132 patients from the Italian center. Results The calculator was able to accurately predict 1-year mortality (96.5% accuracy, ROC 0.97 in the Israeli center and 93.2% accuracy, ROC 0.89 in the Italian center). In the full cohort, left ventricular ejection fraction (LVEF) post-STEMI demonstrated the strongest contribution towards predicted outcome with a mean Shapley value (SHAP) of 0.978, with lower EFs correlating to higher likelihood of one-year mortality (figures 1 and 2). Other strong contributing factors were identified, including glomerular filtration rate (GFR), age, and Killip classification, with mean SHAPs of 0.580, 0.571, and 0.563, respectively. Importantly, the algorithm was designed to also output a personalized assessment of risk for each patient based on their individual variables. Conclusion ML-derived STEMI calculators can determine which risk factors and variables provide highest predictive value in determining outcomes in a personalized manner. They can be leveraged for high-accuracy prognostication and provide guidance for physicians and patients after STEMI.

Effect of sodium-glucose cotransporter-2 inhibitor (SGLT2-i) in patients with LVAD: a systematic review and meta-analysis

Abstract Introduction Sodium-glucose cotransporter-2 inhibitor (SGLT2-i) have been shown to reduce risks of clinical events in patients with heart failure (HF). However, data on the use of SGLT2-i in patients with left ventricular assist devices (LVAD) are scarce. We thought to assess the efficacy and safety of SGLT2-i in patients with LVAD Methods A systematic search was done in PubMed, Scopus, Web of Science, Embase, and Cochrane from inception to December 2023. We used all relevant words for "SGLT2-i" and "LVAD" to search in databases and we included studies and published abstracts in peer-reviewed journals of studies assessed SGLT2-i in patients with LVAD. The efficacy and safety data were extracted across the studies. RevMan 5.4.1 was used for meta-analysis. Results Three studies and eight abstracts totaling 209 patients using SGLT2-i were included. Empagliflozin, Dapagliflozin, and Canagliflozin were the used SGLT2-i across the included studies. SGLT2-i effectively decreased hemoglobin A1c (HbA1c) (Mean = -0.44, 95% CI [-0.79, -0.09], p = 0.01) and diuretic dose (Mean=-2.54, 95% CI [-3.56, 1.51], p< 0.00001) from baseline. No significant improvement was found for glomerular filtration rate (GFR), B-type natriuretic peptide (BNP), or mean pulmonary artery pressure (MPAP). Regarding safety, the pooled percentage of people with driveline infection was 9.33%, 95% CI [2.05, 16.60], p=0.01. Conclusion SGLT2-i effectively improves HbA1c and diuretic dose in patients using LVAD. Further randomized studies with a large number of participants may be warranted.

Utilization and safety of digoxin in patients with chronic heart failure and atrial fibrillation with rapid ventricular rate

Abstract Background Digoxin can reduce symptoms and the risk of tachycardia-induced cardiomyopathy in patients with heart failure (HF) and concomitant atrial fibrillation (AF) with rapid ventricular rate. The effect of digoxin in HF and AF has not been tested in randomized controlled trials, and observational data have shown conflicting results linking digoxin to increased mortality in AF, though the nature of observational data makes it prone to bias and results difficult to interpret. Purpose To assess the utilization of digoxin in patients with HF and AF, and its association with New York Heart Association (NYHA) functional class and survival. Methods We used data from the Norwegian HF registry that collected data from all Norwegian HF clinics between 2013-2022. Data was collected from the first and last visit during optimizization of HF medical therapy. Associations with mortality status from Statistics Norway were assessed in unadjusted time-to-event analysis, and after adjustment for age, sex, body mass index, estimated glomerular filtration rate, aldosterone antagonists, renin-angiotensin-aldosterone system inhibitors, and beta blockers. Results The study included 4,877 HF patients, consisting of 4,067 (83.4%) with ejection fraction (EF) ≤40% and 810 (16.6%) with EF >40%.. The mean age was 67.7±12.0 years; 25.1% were women, and 27.3% had NYHA functional class III/IV. At the first visit, 1,339 (27.5%) patients had AF and 829 (61.9%) of these were treated with ≥50% of the beta-blocker target dose. AF with a ventricular rate ≥100 bpm was present in 277 (20.1%) patients, and 188 (67.9%) of these were on ≥50% beta-blocker target dose. Similarly, 262 (19.6%) of all AF patients and 44 (15.9%) of those with a ventricular rate ≥100 bpm were treated with digoxin. After optimization of HF medical therapy (median duration 140 [Q1–Q3 82–237] days), 1,039 (21.3%) patients had AF. Among these, 227 (21.9%) were treated with digoxin, including 9 (18.0%) patients with ventricular rate ≥100 bpm. Patients with AF who were started on digoxin experienced during the optimization period a larger decline in heart rate compared to those who were not (mean change -23.7±17.2 vs. -5.7±16.7 bpm, p=0.001), and more often an improvement in NYHA functional class (45% vs 30%, p=0.018). During median 779 [Q1–Q3 386–1,334)] days of follow-up after the last optimization visit, digoxin use was associated with lower mortality in HF patients with AF in unadjusted analysis (HR 0.67 [0.46–0.97]). After adjustment for baseline characteristics and other HF medical therapies, the association with mortality was attenuated and no longer significant (HR 0.96 [0.65–1.42]). Conclusion Digoxin was infrequently used in patients with HF and AF with rapid ventricular rate but was associated with a greater decrease in heart rate and improvement in NYHA functional class. The use of digoxin appears safe and was not associated with increased mortality.

Lipid goal attainment across baseline socioeconomic and clinical factors comparing an "inclisiran first" implementation strategy and usual care: subgroup analysis of VICTORION-INITIATE

Abstract Background Addressing inequities in cardiovascular care has become a public health priority. Recent results from VICTORION-INITIATE, a pragmatically designed, randomised clinical trial showed the benefit of using inclisiran immediately if patients with atherosclerotic cardiovascular disease (ASCVD) fail to achieve low-density lipoprotein cholesterol (LDL-C) <70 mg/dL (1.8 mmol/L) on maximally tolerated statins. Purpose To evaluate effectiveness and safety of an "inclisiran first" implementation strategy (IF) versus usual care (UC) in subgroups that may be associated with healthcare inequities. Methods VICTORION-INITIATE was conducted at 45 representative clinical settings across 20 states in the USA. Patients with ASCVD randomised 1:1 (stratified by insurance status) received open-label inclisiran 284 mg at Days 0, 90 and 270) plus UC or UC alone (lipid management directed by treating physicians). Treating physicians had access to LDL-C measurements and were encouraged to intensify treatment per lipid guidelines. We compared efficacy and safety endpoints for IF and UC in prespecified subgroups (race, ethnicity, sex, renal function and statin intensity) and by income level (post-hoc analysis). Results The study randomised 450 patients. Baseline demographic and clinical parameters were balanced between study arms (≥65 years of age: IF: 63.1%, UC: 61.3%; non-White: IF: 15.6%, UC: 15.1%; Hispanic: IF: 13.8%, UC: 16.9%; female: IF: 29.8%, UC: 32.0%; income ≤$50,000: IF: 58.7%, UC: 58.2%; estimated glomerular filtration rate ≥30 to <60 mL/min/1.73m2: IF: 20.0%, UC: 17.8%; no statins at baseline: IF: 9.8%; UC: 10.2%). Across all subgroups, more patients achieved LDL-C goals at Day 330 with IF vs UC (Figure 1). Within the UC arm, the proportions of patients achieving LDL-C <70 mg/dL and <55 mg/dL, respectively, were numerically lower for non-White (8.8% and 2.9%) and Hispanic (10.5% and 2.6%) than White (24.6% and 10.2%) and non-Hispanic (24.9% and 10.3%) patients. We did not observe differences in LDL-C goal attainment for these subgroups in patients receiving IF. Compared with UC, IF resulted in greater mean percentage change in other lipids and lipoproteins from baseline to Day 330, irrespective of subgroup (Figure 2). Incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs compared similarly between IF and UC for each subgroup (IF: 35.5−69.2%, UC: 34.2−84.2%, and IF: 3.2−16.9%, UC: 0.0−36.8%, respectively). Conclusions VICTORION-INITIATE enrolled a diverse population reflective of "real-world" US clinical practice. The IF strategy consistently resulted in higher rates of LDL-C goal attainment for all subgroups studied and did not lead to differences in lipid outcomes by race or ethnicity as compared to usual care. No additional safety concerns for the IF strategy were identified.

Is chronic kidney disease predictive of coronary artery bypass grafting after acute coronary syndrome? A systematic review and meta-analysis

Abstract Background Coronary artery bypass grafting (CABG) provides superior long-term outcomes to percutaneous coronary intervention (PCI) for multi-vessel coronary artery disease. People with chronic kidney disease (CKD) are at increased risk of multi-vessel coronary artery disease, and experience greater morbidity and mortality following acute coronary syndrome (ACS). Purpose To determine whether CKD affects choice of revascularisation strategy after ACS. Methods We searched EMBASE, MEDLINE, SCOPUS, CENTRAL and the NIHR’s website of funded studies to identify articles referring to ACS and invasive coronary management in high-income countries over the past 12 years until 29th September 2023. Full text articles were included if data on rates of CABG were reported in people with and without CKD who were revascularised following ACS. CKD was defined as one or more recording of an estimated glomerular filtration rate (eGFR) <60mls/min/1.73m2, however proxies for this were accepted. Risk of bias was assessed via ROBINS-E. Random effect meta-analyses estimated the odds ratios for CKD and CABG, stratified by ACS type and receipt of dialysis. Certainty of evidence was assessed according to GRADE. Results Initial searches generated 15,138 articles, of which 13 observational studies were included in this review (8,021,743 participants). Amongst people revascularised following ACS, those with CKD were more likely to receive CABG than those without kidney disease (OR for the average exposure effect 1.47 (95% CI 1.30-1.66)). The likelihood of CABG in people with CKD receiving dialysis and those with CKD not receiving dialysis were similar as the 95% confidence intervals demonstrate (ORs 1.25 (95% CI 1.00-1.57) and 1.41 (1.19-1.67) respectively). The effect of CKD on increased likelihood of CABG appeared greater following ST-elevation myocardial infarction (STEMI) than non-ST elevation ACS (NSTE-ACS) (OR 1.53 (95% CI 1.27-1.83) versus 1.10 (0.98-1.25) respectively, p=0.003). Certainty of the evidence was low for receipt of CABG in people with CKD not receiving dialysis, and moderate for all other outcomes. Conclusion In high-income countries, CKD is associated with increased receipt of CABG amongst people revascularised following ACS. This finding is likely explained by the greater prevalence of multi-vessel coronary artery disease in this population. It is however unclear why the association between CKD and receipt of CABG is stronger in those with STEMI compared to NSTE-ACS, and whether this accurately reflects differential need between the two groups.Figure 1Figure 2

Empaglifozin modifies the arterial stiffness in type-2 diabetic patients: a preliminary report.

Abstract Background Sodium-glucose cotransporter-2 (SGLT2) inhibitors demonstrated beneficial effects on cardiovascular and renal events in patients with type 2 diabetes mellitus. The mechanisms underlying these effects are not fully elucidated. Aim of this study was to investigate whether empagliflozin is able to modify the arterial stiffness in type 2 diabetic patients. Methods Pulse wave velocity (PWV) and other parameters of arterial stiffness were assessed before and after adding empagliflozin to a traditional antidiabetic treatment in 16 consecutive T2DM outpatients folowed for 3 months. Arterial stiffness were evaluted using SphygmoCor ECEL measuring the pulse waveform of the arterial pulse moving from tha descending aorta to the femoral artery (PWV). Data obtained from the diabetic population has been compared to 16 T2DM outpatients not treated with SGLT2 inhibitors. Results In the two groups differences according gender distribution or duration of diabetes mellitus did not emerge. However the empagliflozin group was younger compared to controls (64.1±8.68 vs 74.45±8.13, P < 0.05). Empagliflozin treatment significantly decreased HbA1c after 12 weeks of treatment (7.9±0.78 vs 7.04±1.09%, P < 0.008.). After 12 weeks’ treatment, empagliflozin significantly improved PWV compared to controls not treated with SGLT2-i (ΔPWVV -0.68±1.1 vs 0.89±1,6 p <0.004, P = 0.0065 with age and HbA1c as covariates). Moreover body weight significantly decreased in the empagliflozin group (86.75±16.16 vs 81.71±16.5 kg, p =0.001) compared to controls (in whom remained unchanged) as long as BMI (30.48±5.4 versus 28.75±5.66 kg/m2, P < 0.002) compared to controls (in whom remained unchanged). Estimated glomerular filtration rate (eGFR) remained unchanged in the two groups during the study whereas urine Albumin to Creatinine ratio significantly improved using empagliflozin (17.8±46.8 vs 12.2±35.7 mg/mmol, P = 0.049). Conclusion In this ‘real clinical practice’ experience, the potential effect of empagliflozin treatment on arterial stiffness in T2DM patients was extensively investigated. Arterial stiffness was significantly decreased adding empaglifozin to the traditional treatment and this result has been obtained after 3-month. Significantly improvement in urine Albumin to Creatinine ratio might suggest an amelioration of endothelial function in those patients that could be involved in reducing arterial stiffness.

Changes in N-terminal pro b-type natriuretic peptide according to SGLT2 inhibitor utilization patterns in patients hospitalized for decompensated heart failure: a prospective cohort study

Abstract Introduction Sodium-glucose cotransporter-2 (SGLT2) inhibitors have found success in treating patients with chronic heart failure (HF) across the entire spectrum of left ventricular ejection fraction (EF). Their benefits may also extend to patients with acute HF decompensation, as they may aid effective decongestion. Purpose This study aims to present the various patterns in changes of N-terminal pro b-type natriuretic peptide (NT-proBNP) according to SGLT2 inhibitor use in patients hospitalized for acute HF decompensation. Methods In this prospective cohort study, we enrolled consecutive patients hospitalized for HF decompensation during a 4-month period in a cardiology department. Prior medical history and cardiovascular risk factors were recorded. The patterns in SGLT2 inhibitor use were noted and patients were classified into three groups; Group 1 (No SGLT2 inhibitor use/Discontinuation), Group 2 (Prior SGLT2 inhibitor use and continuation), and Group 2 (SGLT2i-naïve and initiation). Categorization according to left ventricular (EF) to HF with reduced EF (HFrEF), HF with mildly reduced EF (HFmrEF), and HF with preserved EF (HFpEF) was also performed. Moreover, estimated glomerular filtration rate (eGFR) was used as an estimate of renal function. Results In this analysis, 159 patients were included (median age: 79 years old, male sex: 64.8%, median duration of hospitalization: 6 days). In this population, 67.9% of the patients were not receiving a SGLT2 inhibitor on admission. Concerning demographic and clinical variables (Figure 1), there were no major differences in age, sex distribution, history of diabetes mellitus, dyslipidemia, and atrial fibrillation, as well as in renal function. Group 2 patients had a lower prevalence of arterial hypertension compared to Group 3 (36.6% vs. 52.6%, p<0.05). Moving to the changes in NTproBNP (Figure 2), we observed that patients who did not use SGLT2 inhibitors and did not initiate them during hospitalization had negligible changes in NTproBNP, either as an absolute change (Group 1: 506 (8792) pg/ml vs. Group 2: -5610 (9461) pg/ml vs. Group 3: -3602 (4409) pg/ml, p=0.001) or as percentage change (Group 1: -2.1 (63.4) % vs. Group 2: -30.3 (39.0) % vs. Group 3: -38.3 (41.5) %, p=0.001), compared to the rest of the study population who were already taking SGLT2 inhibitors or initiated them during hospitalization. Conclusion In this study we found NTproBNP, a widely used biomarker of congestion and prognosis in HF, was significantly reduced in decompensated HF patients receiving SGLT2 inhibitors, with the greatest change being observed in those being treatment-naïve prior to admission. These findings further highlight the role of this drug class even in the acute phase of the disease.Figure 1Figure 2

Longitudinal and cross-sectional associations of NT-proBNP with kidney function and chronic kidney disease: results from KORA cohort studies

Abstract Background Chronic kidney disease (CKD) and cardiovascular disease (CVD) exhibit a bidirectional and complex relationship, and share common risk factors and mechanisms of disease development. Thus, important CVD-related biomarkers, such as N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), may serve as a biomarker for CKD development. Purpose We aimed to investigate the cross-sectional and longitudinal associations of NT-proBNP with kidney function and CKD in data from two population-based cohort studies. Methods We included 5854 men and women, aged 25-74 years, from the Cooperative Health Research in the Region of Augsburg (KORA) cohort studies S3 and S4, and their 1-2 subsequent follow-up surveys, with a median follow-up time of 9.4 and 13.4 years, respectively. Kidney function was assessed by 3 estimated glomerular filtration rate (eGFR) assessments, calculated using creatinine (eGFRcr), cystatin C, and combined creatinine and cystatin C. Serum NT-proBNP was logarithmically transformed followed by Z-score standardization and categorized into 4 groups (G1-4), <48.6, 48.6-125, 125-300, and ≥300 pg/ml. In cross-sectional analysis, linear regression and logistic regression were used to estimate β/odds ratio (OR) and their 95% confidence intervals (CIs) of continuous eGFR or prevalent CKD. For longitudinal analysis of repeated eGFR measurements during follow-up (5854 participants, 11870 observations), linear mixed-effects models were used. For incident CKD associations, interval-censored Cox regression models were performed in participants free of CKD at baseline. Results In cross-sectional analyses, higher NT-proBNP levels were associated with lower eGFR and higher prevalence of CKD across all 3 eGFR assessments. For example, results based on eGFRcr showed that the fully-adjusted β (95% CIs) for per 1 SD increase in log-transformed NT-proBNP were -1.03 (-1.42, -0.64) and -7.01 (-8.93, -5.09) 60 ml/min/1.73m2 for G4 compared to G1, respectively. Corresponding OR (95% CIs) were 2.22 (1.81, 2.74) and 13.8 (5.76, 36.4), respectively. In longitudinal analyses, participants with higher baseline NT-proBNP had a faster decline in eGFR during follow-up. The fully-adjusted β (95% CIs) for 5-year eGFRcr decline were -0.67 (-0.87, -0.47) per 1 SD increase, and -0.37 (-0.79, 0.05), -1.53 (-2.18, -0.88), -4.24 (-5.57, -2.90) 60 ml/min/1.73m2/year for G2-4. Higher NT-proBNP levels were associated with higher incident CKD risks. For associations with incident creatinine-based CKD, hazard ratio (95% CIs) were 1.16 (1.00, 1.33) per 1 SD increase and 1.03 (0.77, 1.38), 1.07 (0.75, 1.52), and 1.81 (1.07, 3.04) for G2-4. Conclusions We found associations of higher NT-proBNP with lower kidney function and higher CKD prevalence. Moreover, higher baseline NT-proBNP levels were associated with faster kidney function decline and higher incident CKD risks. Our findings indicate the potential utility of NT-proBNP as a biomarker of kidney health.Figure 1.Cross-sectional associationsFigure 2.Longitudinal associations

Prognostic importance of persistent elevations in high-sensitivity troponin T in the early convalescent phase (two weeks) following high-risk myocardial infarction: insights from the PARADISE-MI trial

Abstract Introduction Myocardial infarction (MI) is defined by a rise and fall in cardiac troponin (cTn) with clinical evidence of acute myocardial ischemia. How often cTn remains elevated in high-risk patients stabilized following MI and the relation between convalescent cTn levels and subsequent clinical outcomes in these patients is unknown. Aims To evaluate the prognostic importance of high-sensitivity cTn T (hs-cTnT) in the early convalescent phase of a MI for a range of cardiovascular (CV) outcomes in patients enrolled in the Prospective ARNI vs ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI). Methods Patients ≥18 years without prior heart failure (HF) (n=5661) were randomized to sacubitril/valsartan or ramipril within 0.5 to 7 days of MI complicated by transient pulmonary congestion, LVEF ≤40%, or both. Hs-cTnT was measured using the Roche Elecsys Troponin T-high-sensitive assay in 1093 patients two weeks after randomization (median 2.6 weeks after the index MI). Associations between log (2)-transformed hs-cTnT and clinical outcomes were investigated in landmark analyses using Cox regression models adjusted for clinical covariates of known prognostic importance and NT-proBNP (Figure). Results Median week 2 hs-cTnT concentration was 34 ng/L [IQR 17-94 ng/L] and exceeded the 99th percentile upper reference limit in 69% of patients. Patients with persistently elevated hs-cTnT concentrations (n=753) were older, more likely men, more commonly had atrial fibrillation and lower estimated glomerular filtration rate and less likely had a prior MI. They more commonly had presented with ST-segment elevation MI and pulmonary congestion and had higher concentrations of NT-proBNP. Rates of primary reperfusion were similar. Log(2)-transformed hs-cTnT was only weakly correlated with LVEF (rho = -0.15, p<0.001), irrespective of the type of MI. hs-cTnT was independently and linearly associated with the primary composite outcome of CV death or incident HF (adj HR 1.17 per doubling; 95% CI, 1.03 – 1.34), all-cause death (adj HR 1.20; 95% CI, 1.01 – 1.44) and CV death (adj HR 1.25; 95% CI, 1.02 – 1.52) but not with non-CV death (adj HR 1.04; 95% CI, 0.70-1.54). hs-cTnT was not significantly associated with recurrent fatal or non-fatal MI (adj HR 1.00; 95% CI, 0.85-1.18) (Figure). Concentrations of week 2 hs-cTnT were not altered by sacubitril/valsartan relative to ramipril (+4%; 95% CI, -8% to 18%). Conclusions Persistent elevations in hs-cTnT during the early convalescent phase following high-risk MI are common and are associated with heightened risk of all-cause death, CV death and incident HF but not of recurrent MI or non-CV death. hs-cTnT measured ~2.5 weeks after high-risk MI provides incremental prognostic information beyond traditional risk factors and NT-proBNP.

Quality of muscle in the thigh predicts the prognosis in patients with non-ischemic cardiomyopathy

Abstract Background Skeletal muscle atrophy is an independent prognostic predictor for patients with chronic heart failure, and the concept of sarcopenia has garnered scientific attention. Furthermore, the importance of not only muscle mass but also quality of muscle has been pointed out. And a sarcopenia diagnosis is confirmed by the presence of low quality of muscle. However, there is a lack of consensus on the implications of ectopic fat as a quality of muscle for the prognosis in patients with non-ischemic cardiomyopathy. Purpose We investigated whether intramuscular fat (IMF) in the thigh affects the prognosis in patients with non-ischemic cardiomyopathy. Methods We recruited 250 patients who were diagnosed with non-ischemic cardiomyopathy by cardiac catheterization and echocardiographic date between September 2017 and November 2022. Finally, 223 patients enrolled in this prospective study conducted at a single center. Functional status was evaluated by using cardiopulmonary exercise test at baseline. All patients were measured quantity of the percentage of IMF (%IMF) in the thigh using computed tomography scan. Demographic, laboratory and echocardiographic date were collected from the patients’ medical records. Patients were followed up for up to 3 years. Clinical endpoints were cardiovascular death or unexpected rehospitalization because of cardiac events. Results During the follow-up 58 patients had cardiac events. The %IMF was significantly higher in the group with adverse events than without (4.49 ± 4.21 and 3.06 ± 2.39%, respectively; p = 0.001). Spearman correlation coefficient analysis showed a modest correlation between %IMF and exercise tolerance such as anaerobic threshold (Spearman r = -0.367; p < 0.001) and peak oxygen uptake (Spearman r = -0.382; p < 0.001). Patients were divided into 2 groups according to the median values of %IMF. Kaplan-Meier analysis demonstrated that events were significantly higher in the high %IMF group (log-rank p = 0.008). Furthermore, subgroup with left ventricular ejection fraction ≦ 40% or BMI ≧ 22 had a significantly greater frequency of adverse events in the high %IMF group. However, there was no significant difference in %IMF between the groups when divided into two groups at the mean age of this study. Multivariate Cox regression analysis adjusted for left ventricular ejection fraction, estimated glomerular filtration rate, hemoglobin and body mass index found %IMF as an independent factor of adverse events (hazard ratio 1.088; 95% confidential interval 1.024-1.156; p = 0.007). Conclusions In patients with non-ischemic cardiomyopathy, quality of muscle represented by %IMF in the thigh is an independent factor for predicting adverse cardiac events.

The role of semi-quantitative parameters of thallium-201 myocardial perfusion imaging in predicting mortality rate among CKD population

Abstract Background Chronic kidney disease (CKD) is a major public health concern worldwide, with high morbidity and mortality rates. Myocardial perfusion imaging (MPI) is a non-invasive diagnostic tool that can detect early-stage cardiovascular disease in CKD patients. Purpose This study aimed to investigate the role of semi-quantitative parameters of Thallium-201 MPI in predicting mortality rates among CKD patients. Methods This retrospective study included 579 CKD patients who underwent Thallium-201 MPI between October 2005 and December 2019. Semi-quantitative parameters were analyzed using automation software, including transient ischemic dilation (TID), lung-to-heart ratio (LHR), total perfusion deficit (TPD), summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), summed thickening percent (ST%), summed motion percent (SM%), stress end-diastolic volume (EDV), stress end-systolic volume (ESV), and stress left ventricular ejection fraction (LVEF). The primary endpoint was overall mortality. Results During a median follow-up of 52 months, 148 patients died. The older age group, lower hemoglobin levels, and lower estimated glomerular filtration rate (eGFR) were associated with higher mortality rates. The semi-quantitative parameters that predicted overall mortality included LHR above 0.4, elevated ST% , increased stress EDV and ESV, and reduced stress LVEF in a multivariable Cox regression model. Conclusion Thallium-201 MPI with semi-quantitative parameters can predict mortality rates in CKD patients without a definite diagnosis of coronary artery disease. The identified parameters, including LHR above 0.4, elevated ST levels, increased stress EDV and ESV, and reduced stress LVEF can assist in early detection the mortality risk in CKD patients.Characteristics of CKD PatientsMultivariable Analysis

Comparison of the prognosis between complete and incomplete revascularization among moderate to severe chronic kidney disease patients with acute coronary syndrome

Abstract Background Complete revascularization (CR) in acute coronary syndrome patients with multivessel disease (MVD) is recommended in current clinical practice guidelines. However, the benefit of CR in moderate to severe chronic kidney disease (CKD) patients remains controversial. We aimed to compare the clinical outcomes between complete and incomplete revascularization among moderate to severe CKD patients who presented with ACS. Methods Of 1,924 ACS patients who underwent percutaneous coronary intervention (PCI) in our center, 127 patients were CKD. CR was defined as residual SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score ≤ 3. The primary outcome was the patient oriented clinical outcome (POCO) at 1 year, including all-cause death, any myocardial infarction, any revascularization, and heart failure requiring hospitalization. Results The mean age of the patients was 73.89±9.07 years. The median estimated glomerular filtration rate (eGFR) was 32.56±10.68 ml per minute per 1.73 m2. The rate of POCO at 1 year was significantly lower in the CR group (16.3% vs 39.3%; HR 0.36; 95%CI, 0.16-0.81; p=0.014). The primary outcome was mainly driven by 1-year all-cause death which was significantly lower in the CR group (14.0% vs 39.3%; HR 0.32; 95%CI 0.13-0.76; p=0.017). The rate of initiation of renal replacement therapy was comparable (4.7% vs 2.4%; p=0.55). Conclusion CR with a target SYNTAX score ≤ 3 improved 1-year prognosis of POCO and all-cause death in ACS patients with moderate to severe CKD without increasing the rates of renal replacement therapy.1-year POCOPrespecified Subgroup Analysis of POCO

Treatment with mTOR Inhibitors as primary immunosuppression after combined heart and kidney transplantation

Abstract Background It has been hypothesized that combined heart and kidney transplantation (HKT) may lead to immune modulation and attenuation of cardiac allograft vasculopathy (CAV) progression. Sirolimus (SRL) has been shown to mitigate the progression of CAV and confer renal protection. With the increasing use of SRL as primary immunosuppression in heart transplant (HT) recipients, the effect of HKT on CAV progression compared to HT-only remains undetermined. Purpose We sought to investigate the patterns of conversion from calcineurin inhibitors (CNI) to SRL, and its impact on CAV progression and outcomes in HKT compared to HT-only in a cohort with frequent use of SRL as primary immunosuppression. Methods A cohort of 302 patients who underwent either HT only (n=262) or combined HKT (n=40) was analyzed. CAV progression was assessed by measuring the delta (Δ) annual change in plaque volume (PV) normalized to vessel length (PV/VL in mm3/mm) and plaque index (PI) (%) (calculated as the PV to VV ratio) between baseline and last follow-up coronary intravenous ultrasound (IVUS). Clinical adverse outcomes included all-cause death and CAV-associated events. Secondary outcomes included differences in renal function and incidence of SRL-associated proteinuria (defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL) between HT-only and HKT recipients. Results Overall, 217 (72%) patients were converted from CNI to SRL as primary immunosuppression. HT recipients were more likely to be converted to SRL than combined HKT recipients (74% vs. 55%, P=0.01). HKT was associated with significantly higher ΔPV/VL (P=0.01) and a trend toward a higher ΔPI (P=0.06) than HT-only, but this association was markedly attenuated after adjustment to SRL conversion. HKT was associated with similar risk of death (adjusted hazard ratio [HR] 0.69, 95%CI: 0.28-1.71, P=0.43) and CAV-related events (adjusted HR 0.83, 95% CI: 0.30-2.31, P=0.72). Conversion to SRL was significantly associated with decreased risk of death and CAV-related events in the overall cohort. This association was not modified by the type of organ transplantation (Pinteraction=NS), and without a significant effect on estimated glomerular filtration rate (eGFR) or proteinuria. Conclusions HKT recipients compared to HT-only were less likely to be converted from CNI to SRL-based immunosuppression and had a greater CAV progression but without significant differences in all-cause mortality or CAV-related events. The clinical benefit and safety of conversion to SRL appeared similar in the HKT and isolated HT cohorts.

Blood pressure and renal function responses in workers exposed to lead for up to six years

Abstract Background Lead is a widespread environmental toxicant. However, there is currently no consensus whether low-level lead exposure raises blood pressure (BP) or induces kidney dysfunction. Purpose The Study for Promotion of Health in Recycling Lead (SPHERL) assessed the BP and renal function (RF) responses for up to six years in the workers without previous occupational lead exposure. Methods BP was the average of 5 consecutive readings and the estimated glomerular filtration rate was derived from serum creatinine (eGFRcrt) and cystatin C (eGFRcys). Blood lead (BL) was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 mg/dL). The statistical methods included multivariable-adjusted mixed models and interval-censored Cox regression analysis. Results The 234 workers analyzed were on average 28.5 years old and included 91.9% men. The baseline BL concentration was 4.35 µg/dL and increased 3.17-fold over follow-up (median: 2.03 years; range: 0.92-6.45 years). The changes in BP and RF were not significantly correlated with the follow-up-to-baseline BL ratio (p≥0.51 and p≥0.18, respectively). The fully-adjusted changes in systolic/diastolic BP associated with a doubling of BL were -0.25/-0.12 mm Hg (CI: -0.94 to 0.44/-0.66 to 0.42 mm Hg). Accordingly, the incidence of stage-1 or -2 hypertension was not associated with the BL change (p≥0.063). Similarly, the changes in eGFRcrt and eGFRcys associated with a 3-fold BL increment were not significant, amounting to -0.70 mL/min/1.73 m2(CI: -1.70 to 0.30 mL/min/1.73 m2) and -1.06 ml/min/1.73 m2 (-2.16 to 0.03 mL/min/1.73 m2). Conclusion The BP and RF responses to an over 3-fold BL increment were small and not significant confirming the safety of modern lead-handing facilities operating under current safety rules.Figure 1Figure 2

Blood pressure and renal function changes in patients with severe chronic kidney disease undergoing radiofrequency renal denervation: 12 months outcomes from the Global SYMPLICITY Registry DEFINE

Abstract Background Radiofrequency renal denervation (RF RDN) lowers blood pressure (BP) in patients with uncontrolled hypertension (HTN). The impact of renal function on safety and efficacy of RDN is unknown. Purpose To assess BP and renal function in patients with HTN following RDN. Methods All patients treated with RF RDN (n=3332) from the observational Global SYMPLICITY Registry Denervation Findings in Real World (GSR DEFINE) were included. Patients were categorized into CKD stages by the corresponding estimated glomerular filtration rate (eGFR; mL/min/1.73m2): <45 (CKD stage 3b and higher; n=339), 45-59 (CKD stage 3a; n=467), ≥60 (CKD stage 2 and lower; n=2334). BP (office, 24h ambulatory BP), eGFR changes from baseline through 12 months were compared between groups. Comparisons between groups were made after adjusting for baseline BP and change in number of antihypertensive drug classes from baseline. Results At baseline, office systolic SBP (OSBP) in eGFR groups <45, 45-59, and ≥60 ml/min/1.73 m2 was: 164±25, 163±26 and 165±25 mmHg, respectively (p=0.083). 24-h ambulatory systolic BP (ASBP) was: 156±19, 153±20 and 154±19 mmHg, respectively (p=0.082). Mean eGFR was: 32.5±11.2, 53.6±4.4, and 86.8±18.6 ml/min/1.73 m2, respectively. A total of 1.1% of patients were on dialysis. Patients in eGFR group <45 ml/min/1.73 m2 were significantly older, had higher rates of ischemic heart disease, heart failure, diabetes, on more antihypertensive drug classes compared to higher eGFR groups. Patients were on 5.0±1.3, 4.6±1.3, and 4.5±1.4 antihypertensive drugs in eGFR <45, 45-59 and ≥60 ml/min/1.73 m2 groups, respectively (p<0.001). At 12 months, all had significant OSBP drop from baseline within the different eGFR groups (p<0.001). OSBP changed by -10.8±27.8, -10.5±25.9 and -14.7±26.6 mmHg in eGFR <45, 45-59 and ≥60 ml/min/1.73 m2 groups, respectively (adjusted p=0.095; Figure 1A). Similarly at 12 months, all patients had significant ASBP reductions from baseline across the eGFR groups (p<0.01). ASBP changed by -5.2±18.0, -6.9±18.8, and -8.5±18.8 mmHg in eGFR <45, 45-59 and ≥60 ml/min/1.73 m2 subgroups, respectively (adjusted p=0.16). At 12 months, eGFR did not significantly change from baseline in eGFR <45 and 45-59 ml/min/1.73 m2 groups (Figure 1B): 0.1±14.6 (p=0.92) and -0.6±12.8 ml/min/1.73 m2 (p=0.45), respectively. Estimated GFR changed from baseline by -5.6±15.5 ml/min/1.73 m2 in eGFR ≥60 ml/min/1.73 m2 group (p<0.001). Between group differences in eGFR changes were statistically significant (adjusted p<0.001), but by a numerically small difference. The no. of antihypertensive drug classes changed by -0.2±1.3, -0.1±1.0 and -0.1±1.0 in eGFR <45 and 45-59 ml/min/1.73 m2 groups, respectively. Conclusion Patients with uncontrolled HTN with different CKD severity including those with eGFR <45 ml/min/1.73 m2 had significant SBP reductions from baseline through 12 months, whilst renal function was preserved.Figure 1

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.