Search

INTRODUCTION AND OBJECTIVES Advanced lipoprotein phenotyping is a better predictor of atherosclerotic cardiovascular risk than cholesterol concentration alone. Lipoprotein profiling in heart failure (HF) is incompletely characterized. We aimed to describe the lipoprotein profile in patients with chronic HF compared with a matched control population. METHODS This cross-sectional study was performed from May 2006 to April 2014 and included ambulatory patients with chronic HF. Lipid concentrations and the size of main lipoprotein fractions (high-density lipoprotein [HDL], low-density lipoprotein [LDL], and very low-density lipoprotein) and the particle concentration of their 3 subfractions (large, medium and small) were assessed using 1H magnetic resonance spectroscopy. RESULTS The 429 included patients with chronic HF were compared with 428 matched controls. Patients with chronic HF had lower total cholesterol and lower mean LDL (1115 vs 1352 nmol/L; P

Introduction and objectives Microvascular obstruction (MVO) is negatively associated with cardiac structure and worse prognosis after ST-segment elevation myocardial infarction (STEMI). Epithelial cell adhesion molecule (EpCAM), involved in epithelium adhesion, is an understudied area in the MVO setting. We aimed to determine whether EpCAM is associated with the appearance of cardiac magnetic resonance (CMR)-derived MVO and long-term systolic function in reperfused STEMI. Methods We prospectively included 106 patients with a first STEMI treated with percutaneous coronary intervention, quantifying serum levels of EpCAM 24 hours postreperfusion. All patients underwent CMR imaging 1 week and 6 months post-STEMI. The independent correlation of EpCAM with MVO, systolic volume indices, and left ventricular ejection fraction was evaluated. Results The mean age of the sample was 59 ± 13 years and 76% were male. Patients were dichotomized according to median EpCAM (4.48 pg/mL). At 1-week CMR, lower EpCAM was related to extensive MVO (P = .021) and larger infarct size (P = .019). At presentation, EpCAM values were significantly associated with the presence of MVO in univariate (OR, 0.58; 95%CI, 0.38-0.88; P = .011) and multivariate logistic regression models (OR, 0.55; 95%CI, 0.35-0.87; P = .010). Although MVO tends to resolve at chronic phases, decreased EpCAM was associated with worse systolic function: reduced left ventricular ejection fraction (P = .009) and higher left ventricular end-systolic volume (P = .043). Conclusions EpCAM is associated with the occurrence of CMR-derived MVO at acute phases and long-term adverse ventricular remodeling post-STEMI.

Introduction and objectives: Carbohydrate antigen 125 (CA125) has been shown to be useful for risk stratification in patients admitted with acute heart failure (AHF). We sought to determine a CA125 cutpoint for identifying patients at low risk of 1-month death or the composite of death/HF readmission following admission for AHF.Methods: The derivation cohort included 3231 consecutive patients with AHF. CA125 cutoff values with 90% negative predictive value (NPV) and sensitivity up to 85% were identified. The adequacy of these cutpoints and the risk of 1-month death/HF readmission was then tested using the Royston-Parmar method. The best cutpoint was selected and externally validated in a cohort of patients hospitalized from BIOSTAT-CHF (n = 1583).Result: In the derivation cohort, the median [IQR] CA125 was 57 [25.3-157] U/mL. The optimal cutoff value was < 23 U/mL (21.5% of patients), with NPVs of 99.3% and 94.1% for death and the composite endpoint, respectively. On multivariate survival analyses, CA125 < 23 U/mL was independently associated with a lower risk of death (HR, 0.20; 95%Cl, 0.08-0.50; P < .001), and the combined endpoint (HR, 0.63; 95%Cl, 950.45-0.90; P = .009). The ability of this cutpoint to discriminate patients at a low 1-month risk was confirmed in the validation cohort (NPVs of 98.6% and 96.6% for death and the composite endpoint). The predicted ability of this cutoff remained significant at 6 months of follow-up.Conclusion: In patients admitted with AHF, CA125 < 23 U/mL identified a subgroup at low risk of short-term adverse events, a population that may not require intense postdischarge monitoring. (C) 2021 Sociedad Espanola de Cardiologia. Published by Elsevier Espafia, S.L.U. All rights reserved.

AIMS: Chronic obstructive pulmonary disease (COPD) is a frequent comorbidity in patients with heart failure (HF). We assessed the influence of COPD on circulating levels and prognostic value of three HF biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), and soluble suppression of tumorigenesis-2 (sST2).METHODS: Individual data from patients with chronic HF, known COPD status, NT-proBNP and hs-TnT values (n = 8088) were analysed. A subgroup (n = 3414) had also sST2 values.RESULTS: Patients had a median age of 66 years (interquartile interval 57-74), 77% were men and 82% had HF with reduced ejection fraction. NT-proBNP, hs-TnT and sST2 were 1207 ng/l (487-2725), 17 ng/l (9-31) and 30 ng/ml (22-44), respectively. Patients with COPD (n = 1249, 15%) had higher NT-proBNP (P = 0.042) and hs-TnT (P CONCLUSIONS: Among patients with HF, those with COPD have higher NT-proBNP and hs-TnT, but not sST2. All these biomarkers yield prognostic significance regardless of the COPD status.

The Nancy team is supported by the RHU Fight-HF, a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d'Avenir' programme (reference: ANR-15-RHUS-0004), by the French PIA project 'Lorraine Université d'Excellence' (reference: ANR-15-IDEX-04-LUE), the ANR FOCUS-MR (reference: ANR-15-CE14-0032-01), ERA-CVD EXPERT (reference: ANR-16-ECVD-0002-02), the Contrat de Plan Etat Lorraine IT2MP, and FEDER Lorraine. Aims: In ambulatory patients with chronic heart failure (HF), congestion and decongestion assessment may be challenging. The aim of this study is to assess the value of lung ultrasound (LUS) in outpatients with HF in characterizing decompensation and recompensation, and in outcomes prediction. Methods and results: Heart failure outpatients attended to establish HF decompensation were included. LUS was blindly performed at baseline (LUS1) and at clinical recompensation (LUS2). B-lines were counted in eight scanned areas. Diagnosis of no HF decompensation vs. right-sided, left-sided, or global HF decompensation, and patients' management were performed by physicians blinded to LUS1. Outcome was the composite of all-cause death or HF-related hospitalization. Two hundred and thirty-three suspicions of HF decompensation were included in 187 patients (71.4 ± 11.3 years, 66.8% men). Mean B-line (LUS1) was 17.6 ± 11.2 vs. 3.7 ± 4.5 for episodes with and without HF decompensation, respectively (P < 0.001). Global HF decompensation showed the highest number of B-lines (20.6 ± 11), followed by left-sided (19.7 ± 11.6) and right-sided (13.5 ± 9.8). B-lines declined to 6.9 ± 6.7 (LUS2) (P < 0.001 vs. LUS1) after treatment, within a mean time of 24.2 ± 23.7 days [median 13.5 days (interquartile range 6-40)]. B-lines were significantly associated with the composite endpoint at 30 days (hazard ratio [HR] 1.04 [95% confidence interval 1.01-1.07], P = 0.02), but not at 60 (P = 0.22) or 180 days (P = 0.54). In multivariable analysis, B-line number remained as an independent predictor of the composite endpoint at 30 days, [HR 1.04 (1.01-1.07), P = 0.014], with a 4% increase risk per B-line added. B-lines correlated significantly with CA125 (R = 0.30, P = 0.001). Conclusions: Lung ultrasound supports the diagnostic work-up of congestion and decongestion in chronic HF outpatients and identifies patients at high risk of short-term events.

Objectives The goal of this study was to assess the predictive power of N-terminal pro–B-type natriuretic peptide (NT-proBNP) and the decision cutoffs in heart failure (HF) across body mas...

INTRODUCTION: We aimed to evaluate the trajectory of two surrogates of fluid overload -antigen carbohydrate 125 (CA125) and amino-terminal pro-brain natriuretic peptide (NT-proBNP)- after the addition of oral empagliflozin to usual care in a cohort of patients with chronic heart failure (CHF) and type 2 diabetes (T2D). METHODS AND RESULTS: From October 2015 to February 2019, 60 ambulatory patients with CHF and T2D were retrospectively included. The primary endpoint was to assess the longitudinal trajectory of plasma levels of CA125 and NT-proBNP after empagliflozin initiation. Changes in quantitative variables were evaluated using linear mixed regression. Median CA125 and NT-proBNP at baseline were 17 (11-75) U/mL and 1662 (647-4230) pg/mL, respectively. A total of 510 outpatient visits were recorded [median (interquartile range) of visits per patient: 6 (4-11)] during a median of 1.78 years. We found a significant and steady decrease in the log of CA125 after empagliflozin initiation (p < 0.001). Conversely, the log of NT-proBNP predicted trajectory did not significantly change (p = 0.425). CONCLUSION: In this cohort of patients with CHF and T2D, empagliflozin initiation was associated with a significant decrease in CA125 levels without modifying the trajectory of NT-proBNP. Considering that CA125 has emerged as a surrogate marker of tissue congestion, we hypothesize that empagliflozin might predominantly promote extravascular decongestion.

Background Higher body mass index (BMI) is associated with better outcome compared with normal weight in patients with HF and other chronic diseases. It remains uncertain whether the apparent protective role of obesity relates to the absence of comorbidities. Therefore, we investigated the effect of BMI on outcome in younger patients without co-morbidities as compared to older patients with co-morbidities in a large heart failure (HF) population. Methods In an individual patient data analysis from pooled cohorts, 5,819 patients with chronic HF and data available on BMI, co-morbidities and outcome were analysed. Patients were divided into four groups based on BMI (i.e. ≤ 18.5 kg/m2, 18.5–25.0 kg/m2; 25.0–30.0 kg/m2; 30.0 kg/m2). Primary endpoints included all-cause mortality and HF hospitalization-free survival. Results Mean age was 65 ± 12 years, with a majority of males (78%), ischaemic HF and HF with reduced ejection fraction. Frequency of all-cause mortality or HF hospitalization was significantly worse in the lowest two BMI groups as compared to the other two groups; however, this effect was only seen in patients older than 75 years or having at least one relevant co-morbidity, and not in younger patients with HF only. After including medications and N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin concentrations into the model, the prognostic impact of BMI was largely absent even in the elderly group with co-morbidity. Conclusions The present study suggests that obesity is a marker of less advanced disease, but does not have an independent protective effect in patients with chronic HF. Graphic abstract Categories of BMI are only predictive of poor outcome in patients aged > 75 years or with at least one co-morbidity (bottom), but not in those aged

Left ventricular noncompaction (LVNC) is a heterogeneous entity with uncertain prognosis. This study sought to develop and validate a prediction model of major adverse cardiovascular events (MACE) and to identify LVNC cases without events during long-term follow-up. This is a retrospective longitudinal multicenter cohort study of consecutive patients fulfilling LVNC criteria by echocardiography or cardiovascular magnetic resonance. MACE were defined as heart failure (HF), ventricular arrhythmias (VAs), systemic embolisms, or all-cause mortality. A total of 585 patients were included (45 ± 20 years of age, 57% male). LV ejection fraction (LVEF) was 48% ± 17%, and 18% presented late gadolinium enhancement (LGE). After a median follow-up of 5.1 years, MACE occurred in 223 (38%) patients: HF in 110 (19%), VAs in 87 (15%), systemic embolisms in 18 (3%), and 34 (6%) died. LVEF was the main variable independently associated with MACE (P < 0.05). LGE was associated with HF and VAs in patients with LVEF >35% (P < 0.05). A prediction model of MACE was developed using Cox regression, composed by age, sex, electrocardiography, cardiovascular risk factors, LVEF, and family aggregation. C-index was 0.72 (95% confidence interval: 0.67-0.75) in the derivation cohort and 0.72 (95% confidence interval: 0.71-0.73) in an external validation cohort. Patients with no electrocardiogram abnormalities, LVEF ≥50%, no LGE, and negative family screening presented no MACE at follow-up. LVNC is associated with an increased risk of heart failure and ventricular arrhythmias. LVEF is the variable most strongly associated with MACE; however, LGE confers additional risk in patients without severe systolic dysfunction. A risk prediction model is developed and validated to guide management. The project was partially funded by a grant from the Catalan Society of Cardiology (Barcelona, Spain). Hospital Universitario Virgen de la Arrixaca (Murcia, Spain) was supported by a grant from the Foundation Marató TV3 (218/C/2015) (Barcelona, Spain). Hospital Universitario y Politécnico La Fe (Valencia, Spain) was partially supported by Fondo Europeo de Desarrollo Regional (“Unión Europea, Una forma de hacer Europa”) (Madrid, Spain) and the Instituto de Salud Carlos III (La Fe Biobank PT17/0015/ 0043) (Madrid, Spain). Dr Guala was supported by funding from the Spanish Ministry of Science, Innovation and Universities (IJC2018-037349-I) (Madrid, Spain). Dr La Mura was supported by a research grant from the Cardiopath PhD program (Naples, Italy). Prof de la Pompa was supported by grants PID2019-104776RB-I00 and CB16/11/00399 (CIBER CV) from the Spanish Ministry of Science, Innovation and Universities. Dr Bayes-Genis was supported by grants from CIBER Cardiovascular (CB16/11/00403 and 16/11/00420) (Madrid, Spain) and AdvanceCat 2014-2020 (Barcelona, Spain); and has received advisory board and lecture fees from Novartis, Boehringer Ingelheim, Vifor, Roche Diagnostics, and Critical Diagnostics. Dr Pontone has received speaker honorarium and/or institutional research grants from GE Healthcare, Bracco, Boehringer Ingelheim, and HeartFlow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Sí

Background Carbohydrate antigen 125 (CA125) and B-type natriuretic peptides are surrogate markers of congestion in patients with acute heart failure (AHF). The aim of the study was to assess the association between CA125 and NT-proBNP and congestion parameters in patients with AHF. Methods and results Prospective multicentre observational study that included 191 patients hospitalised for AHF. We recorded the presence of pleural effusion, peripheral oedema and inferior vena cava (IVC) diameter during the first 24–48 h after admission and evaluated their independent association with CA125 concentrations and the amino-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP). The mean age was 73.4 ± 12 years, 79 (41.4%) were women, and 127 (66.5%) had left ventricular ejection fraction ≥50%. The median of CA125, NT-proBNP and IVC diameter was 58 (22.7–129) U/mL, 3,985 (1,905–9,775) pg/mL and 21 (17–25) mm, respectively. Multivariate analysis showed that CA125 was positively and independently associated with the presence of peripheral oedema, pleural effusion and elevated IVC levels. NT-proBNP was associated with pleural effusion and IVC diameter but not with oedema. The addition of CA125 increased the discriminatory capacity of the baseline model to identify peripheral oedema and pleural effusion, but not NT-proBNP. The most important predictor of ICV dilation was CA125 (R2 = 48.3%). Conclusion In patients with AHF, serum CA125 levels are associated more significantly than NT-proBNP with a state of congestion.

Clonal hematopoiesis driven by somatic mutations in hematopoietic cells, frequently called clonal hematopoiesis of indeterminate potential (CHIP), has been associated with adverse cardiovascular outcomes in population-based studies and in patients with ischemic heart failure (HF) and reduced left ventricular ejection fraction (LVEF). Yet, the impact of CHIP on HF progression, including nonischemic etiology, is unknown.The purpose of this study was to assess the clinical impact of clonal hematopoiesis on HF progression irrespective of its etiology.The study cohort comprised 62 patients with HF and LVEF 45% (age 74 ± 7 years, 74% men, 52% nonischemic, and LVEF 30 ± 8%). Deep sequencing was used to detect CHIP mutations with a variant allelic fraction2% in 54 genes. Patients were followed for at least 3.5 years for various adverse events including death, HF-related death, and HF hospitalization.CHIP mutations were detected in 24 (38.7%) patients, without significant differences in all-cause mortality (p = 0.151). After adjusting for risk factors, patients with mutations in either DNA methyltransferase 3 alpha (DNMT3A) or Tet methylcytosine dioxygenase 2 (TET2) exhibited accelerated HF progression in terms of death (hazard ratio [HR]: 2.79; 95% confidence interval [CI]: 1.31 to 5.92; p = 0.008), death or HF hospitalization (HR: 3.84; 95% CI: 1.84 to 8.04; p 0.001) and HF-related death or HF hospitalization (HR: 4.41; 95% CI: 2.15 to 9.03; p 0.001). In single gene-specific analyses, somatic mutations in DNMT3A or TET2 retained prognostic significance with regard to HF-related death or HF hospitalization (HR: 4.50; 95% CI: 2.07 to 9.74; p 0.001, for DNMT3A mutations; HR: 3.18; 95% CI: 1.52 to 6.66; p = 0.002, for TET2 mutations). This association remained significant irrespective of ischemic/nonischemic etiology.Somatic mutations that drive clonal hematopoiesis are common among HF patients with reduced LVEF and are associated with accelerated HF progression regardless of etiology.

Background Identifying patients at risk of poor diuretic response in acute heart failure (AHF) is critical to make prompt adjustments in therapy. The objective of this study was to investigate whether the circulating levels of soluble ST2 predict the cumulative diuretic efficiency (DE) at 24 and 72 hours in patients with AHF and concomitant renal dysfunction. Methods and Results This is a post hoc analysis of the IMPROVE-HF trial, in which we enrolled 160 patients with AHF and renal dysfunction (estimated glomerular filtrate rate of Conclusions In patients with AHF and renal dysfunction at presentation, circulating levels of sST2 were independently and negatively associated with a poor diuretic response, both at 24 and 72 hours.

A higher neprilysin activity has been suggested in women. In this retrospective analysis, we evaluated the association of sex and body mass index (BMI) with soluble neprilysin (sNEP) and recurrent admissions among 1021 consecutive HF outpatients. The primary and secondary endpoints were the number of HF hospitalizations and all-cause mortality, respectively. The association between sNEP with either endpoint was evaluated across sex and BMI categories (≥ 25 kg/m2 vs. 2). Bivariate count regression (Poisson) was used, and risk estimates were expressed as incidence rates ratio (IRR). During a median follow-up of 6.65 years (percentile 25%-percentile 75%:2.83–10.25), 702 (68.76%) patients died, and 406 (40%) had at least 1 HF hospitalization. Median values of sNEP and BMI were 0.64 ng/mL (0.39–1.22), and 26.9 kg/m2 (24.3–30.4), respectively. Left ventricle ejection fraction was p = 0.001) but not with mortality (p = 0.241). The predictive value of sNEP for HF hospitalizations varied non-linearly across sex and BMI categories (p-value for interaction = 0.003), with significant and positive effect only on women with BMI ≥ 25 kg/m2 (p = 0.039). For instance, compared to men, women with sNEP of 1.22 ng/mL (percentile 75%) showed a significantly increased risk (IRRs: 1.26; 95% CI: 1.05–1.53). The interaction analysis for mortality did not support a differential prognostic effect for sNEP (p = 0.072). In conclusion, higher sNEP levels in overweight women better predicted an increased risk of HF hospitalization.

Systolic pulmonary artery pressure (SPAP) and right heart adaptation in relation to pre-existing preload are often disregarded. To determine volume-related changes in the pulmonary-right ventricle (RV) unit and the preload dependence of its components, we analysed pulmonary haemodynamics and right ventricular performance, taking advantage of the plasma volume removal associated to haemodialysis (HD). Fifty-three stable patients on chronic HD with LVEF > 50% and without heart failure were recruited (mean age 63.0 ± 12.4 years; 31.2% women; hypertension in 89% and diabetes in 53%) and evaluated just before and after HD (mean ultrafiltration volume 2.4 ± 0.7 l). SPAP from both times were available in 39 patients. After HD, SPAP decreased (42.2 ± 12.6 to 33.7 ± 11.6 mmHg, p 40 mmHg) (OR 1.29 (1.07–1.56), p = 0.006). Rapid volemic changes may affect FTR grading, RV size and contractility, with RV longitudinal strain being less variable than conventional parameters. SPAP decreases after HD, and this reduction is related to age and greater diminution of the E/eʹ ratio.

Definition, clinical implications, and rate of iron deficiency assessment and treatment in the Swedish Heart Failure Registry. FCM, ferric carboxymaltose; HF, heart failue; ID, iron deficiency; TSAT, transferrin sauration.

Predictive factors of significant functional tricuspid regurgitation (FTR) are not completely understood. We investigated sex-related differences in predictors of FTR progression.Clinical and echocardiographic variables were recorded in a prospective single-centre observational cohort of 251 consecutive stable patients with FTR. Multivariable logistic regression analyses stratified by sex were performed to identify predictors of significant FTR.The mean age of the whole cohort was 72.2±11.4 years, and 133 (53%) patients were women. Females tended to have a higher prevalence of significant FTR (22.6% vs 13.6%; p=0.066). Women were also older than men (mean age 74.4 vs 69.6 years; p0.001), with more frequent history of arterial hypertension, worse New York Heart Association functional class, higher E/e' quotient, and higher left ventricular ejection fraction. The independent predictors of significant FTR in women were atrial fibrillation (AF) (odds ratio [OR] 10.8, 95% confidence interval [CI] 2.9-40.7; p0.001), indexed tricuspid diameter annulus (OR 1.24, 95% CI 1.04-1.47; p=0.017), and pulmonary artery systolic pressure (PASP) (OR 1.09, 95% CI 1.04-1.15; p=0.001). The independent predictors of outcome in men were indexed tricuspid tenting height (OR 2.71, 95% CI 1.20-6.11; p=0.016), indexed tricuspid diameter annulus (OR 1.98, 95% CI 1.26-3.09; p=0.003), and PASP (OR 1.08, 95% CI 1.01-1.16; p=0.021).The presence of AF and longer indexed tenting height convey a greater risk of significant FTR in females and males, respectively. These findings suggest the existence of different physiopathological mechanisms involved in the progression of FTR in both sexes.

Up to one-third of patients who undergo cardiac resynchronization therapy do not obtain clinical benefit. A systematic approach can identify treatable causes in many nonresponding patients. We present a case of nonresponse to cardiac resynchronization therapy that resolved by ablation of the atrioventricular node in a patient with complete atrioventricular block. (Level of Difficulty: Advanced.), Graphical abstract

Background An association between interatrial block (IAB) (P wave duration ≥120 ms) and dementia has been suggested. Our objective was to assess the association of IAB with cognitive impairment (CI). Methods The prospective BAYES registry included 552 patients ≥70 years with structural heart disease without documented atrial fibrillation. Cognitive ability was assessed at baseline and every 6 months with the Pfeiffer test. The median follow-up was 22 months. Results Thirty patients (5.4%) had baseline CI, 20 patients with mild CI and 10 with moderate CI. Compared to patients without CI, patients with CI had higher mean age (80.4 ± 6.5 vs. 76.8 ± 5.4 years) and higher prevalence of advanced IAB (with biphasic P-wave ± in inferior leads) (14 [46.7%] vs. 122 [23.4%], p

Funding: This work was supported in part by an unrestricted grant from Vifor Pharma and Proyectos de Investigación de la Sección de Insuficiencia Cardiaca 2017 from Sociedad Española de Cardiología. The mechanisms underlying the beneficial effect of ferric carboxymaltose (FCM) in patients with heart failure (HF) and iron deficiency (ID) have not been completely characterized. The Myocardial-IRON trial was a double-blind, randomized trial that evaluated myocardial iron repletion following FCM vs. placebo in 53 patients with HF and ID. In this post hoc analysis, we evaluated whether treatment with FCM was associated with cardiac magnetic resonance changes in left and right ventricular function (LVEF and RVEF, respectively) at different points of systolic dysfunction. We included patients from the Myocardial-IRON trial with left and right ventricular systolic dysfunction (LVSD and RVSD, respectively) at enrolment. Linear mixed regression models were used to evaluate changes at 7 and 30 days on LVEF and RVEF at cardiac magnetic resonance. At enrolment, 27 (50.9%) and 38 (71.7%) patients had LVEF < 40% (LVSD) or

The association between atrial fibrillation, stroke, and interatrial block (IAB) (P-wave duration ≥120 ms) is well recognized, particularly in the case of advanced IAB. We aimed to assess the association of IAB with mild cognitive impairment. Advanced Characterization of Cognitive Impairment in Elderly with Interatrial Block was a case-control multicenter study, conducted in subjects aged ≥70 years in sinus rhythm without significant structural heart disease. Diagnosis of mild cognitive impairment was performed by an expert geriatrician, internist, or neurologist in the presence of changes in cognitive function (Mini Mental State Examination score 20 to 25) without established dementia. A total of 265 subjects were included. Mean age was 79.6 ± 6.3 years and 174 (65.7%) were women; there were 143 cases with mild cognitive impairment and 122 controls with normal cognitive function. Compared with controls, cases had longer P-wave duration (116.2 ± 13.8 ms vs 112.5 ± 13.3 ms, p = 0.028), higher prevalence of IAB (73 [51.0%] vs 38 [31.1%], p = 0.001), higher prevalence of advanced IAB (28 [19.6%] vs 10 [8.2%], p = 0.002), and higher MVP ECG risk score (2.7 ± 1.4 vs 2.2 ± 1.3, p = 0.004). IAB was independently associated with mild cognitive impairment, both for partial (odds ratio 2.0, 95% CI: 1.1 to 3.9) and advanced IAB (odds ratio 2.8, 95% CI: 1.1 to 6.7). In conclusion, in subjects aged ≥70 years without significant structural heart disease, IAB is independently associated with mild cognitive impairment. This association is stronger in the case of advanced IAB. “Proyecto de la Sociedad Española de Cardiología para investigación clínica en cardiología 2019”, Spanish Society of Cardiology 2.778 JCR (2020) Q3, 81/142 Cardiac & Cardiovascular Systems 1.394 SJR (2020) Q1, 64/349 Cardiology and Cardiovascular Medicine No data IDR 2020 UEM

This is the peer reviewed version of the following article: Aimo, A., Januzzi, J.L., Vergaro, G., Richards, A.M., Lam, C.S.P., Latini, R. ... Emdin, M. (2020). Circulating levels and prognostic value of soluble ST2 in heart failure are less influenced by age than N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T, European Journal of Heart Failure, which has been published in final form at https://doi.org/10.1002/ejhf.1701. . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Aims - N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), high‐sensitivity troponin T (hs‐TnT) and soluble suppression of tumorigenesis‐2 (sST2) predict outcome in chronic heart failure (HF). We assessed the influence of age on circulating levels and prognostic significance of these biomarkers. Methods and results - Individual data from 5301 patients with chronic HF and NT‐proBNP, hs‐TnT, and sST2 data were evaluated. Patients were stratified according to age: Conclusions - Soluble ST2 is less influenced by age than NT‐proBNP or hs‐TnT; all these biomarkers predict outcome regardless of age. The use of age‐ and outcome‐specific cut‐offs of NT‐proBNP, hs‐TnT and sST2 allows more accurate risk stratification than NT‐proBNP alone or the combination of NT‐proBNP and hs‐TnT.

There is scarce information about the clinical profile and prognosis of acute heart failure (AHF) at the extreme ranges of age. We aimed to evaluate the 1-year death (all-cause mortality and HF-death) and HF-rehospitalizations of patients ≥85 years admitted for AHF.We prospectively evaluated a cohort of 3054 patients admitted with AHF from 2007 to 2018 in a third-level center. Age was categorized per 10-year categories (65 years; 65-74 years, 75-84 years, and ≥85 years). The risk of mortality and HF-rehospitalizations across age categories was evaluated with Cox regression analysis and Cox regression adapted for competing events as appropriate.The mean age was 73.6 ± 11.2 years, 48.9% were female, and 52.8% had preserved left ventricular ejection fraction (HFpEF). A total of 414 (13.6%) patients were ≥85 years. Among this group of age, female sex and HFpEF phenotype were more frequent. At 1-year follow-up 667 all-cause deaths (22,1%), 311 HF-deaths (10.1%) and 693 HF-hospitalizations (22,7%) were recorded. After multivariable adjustment, and compared to patients65 years, a stepwise increased risk of all-cause mortality and HF-death was found for each decade increase in age, especially for patients ≥85 years (HR=3.47; 95% CI: 2.49 - 4.84, p0.001, HR=3.31; 95% CI: 1.95 - 5.63; p0.001, respectively). This subgroup of patients also showed an increased risk of HF-rehospitalization (HR=1.58; 95% CI: 1.16 - 2.16, p=0.004).Super elderly patients admitted with AHF showed a dramatically increased risk of 1-year death. This subset of patients also shown an increased risk of 1-year HF-readmission.

Summary Background & aims Nutritional status is an important prognostic factor in patients with heart failure (HF). In a pilot study we previously observed that the Mini Nutritional Assessment Short Form tool (MNA-SF) was the best approach for the screening of nutritional status in HF outpatients over other screening tools. The current study aimed to determine whether the MNA-SF has prognostic value in outpatients with HF and whether the impact of malnutrition differs depending on left ventricular ejection fraction (LVEF). Methods Prospective study performed in outpatients attending a HF clinic at a university hospital. All subjects completed the MNA-SF at study entry. The primary endpoint was all-cause mortality. Secondary end-points were the number of recurrent HF-related hospitalizations and the composite end-point of all-cause death or HF-related hospitalizations. Patients with malnutrition and at risk of malnutrition were merged and considered as having abnormal nutritional status for statistical analysis. Results From October 2016 to November 2017, 555 patients were included (age 69 ± 11.5 years, 71% male, LVEF 44.6 ± 13.2). Abnormal nutritional status was identified in 103 (18.6%) subjects. HF patients with preserved LVEF had a higher proportion of abnormal nutritional status (23%) than patients with HF and mid-range LVEF (HFmrEF) (16.4%) or those with HF with reduced LVEF (HFrEF) (15.9%.). During a mean follow-up of 23.8 ± 6.6 months, 99 patients died (17.8%), 74 were hospitalized due to HF (13.3%) and the composite end-point was observed in 181 (32.6%). In the univariate analysis, abnormal nutritional status was significantly associated with all-cause mortality (p = 0.02) and the composite end-point (p = 0.02) in the total cohort. However, in the multivariate analysis including age, sex, NYHA functional class, BMI, ischemic aetiology, diabetes, hypertension and HF duration, abnormal nutritional status remained significantly associated with all-cause mortality (HR 3.32 [95%CI 1.47–7.52], p = 0.004), and the composite end-point (HR 2.53 [95%CI 1.30–4.94], p = 0.006) only in HFmrEF patients. Patients with abnormal nutritional status suffered double the crude number of recurrent HF-related hospitalizations (16.4 vs. 8.4 per 100 patients-years, p Conclusions The implementation of MNA-SF as a routine screening tool allowed the detection of abnormal nutritional status in almost one out of five ambulatory HF patients. Nutritional status assessed by the MNA-SF was an independent predictor of all-cause death and the composite end-point of all-cause death or HF-related hospitalization in outpatients with HFmrEF. Furthermore, abnormal nutritional status was significantly related to recurrent hospitalizations across the HF spectrum.

BACKGROUND Dietary omega-3 eicosapentaenoic acid (EPA) has multiple cardioprotective properties. The proportion of EPA in serum phosphatidylcholine (PC) mirrors dietary EPA intake during previous weeks. Circulating EPA in ST-segment elevation myocardial infarction (STEMI) relates to smaller infarct size and preserved long-term ventricular function. OBJECTIVES The authors investigated whether serum-PC EPA (proxy for marine omega-3 consumption) levels at the time of STEMI were associated with a lower incidence of major adverse cardiovascular events (MACE), all-cause mortality, and readmission for cardiovascular (CV) causes at 3 years' follow-up. We also explored the association of alpha-linolenic acid (ALA, proxy for vegetable omega-3 intake) with all-cause mortality and MACE. METHODS The authors prospectively included 944 consecutive patients with STEMI (mean age 61 years, 209 women) undergoing primary percutaneous coronary intervention. We determined serum-PC fatty acids with gas chromatography. RESULTS During follow-up, 211 patients had MACE, 108 died, and 130 were readmitted for CV causes. A Cox propor-tional hazards model adjusted for known clinical predictors showed that serum-PC EPA at the time of STEMI was inversely associated with both incident MACE and CV readmission (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.62 to 0.94, and HR: 0.74; 95% CI: 0.58 to 0.95, respectively, for a 1-standard deviation [SD] increase). Serum-PC ALA was inversely related to all-cause mortality (HR: 0.65; 95% CI: 0.44 to 0.96, for a 1-SD increase). CONCLUSIONS Elevated serum-PC EPA and ALA levels at the time of STEMI were associated with a lower risk of clinical adverse events. Consumption of foods rich in these fatty acids might improve the prognosis of STEMI. (c) 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Introduction: The association of pulmonary congestion assessed by lung ultrasound (LUS) and biomarkers—other than N-terminal pro-brain natriuretic peptide (NT-proBNP)—is uncertain. Methods: We investigated the relationship between total B-line count by LUS and several biomarkers in outpatients with suspicion of heart failure (HF). Primary care patients with suspected new-onset nonacute HF were evaluated both with a 12-scan LUS protocol (8 anterolateral areas plus 4 lower posterior thoracic areas) and 11 inflammatory and cardiovascular biomarkers. A cardiologist blinded to LUS and biomarkers except NT-proBNP confirmed HF diagnosis. After log-transformation of biomarkers’ concentrations, unadjusted and adjusted correlations were performed. Results: A total of 170 patients were included (age 76 ± 10 years, 67.6% women). HF diagnosis was confirmed in 38 (22.4%) patients. After adjustment by age, sex, body mass index, and renal function, total B-line sum significantly correlated with NT-proBNP (R = 0.29, p < 0.001), growth/differentiation factor-15 (GDF-15; R = 0.23, p = 0.003), high-sensitive Troponin T (hsTnT; R = 0.36, p < 0.001), soluble interleukin-1 receptor-like 1 (sST2; R = 0.29, p < 0.001), cancer antigen 125 (CA-125; R = 0.17, p = 0.03), high-sensitivity C-reactive protein (hsCRP; R = 0.20, p = 0.009), and interleukin (IL)-6 (R = 0.23, p = 0.003). In contrast, IL-33 (R = −0.01, p = 0.93), IL-1β (R = −0.10, p = 0.20), soluble neprilysin (sNEP; R = 0.09, p = 0.24), tumor necrosis factor-alpha (TNF-α; R = 0.07, p = 0.39), and TNF-α receptor superfamily member 1A (TNFRSF1A; R = 0.14, p = 0.07) did not. Conclusions: Total B-line sum correlated significantly, although moderately, with congestion and several inflammation biomarkers. Unexpectedly, the highest correlation found was with hsTnT.

Preliminary results suggest that high circulating insulin-like growth factor binding protein 2 (IGFBP2) levels are associated with mortality risk in heart failure (HF) patients. As IGFBP2 levels are increased in patients with chronic kidney disease (CKD), which is associated with a higher mortality risk in HF patients, we examined whether IGFBP2 is associated with CKD in HF patients, and whether CKD modifies the prognostic value of this protein in HF patients.HF patients (n=686, mean age 66.6 years, 32.7% women) were enrolled and followed up for a median of 3.5 (min-max range: 0.1-6) years. Patients were classified as having CKD with decreased estimated glomerular filtration rate (eGFR60mL/min/1.73 mIGFBP2 was increased (P.001) in CKD patients with decreased eGFR (n=290, 42.3%) compared with patients with nondecreased eGFR. IGFBP2 was directly associated with NT-proBNP (P.001) and inversely associated with eGFR (P.001), with both associations being independent of confounding factors. IGFBP2 was directly and independently associated with cardiovascular and all-cause death (P.001) in the whole group of patients, but showed a stronger association with cardiovascular death in CKD patients with decreased eGFR (P for interaction.05), improving risk prediction in these patients over clinically relevant risk factors.Serum IGFBP2 is associated with impaired renal function and prognosticates cardiovascular death in patients with HF and CKD with decreased eGFR. Thus, there is an effect modification of CKD on circulating IGFBP2 and on its association with cardiovascular mortality in HF patients.

Introduction and objectives: Treatment with intravenous iron in patients with heart failure (HF) and iron deficiency (ID) improves symptoms, however its impact on survival and safety is unknown. We aimed to evaluate the management of ID and anemia with intravenous iron in patients with HF and long-term safety of intravenous iron. Methods: We evaluated anemia and ID in patients with chronic HF at 3 university hospitals. Anemia was defined using the World Health Organization definition and ID was defined as ferritin

Introduction and objectives In patients with heart failure and reduced ejection fraction (HFrEF), several therapies have been proven to reduce mortality in clinical trials. However, there are few data on the effect of the use of evidence-based therapies on causes of death in clinical practice. Methods This study included 2351 outpatients with HFrEF ( Results Patients in REDINSCOR I more frequently received beta-blockers (85% vs 71%; P Conclusions In ambulatory patients with HFrEF, implementation of evidence-based therapies was associated with a lower risk of death, mainly due to a significant reduction in sudden cardiac death.

Introduction and objectives In patients with heart failure and reduced ejection fraction (HFrEF), several therapies have been proven to reduce mortality in clinical trials. However, there are few data on the effect of the use of evidence-based therapies on causes of death in clinical practice. Methods This study included 2351 outpatients with HFrEF (< 40%) from 2 multicenter prospective registries: MUSIC (n=641, period: 2003-2004) and REDINSCOR I (n=1710, period: 2007-2011). Variables were recorded at inclusion and all patients were followed-up for 4 years. Causes of death were validated by an independent committee. Results Patients in REDINSCOR I more frequently received beta-blockers (85% vs 71%; P

Introduction and objectives Type 2 diabetes mellitus (DM2) is a common comorbidity in patients with heart failure (HF) with preserved ejection fraction (HFpEF). Previous studies have shown that diabetic women are at higher risk of developing HF than men. However, the long-term prognosis of diabetic HFpEF patients by sex has not been extensively explored. In this study, we aimed to evaluate the differential impact of DM2 on all-cause mortality in men vs women with HFpEF after admission for acute HF. Methods We prospectively included 1019 consecutive HFpEF patients discharged after admission for acute HF in a single tertiary referral hospital. Multivariate Cox regression analysis was used to evaluate the interaction between sex and DM2 regarding the risk of long-term all-cause mortality. Risk estimates were calculated as hazard ratios (HR). Results The mean age of the cohort was 75.6 ± 9.5 years and 609 (59.8%) were women. The proportion of DM2 was similar between sexes (45.1% vs 49.1, P = .211). At a median (interquartile range) follow-up of 3.6 (1-4-6.8) years, 646 (63.4%) patients died. After adjustment for risk factors, comorbidities, biomarkers, echo parameters and treatment at discharge, multivariate analysis showed a differential prognostic effect of DM2 (P value for interaction = .007). DM2 was associated with a higher risk of all-cause mortality in women (HR, 1.77; 95%CI, 1.41-2.21; P < .001) but not in men (HR, 1.23; 95%CI, 0.94-1.61; P = .127). Conclusions After an episode of acute HF in HFpEF patients, DM2 confers a higher risk of mortality in women. Further studies evaluating the impact of DM2 in women with HFpEF are warranted. Introducción y objetivos La diabetes mellitus tipo 2 (DM2) es una comorbilidad común en pacientes con insuficiencia cardiaca (IC) con fracción de eyección preservada (ICFEP). Estudios anteriores han demostrado que las mujeres diabéticas tienen mayor riesgo de desarrollar insuficiencia cardiaca que los hombres. Sin embargo, el pronóstico a largo plazo de los pacientes diabéticos con insuficiencia cardiaca en función del sexo no se ha explorado ampliamente. En este estudio, nuestro objetivo fue evaluar el impacto diferencial de la DM2 en la mortalidad por todas las causas en hombres frente a mujeres con ICFEP tras un ingreso por IC aguda. Métodos Se incluyeron prospectivamente 1.019 pacientes consecutivos con ICFEP dados de alta tras un episodio de IC aguda en hospital terciario. Se empleó un análisis de regresión de Cox multivariante para evaluar la interacción entre el sexo y la DM2 con respecto al riesgo de mortalidad total a largo plazo. Las estimaciones de riesgo se expresaron como razones de riesgo (HR). Resultados La edad media de la cohorte fue de 75,6 ± 9,5 años y 609 (59,8%) eran mujeres. La proporción de DM2 fue similar entre ambos sexos (45,1% frente a 49,1;p = 0,211). Tras una mediana de seguimiento (intervalo intercuartílico) de 3,6 (1-4-6,8) años, 646 (63,4%) pacientes murieron. Tras ajustar por factores de riesgo, comorbilidades, biomarcadores, parámetros ecográficos y tratamiento al alta, el análisis multivariate mostró un efecto pronóstico diferencial de DM2 (valor de p para la interacción = 0,007). La DM2 se asoció con un mayor riesgo de mortalidad por todas las causas en mujeres (HR = 1,77; IC95%, 1,41-2,21; P < ,001) pero no en varones (HR = 1,23; IC95%, 0,94-1,61; p = 0,127). Conclusiones Tras un episodio de IC aguda en pacientes con ICFEF, la DM2 confiere un mayor riesgo de mortalidad en las mujeres. Se requieren más estudios que evalúen el impacto de la DM2 en mujeres con ICFEP.

Aims Systolic pulmonary artery pressure (SPAP), tricuspid annular plane systolic excursion (TAPSE), and TAPSE/SPAP ratio trajectories are not fully characterized in chronic heart failure (HF). We assessed very long-term longitudinal SPAP, TAPSE and TAPSE/SPAP trajectories in HF patients, and their dynamic changes in outcomes. Methods and results Prospective, consecutive, observational registry of real-life HF patients, performing echocardiography studies at baseline and according to a prospectively structured schedule after 1 year, and then every 2 years, up to 15 years. Pulmonary hypertension (PH) was defined as SPAP ≥40 mmHg; right ventricular dysfunction (RVD) was defined at TAPSE ≤16 mm; and TAPSE/SPAP ratio was dichotomized at 0.36 mm/mmHg. The clinical endpoints were all-cause death, the composite endpoint of mortality or HF hospitalization and the number of recurrent HF hospitalizations. The study cohort included 1557 patients. Long-term SPAP trajectory Loess curves were U-shaped with a nadir at 7 years. TAPSE Loess curves showed a marked rise during the first year, with stabilization thereafter. TAPSE/SPAP ratio Loess splines were similar to the later with a smooth decline towards the end. Patients who died had higher SPAP, lower TAPSE and lower TAPSE/SPAP ratio in the preceding period than survivors. Baseline PH and/or RVD were independently associated with mortality and HF-related hospitalizations, and the persistence of one or both entities at 1 year conferred a worse long-term prognosis. Conclusions Long-term trajectories for SPAP, TAPSE and TAPSE/SPAP ratio are reported in patients with chronic HF. An increasing SPAP and declining TAPSE and TAPSE/SPAP ratio in the preceding period is associated with higher mortality.

Objectives The aim of this study was to evaluate the association between antigen carbohydrate 125 (CA125) and the risk of 1-year clinical outcomes in patients with worsening heart failure (HF). Background CA125 is a widely available biomarker that is up-regulated in patients with acute HF and has been postulated as a useful marker of congestion and risk stratification. Methods In a large multicenter cohort of patients with worsening HF, either in-hospital or in the outpatient setting, the independent associations between CA125 and 1-year death and the composite of death/HF readmission (adjusted for outcome-specific prognostic risk score [BIOSTAT risk score]) were determined by using the Royston-Parmar method (N = 2,356). In a sensitivity analysis, the prognostic implications of CA125 were also adjusted for a composite congestion score (CCS). Data were validated in the BIOSTAT-CHF (Biology Study to Tailored Treatment in Chronic Heart Failure validation) cohort (N = 1,630). Results Surrogates of congestion, such as N-terminal pro–B-type natriuretic peptide and CCS, emerged as independent predictors of CA125. In multivariable survival analyses, higher CA125 was associated with an increased risk of mortality and the composite of death/HF readmission (p Conclusions In patients with worsening HF, higher levels of CA125 were positively associated with parameters of congestion. Furthermore, CA125 remained independently associated with a higher risk of clinical outcomes, even beyond a predefined risk model and clinical surrogates of congestion.

espanolIntroduccion y objetivos: Las lesiones coronarias calcificadas pueden impedir una correcta expansion del stent que en ocasiones conduce a eventos adversos. La litotricia intracoronaria es una nueva herramienta de modificacion de la placa, cuyas seguridad y viabilidad en pacientes con enfermedad coronaria estable han sido evaluadas en el ensayo Disrupt CAD II. Aunque su uso ha aumentado rapidamente, hasta el momento solo se han comunicado casos aislados en escenarios concretos. Se presentan los resultados en pacientes clinicamente complejos de la vida real con calcificacion coronaria grave. Metodos: Entre octubre de 2018 y marzo de 2019 se trato a 25 pacientes (37 lesiones) en 2 centros espanoles, lo que representa el 2,7% de los pacientes tratados con intervencion coronaria percutanea. Resultados: Las tasas de exito clinico y del dispositivo fueron del 84 y el 95%, y no se observaron complicaciones relacionadas con el procedimiento. En todos los casos se consiguio cruzar la lesion con el balon de litotricia intracoronaria, si bien en el 8% de los casos se rompio el balon durante el inflado. Se trataron con exito lesiones complejas, como oclusiones coronarias totales y estenosis del tronco comun. En comparacion con el estudio Disrupt CAD II, nuestros pacientes eran mas jovenes, pero tenian peor escenario clinico, con mayor prevalencia de diabetes (68%) e insuficiencia renal (22%), y hasta el 76% se presento como sindrome coronario agudo. En 3 de 4 pacientes con infraexpansion de stent tratados con litotricia intracoronaria no se consiguio una expansion adecuada tras el procedimiento. No hubo complicaciones ni mortalidad hospitalaria. Un paciente fallecio por causa no cardiaca a los 30 dias de seguimiento. Conclusiones: La litotricia intracoronaria se ha demostrado efectiva y segura en una cohorte de pacientes complejos de la vida real con lesiones calcificadas. EnglishIntroduction and objectives: Complex calcified lesions can affect stent expansion and lead to stent failure and adverse outcomes. Intracoronary lithotripsy (ICL) has emerged as a new tool that enables calcium modification. The Disrupt CAD II clinical trial has recently evaluated the safety and feasibility of ICL in patients with stable coronary disease and calcified coronary lesions. Although its use has increased rapidly, the experience already reported with this new device is limited. We report the results in real-life complex patients with heavy coronary calcification. Methods: From October 2018 to March 2019, 25 patients (37 calcified lesions) were treated in 2 Spanish centers, which accounted for 2.7% of the patients treated with percutaneous coronary intervention. Results: The device and clinical success rates were 84% and 95%, respectively. No procedure-related complications were seen. The crossing rate of the ICL balloon was 100% and balloon rupture during inflation occurred in 8%. The ICL was performed in a subset of highly complex lesions like left main coronary artery lesions and chronic total coronary occlusions. Compared to the Disrupt CAD II trial, our patients were younger but their clinical scenario was worse with a higher prevalence of diabetes (68%), renal failure (22%), and up to 76% suffered from acute coronary syndrome. The ICL failed to reach proper expansion in 3 out of 4 cases of stent underexpansion. The procedure was performed safely, and clinical and device success were high with no in-hospital mortality. One patient died of non-cardiac causes at the 30-day follow-up. Conclusions: The ICL-assisted percutaneous coronary intervention was performed safely and effectively in a real-life cohort of patients with calcified and highly complex lesions.

Atrial dysfunction has been widely considered a marker or consequence of other cardiac conditions rather than the cause itself. Here, we propose the term atrial failure as a clinically relevant entity, defined as any atrial dysfunction causing impaired heart performance, symptoms, and worsening quality of life or life expectancy. Aspects of the etiology, mechanisms, and consequences of atrial failure are discussed. Recent advances in cardiac electrophysiology and imaging have improved our understanding of the highly complex atrial anatomy and function, underlying the paramount importance of the atria in optimal heart performance. It is time to reappraise the concept of the failing atrium as a primary cause or aggravating factor of the symptoms in many of our patients. The concept of atrial failure may foster basic and translational research to gain a better understanding of how to identify and manage atrial dysfunction.

Visual Abstract, Highlights • Using artificial intelligence, followed by in vivo validation, this study identified the key cardiac mechanism of action of empagliflozin in heart failure in patients with or without diabetes mellitus. • The most robust mechanism of action involved the NHE-1 co-transporter with 94.7% accuracy. • NHE-1 blockade by empagliflozin administration in rats restored the antiapoptotic activity of XIAP and BIRC5. • The beneficial reduction in cardiomyocyte cell death after empagliflozin treatment is independent of the presence of diabetes mellitus. • Empagliflozin could emerge as a new treatment for heart failure patients regardless of their glycemic status., Summary The mechanism of action of empagliflozin in heart failure with reduced ejection fraction (HFrEF) was deciphered using deep learning in silico analyses together with in vivo validation. The most robust mechanism of action involved the sodium-hydrogen exchanger (NHE)-1 co-transporter with 94.7% accuracy, which was similar for diabetics and nondiabetics. Notably, direct NHE1 blockade by empagliflozin ameliorated cardiomyocyte cell death by restoring expression of X-linked inhibitor of apoptosis (XIAP) and baculoviral IAP repeat-containing protein 5 (BIRC5). These results were independent of diabetes mellitus comorbidity, suggesting that empagliflozin may emerge as a new treatment in HFrEF.

[Abstract] Introduction and objectives: Circulating galectin-3 (Gal-3) is elevated and significantly correlates with all-cause and cardiovascular mortality in patients with heart failure. However, the relationship between serum Gal-3 and heart transplant (HT) outcomes is unclear. The aim of this study was to describe the longitudinal trend and prognostic value of Gal-3 levels after HT. Methods: Banked serum samples were available from 122 HT recipients, collected before transplant and at 1, 3, 6, and 12 months posttransplant. Gal-3 levels in these serum samples were measured by enzyme immune assay. Multivariable Cox regression was performed to determine the prognostic value of 12-month posttransplant Gal-3 serum levels. The primary endpoint was the composite variable all-cause death or graft failure over long-term posttransplant follow-up. Results: Circulating Gal-3 concentration steadily decreased during the first year after HT (median values: pretransplant, 19.1 ng/mL; 1-year posttransplant, 14.6 ng/mL; P

BACKGROUND Chronotropic incompetence has shown to be associated with a decrease in exercise capacity in heart failure with preserved ejection fraction (HFpEF), yet b-blockers are commonly used in HFpEF despite the lack of robust evidence. OBJECTIVES This study aimed to evaluate the effect of b-blocker withdrawal on peak oxygen consumption (peak VO2) in patients with HFpEF and chronotropic incompetence. METHODS This is a multicenter, randomized, investigator-blinded, crossover clinical trial consisting of 2 treatment periods of 2 weeks separated by a washout period of 2 weeks. Patients with stable HFpEF, New York Heart Association functional classes II and III, previous treatment with b-blockers, and chronotropic incompetence were first randomized to withdrawing from (arm A: n ¼ 26) versus continuing (arm B: n ¼ 26) b-blocker treatment and were then crossed over to receive the opposite intervention. Changes in peak VO2 and percentage of predicted peak VO2 (peak VO2%) measured at the end of the trial were the primary outcome measures. To account for the paired-data nature of this crossover trial, linear mixed regression analysis was used. RESULTS The mean age was 72.6 13.1 years, and most of the patients were women (59.6%) in New York Heart Association functional class II (66.7%). The mean peakVO2 and peak VO2% were 12.4 2.9 mL/kg/min, and 72.4 17.8%, respectively. No significant baseline differences were found across treatment arms. Peak VO2 and peak VO2% increased significantly after b-blocker withdrawal (14.3 vs 12.2 mL/kg/min [D þ2.1 mL/kg/min]; P < 0.001 and 81.1 vs 69.4% [D þ11.7%]; P < 0.001, respectively). CONCLUSIONS b-blocker withdrawal improved maximal functional capacity in patients with HFpEF and chronotropic incompetence. b-blocker use in HFpEF deserves profound re-evaluation. (b-blockers Withdrawal in Patients With HFpEF and Chronotropic Incompetence: Effect on Functional Capacity [PRESERVE-HR]; NCT03871803; 2017-005077-39) (J Am Coll Cardiol 2021;78:2042–2056) © 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Aims The aim of this study was to determine the contemporary use of reperfusion therapy in the European Society of Cardiology (ESC) member and affiliated countries and adherence to ESC clinical practice guidelines in patients with ST-elevation myocardial infarction (STEMI). Methods and results Prospective cohort (EURObservational Research Programme STEMI Registry) of hospitalized STEMI patients with symptom onset Conclusions The use of reperfusion therapy for STEMI in the ESC member and affiliated countries was high. Primary PCI was the most frequently used treatment and associated total in-hospital mortality was below 5%. However, there was geographic variation in the use of primary PCI, which was associated with differences in in-hospital mortality.

Background Real-life clinical practice has confirmed the value of pulmonary artery (PA) pressure-guided therapy in patients with heart failure (HF) and history of repeated HF hospitalizations (HFH), to greater extent to that reported in the pivotal clinical trial CHAMPION-HF. The value of hemodynamic monitoring in a population of patients with HF and elevated natriuretic peptides, but without recent HFH, is unknown. Objective To assess N-terminal-pro-brain natriuretic peptide (NTproBNP) dynamics before and 6 months after PA pressure sensor implantation. Methods Ten patients managed in a multidisciplinary HF clinic implanted with the CardioMEMS PA pressure sensor were consecutively included from June 2019 to July 2020. Mean age was 63.1±23.5 years, 30% were women, 40% had HF with reduced EF (EF Results Mean daily pressure transmission rate was 92.4±5.1%. During the six-month study period 90% of patients had a change in medication related to PA pressure, with an average of 0.21 [0.17–0.66] changes per patient per month. Mean PA pressure at baseline was 28.5±9.5 mmHg, and decreased by 5.5 mmHg at 6 months (p=0.01) (Figure 1). NTproBNP was also significantly lower six months post CardioMEMS implantation; decreasing from 1696 pg/ml [976–2930] at baseline to 1046 pg/ml [616–2076] after six months (p=0.04) (Figure 2). There was a weak correlation between the change in NTproBNP and the change in mean PA pressure (R2=0.22, p=0.17). Conclusions NTproBNP values were significantly lower 6-months following implantation of a PA pressure sensor to guide HF management. Mean PA pressures were also significantly reduced. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Hospital Universitari Germans Trias i Pujol Figure 1. Change in mean PA pressure over time.Figure 2. Change in NTproBNP after PAP monitoring.

Background Heart failure (HF) is characterized by alterations in kidney function that are associated with poor prognosis and can be related to the evolution of the disease or induced by medical treatment. High temperatures during summer may result in some degree of dehydration, especially in patients treated with diuretics, and may contribute to transient glomerular filtration rate (eGFR) reduction. Objective To assess creatinine and eGFR changes during summer in ambulatory heart failure patients. Methods Consecutive patients with HF admitted at our HF Clinic (Spain) from August 2001 to December 2020 were included. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. We included in the analysis creatinine and eGFR values that were assessed at planned visits only, discarding urgent renal function assessments. Creatinine and eGFR values were grouped according to the period of the year (summer [from June to September, both included] vs. the rest of the year). Changes in creatinine and eGFR between the rest of the year and summer for each patient were evaluated using paired samples t-test. Results Out of 37360 creatinine and eGFR values, 25458 were included in the analysis for a total of 2423 patients (median number of observations for each patient: 8, IQR 4–15). Mean creatinine and eGFR were 1.4±1.0 mg/dl and 63.0±27.7 ml/min, respectively. Table 1 shows baseline patient characteristics. Creatinine increased significantly during summer (1.44±0.9 mg/dl vs. 1.48±1.1 mg/dl, p Conclusions In ambulatory HF patients in a Mediterranean area, we found significant worsening of renal function during summer, likely related to an imbalance between water intake and fluid loss. To prevent summer-driven kidney stress, diuretic treatment should be carefully adjusted during the hottest months of the year. Funding Acknowledgement Type of funding sources: None. Table 1

Objective: To determine the effect of marathon running on serum levels of inflammatory, high energy, and cartilage matrix biomarkers and to ascertain whether these biomarkers levels correlate.Design: Blood samples from 17 Caucasian male recreational athletes at the Barcelona Marathon 2017 were collected at the baseline, immediately and 48 h post-race. Serum C reactive protein (CRP), creatin kinase (CK), and lactate dehydrogenase (LDH) were determined using an AU-5800 chemistry analyser. Serum levels of hyaluronan (HA), cartilage oligomeric matrix protein (COMP), aggrecan chondroitin sulphate 846 (CS846), glycoprotein YKL-40, human procollagen II N-terminal propeptide (PIINP), human type IIA collagen N-propeptide (PIIANP), and collagen type II cleavage (C2C) were measured by sandwich enzyme-linked immune-sorbent assay (ELISA).Results: Medians CK and sLDH levels increased (three-fold, two-fold) post-race [429 (332) U/L, 323 (69) U/L] (p < 0.0001; p < 0.0001) and (six-fold, 1.2-fold) 48 h post-race [658 (1,073) U/L, 218 (45) U/L] (p < 0.0001; p < 0.0001). Medians CRP increased (ten-fold) after 48 h post-race [6.8 (4.1) mg/L] (p < 0.0001). Mean sHA levels increased (four-fold) post-race (89.54 ± 53.14 ng/ml) (p < 0.0001). Means PIINP (9.05 ± 2.15 ng/ml) levels increased post-race (10.82 ± 3.44 ng/ml) (p = 0.053) and 48 h post-race (11.00 ± 2.96 ng/ml) (p = 0.001). Mean sC2C levels (220.83 ± 39.50 ng/ml) decreased post-race (188.67 ± 38.52 ng/ml) (p = 0.002). In contrast, means COMP, sCS846, sPIIANP, and median sYKL-40 were relatively stable. We found a positive association between sCK levels with sLDH pre-race (r = 0.758, p < 0.0001), post-race (r = 0.623, p = 0.008) and 48-h post-race (r = 0.842, p < 0.0001); sHA with sCRP post-race vs. 48 h post-race (r = 0.563, p = 0.019) and sPIINP with sCK pre-race vs. 48-h post-race (r = 0.499, p = 0.044) and with sLDH 48-h pre-race vs. post-race (r = 0.610, p = 0.009) and a negative correlation of sPIIANP with sCRP 48-h post-race (r = −0.570, p = 0.017).Conclusion: Marathon running is an exercise with high-energy demands (sCK and sLDH increase) that provokes a high and durable general inflammatory reaction (sCRP increase) and an immediately post-marathon mechanism to protect inflammation and cartilage (sHA increase). Accompanied by an increase in type II collagen cartilage fibrils synthesis (sPIINP increase) and a decrease in its catabolism (sC2C decrease), without changes in non-collagenous cartilage metabolism (sCOMP, sC846, and sYKL-40). Metabolic changes on sPIINP and sHA synthesis may be related to energy consumption (sCK, sLDH) and the inflammatory reaction (sCRP) produced.

Background Soluble suppression of tumorigenesis-2 (sST2) is released in response to inflammation and vascular injury, and holds prognostic value in heart failure (HF). Type 2 diabetes (T2D) is characterized by a pro-inflammatory status and is highly prevalent among HF patients, with adverse impact on outcomes. The clinical value of sST2 in HF patients with T2D has never been characterized. Purpose We aimed to assess sST2 clinical correlates and prognostic value in HF patients with T2D. Methods Individual data of 3476 patients with stable chronic HF from 5 cohorts from the BIOS (Biomarkers In Heart Failure Outpatient Study) dataset were analysed, with available N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), and sST2 levels. Results Mean age was 65±12 years (75% males). T2D was present in 1386 patients (40%), who had higher body mass index (BMI, 27 [24–30] vs. 26 [23–29] kg/m2, p Conclusions sST2 is higher in HF patients with T2D and likely linked to a pro-inflammatory status. sST2 maintains its prognostic value both in diabetic and non-diabetic HF patients, independently of NT-proBNP, hs-TnT and hs-CRP. Funding Acknowledgement Type of funding sources: None. Figure 1

Background Limited data are available on the very long-term trajectory of glomerular filtration rate (GFR) in patients with chronic heart failure (HF). Purpose To assess the GFR dynamics estimated by CKD-EPI in a real-life cohort of HF patients over a 14-year follow-up. Methods In a prospective observational registry of real-life HF outpatients, estimated GFR (eGFR) was calculated by CKD-EPI at baseline and on a structured schedule every 3 months up to 14 years. We included in the analysis only eGFR values that were assessed at scheduled visits, discarding urgent renal function assessments. Loess (locally weighted error sum of squares) curves were plotted for the whole cohort and subgroups according to vital status up to 14 years of follow-up. Loess curves are useful to observe a trend or relationship on nonlinear data observed over time. Results 2423 patients were consecutively included from August 2001 to December 2018. Mean age was 67.0±12.7 years, 28,8% were women and 71.1% had HF with reduced ejection fraction (EF Significant changes occurred along the whole trajectory. An initial decline in eGFR was observed during the first three years of follow-up. Subsequently, there was an upward trend during the following five years and after that period a progressive decline was seen until the end of follow-up (Figure 1). In the sub-group of patients who died during follow-up the eGFR slope showed a persistent decline over time of ∼1ml/min/1.73m2 per year. On the contrary, patients who survived to follow-up maintained a stable eGFR (Figure 2). Conclusions The eGFR long-term trajectory in patients with chronic HF showed a snaky pattern with an early decrease, mid-term improvement and late progressive decline. Patients who died during follow-up presented a progressive decline from the beginning. Funding Acknowledgement Type of funding sources: None. Figure 1. Long-term evolution of eGFRFigure 2. eGFR evolution according to vital status

Severe tricuspid regurgitation remains a challenging heart-valve disease to effectively treat with high morbidity and mortality at mid-term. Currently guideline-directed medical treatment is limited to escalating dose of diuretics, and the rationale and timing of open-heart surgery remains controversial. Emerging percutaneous therapies for severe tricuspid regurgitation continue to show promising results in early feasibility studies. However, randomized trial data is lacking. Additionally, many patients are deemed unsuitable for these emerging therapies due to anatomical or imaging constraints. Given the technical simplicity of the bicaval valve implantation (CAVI) technique compared to other transcatheter devices, CAVI is postulated as a suitable alternative for a wide variety of patients affected with severe+ tricuspid regurgitation. In this review we illustrate the current evidence and ongoing uncertainties of CAVI, focusing on the novel CAVI-specific devices.

Background N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure (HF) in hypertrophic cardiomyopathy (HCM), however, evidence regarding soluble interleukin-1 receptor-like 1 (ST2) in this population is lacking. Purpose To assess the ST2 and NT-proBNP significance for risk stratification of patients with HCM during long-term follow-up. Methods We prospectively enrolled a cohort of consecutive patients with HCM admitted to an ambulatory HF Unit in a Tertiary University Hospital. All patients had clinical and echocardiographic evaluation and measurement of NT-proBNP and ST2 at inclusion. The primary endpoint was the composite of all-cause death or HF-related hospitalization. Results 103 patients were enrolled, 68% (n=70) males with a median (IQR) age of 60 (50–71) years. The median (IQR) of ST2 was 31.5 (IQR: 24.5 – 40.7) pg/mL. During a median follow-up of 2.5 years, 17 patients had the primary endpoint. Both, NT-proBNP and ST2 (both log-transformed) were associated with the primary endpoint in the univariable analyses (p Conclusions ST2 appears to be a valuable biomarker for the prediction of death and heart failure related hospitalization in patients with HCM, outperforming the prognostic value of NT-proBNP. Future research should delve into this association. Funding Acknowledgement Type of funding sources: None.

Background Right ventricular-pulmonary circulation coupling (RVPAC), which can be measured by the relation between tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (SPAP) by echocardiography, has been postulated as an independent prognostic factor of hospitalizations and mortality in heart failure (HF) patients. Purpose Our aim was to know the predictors of RVPAC improvement in a chronic HF cohort. Methods Retrospective analysis of a prospectively studied cohort of HF outpatients of different aetiologies attended in a multidisciplinary HF Unit. Prospectively scheduled echo-Doppler studies were performed at first visit and 1 year. A TAPSE/SPAP ratio Results From August 2001 to July 2017, 554 patients with TAPSE and SPAP data in the initial visit were included. Mean follow-up time was 4.6±3.7 years. At first visit 252 (45.5%) patients had RVPAC Conclusions Atrial fibrillation/flutter, increasing SPAP and female gender hamper RVPAC improvement at 1 year in HF patients with baseline TAPSE/SPAP ratio Funding Acknowledgement Type of funding sources: None. Multivariate regression analysis

Background Recent evidence confirms the elevation of CA 125 in non-tumor processes such as acute heart failure (AHF). However, the utility of this novel biomarker for diagnosis, prognosis, and therapy guidance in AHF remains unclear. Purpose To investigate the potential of CA 125 for diagnosis, prognosis and therapy guidance in unselected AHF patients presenting with acute dyspnea to the emergency department (ED). Methods We quantified CA 125 in a blinded fashion among patients presenting with acute dyspnea to the ED in a multicenter diagnostic study. Final diagnosis of AHF including AHF-phenotype was centrally adjudicated by two independent cardiologists. To further characterize CA 125's potential in AHF correlations with established biochemical and imaging markers were assessed. Diagnostic accuracy for AHF was quantified by the area under the receiver operating characteristic curve (AUC). All-cause mortality within 360 days was the prognostic endpoint. Results Among 470 patients eligible for this analysis, 268 (57.0%) had adjudicated AHF. CA 125 concentrations at presentation were significantly higher among AHF patients vs. patients with other final diagnoses (45.8 U/ml [interquartile range (IQR), 18.5–110.3] vs. 16.2 U/ml [IQR, 9.6–31.6], p Conclusion CA 125 may aid physicians in the risk stratification and rapid triage of patients with suspected AHF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swiss National Science FoundationSwiss Heart Foundation Figure 1. ROC curve comparisonFigure 2. Kaplan-Meier curve 360 days mortality