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Aims: It is common practice for clinicians to advise fluid restriction in patients with heart failure (HF), but data from clinical trials are lacking. Moreover, fluid restriction is associated with thirst distress and may adversely impact quality of life (QoL). To address this gap in evidence, the Fluid REStriction in Heart failure vs liberal fluid UPtake (FRESH-UP) study was initiated. Methods: The FRESH-UP study is a randomized, controlled, open-label, multicenter trial to investigate the effects of a 3-month period of liberal fluid intake vs fluid restriction (1500 mL/day) on QoL in outpatients with chronic HF (New York Heart Association Classes II-III). The primary aim is to assess the effect on QoL after 3 months using the Overall Summary Score of the Kansas City Cardiomyopathy Questionnaire (KCCQ). Thirst distress, as assessed by the Thirst Distress Scale for patients with HF, KCCQ Clinical Summary Score, each of the KCCQ domains and clinically meaningful changes in these scores, the EQ-5D-5L, patient-reported fluid intake and safety (ie, death, HF hospitalizations) are secondary outcomes. The FRESH-UP study is registered at ClinicalTrials.gov (NCT04551729). Conclusion: The results of the FRESH-UP study will add substantially to the level of evidence concerning fluid management in chronic HF and may impact the QoL of these patients. Funding Agencies|Dutch Heart Foundation [2019T100]; Radboud University Medical Centre in Nijmegen [R0005106]; Maastricht University Medical Centre [R0005106]

Aims We sought to compare the generalizability and prognostic implications of heart failure with preserved ejection fraction (HFpEF) scores (HFA-PEFF and H2 FPEF score) in Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) and Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial participants and matched controls from the Atherosclerosis Risk in Community (ARIC) study. Methods and results Based on the respective scores, the study participants from the TOPCAT (N = 356), RELAX (N = 216), and ARIC (N = 379) studies were categorized as having a low, intermediate, or high likelihood of HFpEF. Age, sex, and race matched controls free of cardiovascular disease who had unexplained dyspnoea were used to evaluate the diagnostic performance. The prognostic value of scores was assessed using multivariable-adjusted Cox regression analyses. The median HFA-PEFF scores in the TOPCAT, RELAX, and ARIC studies were 5.0 [interquartile range (IQR): 5.0-6.0], 4.0 (IQR: 2.0-4.0), and 3.0 (IQR: 2.0-4.0), respectively. The median H2 FPEF scores in the three studies were 5.5 (IQR: 4.0-7.0), 6.0 (IQR: 4.0-7.0), and 3.0 (IQR: 2.0-5.0), respectively. A low HFA-PEFF and H2 FPEF score can rule out HFpEF with high sensitivity (99.5% and 99.6%, respectively) and negative predictive value (95.7% and 98.3%, respectively). A high HFA-PEFF and H2 FPEF score can rule-in HFpEF with good specificity (82.8% and 95.6%, respectively) and positive predictive value (79.9% and 90.4%, respectively). Among TOPCAT participants, the hazard for adverse cardiovascular events per point increase in HFA-PEFF and H2 FPEF score was 1.26 (95% confidence interval: 0.98-1.63) and 1.01 (95% confidence interval: 0.88-1.15), respectively. A higher H2 FPEF score was associated with lower peak oxygen intake in RELAX trial participants (adjusted P = 0.01). Conclusions The HFA-PEFF and the H2 FPEF scores are reliable diagnostic tools for HFpEF. The prognostic utility of HFpEF scores requires further validation in larger rigorously phenotyped populations.

Background: A systemic proinflammatory state has been hypothesized to mediate the association between comorbidities and abnormal cardiac structure/function in heart failure with preserved ejection fraction (HFpEF). We conducted a proteomic analysis to investigate this paradigm. Methods: In 228 patients with HFpEF from the multicenter PROMIS-HFpEF study (Prevalence of Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction), 248 unique circulating proteins were quantified by a multiplex immunoassay (Olink) and used to recapitulate systemic inflammation. In a deductive approach, we performed principal component analysis to summarize 47 proteins known a priori to be involved in inflammation. In an inductive approach, we performed unbiased weighted coexpression network analyses of all 248 proteins to identify clusters of proteins that overrepresented inflammatory pathways. We defined comorbidity burden as the sum of 8 common HFpEF comorbidities. We used multivariable linear regression and statistical mediation analyses to determine whether and to what extent inflammation mediates the association of comorbidity burden with abnormal cardiac structure/function in HFpEF. We also externally validated our findings in an independent cohort of 117 HFpEF cases and 30 comorbidity controls without heart failure. Results: Comorbidity burden was associated with abnormal cardiac structure/function and with principal components/clusters of inflammation proteins. Systemic inflammation was also associated with increased mitral E velocity, E/e′ ratio, and tricuspid regurgitation velocity; and worse right ventricular function (tricuspid annular plane systolic excursion and right ventricular free wall strain). Inflammation mediated the association between comorbidity burden and mitral E velocity (proportion mediated 19%–35%), E/e′ ratio (18%–29%), tricuspid regurgitation velocity (27%–41%), and tricuspid annular plane systolic excursion (13%) ( P Conclusions: Proteins involved in inflammation form a conserved network in HFpEF across 2 independent cohorts and may mediate the association between comorbidity burden and echocardiographic indicators of worse hemodynamics and right ventricular dysfunction. These findings support the comorbidity-inflammation paradigm in HFpEF.

European journal of heart failure (2020). doi:10.1002/ejhf.1749, Published by Wiley, Oxford

ObjectivesPredicting the presence or absence of coronary artery disease (CAD) is clinically important. Pretest probability (PTP) and CAD consortium clinical (CAD2) model and risk scores used in the guidelines are not sufficiently accurate as the only guidance for applying invasive testing or discharging a patient. Artificial intelligence without the need of additional non-invasive testing is not yet used in this context, as previous results of the model are promising, but available in high-risk population only. Still, validation in low-risk patients, which is clinically most relevant, is lacking.DesignRetrospective cohort study.SettingSecondary outpatient clinic care in one Dutch academic hospital.ParticipantsWe included 696 patients referred from primary care for further testing regarding the presence or absence of CAD. The results were compared with PTP and CAD2 using receiver operating characteristic (ROC) curves (area under the curve (AUC)). CAD was defined by a coronary stenosis >50% in at least one coronary vessel in invasive coronary or CT angiography, or having a coronary event within 6 months.Outcome measuresThe first cohort validating the memetic pattern-based algorithm (MPA) model developed in two high-risk populations in a low-risk to intermediate-risk cohort to improve risk stratification for non-invasive diagnosis of the presence or absence of CAD.ResultsThe population contained 49% male, average age was 65.6±12.6 years. 16.2% had CAD. The AUCs of the MPA model, the PTP and the CAD2 were 0.87, 0.80, and 0.82, respectively. Applying the MPA model resulted in possible discharge of 67.7% of the patients with an acceptable CAD rate of 4.2%.ConclusionsIn this low-risk to intermediate-risk population, the MPA model provides a good risk stratification of presence or absence of CAD with a better ROC compared with traditional risk scores. The results are promising but need prospective confirmation.

BACKGROUND: The relationship between longitudinal clinical congestion pattern and heart failure outcome is uncertain. This study was designed to assess the prevalence of congestion over time and to investigate its impact on outcome in chronic heart failure.METHODS: A total of 588 patients with chronic heart failure older than 60 years of age with New York Heart Association (NYHA) functional class >= II from the TIME-CHF study were included. The endpoints for this study were survival and hospitalization-free heart failure survival. Orthopnea, NYHA >= III, paroxysmal nocturnal dyspnea, hepatomegaly, peripheral pitting edema, jugular venous distension, and rales were repeatedly investigated and related to outcomes. These congestion-related signs and symptoms were used to design a 7-item Clinical Congestion Index.RESULTS: Sixty-one percent of patients had a Clinical Congestion Index >= 3 at baseline, which decreased to 18% at month 18. During the median [interquartile range] follow-up of 27.2 [14.3-39.8] months, 17%, 27%, and 47% of patients with baseline Clinical Congestion Index of 0, 1-2, and >= 3 at inclusion, respectively, died (P CONCLUSIONS: The extent of congestion as assessed by means of clinical signs and symptoms decreased over time with intensified treatment, but it remained present or relapsed in a substantial number of patients with heart failure and was associated with poor outcome. This highlights the importance of appropriate decongestion in chronic heart failure. (C) 2019 Elsevier Inc. All rights reserved.

Aims This study assessed the prognostic implications of mechanical atrial dysfunction in heart failure with preserved ejection fraction (HFpEF) patients with different stages of atrial fibrillation (AF) in detail. Methods and results HFpEF patients (n = 258) systemically underwent an extensive clinical characterization, including 24-h Holter monitoring and speckle-tracking echocardiography. Patients were categorized according to rhythm and stages of AF: 112 with no history of AF (no AF), 56 with paroxysmal AF (PAF), and 90 with sustained (persistent/permanent) AF (SAF). A progressive decrease in mechanical atrial function was seen: left atrial reservoir strain (LASr) 30.5 ± 10.5% (no AF), 22.3 ± 10.5% (PAF), and 13.9 ± 7.8% (SAF), P, Graphical Abstract

Background The phenotypically heterogeneous syndrome of heart failure with preserved ejection fraction (HFpEF) is challenging to diagnose. The HFA-PEFF and H2FPEF scores were developed to guide HFpEF diagnosis but have not been directly compared. We evaluated the generalizability and prognostic implications of the two scores in Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) and PDE-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF (RELAX) trial participants and matched controls from Atherosclerosis Risk in Community (ARIC) study. Methods Participants from TOPCAT, RELAX, and ARIC studies were categorized as having low, intermediate, and high likelihood of HFpEF based on the respective scores. Diagnostic performance was evaluated using age, sex, and race matched controls, free of cardiovascular disease from ARIC study. Multivariable-adjusted Cox regression was used to assess the prognostic value of the scores. Results The median HFA-PEFF score in TOPCAT, RELAX and ARIC was 5.0 (IQR:5.0-6.0), 4.0 (IQR:2.0-4.0) and 3 (IQR:2.0-4.0), respectively. The median H2FPEF score in the three populations was 5.0 (IQR:4.0-7.0), 6.0 (IQR:4.0-7.0), and 2.5 (IQR:2.0-4.0), respectively. High HFA-PEFF scores were seen in 75.8%, 20.4%, and 16.5% of in the three populations, respectively. High H2FPEF scores were seen in 42.3%, 55.3%, and 1.9% of the three populations, respectively. Application of HFA-PEFF score categories to patients categorized using H2FPEF score led to 84.2% of TOPCAT, and 50.5% of RELAX participants being reclassified (Figure 1A,B). Using low HFA-PEFF and H2FPEF scores, HFpEF can be ruled-out with high sensitivity (99.5% and 99.9%, respectively) and high negative predictive value (95.7% and 98.5%, respectively). A high HFA-PEFF and H2FPEF score can rule-in HFpEF with good specificity (83.5% and 98.1%, respectively) and positive predictive value (80.6% and 95.5%, respectively). Among TOPCAT participants, the hazard for adverse cardiovascular events per point increase in HFA-PEFF and H2FPEF score was 1.32 (95% CI: 1.03-1.69) and 1.03 (95% CI: 0.91-1.17), respectively (Figure 1 C,D). Conclusion The HFA-PEFF and the H2FPEF scores are reliable diagnostic tools for HFpEF. The scores also provide prognostic value for the risk stratification of HFpEF patients.

BACKGROUND: The GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) trial prospectively compared the efficacy of a NT-proBNP-guided heart failure treatment strategy (target NT-proBNP level

Background: Published studies have generated mixed, controversial results regarding the Cost-effectiveness of heart failure disease management programs (HF-DMPs). This study assessed the cost-effectiveness of an HF-DMP in ambulatory patients compared with usual care (UC).Methods: In the prospective randomized REMADHE trial, we evaluated incremental costs per quality adjusted life-year (QALY) and life-year (LY) gained as effectiveness ratios (ICERs) over a study period of 2.47 +/- 1.75 years.Results: The REMADHE HF-DMP was more effective and less costly than UC in terms of both QALYs and LYs (95% and 55% chance of dominance, respectively). Average saving was US$7345 (2.5%-97.5% bootstrapped confidence interval similar to 16,573 to +921). The chance of DMP being cost-effective at a willingness to pay US$10,000 per QALY or LY was 99% and 96%, respectively. Cost-effectiveness of HF-DMP was highest in subgroups with left ventricular ejection fraction 50 years, male sex, New York Heart Association (NYHA) functional class >= III, and ischemic etiology. The chance of DMP being cost-effective at a willingness to pay US$10,000 per QALY was >= 90% in all subgroups apart from NYHA functional class I-II, where it was 70%. Even when the intervention costs increased by 500% or when excluding outliers in costs, DMP had a high chance of being cost-effective (87%-99%).Conclusions: The HF-DMP of the REMADHE trial, which encompasses long-term repeated education alongside telephone monitoring, has a high probability of being cost-effective in ambulatory patients with HF.

Aims Heart failure (HF) management is complicated by difficulties in clinical assessment. Biomarkers may help guide HF management, but the correspondence between clinical evaluation and biomarker serum levels has hardly been studied. We investigated the correlation between biomarkers and clinical signs and symptoms, the influence of patient characteristics and comorbidities on New York Heart Association (NYHA) classification and the effect of using biomarkers on clinical evaluation. Methods and results This post-hoc analysis comprised 622 patients (77 ± 8 years, 76 % NYHA class ≥3, 80 % LVEF ≤45 %) participating in TIME-CHF, randomising patients to either NT-proBNP-guided or symptom-guided therapy. Biomarker measurements and clinical evaluation were performed at baseline and after 1, 3, 6, 12 and 18 months. NT-proBNP, GDF-15, hs-TnT and to a lesser extent hs-CRP and cystatin-C were weakly correlated to NYHA, oedema, jugular vein distension and orthopnoea (ρ-range: 0.12–0.33; p

Objectives This study aimed to assess cost-effectiveness of N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided versus symptom-guided therapy in heart failure (HF) patients ≥60 years old. Background Cost-effectiveness of NT-proBNP guidance in HF patients is unclear. It may create additional costs with uncertain benefits. Methods In the TIME-CHF (Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure), patients with left ventricular ejection fraction (LVEF) of ≤45% were randomized to receive intensified NT-proBNP-guided therapy or standard, symptom-guided therapy. For cost-effectiveness analysis, 467 (94%) patients (age 76 ± 7 years, 66% male) were eligible. Incremental cost-effectiveness was calculated as incremental costs per gained life-year and quality-adjusted life-year (QALY) within the 18-month trial period, as defined per protocol. Results NT-proBNP-guided therapy was dominant (i.e., more effective and less costly) over symptom-guided therapy, saving $2,979 USD (2.5 to 97.5% confidence interval [CI]: $8,758 to $3,265) per patient, with incremental effectiveness of +0.07 life-years and +0.05 QALYs. The probability of NT-proBNP-guided therapy being dominant was 80%, and the probability of saving 1 life-year or QALY at a cost of $50,000 was 97% and 93%, respectively. Exclusion of residence costs resulted in an incremental cost-effectiveness ratio (ICER) of $5,870 per life-year gained. Cost-effectiveness of NT-proBNP-guided therapy was most pronounced in patients l75 years old and in those with l2 significant comorbidities, being dominant in all sensitivity analyses. In the worst-case scenario (excluding residence costs in those with ≥2 comorbidities), the ICER was $11,935 per life-year gained. Conclusions NT-proBNP-guided therapy has a high probability of being cost effective in HF patients with reduced LVEF, particularly in patients age 60 to 75 years or with less than 2 comorbidities. (Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure [TIME-CHF]; ISRCTN43596477 )

Objectives The study aim was to determine the prognostic value of a multimarker strategy for risk-assessment in patients presenting to the emergency department (ED) with dyspnea. Background Combining biomarkers with different pathophysiological backgrounds may improve risk stratification in dyspneic patients in the ED. Methods The study prospectively investigated the prognostic value of the biomarkers N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), Cystatin-C (Cys-C), high-sensitivity C-reactive protein (hs-CRP), and Galectin-3 (Gal-3) for 90-day mortality in 603 patients presenting to the ED with dyspnea as primary complaint. Results hs-CRP, hs-cTnT, Cyst-C, and NT-proBNP were independent predictors of 90-day mortality. The number of elevated biomarkers was highly associated with outcome (odds ratio: 2.94 per biomarker, 95% confidence interval [CI]: 2.29 to 3.78, p Conclusions A multimarker strategy provided superior risk stratification beyond any single-marker approach. The MARKED-risk score that incorporates hs-cTnT, hs-CRP, and Cys-C along with clinical risk factors accurately identifies patients with very low, intermediate, and high risk.

Background: To investigate the prevalence and prognostic relevance of cardiac involvement in an ANCA-associated vasculitis (AAV) population of eosinophilic granulomatosis with polyangiitis (EGPA) and granulomatosis with polyangiitis (GPA) patients. Methods: Prospective cohort study of fifty EGPA and forty-oneGPA patients in sustained remission without previous in-depth cardiac screening attending our clinical immunology outpatient department. Cardiac screening included clinical evaluation, ECG, 24-hour Holter registration, echocardiography and cardiac magnetic resonance imaging (CMR) with coronary angiography and endomyocardial biopsy upon indication. Fifty age-, sex- and cardiovascular risk factor-matched control subjects were randomly selected from a population study. Long-term outcome was assessed using all-cause and cardiovascular mortality. Results: A total of 91 AAV-patients (age 60 +/- 11, range 63-87 years) were compared to 50-matched control subjects (age 60 +/- 9 years, range 46-78 years). ECG and echocardiography demonstrated cardiac abnormalities in 62% EGPA and 46% GPA patients vs 20% controls (P

This editorial refers to ‘Mid-regional pro-atrial natriuretic peptide and pro-adrenomedullin testing for the diagnostic and prognostic evaluation of patients with acute dyspnoea’, by R.V. Shah et al. , doi:10.1093/eurheartj/ehs136 When patients present with acute dyspnoea, clinicians are faced with relevant issues. Particularly, making the right diagnosis and choosing the best therapies in a timely manner are crucial. To assess the latter, it may help to know the patient's risk, both short and long term, but the direct clinical benefit is less certain. History, physical examination, lab testing, and imaging techniques are cornerstones in order to come to the right conclusions, but they leave important open questions. Biomarkers circulating in the blood are attractive tools to improve care since they represent underlying pathophysiological processes and are relatively easy to measure. However, the question remains of what is their actual role in the clinical setting of acute dyspnoea ( Figure 1 ). Figure 1 Potential clinical usefulness of biomarkers (right-hand side) in the process of heart failure (left-hand side) with respect to diagnosis (green arrows), prognostic assessment (blue arrows), and therapy guidance (yellow arrows). The arrows point to the situation when biomarkers are applicable or of potential benefit. Level of evidence and clinical usefulness: ++, documented in large prospective trials, established, and useful; +, some data, probably useful; ††, well documented, but of unknown clinical benefit; †, less well established, unknown clinical benefit; 0, potential clinical benefit, but little or no data available; aStudy by Shah et al. ;13 brenal markers = serum creatinine, urea, uric acid, and to some extent cystatin C, newer renal markers such as KIM-1, or NGAL which are less well established; ca large number of other biomarkers have been shown to be related to poor outcome,11 of which (hs-)cTnT, haemoglobin, and creatinine are among …

OBJECTIVE: The aim of this work was to assess the prognostic value of absolute N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration in combination with changes during admission because of acute heart failure (AHF) and early after hospital discharge.BACKGROUND: In AHF, readmission and mortality rates are high. Identifying those at highest risk for events early after hospital discharge might help to select patients in need of intensive outpatient monitoring.METHODS AND RESULTS: We evaluated the prognostic value of NT-proBNP concentration on admission, at discharge, 1 month after hospital discharge and change over time in 309 patients included in the PRIMA (Can PRo-brain-natriuretic peptide guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality?) study. Primary outcome measures were mortality and the combined end point of heart failure (HF) readmission or mortality. In a multivariate Cox regression analysis, change in NT-proBNP concentration during admission, change from discharge to 1 month after discharge, and the absolute NT-proBNP concentration at 1 month after discharge were of independent prognostic value for both end points (hazard ratios for HF readmission or mortality: 1.71, 95% confidence interval [CI] 1.13-2.60, Wald 6.4 [P = .011] versus 2.71, 95% CI 1.76-4.17, Wald 20.5 [P < .001] versus 1.81, 95% CI 1.13-2.89, Wald 6.1 [P = .014], respectively.CONCLUSIONS: Knowledge of change in NT-proBNP concentration during admission because of AHF in combination with change early after discharge and the absolute NT-proBNP concentration at 1 month after discharge allows accurate risk stratification.

This study aimed to assess cost-effectiveness of N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided versus symptom-guided therapy in heart failure (HF) patients ≥60 years old.Cost-effectiveness of NT-proBNP guidance in HF patients is unclear. It may create additional costs with uncertain benefits.In the TIME-CHF (Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure), patients with left ventricular ejection fraction (LVEF) of ≤45% were randomized to receive intensified NT-proBNP-guided therapy or standard, symptom-guided therapy. For cost-effectiveness analysis, 467 (94%) patients (age 76 ± 7 years, 66% male) were eligible. Incremental cost-effectiveness was calculated as incremental costs per gained life-year and quality-adjusted life-year (QALY) within the 18-month trial period, as defined per protocol.NT-proBNP-guided therapy was dominant (i.e., more effective and less costly) over symptom-guided therapy, saving $2,979 USD (2.5 to 97.5% confidence interval [CI]: $8,758 to $3,265) per patient, with incremental effectiveness of +0.07 life-years and +0.05 QALYs. The probability of NT-proBNP-guided therapy being dominant was 80%, and the probability of saving 1 life-year or QALY at a cost of $50,000 was 97% and 93%, respectively. Exclusion of residence costs resulted in an incremental cost-effectiveness ratio (ICER) of $5,870 per life-year gained. Cost-effectiveness of NT-proBNP-guided therapy was most pronounced in patients 75 years old and in those with2 significant comorbidities, being dominant in all sensitivity analyses. In the worst-case scenario (excluding residence costs in those with ≥2 comorbidities), the ICER was $11,935 per life-year gained.NT-proBNP-guided therapy has a high probability of being cost effective in HF patients with reduced LVEF, particularly in patients age 60 to 75 years or with less than 2 comorbidities. (Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure [TIME-CHF]; ISRCTN43596477).

The study aim was to determine the prognostic value of a multimarker strategy for risk-assessment in patients presenting to the emergency department (ED) with dyspnea.Combining biomarkers with different pathophysiological backgrounds may improve risk stratification in dyspneic patients in the ED.The study prospectively investigated the prognostic value of the biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), Cystatin-C (Cys-C), high-sensitivity C-reactive protein (hs-CRP), and Galectin-3 (Gal-3) for 90-day mortality in 603 patients presenting to the ED with dyspnea as primary complaint.hs-CRP, hs-cTnT, Cyst-C, and NT-proBNP were independent predictors of 90-day mortality. The number of elevated biomarkers was highly associated with outcome (odds ratio: 2.94 per biomarker, 95% confidence interval [CI]: 2.29 to 3.78, p0.001). A multimarker approach had incremental value beyond a single-marker approach. Our multimarker emergency dyspnea-risk score (MARKED-risk score) incorporating age ≥75 years, systolic blood pressure110 mm Hg, history of heart failure, dyspnea New York Heart Association functional class IV, hs-cTnT ≥0.04 μg/l, hs-CRP ≥25 mg/l, and Cys-C ≥1.125 mg/l had excellent prognostic performance (area under the curve: 0.85, 95% CI: 0.81 to 0.89), was robust in internal validation analyses and could identify patients with very low (3 points), intermediate (≥3,5 points), and high risk (≥5 points) of 90-day mortality (2%, 14%, and 44% respectively; p0.001).A multimarker strategy provided superior risk stratification beyond any single-marker approach. The MARKED-risk score that incorporates hs-cTnT, hs-CRP, and Cys-C along with clinical risk factors accurately identifies patients with very low, intermediate, and high risk.

Purpose: Several studies have shown that heart failure (HF) patients with preserved (HFPEF) versus those with reduced ejection fraction (HFREF) are distinctly different with more comorbidities. They are older, more often female, more likely to have hypertension, atrial fibrillation (AF) and a higher body mass index (BMI). It is unclear to what extent age, gender differences and BMI explain the other differences between HFPEF and HFREF. Methods: All 123 HFPEF patients from TIME-CHF were matched 1:1 to 499 HFREF patients for age (80±7 vs 80±7,P=0.60), gender (66% vs 66% female) and BMI (26.7±5.4 vs 26.7±4.1, P=0.50). Results: HFPEF patients had more frequently hypertension and less frequently coronary artery disease as cause of HF compared to HFREF patients. Number of comorbidities reflected by the Charlson score was similar in both groups. Strikingly, AF was not more common in the HFPEF group. Other specific comorbidities, including COPD, diabetes, stroke, arthritis did also not differ between groups. Symptom severity assessed by NYHA class did also not differ between groups. Laboratory findings including creatinine, urea and liver enzymes were similar in both groups, except for haemoglobin and N-terminal brain natriuretic peptide. The pulse pressure, reflecting arterial stiffness, was significantly higher in HFPEF patients. View this table: Baseline characteristics Conclusion: After matching for age, gender and BMI, prevalence of comorbidities and symptom severity is strikingly similar in HFPEF vs HFREF suggesting that age, gender or BMI may largely explain the differences between HF-groups. This study confirms that hypertension is a more common underlying cause of HFPEF and suggests that vascular stiffness may play a role in pathophysiology of HFPEF.