Background Frailty is common and significantly impacts prognosis in heart failure(HF).The Vulnerable Elders Survey-13(VES-13),widely used in oncogeriatrics and public health,remains unexplored as a frailty screening tool in HF outpatients.In this study,we prospectively evaluated VES-13 against a multimodal screening assessment in detecting frailty and predicting indi-vidual risk of adverse prognosis. Methods Frailty was assessed at the initial visit using both a multimodal approach,incorporating Barthel Index,Older Americ-an Resources and Services scale,Pfeiffer Test,abbreviated Geriatric Depression Scale,age>85 years,lacking support systems,and VES-13.Patients scoring≥3 on VES-13 or meeting at least one multimodal criterion were classified as frail.Endpoints in-cluded all-cause mortality,a composite of death or HF hospitalization,and recurrent HF hospitalizations. Results A total of 301 patients were evaluated.VES-13 identified 40.2%as frail and the multimodal assessment 33.2%.In Cox regression analyses,frailty identified by VES-13 showed greater prognostic significance than the multimodal assessment for all-cause mortality(HR=3.70[2.15-6.33],P<0.001 vs.2.40[1.46-4.0],P=0.001)and the composite endpoint(HR=3.13[2.02-4.84],P<0.001 vs.1.96[1.28-2.99],P=0.002).Recurrent HF hospitalizations were four times more frequent in VES-13 frail patients while two times in those identified as frail by the multimodal assessment.Additionally,stratifying patients by VES-13 tertiles provided robust risk differentiation. Conclusions VES-13,a simple frailty tool,outperformed a comprehensive multimodal assessment and could be easily integ-rated into routine HF care,highlighting its clinical utility in identifying patients at risk for poor outcomes.

Background Secondary mitral regurgitation (SMR) frequently accompanies heart failure with reduced ejection fraction (HFrEF) and may regress with guideline-directed medical therapy (GDMT). However, real-world data on SMR trajectories and prognostic implications remain scarce. Objectives The purpose of this study was to characterize 12-month trajectories of SMR under optimized GDMT in ambulatory patients with HFrEF and to evaluate the long-term prognostic impact. Methods The authors prospectively studied 2,254 ambulatory HFrEF patients who underwent baseline and 12-month transthoracic echocardiography (TTE), excluding those with mitral valve interventions. The primary endpoint was all-cause mortality, and the secondary endpoint was a composite of all-cause mortality or heart failure hospitalization (HFH) over a median follow-up period of 4.5 years after the 12-month TTE. Results At baseline, 67.6% of patients had none or mild (nonsignificant) SMR, 25.2% had moderate SMR, and 7.3% had severe SMR. After 12 months of optimized GDMT, the distribution shifted (P < 0.001): 79.5%, 16.5%, and 4.2% had nonsignificant, moderate, and severe SMR, respectively. Among the 731 patients with significant SMR (moderate/severe) at baseline, 57.5% improved to nonsignificant SMR. Improvement from significant to nonsignificant SMR within 12 months was associated with a favorable long-term prognosis, comparable to patients who consistently had nonsignificant SMR. Conversely, patients with persistent significant SMR had a higher risk of all-cause mortality (HR: 1.60; 95% CI: 1.36-1.89; P < 0.001) and the composite outcome of mortality or HFH (HR: 1.59; 95% CI: 1.36-1.85; P < 0.001). Conclusions In this real-world HFrEF cohort, optimizing GDMT use led to SMR improvement in over half of patients with moderate or severe SMR. Nevertheless, both persistent moderate and severe SMR were associated with poor outcomes, underscoring the known benefit of mitral intervention in severe SMR and its potential in moderate SMR.

BACKGROUND:With the increasing diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) at earlier stages and new therapies, there is a rising demand for tools to stratify risk and prognosis. We evaluated the prognostic value of multiple circulating biomarkers for predicting outcomes in ATTR-CM. METHODS:We evaluated 12 different circulating biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin I [hsTnI], mid-regional pro-adrenomedullin [MR-proADM], carbohydrate antigen 125 [CA125], soluble suppressor of tumorigenicity 2 [sST2], cluster of differentiation antigen 146 [CD146], growth/differentiation factor-15 [GDF-15], alpha-klotho, fibroblast growth factor 23 [FGF-23], galectin-3, insulin-like growth factor-binding protein 7 [IGFBP-7], and estimated glomerular filtration rate [eGFR]) in 337 ATTR-CM patients from Spain. Cox models were employed to determine their predictive abilities. Findings were validated in 2 independent external cohorts of 210 patients from the United States and 416 patients from the ATTR-ACT trial, respectively. RESULTS:Over a median follow-up of 19.7 months (IQR, 6.5-42.3), 67 patients (19.9%) died/underwent heart transplantation, and 81 (24%) had heart failure events. MR-proADM was the biomarker with the strongest prognostic performance, with a C-index of 0.788 (95% CI, 0.723-0.851) for all-cause mortality and 0.721 (95% CI, 0.669-0.772) for the composite endpoint of death and heart failure events. MR-proADM was associated with multiple parameters of ATTR-CM severity and was independently associated with mortality, heart failure events, and the composite endpoint. MR-proADM ≥1.1 nmol/L was identified as the optimal prognostic threshold, and it improved prediction of mortality when added to the National Amyloid Center (area under the curve [AUC], 0.682 versus 0.737; P<0.001), Mayo (AUC, 0.659 versus 0.749; P<0.001), and the Columbia staging systems (AUC, 0.699 versus 0.768; P<0.001). In both validation cohorts, patients with MR-proADM ≥1.1 nmol/L had worse outcomes (P<0.001). This association was also confirmed in patients receiving tafamidis. CONCLUSIONS:In patients with ATTR-CM, MR-proADM levels are associated with disease severity and worse prognosis. MR-proADM improves prediction of all-cause mortality and captures heart failure events.

BACKGROUND:The specific contribution of left ventricular chamber dimensions to amino-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations in heart failure remains underexplored. We evaluated the association between left ventricular end-diastolic diameter (LVEDD) and circulating NT-proBNP levels across the spectrum of acute and chronic heart failure. METHODS:We conducted a multicenter retrospective analysis of 8,361 patients (4,374 with acute heart failure and 3,987 with chronic heart failure) from four independent cohorts. NT-proBNP levels and echocardiographic measurements were collected during hospitalization or ambulatory visits. Quantile regression models were used to assess the independent association between LVEDD and NT-proBNP. RESULTS:Larger LVEDD was consistently associated with higher NT-proBNP concentrations across the four heart failure cohorts (P < 0.05). This direct linear relationship persisted after multivariable adjustment and across left ventricular ejection fraction categories. A 10 mm increase in LVEDD was associated with an increase in NT-proBNP of 444 pg/mL (95% CI: 266-623, P < 0.001) at admission in the acute heart failure derivation cohort of 158 pg/ml (95% CI: 10-305, P = 0.036) in the chronic heart failure derivation cohort. In the subset of patients in which CMR was performed, CMR-iLVEDV was also positive and linearly associated with NT-proBNP levels. For each 10 ml/m2 increase, NT-proBNP on admission increased by 290 pg/ml (95% CI: 122-458, P < 0.001). Conversely, patients with smaller left ventricular chambers consistently exhibited lower NT-proBNP concentrations. CONCLUSIONS:Left ventricular chamber size is an independent factor associated with NT-proBNP levels in both acute and chronic heart failure. These findings underscore the importance of incorporating left ventricular dimensions into the interpretation of natriuretic peptide concentrations.

BACKGROUND AND AIMS:Worsening kidney function is a key prognostic factor in heart failure (HF) with reduced ejection fraction (HFrEF). However, associations between kidney function trajectories and HF-related events remain unclear. METHODS:Longitudinal changes in estimated glomerular filtration rate (eGFR) before and after a HF-related event, defined as HF hospitalization or HF death, were examined using individual patient data from two clinical trials (EPHESUS and EMPHASIS-HF) and a real-world cohort (BARCELONA). RESULTS:HF-related events occurred in 14.1% of 8587 patients [EPHESUS/EMPHASIS-HF; median follow-up 17.1 (12.4-22.7) months] and 33.8% of 2048 patients [BARCELONA; median 47.0 (18.8-90.6) months]. In EPHESUS and EMPHASIS-HF, patients who experienced an HF-related event had a steeper decline in eGFR in the year preceding the event (average -4.83 mL/min/1.73 m²/year) compared with those who did not have an HF-related event (-1.18 mL/min/1.73 m²/year). Over the 1 year following an HF-related event, eGFR continued to decline, though at a slower rate (average -3.45 mL/min/1.73 m²/year). Similar kidney function trajectories were observed in BARCELONA (average eGFR decline -1.35 mL/min/1.73 m²/year in patients without HF event vs -5.77 mL/min/1.73 m²/year 1 year before an event and -3.04 mL/min/1.73 m²/year over the year after an event). Worsening New York Heart Association class paralleled steeper eGFR decline prior to HF events. CONCLUSIONS:In HFrEF, kidney function decline may precede a HF hospitalization or death by up to 1 year, linking to symptomatic congestion. Monitoring eGFR slopes rather than relying solely on specific cut-off values may allow early detection of at-risk patients.

AIMS:To investigate the distribution of left atrioventricular coupling index (LACI) among patients with heart failure and left ventricular ejection fraction (LVEF) < 50% and to explore its association with the combined endpoint of all-cause death or HF hospitalization at long-term follow-up. METHODS AND RESULTS:Patients with HF and LVEF < 50% undergoing cardiac magnetic resonance were evaluated. Patients with atrial fibrillation or flutter were excluded. Left atrioventricular coupling index was measured as the ratio between the left atrial (LA) and the LV end-diastolic volumes. Patient population was divided according to LACI tertiles and followed up. Total of 478 patients (mean age 62 ± 12 years, 78% male) were included. The median value of LACI was 27.1% (interquartile range 19.9-34.5). Patients within the worst LACI tertile (≥30.9%) showed smaller LV volumes and larger LA volumes as compared with patients in the first or second tertile (LACI 6.2-22.2 and LACI 22.3-30.9, respectively). Left atrioventricular coupling index was significantly associated with the combined endpoint [hazard ratio (HR) 1.87, P = 0.01]. After adjusting for sex, age, ischaemic HF aetiology, LVEF, LA reservoir strain, diabetes mellitus, LV scar, mitral regurgitation, and LVEDVi, LACI remained significantly associated with the combined endpoint (HR 1.77, P = 0.02). Patients with the highest LACI values had worse outcomes compared with patients in first and second tertiles (HR 1.69, P = 0.02 and HR 1.77, P = 0.02, respectively). CONCLUSION:In patients with HF and LVEF <50%, LACI is independently associated with adverse events. Patients with most impaired left atrioventricular coupling have the worst clinical outcomes.

Although previous studies have evaluated renal function decline in patients with heart failure (HF), there is limited evidence on long-term renal trajectories, especially in patients with concomitant HF and type 2 diabetes (T2D). This study aims to provide a detailed analysis of renal function decline over an extended follow-up period in a well-characterized cohort of patients with HF and T2D. This is a post hoc subanalysis of a prospective registry involving ambulatory patients with HF and T2D referred to a specialized HF clinic. The estimated glomerular filtration rate (eGFR) was assessed at baseline and during scheduled follow-up visits every three months using the Chronic Kidney Disease Epidemiology Collaboration formula. Loess curves were plotted for predefined subgroups, and multivariable longitudinal Cox regression analyses were performed to evaluate the associations between eGFR trajectories and all-cause mortality. A total of 1,114 patients with HF and T2D were included, with a mean age of 69.3 ± 10.3 years, and 68.2

AbstractAimsMortality in cardiogenic shock (CS) remains elevated, with the potential for CS causes to impact prognosis and risk stratification. The aim was to investigate in‐hospital prognosis and mortality in CS patients according to aetiology. We also assessed the prognostic accuracy of CardShock and IABP‐SHOCK II scores.MethodsShock‐CAT study was a multicentre, prospective, observational study conducted from December 2018 to November 2019 in eight university hospitals in Catalonia, including non‐selected consecutive CS patients. Data on clinical presentation, management, including mechanical circulatory support (MCS) were analysed comparing acute myocardial infarction (AMI) related CS and non‐AMI‐CS. The accuracy of CardShock and IABP‐SHOCK II scores to assess 90 day mortality risk were also compared.ResultsA total of 382 CS patients were included, age 65.3 (SD 13.9) years, 75.1% men. Patients were classified as AMI‐CS (n = 232, 60.7%) and non‐AMI‐CS (n = 150, 39.3%). In the AMI‐CS group, 77.6% were STEMI. Main aetiologies for non‐AMI‐CS were heart failure (36.2%), arrhythmias (22.1%) and valve disease (8.0%). AMI‐CS patients required more MCS than non‐AMI‐CS (43.1% vs. 16.7%, P < 0.001). In‐hospital mortality was higher in AMI‐CS (37.1 vs. 26.7%, P = 0.035), with a two‐fold increased risk after multivariate adjustment (odds ratio 2.24, P = 0.019). The IABP‐SHOCK II had superior discrimination for predicting 90 day mortality when compared with CardShock in AMI‐CS patients [area under the curve (AUC) 0.74 vs. 0.66, P = 0.047] although both scores performed similarly in non‐AMI‐CS (AUC 0.64 vs. 0.62, P = 0.693).ConclusionsIn our cohort, AMI‐CS mortality was increased by two‐fold when compared with non‐AMI‐CS. IABP‐SHOCK II score provides better 90 day mortality risk prediction than CardShock score in AMI‐CS, but both scores performed similar in non‐AMI‐CS patients.

AIMS:To assess the agreement between left ventricular end-diastolic diameter index (LVEDDi) and volume index (LVEDVi) to define LV dilatation and to investigate the respective prognostic implications in patients with heart failure (HF). METHODS AND RESULTS:Patients with HF symptoms and LV ejection fraction (LVEF) < 50% undergoing cardiac magnetic resonance were evaluated retrospectively. LV dilatation was defined as LVEDDi or LVEDVi above the upper normal limit according to published reference values. Patients were followed up for the combined endpoint of cardiovascular death or HF hospitalization during 5 years. A total of 564 patients (median age 64 years; 79% men) were included. LVEDDi had a modest correlation with LVEDVi (r = 0.682, P < 0.001). LV dilatation was noted in 84% of patients using LVEDVi-based definition and in 73% using LVEDDi-based definition, whereas 20% of patients displayed discordant definitions of LV dilatation. During a median follow-up of 2.8 years, patients with both dilated LVEDDi and LVEDVi had the highest cumulative event rate (HR 3.00, 95% CI 1.15-7.81, P = 0.024). Both LVEDDi and LVEDVi were independently associated with the primary outcome (hazard ratio 3.29, 95%, P < 0.001 and 2.8, P = 0.009; respectively). CONCLUSION:The majority of patients with HF and LVEF < 50% present both increased LVEDDi and LVEDVi whereas 20% show discordant linear and volumetric definitions of LV dilatation. Patients with increased LVEDDi and LVEDVi have the worst clinical outcomes suggesting that the assessment of these two metrics is needed for better risk stratification.

AbstractAimsInter‐atrial block (IAB), a marker of electrical atrial dysfunction, is associated with an increased risk of atrial fibrillation (AF) and adverse events in various populations. The prognostic impact of IAB in heart failure (HF) with preserved ejection fraction (HFpEF) remains unknown. The aim of this study is to determine the prevalence of IAB and the association of IAB and AF with adverse events in HFpEF across different healthcare settings.Methods and resultsTo identify electrical atrial dysfunction, baseline ECG's and medical history were analysed in HFpEF patients in an ambulatory setting and after recent HF hospitalisation. Patients were categorised into (i) HFpEFNo IAB, (ii) HFpEFIAB, or (iii) HFpEFAF. Adverse events included HF hospitalisation, cardiac/sudden death and a composite of both. The ambulatory cohort included 372 patients [mean age 75 ± 7 years, 252 (68%) females]. The recently hospitalised cohort included 132 patients [mean age 81 ± 10 years, 80 (61%) females]. Ambulatory patients included 17 (4%) HFpEFnoIAB, 114 (31%) HFpEFIAB and 241 (65%) HFpEFAF, while recently hospitalised patients included 31 (23%), 73 (55%) and 28 (21%), respectively. After 33 months of follow‐up of ambulatory patients, composite endpoints occurred in 0 (0%) HFpEFnoIAB, 12 (11%) HFpEFIAB [HR 4.1 (95% CI 0.5–522.6)] and 59 (24%) HFpEFAF patients [HR 10.1 (95% CI 1.5–1270.4), P < 0.001]. Recently hospitalised patients showed a similar trend, with composite endpoints in 10 (32%) HFpEFnoIAB, 31 (42%) HFpEFIAB (HR 1.5 [95% CI 0.7–3.1]) and 22 (79%) HFpEFAF (HR 3.8 [95% CI 1.8–8.1], P < 0.001).ConclusionsProgressive stages of electrical atrial dysfunction appeared to be prognostic markers of adverse outcomes in ambulatory and recently hospitalised patients with HFpEF. Ambulatory patients with HFpEF and no early stages of electrical atrial dysfunction showed to be at very low risk for adverse outcomes. Whether such patients benefit less strict management remains to be investigated.

The objective of this study was to perform a cost–benefit analysis of the CardioMEMS HF System (Abbott Laboratories, Abbott Park, IL, USA) in a heart failure (HF) clinic in Spain by evaluating the real-time remote monitoring of pulmonary artery pressures, which has been shown to reduce HF-related hospitalizations and improve the quality of life for selected HF patients. Particularly, the study aimed to determine the value of CardioMEMS in Southern Europe, where healthcare costs are significantly lower and its effectiveness remains uncertain. This single-centre study enrolled all consecutive HF patients ( N  = 43) who had been implanted with a pulmonary artery pressure sensor (CardioMEMS HF System); 48.8% were females, aged 75.5 ± 7.0 years, with both reduced and preserved left ventricular ejection fraction; 67.4% of them were in New York Heart Association Class III. The number of HF hospitalizations in the year before and the year after the sensor implantation was compared. Quality-adjusted life years gained based on a literature review of previous studies were calculated. The rate of HF hospitalizations was significantly lower at 1 year compared with the year before CardioMEMS implantation (0.25 vs. 1.10 events/patient-year, hazard ratio 0.22, P  = 0.001). At the end of the first year, the usual management outperformed the CardioMEMS HF System. By the end of the second year, the CardioMEMS system is estimated to reduce costs compared with usual management (net benefits of €346). Based on the results, we suggest that remote monitoring of pulmonary artery pressure with the CardioMEMS HF System represents a midterm and long-term efficient strategy in a healthcare setting in Southern Europe.

BACKGROUND:Limited data are available on the long-term trajectory of estimated glomerular filtration rate (eGFR) in patients with chronic heart failure. OBJECTIVES:The authors evaluated eGFR dynamics using the 2009 Chronic Kidney Disease Epidemiology Collaboration equation and its prognostic significance in a real-world cohort over a 15-year follow-up. METHODS:A prospective observational registry of ambulatory heart failure outpatients was conducted, with regular eGFR assessments at baseline and on a 3-month schedule for ≤15 years. Urgent kidney function assessments were excluded. Locally weighted error sum of squares curves were plotted for predefined subgroups. Multivariable longitudinal Cox regression analyses were conducted to assess associations with all-cause and cardiovascular death. RESULTS:A total of 2,672 patients were enrolled consecutively between August 2001 and December 2021. The average age was 66.8 ± 12.6 years, and 69.8% were men. Among 40,970 creatinine measurements, 28,634 were used for eGFR analysis, averaging 10.7 ± 8.5 per patient. Over the study period, a significant decline in eGFR was observed in the entire cohort, with a slope of -1.70 mL/min/1.73 m2 per year (95% CI: -1.75 to -1.66 mL/min/1.73 m2 per year). Older patients, those with diabetes, a preserved ejection fraction, a higher baseline eGFR, elevated hospitalization rates, and those who died during follow-up experienced more pronounced decreases in the eGFR. Moreover, the decrease in kidney function correlated independently with all-cause mortality and cardiovascular death. CONCLUSIONS:These findings highlight the sustained decline in eGFR over 15 years in patients with heart failure, with variations based on clinical characteristics, and emphasize the importance of regular eGFR monitoring in this population.

Subjects with type 2 diabetes mellitus (T2D) are at increased risk for heart failure (HF). The cardiac-specific (FABP3) and adipose-tissue-specific (FABP4) types of the fatty acid binding proteins have been associated with both all-cause and cardiovascular (CV) mortality. The aim of this study was to explore the prognosis value of FABP3 and FABP4 in ambulatory subjects with chronic HF (CHF), with and without T2D. A prospective study involving 240 ambulatory CHF subjects was performed. Patients were followed-up for a mean of 5.78 ± 3.30 years and cause of death (if any) was recorded. Primary endpoints were defined as all-cause and CV death, and a composite endpoint that included CV death or hospitalization for HF was included as a secondary endpoint. Baseline serum samples were obtained and the serum FABP3 and FABP4 concentrations were assessed by sandwich enzyme-linked immunosorbent assay. Survival analysis was performed with multivariable Cox regressions, using Fine and Gray competing risks models when needed, to explore the prognostic value of FABP3 and FABP4 concentrations, adjusting for potential confounders. Type 2 diabetes mellitus was highly prevalent, accounting for 47.5% for total subjects with CHF. Subjects with T2D showed higher mortality rates (T2D: 69.30%; non-T2D: 50.79%, p = 0.004) and higher serum FABP3 (1829.3 (1104.9–3440.5) pg/mL vs. 1396.05 (820.3–2362.16) pg/mL, p = 0.007) and FABP4 (45.5 (27.6–79.8) ng/mL vs. 34.1 (24.09–55.3) ng/mL, p = 0.006) concentrations compared with non-T2D CHF subjects. In the whole study cohort, FABP3 was independently associated with all-cause death, and both FABP3 and FABP4 concentrations were associated with CV mortality. The predictive values of these two molecules for all-cause (FABP3: HR 1.25, 95% CI 1.09–1.44; p = 0.002. FABP4: HR 2.21, 95% CI 1.12–4.36; p = 0.023) and CV mortality (FABP3: HR 1.28, 95% CI 1.09–1.50; p = 0.002. FABP4: HR 4.19, 95% CI 2.21–7.95; p < 0.001) were only statistically significant in the subgroup of subjects with T2D. Notably, FABP4 (HR 2.07, 95% CI 1.11–3.87; p = 0.022), but not FABP3, also predicted the occurrence of the composite endpoint (death or hospitalization for HF) only in subjects with T2D. All these associations were not found in CHF subjects without T2D. Our findings support the usefulness of serum FABP3 and FABP4 concentrations as independent predictors for the occurrence of all-cause and CV mortality in ambulatory subjects with CHF with T2D.

BACKGROUND:Age-specific and gender-specific reference values for left ventricular (LV) and right ventricle volumes are available. The prognostic implications of the ratio between these volumes in heart failure and preserved ejection fraction (HFpEF) have never been evaluated. METHODS:We examined all HFpEF outpatients undergoing a cardiac magnetic resonance from 2011 to 2021. The left-to-right ventricular volume ratio (LRVR) was defined as the ratio between the LV and right ventricle end-diastolic volume indexes (LVEDVi/RVEDVi). RESULTS:Among 159 patients [median age 58 years (interquartile range 49-69), 64% men, LV ejection fraction 60% (54-70%)] the median LRVR was 1.21 (1.07-1.40). Over 3.5 years (1.5-5.0), 23 patients (15%) experienced all-cause death or heart failure hospitalization, and 22 (14%) cardiovascular death or heart failure hospitalization. The risk of all-cause death or heart failure hospitalization increased with an LRVR less than 1.0 or at least 1.4. An LRVR less than 1.0 was associated with a higher risk of all-cause death or heart failure hospitalization [hazard ratio 5.95, 95% confidence interval (CI) 1.67-21.28; P = 0.006] and cardiovascular death or heart failure hospitalization (hazard ratio 5.68, 95% CI 1.58-20.35; P = 0.008) as compared with LRVR 1.0-1.3. Furthermore, an LRVR at least 1.4 was associated with a higher risk of all-cause death or heart failure hospitalization (hazard ratio 4.10, 95% CI 1.58-10.61; P = 0.004) and cardiovascular death or heart failure hospitalization (hazard ratio 3.71, 95% CI 1.41-9.79; P = 0.008) as compared with LRVR 1.0-1.3. These results were confirmed in patients without dilation of either ventricle. CONCLUSION:LRVR values less than 1.0 or at least 1.4 are associated with worse outcomes in HFpEF. LRVR may become a valuable tool for risk prediction in HFpEF.

European Journal of Heart FailureEarly View Invited Editorial Quality over quantity: assessing the need for multiple biomarkers in predicting heart failure outcomes Antoni Bayes-Genis, Corresponding Author Antoni Bayes-Genis [email protected] orcid.org/0000-0002-3044-197X Heart Institute, University Hospital Germans Trias i Pujol, Badalona, Spain Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain CIBERCV, Instituto de Salud Carlos III, Madrid, Spain Corresponding author. Heart Institute, Hospital Universitari Germans Trias i Pujol, Department of Medicine, Universitat Autònoma de Barcelona, Carretera del Canyet s/n, 08916 Badalona, Spain. Tel: +34 934 978915, Fax: +34 934 978939, Email: [email protected]Search for more papers by this authorJosep Lupón, Josep Lupón Heart Institute, University Hospital Germans Trias i Pujol, Badalona, Spain CIBERCV, Instituto de Salud Carlos III, Madrid, SpainSearch for more papers by this authorPau Codina, Pau Codina Heart Institute, University Hospital Germans Trias i Pujol, Badalona, Spain CIBERCV, Instituto de Salud Carlos III, Madrid, SpainSearch for more papers by this author Antoni Bayes-Genis, Corresponding Author Antoni Bayes-Genis [email protected] orcid.org/0000-0002-3044-197X Heart Institute, University Hospital Germans Trias i Pujol, Badalona, Spain Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain CIBERCV, Instituto de Salud Carlos III, Madrid, Spain Corresponding author. Heart Institute, Hospital Universitari Germans Trias i Pujol, Department of Medicine, Universitat Autònoma de Barcelona, Carretera del Canyet s/n, 08916 Badalona, Spain. Tel: +34 934 978915, Fax: +34 934 978939, Email: [email protected]Search for more papers by this authorJosep Lupón, Josep Lupón Heart Institute, University Hospital Germans Trias i Pujol, Badalona, Spain CIBERCV, Instituto de Salud Carlos III, Madrid, SpainSearch for more papers by this authorPau Codina, Pau Codina Heart Institute, University Hospital Germans Trias i Pujol, Badalona, Spain CIBERCV, Instituto de Salud Carlos III, Madrid, SpainSearch for more papers by this author First published: 04 July 2023 https://doi.org/10.1002/ejhf.2956 The opinions expressed in this article are not necessarily those of the Editors of the European Journal of Heart Failure or of the European Society of Cardiology. doi: 10.1002/ejhf.2887 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Revuelta-López E, Barallat J, Cserkóová A, Gálvez-Montón C, Jaffe AS, Januzzi JL, et al. Pre-analytical considerations in biomarker research: Focus on cardiovascular disease. Clin Chem Lab Med 2021; 59: 1747–1760. https://doi.org/10.1515/cclm-2021-0377 2Meijers WC, Bayes-Genis A, Mebazaa A, Bauersachs J, Cleland JGF, Coats AJS, et al. Circulating heart failure biomarkers beyond natriuretic peptides: Review from the Biomarker Study Group of the Heart Failure Association (HFA), European Society of Cardiology (ESC). Eur J Heart Fail 2021; 23: 1610–1632. https://doi.org/10.1002/ejhf.2346 3Mueller C, McDonald K, de Boer RA, Maisel A, Cleland JGF, Kozhuharov N, et al. Heart Failure Association of the European Society of Cardiology practical guidance on the use of natriuretic peptide concentrations. Eur J Heart Fail 2019; 21: 715–731. https://doi.org/10.1002/ejhf.1494 4Bayes-Genis A, Richards AM, Maisel AS, Mueller C, Ky B. Multimarker testing with ST2 in chronic heart failure. Am J Cardiol 2015; 115: 76B–80B. https://doi.org/10.1016/j.amjcard.2015.01.045 5McDowell K, Campbell R, Simpson J, Cunningham JW, Desai AS, Jhund PS, et al. Incremental prognostic value of biomarkers in PARADIGM-HF. Eur J Heart Fail. https://doi.org/10.1002/ejhf.2887 Published online ahead of print 16/05/23. 6Simpson J, Jhund PS, Lund LH, Padmanabhan S, Claggett BL, Shen L, et al. Prognostic models derived in PARADIGM-HF and validated in ATMOSPHERE and the Swedish Heart Failure Registry to predict mortality and morbidity in chronic heart failure. JAMA Cardiol 2020; 5: 432–441. https://doi.org/10.1001/jamacardio.2019.5850 7Codina P, Lupón J, Borrellas A, Spitaleri G, Cediel G, Domingo M, et al. Head-to-head comparison of contemporary heart failure risk scores. Eur J Heart Fail 2021; 23: 2035–2044. https://doi.org/10.1002/ejhf.2352 8Packer M, Januzzi JL, Ferreira JP, Anker SD, Butler J, Filippatos G, et al.; EMPEROR-Reduced Trial Committees and Investigators. Concentration-dependent clinical and prognostic importance of high-sensitivity cardiac troponin T in heart failure and a reduced ejection fraction and the influence of empagliflozin: The EMPEROR-Reduced trial. Eur J Heart Fail 2021; 23: 1529–1538. https://doi.org/10.1002/ejhf.2256 9Pocock SJ, Ferreira JP, Gregson J, Anker SD, Butler J, Filippatos G, et al. Novel biomarker-driven prognostic models to predict morbidity and mortality in chronic heart failure: The EMPEROR-Reduced trial. Eur Heart J 2021; 42: 4455–4464. https://doi.org/10.1093/eurheartj/ehab579 10Bayés-Genís A, Núñez J, Lupón J. Soluble ST2 for prognosis and monitoring in heart failure: The new gold standard? J Am Coll Cardiol 2017; 70: 2389–2392. https://doi.org/10.1016/j.jacc.2017.09.031 11González A, Richards AM, de Boer RA, Thum T, Arfsten H, Hülsmann M, et al. Cardiac remodelling – Part 1: From cells and tissues to circulating biomarkers. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2022; 24: 927–943. https://doi.org/10.1002/ejhf.2493 12Núñez J, de la Espriella R, Miñana G, Santas E, Llácer P, Núñez E, et al. Antigen carbohydrate 125 as a biomarker in heart failure: A narrative review. Eur J Heart Fail 2021; 23: 1445–1457. https://doi.org/10.1002/ejhf.2295 Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

Risk estimates for an individual patient with heart failure (HF) is fundamental and should be routine for practicing physicians. Several risk prediction models have been recently compared, with variable discrimination and calibration properties.1 This head-to-head comparison concluded that ‘regular updating and calibration of the online web calculators might help in improving accuracy of these tools in estimating risk of death’. On the other hand HF treatment is evolving at a fast pace and a new kid on the block, sodium–glucose cotransporter 2 inhibitors (SGLT2i),2,3 entered with robust evidence in HF across the spectrum of ejection fraction. The Barcelona (BCN) Bio-HF calculator (www.bcnbiohfcalculator.org) was developed in 20144 and updated in 2017 (version 2.0),5 with the inclusion of angiotensin receptor–neprilysin inhibitors (ARNI) and

FGF15 and its human orthologue, FGF19, are members of the endocrine FGF family and are secreted by ileal enterocytes in response to bile acids. FGF15/19 mainly targets the liver, but recent studies indicate that it also regulates skeletal muscle mass and adipose tissue plasticity. The aim of this study was to determine the role(s) of the enterokine FGF15/19 during the development of cardiac hypertrophy. Studies in a cohort of humans suffering from heart failure showed increased circulating levels of FGF19 compared with control individuals. We found that mice lacking FGF15 did not develop cardiac hypertrophy in response to three different pathophysiological stimuli (high‐fat diet, isoproterenol, or cold exposure). The heart weight/tibia length ratio and the cardiomyocyte area (as measures of cardiac hypertrophy development) under hypertrophy‐inducing conditions were lower in Fgf15‐null mice than in wild‐type mice, whereas the levels of the cardiac damage marker atrial natriuretic factor (Nppa) were up‐regulated. Echocardiographic measurements showed similar results. Moreover, the genes involved in fatty acid metabolism were down‐regulated in Fgf15‐null mice. Conversely, experimental increases in FGF15 induced cardiac hypertrophy in vivo, without changes in Nppa and up‐regulation of metabolic genes. Finally, in vitro studies using cardiomyocytes showed that FGF19 had a direct effect on these cells promoting hypertrophy. We have identified herein an inter‐organ signaling pathway that runs from the gut to the heart, acts through the enterokine FGF15/19, and is involved in cardiac hypertrophy development and regulation of fatty acid metabolism in the myocardium. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Introduction and objectives: Prognosis in ST-elevation myocardial infarction (STEMI) is determined by delay in primary percutaneous coronary intervention (PPCI). The impact of first medical contact (FMC) facility type on reperfusion delays and mortality remains controversial. Methods: We performed a prospective registry of primary coronary intervention (PCI)-treated STEMI patients (2010-2020) in the Codi Infart STEMI network. We analyzed 1-year all-cause mortality depending on the FMC facility type: emergency medical service (EMS), community hospital (CH), PCI hospital (PCI-H), or primary care center (PCC). Results: We included 18 332 patients (EMS 34.3%; CH 33.5%; PCI-H 12.3%; PCC 20.0%). Patients with Killip-Kimball classes III -IV were: EMS 8.43%, CH 5.54%, PCI-H 7.51%, PCC 3.76% (P < .001). All comorbidities and first medical assistance complications were more frequent in the EMS and PCI-H groups (P < .05) and were less frequent in the PCC group (P < .05 for most variables). The PCI-H group had the shortest FMC-to-PCI delay (median 82 minutes); the EMS group achieved the shortest total ischemic time (median 151 minutes); CH had the longest reperfusion delays (P < .001). In an adjusted logistic regression model, the PCI-H and CH groups were associated with higher 1-year mortality, OR, 1.22 (95%CI, 1.00-1.48; P = .048), and OR, 1.17 (95%CI 1.02-1.36; P = .030), respectively, while the PCC group was associated with lower 1-year mortality than the EMS group, OR, 0.71 (95%CI 0.58-0.86; P < .001). Conclusions: FMC with PCI-H and CH was associated with higher adjusted 1-year mortality than FMC with EMS. The PCC group had a much lower intrinsic risk and was associated with better outcomes despite longer revascularization delays. (c) 2023 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.