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Abstract Inflammation is relevant in the pathogenesis and progression of heart failure (HF). Previous studies have shown that elevated high-sensitivity C-reactive protein (hsCRP) are associated with greater severity and may be associated with adverse outcomes. In this study, we sought to evaluate the prognostic role of hsCRP in a non-selected cohort of patients with acute HF. We prospectively included a multicenter cohort of 3,395 patients following an admission for acute HF. HsCRP levels were evaluated during the first 24 h following admission. Study endpoints were the risks of all-cause mortality, CV-mortality, and total HF readmissions. The mean age was 74.2 ± 11.2 years and 1,826 (53.8%) showed a left ventricular ejection fraction (LVEF) ≥ 50%. Median hsCRP was 12.9 mg/L (5.4–30 mg/L). Over a median follow-up of 1.8 (0.6–4.1) years, 1,574 (46.4%) patients died, and 1,341 (39.5%) patients were readmitted for worsening HF. After multivariable adjustment, hsCRP values were significantly and positively associated with a higher risk of all-cause and CV mortality (p = 0.003 and p = 0.001, respectively), as well as a higher risk of recurrent HF admissions (p

Abstract Background Carbohydrate antigen 125 (CA125) is a proteolytic fragment of MUC-16 that is increased in heart failure (HF) and associated with inflammation, fluid overload, and worse adverse events. Our main objective was to study the expression of CA125 on epicardium and its association with inflammation, adipogenesis, and fibrosis. Methods Epicardial fat biopsies and blood were obtained from 151 non-selected patients undergoing open heart surgery. Immunohistochemistry, ELISA, or real-time PCR were used for analyzing protein or mRNA expression levels of CA125 and markers of inflammatory cells, fibroblasts, and adipocytes. Epithelial or stromal cells from epicardium were isolated and cultured to identify CA125 and its association with the adipogenesis and fibrosis pathways, respectively. Results The median age was 71 (63–74) years, 106 patients (70%) were male, and 62 (41%) had an established diagnosis of HF before surgery. The slice of epicardial fat biopsy determined a positive and colorimetric staining on the epithelial layer after incubating with the CA125 M11 antibody, providing the first description of CA125 expression in the human epicardium. Epicardial CA125 showed a strong and positive correlation with markers of inflammation and fibrosis in the epicardial fat tissue while exhibiting a negative correlation with markers of the adipogenesis pathway. This relationship remained significant after adjusting for potential confounders such as a prior HF diagnosis and plasma CA125 levels. Conclusion Epicardial cells express CA125, which is positively associated with inflammatory and fibroblast markers in epicardial adipose tissue. These results suggest that CA125 may be biologically involved in HF progression (transition from adipogenesis to fibrosis). Graphical Abstract

Abstract Background Iron deficiency (ID) is associated with impaired functional capacity in patients with heart failure (HF), even in those with preserved ejection fraction (HFpEF). This study aimed to evaluate the effect of baseline ferrokinetics on peak oxygen consumption (peakVO2) improvement after a 12‐week physical therapy programme in patients with stable HFpEF. Methods This study is a post‐hoc sub‐analysis of a randomized clinical trial in which 59 stable patients with HFpEF were randomized to receive a 12‐week programme of inspiratory muscle training (IMT), functional electrical stimulation (FES), IMT + FES or usual care (UC) to evaluate change in peakVO2 (NCT02638961). Serum ferritin and transferrin saturation (TSAT) determinations were assessed at baseline. ID was defined as ferritin

Abstract Aims Iron deficiency (ID) is associated with an impaired cardiac function and remodelling in heart failure (HF). Treatment with ferric carboxymaltose (FCM) has been showed recently to improve biventricular systolic function and ventricular strain parameters in patients with HF with reduced ejection fraction and ID, but there is no evidence on the benefit of FCM on the left atrium (LA). In this study, we aimed to evaluate the effect of FCM on LA longitudinal strain (LA‐LS). Methods and results This is a post hoc subanalysis of a double‐blind, placebo‐controlled, randomized clinical trial that enrolled 53 ambulatory patients with HF, left ventricular ejection fraction (LVEF)

RESUMEN Introducción y objetivos: Las intervenciones coronarias percutáneas (ICP) sobre oclusiones totales crónicas (OTC) son procedimientos largos en los que muchos pacientes sufren ansiedad y dolor. La realidad virtual ha demostrado reducir el dolor y la ansiedad en muchos procedimientos médicos. Nuestro objetivo es demostrar que el uso de la realidad virtual durante la ICP de OTC reduce la ansiedad y el dolor en comparación con la práctica convencional. Métodos: Ensayo clínico aleatorizado, controlado, abierto y de superioridad con 2 grupos paralelos en el que 58 pacientes con una ICP de OTC programada serán aleatorizados 1:1 al uso de realidad virtual frente al tratamiento convencional. La administración de fármacos ansiolíticos será a criterio del operador principal y en función del grado de ansiedad o dolor percibido. El resto de las acciones para el tratamiento de la ansiedad serán idénticas en ambos grupos. El objetivo primario será el nivel máximo de ansiedad percibido por el paciente. Los objetivos secundarios serán el nivel de dolor percibido por el paciente, la necesidad de tratamiento farmacológico ansiolítico, la dosis de fármaco administrada y la satisfacción con la realidad virtual. Resultados: Los resultados de este estudio añadirán conocimientos importantes sobre la utilidad de la realidad virtual en la reducción de la ansiedad en los procedimientos de ICP de OTC. Conclusiones: El ensayo ReViCTO es el primer ensayo clínico aleatorizado que utiliza la realidad virtual durante la ICP en OTC. Sus resultados mostrarán la utilidad de esta tecnología para reducir la ansiedad y el dolor en esta intervención. Diseño del ensayo registrado en ClinicalTrials.gov (identificador: NCT05458999).

ABSTRACT Introduction and objectives: Percutaneous coronary interventions (PCI) of chronic total occlusions (CTO) are long procedures where many patients suffer moderate-to-high level anxiety and pain. Virtual reality (VR) has proven capable of reducing procedural pain and anxiety in many medical procedures. The objective of this study is to demonstrate that the use of VR during CTO PCI reduces anxiety and pain compared to conventional routine clinical practice. Methods: Randomized, controlled, open-label, superiority trial clinical trial with 2 parallel arms including 58 patients with a scheduled CTO PCI randomized on a 1:1 ratio to VR during the procedure or conventional management. In both arms, the administration of anxiolytic drugs will be left to the lead operator’s discretion and based on the degree of anxiety o pain perceived. The remaining actions for the management of pre- and perioperative anxiety will be identical in both arms. The primary endpoint will be the maximum level of anxiety perceived by the patient. Secondary endpoints will be the level of patient-perceived pain, the need for intraoperative anxiolytic drug therapy, dose of drug administered, and satisfaction with the VR goggles. Results: The results of this study will add significant knowledge on the utility of VR regarding anxiety reduction in CTO PCIs. Conclusions: The ReViCTO trial is the first randomized clinical trial to use VR during a PCI CTO. Its results will show the utility of this technology to reduce anxiety and pain in PCIs performed on CTOs. Diseño del ensayo registrado en ClinicalTrials.gov (identificador: NCT05458999).

Abstract Circulating antigen carbohydrate 125 (CA125) has emerged as a proxy of fluid overload in heart failure. This study aimed to evaluate the effect of dapagliflozin on short-term CA125 levels in patients with stable heart failure with reduced ejection fraction (HFrEF) and whether these changes mediated the effects on peak oxygen consumption (peakVO2). This study is a post-hoc sub-analysis of a randomized, double-blinded clinical trial in which 90 stable patients with HFrEF were randomly assigned to receive either dapagliflozin or placebo to evaluate change in peakVO2 (NCT04197635). We used linear mixed regression analysis to compare changes in the natural logarithm of CA125 (logCA125) and percent changes from baseline (Δ%CA125). We used the “rwrmed” package to perform mediation analyses. CA125 was available in 87 patients (96.7%). LogCA125 significantly decreased in patients on treatment with dapagliflozin [1-month: Δ − 0.18, (CI 95% = − 0.33 to − 0.22) and 3-month: Δ − 0.23, (CI 95% = − 0.38 to − 0.07); omnibus p-value = 0.012]. Δ%CA125 decreased by 18.4% and 31.4% at 1 and 3-month, respectively (omnibus p-value = 0.026). Changes in logCA125 mediated the effect on peakVO2 by 20.4% at 1 month (p

Abstract Aims Traditional adverse events in chronic coronary syndrome (CCS) include atherothrombotic events but usually exclude heart failure (HF). Data are scarce about how new‐onset HF modifies mortality risk. We aimed to determine the incidence of HF and compare its long‐term mortality risk with myocardial infarction (MI) and stroke in patients with known or suspected CCS. Methods We prospectively evaluated 5811 consecutive HF‐free patients submitted to vasodilator stress cardiac magnetic resonance (CMR) for known or suspected CCS. Ischaemic burden and left ventricular ejection fraction were assessed by CMR. HF included outpatient diagnosis or acute HF hospitalization. The mortality risk for the incident events and their cross‐comparisons were evaluated using a Markov illness–death model with transition‐specific survival models. Results The mean age was 55 ± 11 years, and 38.9% were female. At a median follow‐up of 5.44 (IQR = 2.53–8.55) years, 591 deaths were registered (1.79 per 100 P‐Y). The rates of new‐onset HF were higher compared with MI and stroke [1.02, 0.62, and 0.51, respectively (P

RESUMEN Introducción y objetivos: La posdilatación de stents coronarios con balones no distensibles mejora los resultados clínicos. Los balones no distensibles normales (RegNC) presentan peor navegabilidad y tienen una punta cónica que puede dificultar la posdilatación exitosa. Las condiciones mecánicas de un nuevo balón no distensible con punta esférica (EsfNC) podrían facilitar la posdilatación del stent. Evaluamos la efectividad del EsfNC en la posdilatación coronaria para la intervención coronaria percutánea en la práctica clínica habitual. Métodos: Registro técnico prospectivo y multicéntrico para evaluar la efectividad de un nuevo EsfNC en posdilatación coronaria, con 2 grupos de estudio: uso de EsfNC como primera opción o uso de EsfNC ante el fracaso de RegNC. El evento primario fue el éxito técnico, definido como conseguir avanzar el EsfNC hasta el segmento que posdilatar dentro del stent. Los eventos secundarios fueron el éxito angiográfico, definido como éxito técnico junto con estenosis residual < 30% con flujo final TIMI 3, y el éxito del procedimiento, definido como éxito angiográfico sin complicación mecánica del stent ni eventos cardiovasculares mayores periprocedimiento. Resultados: Se usó EsfNC en 263 lesiones (en 177 como primera opción y en 86 tras el fracaso de RegNC), en 250 procedimientos. Se usaron técnicas complejas para avanzar el EsfNC en el 9,9% de los procedimientos. Los porcentajes de éxito técnico, angiográfico y de procedimiento fueron del 98,9%, el 98,3% y el 98,3% como primera opción, y del 98,8%, el 97,7% y el 96,5% tras fracaso de RegNC, respectivamente. Los EsfNC tuvieron similar calibre (3,39 ± 0,6 frente a 3,34 ± 0,6 mm; p = no significativo) y longitud más corta (11 ± 2 frente a 12 ± 3 mm; p = 0,005) que los RegNC. No se comunicaron complicaciones mecánicas del stent. Conclusiones: La posdilatación coronaria con EsfNC para la intervención coronaria percutánea en la práctica clínica habitual muestra un porcentaje muy alto de éxito técnico, tanto en primera opción (98,9%) como en casos de fracaso de RegNC (98,8%), con baja necesidad de técnicas complejas y buen perfil de seguridad.

ABSTRACT Introduction and objectives: Noncompliant balloon postdilatation of coronary stents improves clinical results. Regular noncompliant balloons (RegNC) have less crossability and a tapered-tip that can complicate successful stent postdilatation. The mechanical conditions of a new spherical tip non-compliant balloon (SphNC) could facilitate stent postdilatation. We tried to evaluate the effectiveness of a new SphNC in the routine percutaneous coronary intervention (PCI) practice. Methods: Prospective multicenter technical registry to assess the effectiveness of a new SphNC for stent postdilatation with 2 study arms: use of SphNC as the first choice or as the secondary choice after RegNC failure. The primary endpoint was technical success defined as advancing the SphNC across the stent segment. Secondary endpoints were angiographic success defined as technical success and residual stenosis < 30% with final TIMI grade-3 flow, and procedural success defined as angiographic success without mechanical stent complications or any perioperative major adverse cardiovascular events. Results: The SphNC was used in 263 lesions (177 lesions as first choice, and 86 after RegNC failure) in 250 procedures. The use of the complex technique to advance the SphNC was low (9.9%). Technical, angiographic, and procedural success rates were 98.9%, 98.3%, and 98.3%, respectively, as the first choice, and 98.8%, 97.7%, and 96.5%, respectively, after RegNC failure. SphNC had similar size (3.39 mm ± 0.6 mm vs 3.34 mm ± 0.6 mm; P = nonsignificant), and shorter lengths (11 mm ± 2 mm vs 12 mm ± 3 mm; P = .005) compared to RegNC. No stent-related mechanical complications were reported. Conclusions: SphNC for coronary stent postdilatation in the routine PCI clinical practice has a very high technical success rate as the first choice (98.9%), as well as in cases of RegNC failure (98.8% with low complex technique requirements, and a safe profile).

The klotho and fibroblast growth factor 23 (FGF-23) pathway is implicated in cardiovascular pathophysiology. This substudy aimed to assess the changes in klotho and FGF-23 levels 1-month after dapagliflozin in patients with stable heart failure and reduced ejection fraction (HFrEF). The study included 29 patients (32.2% of the total), with 14 assigned to the placebo group and 15 to the dapagliflozin, as part of the double-blind, randomized clinical trial [DAPA-VO2 (NCT04197635)]. Blood samples were collected at baseline and after 30 days, and Klotho and FGF-23 levels were measured using ELISA Kits. Between-treatment changes (raw data) were analyzed by using the Mann-Whitney test and expressed as median (p25%–p75%). Linear regression models were utilized to analyze changes in the logarithm (log) of klotho and FGF-23. The median age was 68.3 years (60.8–72.1), with 79.3% male and 81.5% classified as NYHA II. The baseline medians of left ventricular ejection fraction, glomerular filtration rate, NT-proBNP, klotho, and FGF-23 were 35.8% (30.5–37.8), 67.4 ml/min/1.73 m2 (50.7–82.8), 1,285 pg/ml (898–2,305), 623.4 pg/ml (533.5–736.6), and 72.6 RU/ml (62.6–96.1), respectively. The baseline mean peak oxygen uptake was 13.1 ± 4.0 ml/kg/min. Compared to placebo, patients on dapagliflozin showed a significant median increase of klotho [Δ+29.5, (12.9–37.2); p = 0.009] and a non-significant decrease of FGF-23 [Δ−4.6, (−1.7 to −5.4); p = 0.051]. A significant increase in log-klotho (p = 0.011) and a decrease in log-FGF-23 (p = 0.040) were found in the inferential analysis. In conclusion, in patients with stable HFrEF, dapagliflozin led to a short-term increase in klotho and a decrease in FGF-23.

Abstract We aimed to assess the association between CA125 and the long-term risk of total acute heart failure (AHF) admissions in patients with an index hospitalization with AHF and preserved ejection fraction (HFpEF). We prospectively included 2369 patients between 2008 and 2019 in three centers. CA125 and NT-proBNP were measured during early hospitalization and evaluated as continuous and categorized in quartiles (Q). Negative binomial regressions were used to assess the association with the risk of recurrent AHF admission. The mean age of the sample patients was 76.7 ± 9.5 years and 1443 (60.9%) were women. Median values of CA125 and NT-proBNP were 38.3 (19.0–90.0) U/mL, and 2924 (1590–5447) pg/mL, respectively. During a median follow-up of 2.2 (0.8–4.6) years, 1200 (50.6%) patients died, and 2084 AHF admissions occurred in 1029 (43.4%) patients. After a multivariate adjustment, CA125, but not NT-proBNP, was positively and non-linearly associated with the risk of cumulative AHF-readmission (p

Abstract 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.

AimsVenous leg compression (VLC) with elastic bandages has been proposed as a potentially useful strategy for decreasing tissue congestion. We aimed to evaluate the effect of VLC on short-term changes on intravascular refill, assessed by inferior vena cava (IVC) diameter in patients with worsening heart failure (WHF) requiring parenteral furosemide. Additionally, we sought to evaluate whether early changes in IVC were related to short-term decongestion.MethodsThis is a prospective study in which we included 20 consecutive ambulatory patients with WHF treated with subcutaneous furosemide and VLC for at least 72 h. The endpoints were (a) short-term changes in IVC, (b) the association between decongestion and 3-h IVC changes following VLC. Changes in continuous endpoints and their longitudinal trajectories were estimated with linear mixed regression models. All analyses were adjusted for multiple comparisons.ResultsFollowing administration of subcutaneous furosemide and VLC, we found a significant increase in 3-h IVC diameter (ΔIVC = 1.6 mm, CI 95%: 0.7–2.5; p < 0.001), with a greater increase in those with baseline IVC≤21 mm (2.4 vs. 0.8 mm; p < 0.001). 3-h intravascular refill (increase in IVC≥2 mm) was associated with greater decongestion (natriuresis, weight, peripheral edemas, and dyspnea) in those with baseline IVC≤21 mm but not when IVC>21 mm (p < 0.05 for all comparisons).ConclusionsIn this cohort of patients with congestive WHF treated with subcutaneous furosemide and VLC, we found a greater increase in short-term IVC in those with IVC ≤21 mm at baseline. In this subset of patients, a 3-h increase in IVC≥2 mm was associated with greater short-term decongestion.

Objective: To evaluate the 5 components of the Fried frailty phenotype (self-reported unintentional weight loss, physical activity questionnaire, gait speed, grip strength, and self-reported exhaustion) for long-term outcomes in elderly survivors of acute coronary syndrome. Methods: A total of 342 consecutive patients (from October 1, 2010, to February 1, 2012) were included. The 5 components of the Fried score and albumin concentration, as malnutrition index, were assessed before hospital discharge. Patients were followed up until April 2020 (median follow-up, 8.7 years). The end point was postdischarge all-cause mortality. Results: Mean ± SD age was 77±7 years and mean ± SD Fried score was 2.0±1.1 points. A total of 216 (63%) patients died. After adjusting for clinical covariates, the Fried phenotype was associated with mortality (per points, hazard ratio [HR], 1.35; 95% CI, 1.17 to 1.57; P

Abstract Aims The aim of this study was to evaluate the safety profile in terms of changes in renal function after co‐treatment with sacubitril/valsartan and empagliflozin in patients with type 2 diabetes (T2D) and heart failure with reduced ejection fraction (HFrEF). Methods and results This multicentre observational analysis included 108 patients with T2D and HFrEF treated with both agents: baseline sacubitril/valsartan (Group A; n = 43), baseline empagliflozin (Group B; n = 42), or both agents initiated simultaneously (Group C; n = 23). The primary endpoint was estimated glomerular filtration rate (eGFR) dynamics across treatment groups. A binary characterization of worsening renal function (WRF)/improved renal function (IRF) was included in the primary endpoint. WRF and IRF were defined as an increase/decrease in serum creatinine ≥ 0.3 mg/dL or GFR ≥ 20%. Changes in quantitative variables were evaluated using joint modelling of survival and longitudinal data (JM). Rates and their treatment differences were determined by Poisson regression. The mean left ventricle ejection fraction and eGFR were 32 ± 6% and 70 ± 28 mL/min/1.73 m2, respectively. At a median follow‐up of 1.01 years (inter‐quartile range 0.71–1.50), 377 outpatient visits were recorded. Although there were differences in GFR trajectories over time within each treatment, they did not achieve statistical significance (omnibus P = 0.154). However, when these differences were contrasted among groups, there was a significant decrease in GFR in Group A as compared with Group B (P = 0.002). The contrast between Groups C and B was not significant (P = 0.430). These differences were also reflected when the rates for WRF and IRF were contrasted among treatments. Conclusions The co‐administration of sacubitril/valsartan and empagliflozin in patients with HFrEF and concomitant T2D appears to be safe in terms of renal function.

Abstract Aims Type 2 diabetes mellitus (T2DM) is common in patients with heart failure (HF) and is related with worse outcomes. Insulin treatment is associated with sodium and water retention, weight gain, and hypoglycaemia—all pathophysiological mechanisms related to HF decompensation. This study aimed to evaluate the association between insulin treatment and the risk of 1 year readmission for HF in patients discharged for acute HF. Methods and results We prospectively included 2895 consecutive patients discharged after an episode of acute HF in a single tertiary hospital. Multivariable Cox regression, adapted for competing events, was used to assess the association between insulin treatment and 1 year readmission for HF in patients discharged after acute HF. Participants' mean age was 73.4 ± 11.2 years, 50.8% were women, 44.7% had T2DM [including 527 (18.2%) on insulin therapy], and 52.7% had preserved ejection fraction. At 1 year follow‐up, 518 (17.9%) patients had died and 693 (23.9%) were readmitted for HF. The crude risk of readmission for HF was higher in patients on insulin, with no differences in 1 year mortality. After multivariable adjustment, patients on insulin were at significantly higher risk of 1 year readmission for HF than patients with diabetes who were not on insulin (hazard ratio 1.28; 95% confidence interval 1.04–1.59, P = 0.022) and patients without diabetes (hazard ratio 1.26; 95% confidence interval 1.02–1.55, P = 0.035). Conclusion Following acute HF, patients with T2DM on insulin therapy are at increased risk of readmission for HF. Further studies unravelling the mechanisms behind this association are warranted.

Abstract Aims 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. Methods and results 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

Abstract Aims Heart failure with mid‐range ejection fraction (HFmrEF) has been proposed as a distinct HF phenotype, but whether patients on this category fare worse, similarly, or better than those with HF with reduced EF (HFrEF) or preserved EF (HFpEF) in terms of rehospitalization risks over time remains unclear. Methods and results We prospectively included 2961 consecutive patients admitted for acute HF (AHF) in our institution. Of them, 158 patients died during the index admission, leaving the sample size to be 2803 patients. Patients were categorized according to their EF: HFrEF if EF ≤ 40% (n = 908, 32.4%); HFmrEF if EF = 41–49% (n = 449, 16.0%); and HFpEF if EF ≥ 50% (n = 1446, 51.6%). Covariate‐adjusted incidence rate ratios (IRRs) were used to evaluate the association between EF status and recurrent all‐cause and HF‐related admissions. At a median follow‐up of 2.6 years (inter‐quartile range: 1.0–5.3), 1663 (59.3%) patients died, and 6035 all‐cause readmissions were registered in 2026 patients (72.3%), 2163 of them HF related. Rates of all‐cause readmission per 100 patients‐years of follow‐up were 150.1, 176.9, and 163.6 in HFrEF, HFmrEF, and HFpEF, respectively (P = 0.097). After multivariable adjustment, when compared with that of patients with HFrEF and HFpEF, HFmrEF status was not significantly associated with a different risk of all‐cause readmissions (IRR = 0.99; 95% confidence interval [CI], 0.77–1.27; P = 0.926; and IRR = 0.93; 95% CI, 0.74–1.18; P = 0.621, respectively) or HF‐related readmissions (IRR = 1.06; 95% CI, 0.77–1.46; P = 0.725; and IRR = 1.11; 95% CI, 0.82–1.50; P = 0.511, respectively). Conclusions Following an admission for AHF, patients with HFmrEF had a similar rehospitalization burden and a similar risk of recurrent all‐cause and HF‐related admissions than had patients with HFrEF or HFpEF. Regarding morbidity risk, HFmrEF seems not to be a distinct HF phenotype.

Abstract Aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for reducing plasma low‐density lipoprotein cholesterol. Beyond lipid control, recent findings suggest a deleterious effect of this protein in the pathogenesis of postmyocardial infarction left ventricle remodelling and heart failure‐related complications. The aim of this study was to assess the relationship between circulating PCSK9 and 6 month cardiac magnetic resonance imaging‐derived left ventricular ejection fraction (LVEF) after a first ST‐segment elevation myocardial infarction (STEMI). Methods and results We prospectively evaluated 40 patients with a first STEMI, LVEF < 50% and treated with primary percutaneous coronary intervention in which PCSK9 was measured 24 h postreperfusion. All patients underwent cardiac magnetic resonance imaging 1 week and 6 months after STEMI. Baseline characteristics were compared across median values of PCSK9. The association between PCSK9 levels and LVEF at 6 months was evaluated by analysis of covariance. The mean age of the sample was 60 ± 12 years and 33 (82.5%) were male patients. The infarct location was anterior in 27 patients (67.5%), and 9 patients (22.5%) were Killip class ≥ II. The mean 1 week and 6 month LVEF were 41 ± 7% and 48 ± 10%, respectively. The mean PCSK9 was 1.93 ± 0.38 U/mL. Testing the association between serum PCSK9 and 6 month LVEF with analysis of covariance revealed an inverse relationship (r = −0.35, P = 0.028). After multivariate adjustment, circulating PCSK9 remained significant and inversely associated with 6 month LVEF (P = 0.002). Conclusions In patients with a first STEMI with reduced ejection fraction at index admission and treated with primary percutaneous coronary intervention, circulating PCSK9 was associated with lower LVEF at 6 months.

Abstract Refractory congestive heart failure is associated with an ominous prognosis in which the treatments strategies remain scarce and not well validated. In the last years, continuous ambulatory peritoneal dialysis (CAPD) has emerged as a therapeutic alternative in this subset of patients. So far, it has been associated with a significant improvement in functional capacity and quality of life, together with a striking reduction in the risk of readmissions. We present the case of an elderly patient with severe left ventricular dysfunction and severe mitral and tricuspid regurgitation who presents recurrent admissions for anasarca. After its inclusion in a CAPD programme, the patient experienced a marked clinical and biochemical improvement despite the persistence of cardiac abnormalities. CAPD onset translates into greater sodium removal. We want to emphasize the usefulness of this therapy in the management of volume excess in patients with refractory heart failure and renal failure promoting a greater sodium removal compared with traditional diuretic strategies.

Background The mechanisms explaining the clinical benefits of ferric carboximaltose (FCM) in patients with heart failure, reduced or intermediate left ventricular ejection fraction, and iron deficiency remain not fully clarified. The Myocardial‐IRON trial showed short‐term cardiac magnetic resonance (CMR) changes suggesting myocardial iron repletion following administration of FCM but failed to find a significant increase in left ventricular ejection fraction in the whole sample. Conversely, the strain assessment could evaluate more specifically subtle changes in contractility. In this subanalysis, we aimed to evaluate the effect of FCM on the short‐term left and right ventricular CMR feature tracking derived strain. Methods and Results This is a post hoc subanalysis of the double‐blind, placebo‐controlled, randomized clinical trial that enrolled 53 ambulatory patients with heart failure and left ventricular ejection fraction

Background Following a heart failure (HF)‐decompensation, there is scarce data about sex‐related prognostic differences across left ventricular ejection fraction (LVEF) status. We sought to evaluate sex‐related differences in 6‐month mortality risk across LVEF following admission for acute HF. Methods and Results We retrospectively evaluated 4812 patients consecutively admitted for acute HF in a multicenter registry from 3 hospitals. Study end points were all‐cause, cardiovascular, and HF‐related mortality at 6‐month follow‐up. Multivariable Cox regression models were fitted to investigate sex‐related differences across LVEF. A total of 2243 (46.6%) patients were women, 2569 (53.4%) were men, and 2608 (54.2%) showed LVEF≥50%. At 6‐month follow‐up, 645 patients died (13.4%), being 544 (11.3%) and 416 (8.6%) cardiovascular and HF‐related deaths, respectively. LVEF was not independently associated with mortality (HR, 1.02; 95% CI 0.99–1.05; P=0.135). After multivariable adjustment, we found no sex‐related differences in all‐cause mortality (P value for interaction=0.168). However, a significant interaction between sex and cardiovascular and HF mortality risks was found across LVEF (P value for interaction=0.030 and 0.007, respectively). Compared with men, women had a significantly lower risk of cardiovascular and HF‐mortality at LVEF80%). Conclusions Following an admission for acute HF, no sex‐related differences were found in all‐cause mortality risk. However, when compared with men, women showed a lower risk of cardiovascular and HF‐mortality at the lower extreme of LVEF. On the contrary, they showed a higher risk of HF death at the upper extreme.

Objective We assessed the influence of the ischaemic burden (IB) as derived from vasodilator stress cardiovascular magnetic resonance (CMR) on the risk of death and the effect of revascularisation across sex.Methods We evaluated 6237 consecutive patients with known or suspected chronic coronary syndrome (CCS). Extensive ischaemia was defined as >5 segments with perfusion deficit. Multivariate Cox proportional hazard regression models were used.Results A total of 2371 (38.0%) patients were women and 583 (9.3%) underwent CMR-related revascularisation. During a median follow-up of 5.13 years, 687 (11.0%) deaths were reported. We found an adjusted differential effect of CMR-derived IB across sex (p value for interaction=0.039). Women exhibited an adjusted lower risk of death and only equaled men’s risk when extensive ischaemia was present. Likewise, CMR-related revascularisation was shown to be differentially associated with the risk of mortality across sex (p value for interaction=0.025). In patients with non-extensive ischaemia, revascularisation was associated with a higher risk of death, with a greater extent in women. At higher IB, revascularisation was associated with a lower risk in men, with more uncertain results in women.Conclusions CMR-derived IB allows predicting the risk of death and gives insight into the potential effect of revascularisation in men and women with CCS. Compared with men, women with non-extensive ischaemia displayed a lower risk and a similar risk with a higher IB. The impact of CMR-related revascularisation on mortality risk was also significantly different according to IB and sex. Further research will be needed to confirm these hypothesis-generating findings.

BackgroundWe aimed to compare the performance of the recent CASTLE score to J-CTO, CL and PROGRESS CTO scores in a comprehensive database of percutaneous coronary intervention of chronic total occlusion procedures.MethodsScores were calculated using raw data from 1,342 chronic total occlusion procedures included in REBECO Registry that includes learning and expert operators. Calibration, discrimination and reclassification were evaluated and compared.ResultsMean score values were: CASTLE 1.60±1.10, J-CTO 2.15±1.24, PROGRESS 1.68±0.94 and CL 2.52±1.52 points. The overall percutaneous coronary intervention success rate was 77.8%. Calibration was good for CASTLE and CL, but not for J-CTO or PROGRESS scores. Discrimination: the area under the curve (AUC) of CASTLE (0.633) was significantly higher than PROGRESS (0.557) and similar to J-CTO (0.628) and CL (0.652). Reclassification: CASTLE, as assessed by integrated discrimination improvement, was superior to PROGRESS (integrated discrimination improvement +0.036, pConclusionProcedural percutaneous coronary intervention difficulty is not consistently depicted by available chronic total occlusion scores and is influenced by the characteristics of each chronic total occlusion cohort. In our study population, including expert and learning operators, the CASTLE score had slightly better overall performance along with CL score. However, we found only intermediate performance in the c-statistic predicting chronic total occlusion success among all scores.

Background Intravenous ferric carboxymaltose (FCM) improves symptoms, functional capacity, and quality of life in heart failure and iron deficiency. The mechanisms underlying these effects are not fully understood. The aim of this study was to examine changes in myocardial iron content after FCM administration in patients with heart failure and iron deficiency using cardiac magnetic resonance. Methods and Results Fifty‐three stable heart failure and iron deficiency patients were randomly assigned 1:1 to receive intravenous FCM or placebo in a multicenter, double‐blind study. T2* and T1 mapping cardiac magnetic resonance sequences, noninvasive surrogates of intramyocardial iron, were evaluated before and 7 and 30 days after randomization using linear mixed regression analysis. Results are presented as least‐square means with 95% CI. The primary end point was the change in T2* and T1 mapping at 7 and 30 days. Median age was 73 (65–78) years, with N‐terminal pro‐B‐type natriuretic peptide, ferritin, and transferrin saturation medians of 1690 pg/mL (1010–2828), 63 ng/mL (22–114), and 15.7% (11.0–19.2), respectively. Baseline T2* and T1 mapping values did not significantly differ across treatment arms. On day 7, both T2* and T1 mapping (ms) were significantly lower in the FCM arm (36.6 [34.6–38.7] versus 40 [38–42.1], P=0.025; 1061 [1051–1072] versus 1085 [1074–1095], P=0.001, respectively). A similar reduction was found at 30 days for T2* (36.3 [34.1–38.5] versus 41.1 [38.9–43.4], P=0.003), but not for T1 mapping (1075 [1065–1085] versus 1079 [1069–1089], P=0.577). Conclusions In patients with heart failure and iron deficiency, FCM administration was associated with changes in the T2* and T1 mapping cardiac magnetic resonance sequences, indicative of myocardial iron repletion. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03398681.

OBJECTIVE:We characterized the dynamics of eosinophils in blood and in the infarcted myocardium in patients and in a swine model of reperfused myocardial infarction (MI). The association of eosinophil dynamics with various outcomes was assessed. METHODS:Serial eosinophil count and pre-discharge cardiac magnetic resonance were carried out in a prospective series of 620 patients with a first ST-elevation MI. In a swine model of reperfused MI, the dynamics of circulating eosinophils and their presence in the infarcted myocardium were determined. In autopsies from chronic MI patients, eosinophils were quantified. RESULTS:Patient eosinophil count sharply decreased 12h post-reperfusion compared to arrival. A lower minimum eosinophil count was associated with more extensive edema, microvascular obstruction, and infarct size as measured by cardiac magnetic resonance, and also with a higher rate of cardiac events (death, re-infarction, or heart failure) during follow-up. In the experimental model, eosinophil count boosted during ischemia and dropped back immediately post-reperfusion. Myocardial samples revealed progressive eosinophil migration into the infarcted myocardium, especially areas with microvascular obstruction. Markers of eosinophil maturation and survival (interleukin-5), degranulation (eosinophil cationic protein) and migration (eotoxin-1) were detected in the blood of patients, and in porcine myocardium. Eosinophil infiltration was detected in autopsies from chronic MI patients. CONCLUSION:Eosinopenia post-MI was associated with an impaired cardiac structure and adverse events. The decay in circulating eosinophils soon after reperfusion mirrors their migration into the infarcted myocardium, as reflected by their presence in heart samples from swine and patients. Further studies are needed to understanding this unexplored pathway and its therapeutic implications.

BackgroundOur aim was to evaluate the association between the soluble form of neprilysin (sNEP) levels and long‐term all‐cause, cardiovascular, and acute heart failure (AHF) recurrent admissions in an ambulatory cohort of patients with heart failure. sNEP has emerged as a new biomarker with promising implications for prognosis and therapy in patients with heart failure. Reducing the recurrent admission rate of heart failure patients has become an important target of public health planning strategies. Methods and ResultsWe measured sNEP levels in 1021 consecutive ambulatory heart failure patients. End points were the number of all‐cause, cardiovascular, and AHF hospitalizations during follow‐up. We used covariate‐adjusted incidence rate ratios to identify associations. At a median follow‐up of 3.4 years (interquartile range: 1.8–5.7), 391 (38.3%) patients died, 477 (46.7%) patients had 1901 all‐cause admissions, 324 (31.7%) patients had 770 cardiovascular admissions, and 218 (21.4%) patients had 488 AHF admissions. The medians for sNEP and amino‐terminal pro‐brain natriuretic peptide were 0.64 ng/mL (interquartile range: 0.39–1.22) and 1248 pg/mL (interquartile range: 538–2825), respectively. In a multivariate setting, the adjusted incidence rate ratios for the top (>1.22 ng/mL) versus the bottom (≤0.39 ng/mL) quartiles of sNEP were 1.37 (95% confidence interval: 1.03–1.82), P=0.032; 1.51 (95% confidence interval: 1.10–2.06), P=0.010; and 1.51 (95% confidence interval: 1.05–2.16), P=0.026 for all‐cause, cardiovascular, and AHF admissions, respectively. ConclusionsElevated sNEP levels predicted an increased risk of recurrent all‐cause, cardiovascular, and AHF admissions in ambulatory patients with heart failure.

AIMS:Galectin-3 (Gal-3) and carbohydrate antigen 125 (CA125) have emerged as robust prognostic biomarkers in heart failure. Experimental data have also suggested a potential molecular interaction between CA125 and Gal-3; however, the biological and clinical relevance of this interaction is still uncertain. We sought to evaluate, in patients admitted for acute heart failure, the association between plasma Gal-3 with all-cause mortality and the risk for rehospitalizations among high and low levels of CA125. METHODS AND RESULTS:We included 264 consecutive patients admitted for acute heart failure to the Cardiology Department in a third-level center. Both biomarkers were measured on admission. Negative binomial and Cox regression models were used to evaluate the prognostic effect of the interaction between Gal-3 and CA125 (dichotomized by its median) with hospital readmission and all-cause mortality, respectively. During a median follow-up of 2 years (IQR = 1-2.8), 108 (40.9%) patients deaths and 365 rehospitalizations in 171 (69.5%) patients were registered. In a multivariable setting, the effect of Gal-3 on mortality and rehospitalization was differentially mediated by CA125 (p = 0.007 and p67 U/ml), values across the continuum of Gal-3 showed a positive and almost linear relationship with either the risk of death or rehospitalization. Conversely, when CA125 was below median (≤67 U/ml), Gal-3 lacked any prognostic effect on both endpoints. CONCLUSION:In patients with acute heart failure, Gal-3 was strongly associated with higher risk of long-term mortality and repeated rehospitalizations, but only in those patients exhibiting higher values of CA125 (above 67 U/ml).