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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.

INTRODUCTION AND OBJECTIVES: Severe calcification is present in>50% of coronary chronic total occlusions (CTOs) undergoing percutaneous intervention. We aimed to describe the contemporary use and outcomes of plaque modification devices (PMDs) in this context. METHODS: Patients were included in the prospective, consecutive Iberian CTO registry (32 centers in Spain and Portugal), from 2015 to 2020. Comparison was performed according to the use of PMDs. RESULTS: Among 2235 patients, wire crossing was achieved in 1900 patients and PMDs were used in 134 patients (7%), requiring more than 1 PMD in 24 patients (1%). The selected PMDs were rotational atherectomy (35.1%), lithotripsy (5.2%), laser (11.2%), cutting/scoring balloons (27.6%), OPN balloons (2.9%), or a combination of PMDs (18%). PMDs were used in older patients, with greater cardiovascular burden, and higher Syntax and J-CTO scores. This greater complexity was associated with longer procedural time but similar total stent length (52 vs 57mm; P=.105). If the wire crossed, the procedural success rate was 87.2% but increased to 96.3% when PMDs were used (P=.001). Conversely, PMDs were not associated with a higher rate of procedural complications (3.7 vs 3.2%; P=.615). Despite the worse baseline profile, at 2 years of follow-up there were no differences in the survival rate (PMDs: 94.3% vs no-PMDs: 94.3%, respectively; P=.967). CONCLUSIONS: Following successful wire crossing in CTOs, PMDs were used in 7% of the lesions with an increased success rate. Mid-term outcomes were comparable despite their worse baseline profile, suggesting that broader use of PMDs in this setting might have potential technical and prognostic benefits.

Discordant data have been reported on the prognosis of myocardial infarction with nonobstructive coronary arteries (MINOCA). Moreover, few data are available on the impact of angiographic subtypes. The objectives of this study were to assess the prognostic impact on the long-term follow-up of the diagnosis of MINOCA and its angiographic subtypes.We included 591 consecutive patients with non-ST-segment elevation myocardial infarction (NSTEMI) who underwent coronary angiography. MINOCA was classified according to angiographic findings as smooth coronary arteries, mild irregularities (30% stenosis), and moderate atherosclerosis (30%-49% stenosis). The primary endpoint was a composite of mortality, nonfatal myocardial infarction, and revascularization (MACE) at a median of 5 years of follow-up.A total of 121 patients (20.5%) showed no obstructive lesions. MINOCA was associated with a lower occurrence of MACE (P=.014; HR, 0.63; 95%CI, 0.44-0.91) and was confirmed as an independent factor in the multivariate analysis (P=.018; HR, 0.63; 95%CI, 0.43-0.92). On analysis of the separate components of the main endpoint, MINOCA was significantly associated with a lower rate of myocardial infarction and revascularization, but not with mortality. Analysis of angiographic subtypes among MINOCA patients showed that smooth coronary arteries were a statistically significant protective factor on both univariate and multivariate analysis, while mild irregularities and 30% to 49% plaques were associated with a higher risk of MACE.MINOCA is associated with a lower rate of MACE, driven by fewer reinfarctions and revascularizations. Within the angiographic subtypes of MINOCA, smooth arteries were independently associated with a lower number of MACE.

Aims The role of revascularization in chronic coronary syndrome (CCS) and the value of ischaemia vs. anatomy to guide decision-making are in constant debate. We explored the potential of a combined assessment of ischaemic burden by vasodilator stress cardiovascular magnetic resonance (CMR) and presence of multivessel disease by angiography to predict the effect of revascularization on all-cause mortality in CCS. Methods and results The study group comprised 1066 CCS patients submitted to vasodilator stress CMR pre-cardiac catheterization (mean age 66 ± 11 years, 69% male). Stress CMR-derived ischaemic burden (extensive if >5 ischaemic segments) and presence of multivessel disease in angiography (two- or three-vessel or left main stem disease) were computed. The influence of revascularization on all-cause mortality was explored and adjusted hazard ratios (HRs) with the corresponding 95% confidence intervals were obtained. During a median 7.51-year follow-up, 557 (52%) CMR-related revascularizations and 308 (29%) deaths were documented. Revascularization exerted a neutral effect on all-cause mortality in the whole study group [HR 0.94 (0.74–1.19), P = 0.6], in patients without multivessel disease [n = 598, 56%, HR 1.12 (0.77–1.62), P = 0.6], and in those with multivessel disease without extensive ischaemic burden [n = 181, 17%, HR 1.66 (0.91–3.04), P = 0.1]. However, compared to non-revascularized patients, revascularization significantly reduced all-cause mortality in patients with simultaneous multivessel disease and extensive ischaemic burden (n = 287, 27%): 3.77 vs. 7.37 deaths per 100 person-years, HR 0.60 (0.40–0.90), P = 0.01. Conclusions In patients with CCS submitted to catheterization, evidence of simultaneous extensive CMR-related ischaemic burden and multivessel disease identifies the subset in whom revascularization can reduce all-cause mortality.

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.

In this study, we evaluated the association between symptoms-guided revascularization occurred within three months following a negative vasodilator stress cardiovascular magnetic resonance (negative stress-CMR) and long-term adverse events in patients with known or suspected chronic coronary syndrome (CCS).We retrospectively evaluated 3517 patients in which the stress first-pass perfusion imaging revealed no ischemia. The primary endpoint was the composite of death, spontaneous myocardial infarction, heart failure (HF), or stroke. The association between symptoms-guided revascularization after a negative stress-CMR and the endpoint was assessed using the multivariable Cox proportional hazard regression model.The mean age was 64.7 ± 11.9 years and 45.4% were females. Coronary angiography and revascularization following a negative stress-CMR were performed in 176 (5%) and 59 (1.7%) patients. At a median follow-up of 4.8 years (2.0-8.2), 529 (15%) patients experienced the primary endpoint (2.0 per 100 person-years). Revascularization following a negative CMR was associated with a higher incidence of the composite (4.85 vs. 1.96 per 100 person-years, p0.001) and each of the isolated components of the endpoint, except for the HF endpoint, in which differences were borderline significant. After multivariate adjustment, revascularization remained associated with an excess of risk (HR = 2.01, 95% CI:1.21-3.30; p = 0.007).In CCS patients with persistent symptoms but without evidence of ischemia in vasodilator stress CMR, revascularization was associated with a higher risk of adverse clinical events.

Resumen Introduccion y objetivos El sodio urinario (UNa+) ha surgido como un biomarcador util para predecir eventos clinicos desfavorables en pacientes con insuficiencia cardiaca aguda (ICA). En este estudio pretendemos evaluar: a) la utilidad de una unica determinacion precoz de UNa+ para predecir eventos adversos en pacientes con ICA e insuficiencia renal (IR) concomitante, y b) si los cambios en el UNa+ a las 24 horas (ΔUNa24 h) anaden informacion pronostica adicional sobre los valores basales. Metodos Analisis post-hoc del ensayo clinico multicentrico, abierto y paralelo (IMPROVE-HF), (ClinicalTrials.gov NCT02643147) en el que 160 pacientes con ICA e IR concomitante al ingreso fueron aleatorizados a: a) estrategia diuretica convencional, o b) estrategia basada en los niveles del antigeno carbohidrato 125. El objetivo primario fue la mortalidad total y el numero total de ingresos recurrentes. Resultados La edad media fue 78 ± 8 anos, y la tasa media de filtrado glomerular fue 34,0 ± 8,5 ml/min/1,73 m2. La mediana de UNa+ fue 90 mmol/L (65-111). Tras una mediana de seguimiento de 1,73 anos [IQR 0,48-2,35], se registraron 83 muertes (51,9%) y 263 rehospitalizaciones totales en 110 patientes. El UNa+ se asocio de forma independiente con la mortalidad por todas las causas (HR = 0,75, IC95%, 0,65-0,87; p 50 mmol/l. Conclusiones En pacientes con ICA e IR, una unica determinacion precoz de UNa+ ≤ 50 mmol/l identifica a pacientes con mayor riesgo de muerte por todas las causas y hospitalizaciones recurrentes. El ΔUNa24 h anade informacion pronostica adicional sobre los valores basales solo cuando el UNa+ al ingreso es ≤ 50 mmol/l.

Resumen Antecedentes El antigeno carbohidrato 125 (CA125) y los peptidos natriureticos tipo B son marcadores subrogados de congestion en pacientes con insuficiencia cardiaca aguda (ICA). El objetivo del estudio fue valorar la asociacion entre CA125 y NT-proBNP y parametros de congestion en pacientes con ICA. Metodos y resultados Estudio observacional prospectivo multicentrico, que incluyo a 191 pacientes hospitalizados por ICA. Se registro la presencia de derrame pleural, edema periferico y diametro de vena cava inferior (V C I) durante las primeras 24-48 horas tras el ingreso y se evaluo su asociacion independiente con las concentraciones de CA125 y la fraccion amino-terminal del peptido natriuretico tipo B (NT-proBNP). La edad media fue de 73,4 ± 12 anos, 79 (41,4%) eran mujeres y 127 (66,5%) tenian fraccion de eyeccion ventricular izquierda ≥ 50%. La mediana de CA125, NT-proBNP y diametro VCI fue de 58 (22,7-129) U/mL, 3.985 (1.905-9.775) pg/mL y 21 (17-25) mm, respectivamente. El analisis multivariante mostro que el CA125 se asocio positiva e independientemente con presencia de edema periferico, derrame pleural y valores elevados de VCI. El NT-proBNP se relaciono con el derrame pleural y el diametro de VCI, pero no con el edema. La adicion del CA125 incremento la capacidad discriminativa del modelo basal para identificar edema periferico y derrame pleural, no asi el NT-proBNP. El predictor mas importante para la dilatacion de la VCI fue el CA125 (R2 = 48,3%). Conclusion En pacientes con ICA, los niveles sericos de CA125 se asocian de forma mas significativa que los de NT-proBNP con el estado de congestion.

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.

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.

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.

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

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

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.

Background Undetectable high-sensitivity cardiac troponin (hs-cTn) in a single determination upon admission may rule out acute coronary syndrome. We investigated undetectable hs-cTnT ( Methods This study was a retrospective design involving 2254 consecutive patients (July 2016–November 2017). The primary endpoint was one-year death or acute myocardial infarction; the secondary endpoint added unstable angina requiring revascularization. Early ( Results A total of 56 (2.5%) patients reached the primary endpoint and 91 (4%) the secondary endpoint. Undetectable hs-cTnT had a poor C-statistic in early and late presenters (0.648 and 0.703, respectively). Adding hs-cTnT measurable concentrations above the detection limit (as continuous variable) significantly enhanced the C-statistics (0.754 and 0.847, respectively). Addition of the HEART (0.809, p = 0.005) or simple clinical scores (0.804, p = 0.02) further improved the model and significantly reclassified patient risk, in early presenters. The results were similar for the secondary endpoint. The TIMI risk score performed worse and the GRACE score did not give additional information. In late presenters, no clinical score provided significant additional information over hs-cTnT. Conclusions Diagnostic algorithms should consider not only whether hs-cTnT is above or below the detection limit but also its concentration if above, for risk stratification over one year in patients with initial normal hs-cTnT. The clinical scores provide valuable additional information in early presenters.

Objectives This study explored the association of ischemic burden, as measured by vasodilator stress cardiovascular magnetic resonance (CMR), with all-cause mortality and the effect of revascularization on all-cause mortality in patients with stable ischemic heart disease (SIHD). Background In patients with SIHD, the association of ischemic burden, derived from vasodilator stress CMR, with all-cause mortality and its role for decision-making is unclear. Methods The registry consisted of 6,389 consecutive patients (mean age: 65 ± 12 years; 38% women) who underwent vasodilator stress CMR for known or suspected SIHD. The ischemic burden (at stress first-pass perfusion imaging) was computed (17-segment model). The effect of CMR-related revascularization (within the following 3 months) on all-cause mortality was retrospectively explored using the electronic regional health system registry. Results During a 5.75-year median follow-up, 717 (11%) deaths were documented. In multivariable analyses, more extensive ischemic burden (per 1-segment increase) was independently related to all-cause mortality (hazard ratio: 1.04; 95% confidence interval: 1.02 to 1.07; p 5 segments, n = 432; 10% vs. 24%; p = 0.01). Conclusions In a large retrospective registry of unselected patients with known or suspected SIHD who underwent vasodilator stress CMR, extensive ischemic burden was related to a higher risk of long-term, all-cause mortality. Revascularization was associated with a protective effect only in the restricted subset of patients with extensive CMR-related ischemia. Further research will be needed to confirm this hypothesis-generating finding.

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.

Background In established ischemic heart disease, the relationship between lipoprotein(a) and new cardiovascular events showed contradictory results. Our aim was to assess the relationship between lipoprotein(a) and very long-term recurrent myocardial infarction (MI) after an index episode of ST-segment elevation acute myocardial infarction (STEMI). Methods We included 435 consecutive STEMI patients discharged from October 2000 to June 2003 in a single teaching center. The relationship between lipoprotein(a) at discharge and recurrent MI was evaluated through negative binomial regression and Cox regression analysis. Results The mean age was 65 years (55-74 years), 25.5% were women, 34.7% were diabetic, and 66% had a MI of anterior location. Fibrinolysis, rescue, or primary angioplasty was performed in 215 (49.4%), 19 (4.4%), and 18 (4.1%) patients, respectively. The median lipoprotein(a) was 30.4 mg/dL (12-59.4 mg/dL). After a median follow-up of 9.6 years (4.1-15 years), 180 (41.4%) deaths and 187 MI in 133 (30.6%) patients were recorded. After a multivariate adjustment, the risk gradient of lipoprotein(a) showed a neutral effect along most of the continuum and only extreme higher values identified those at higher risk of recurrent MI (P = 0.020). Those with lipoprotein(a) values >95th percentile (≥135 mg/dL) showed a higher risk of recurrent MI (incidence rate ratio, 2.34; 95% confidence interval, 1.37-4.02; P = 0.002). Lipoprotein(a) was not related to the risk of mortality (P = 0.245). Conclusions After an episode of STEMI, only extreme high values of lipoprotein(a) were associated with an increased risk of long-term recurrent MI.

Resumen Introduccion y objetivos La diabetes mellitus tipo 2 (DM2) es una comorbilidad comun en pacientes con insuficiencia cardiaca (IC) con fraccion de eyeccion conservada (ICFEP). Estudios anteriores han demostrado que las mujeres diabeticas tienen mayor riesgo de desarrollar insuficiencia cardiaca que los hombres. Sin embargo, el pronostico a largo plazo de los pacientes diabeticos con insuficiencia cardiaca en funcion 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. Metodos Se incluyeron prospectivamente 1.019 pacientes consecutivos con ICFEP dados de alta tras un episodio de IC aguda en hospital terciario. Se empleo un analisis de regresion de Cox multivariante para evaluar la interaccion 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 anos y 609 (59,8%) eran mujeres. La proporcion de DM2 fue similar entre ambos sexos (45,1 frente al 49,1%; p = 0,211). Tras una mediana de seguimiento (intervalo intercuartilico) de 3,6 (1-4-6,8) anos, 646 (63,4%) pacientes murieron. Tras ajustar por factores de riesgo, comorbilidades, biomarcadores, parametros ecograficos y tratamiento al alta, el analisis multivariate mostro un efecto pronostico diferencial de DM2 (valor de p para la interaccion = 0,007). La DM2 se asocio con un mayor riesgo de mortalidad por todas las causas en mujeres (HR = 1,77; IC95%, 1,41-2,21; p Conclusiones Tras un episodio de IC aguda en pacientes con ICFEF, la DM2 confiere un mayor riesgo de mortalidad en las mujeres. Se requieren mas estudios que evaluen el impacto de la DM2 en mujeres con ICFEP.

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.

Low lymphocyte count, as a marker of inflammation and immunosuppression, may be useful for identifying frail patients. In this work, we aimed to evaluate the association between low-relative lymphocyte count (Lymph%) and frailty status in patients >65 years old with acute coronary syndromes (ACS), and whether Lymph% is associated with morbimortality beyond standard prognosticators and frailty. In this prospective observational study, we included 488 hospital survivors of an episode of an ACS >65 years old. Total and differential white blood cells and frailty status were assessed at discharge. Frailty was evaluated using the Fried score at discharge and defined as Fried≥3. The independent association between Lymph% and Fried≥3 was evaluated by multivariate logistic regression analysis. The associations between Lymph% with long-term all-cause mortality and recurrent admission were evaluated with Cox regression and shared frailty regression, respectively. The mean age of the sample was 78 ± 7 years and 41% were females. The median (interquartile range) of the Lymph% was 21% (15 to 27) and 41% showed Fried≥3. In multivariate analysis, Lymph% was inversely related to the odds of frailty with an exponential increase risk from values below 15% (p = 0.001). Likewise, Lymph% was inverse and independently associated with a higher risk of long-term mortality (p = 0.011), recurrent all-cause (p = 0.020), and cardiovascular readmissions (p = 0.024). In conclusion, in patients >65 years with a recent ACS, low Lymph% evaluated at discharge is associated with a higher risk of frailty. Low Lymph% was also associated with a higher risk of long-term mortality and recurrent admissions beyond standard prognosticators and Fried score.

BACKGROUND: Cardiac magnetic resonance (CMR) performed early after ST-segment elevation myocardial infarction (STEMI) can improve major adverse cardiac event (MACE) risk prediction. We aimed to create a simple clinical-CMR risk score for early MACE risk stratification in STEMI patients.; METHODS: We performed a multicenter prospective registry of reperfused STEMI patients (n=1118) in whom early (1-week) CMR-derived left ventricular ejection fraction (LVEF), infarct size and microvascular obstruction (MVO) were quantified. MACE was defined as a combined clinical endpoint of cardiovascular (CV) death, non-fatal myocardial infarction (NF-MI) or re-admission for acute decompensated heart failure (HF).; RESULTS: During a median follow-up of 5.52 [2.63-7.44] years, 216 first MACE (58 CV deaths, 71 NF-MI and 87 HF) were registered. Mean age was 59.3±12.3years and most patients (82.8%) were male. Based on the four variables independently associated with MACE, we computed an 8-point risk score: time to reperfusion >4.15h (1 point), GRACE risk score>155 (3 points), CMR-LVEF 1.5 segments (1 point). This score permitted MACE risk stratification: MACE per 100 person-years was 1.96 in the low-risk category (0-2 points), 5.44 in the intermediate-risk category (3-5 points), and 19.7 in the high-risk category (6-8 points): p4.15h and GRACE risk score>155) and CMR (LVEF 1.5 segments) variables allows for simple and straightforward MACE risk stratification early after STEMI. External validation should confirm the applicability of the risk score. Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

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.

Introduction The prognostic value and therapeutic implications of ischemia as derived from vasodilator stress cardiovascular magnetic resonance (CMR) could differ in men and women, but it has not been stablished. Purpose We assessed the influence of the ischemic burden as derived from CMR on the risk of death and the effect of revascularization across sex. Methods We evaluated 6,237 consecutive patients with known or suspected chronic coronary syndrome (CCS). Extensive ischemia was defined as >5 segments with perfusion deficit. Multivariate Cox proportional hazard regression models were used. Results A total of 2,371 (38.0%) patients were women and 583 (9.3%) underwent CMR-related revascularization. During a median follow-up of 5.13 years, 687 (11.0%) deaths were reported. We found an adjusted differential effect of CMR-derived ischemic burden across sex (p-value for interaction=0.039). Women exhibited an adjusted lower risk of death along most of the continuous ischemic burden but equalled men's risk when extensive ischemia was present. Likewise, CMR-related revascularization was shown to be differentially associated with the risk of mortality across sex (p-value for interaction=0.025). In patients with non-extensive ischemia, revascularization was related to a higher risk of death, with a greater extent in women. At higher ischemic burden, revascularization was associated with a lower risk in men, with more uncertain results in women. Conclusions CMR-derived ischemic burden allows predicting the risk of death and gives insight into the potential effect of revascularization in men and women with CCS. Compared to men, women with nonextensive ischemia displayed a lower risk and a similar risk with a higher ischemic burden. The impact of CMR-related revascularization on mortality risk was also significantly different according to ischemic burden and sex. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was supported by the Instituto de Salud Carlos III and cofunded by the European Regional Development Fund (ERDF).

We aimed to compare the prognostic value of two different measures, the Fried’s Frailty Scale (FFS) and the Clinical Frailty Scale (CFS), following myocardial infarction (MI). We included 150 patients ≥ 70 years admitted from AMI. Frailty was evaluated on the day before discharge. The primary endpoint was number of days alive and out of hospital (DAOH) during the first 800 days. Secondary endpoints were mortality and a composite of mortality and reinfarction. Frailty was diagnosed in 58% and 34% of patients using the FFS and CFS scales, respectively. During the first 800 days 34 deaths and 137 admissions occurred. The number of DAOH decreased significantly with increasing scores of both FFS (p < 0.001) and CFS (p = 0.049). In multivariate analysis, only the highest scores (FFS = 5, CFS ≥ 6) were independently associated with fewer DAOH. At a median follow-up of 946 days, frailty assessed both by FFS and CFS was independently associated with death and MI (HR = 2.70 95%CI = 1.32–5.51 p = 0.001; HR = 2.01 95%CI = 1.1–3.66 p = 0.023, respectively), whereas all-cause mortality was only associated with FFS (HR = 1.51 95%CI = 1.08–2.10 p = 0.015). Frailty by FFS or CFS is independently associated with shorter number DAOH post-MI. Likewise, frailty assessed by either scale is associated with a higher rate of death and reinfarction, whereas FFS outperforms CFS for mortality prediction.

Objective: In acute heart failure (AHF), early assessment of spot urinary sodium (UNa) has emerged as a useful biomarker for risk stratification and monitoring. The objective of this study was to investigate (a) whether early spot UNa predicts 24-h diuretic efficiency and (b) the clinical factors associated with early spot UNa in patients with AHF and concomitant renal dysfunction (RD). Methods: This is a post hoc analysis of the IMPROVE-HF trial, in which 160 patients with AHF and RD (estimated glomerular filtrate rate [eGFR] 2) were included. Diuretic efficiency was calculated as the net fluid output produced per 40 mg of furosemide equivalents in 24 h. The association between early spot UNa and diuretic efficiency and clinical variables associated with UNa were evaluated using multivariate linear regression analysis. The contribution of the exposures in the predictability of the models was assessed with the coefficient of determination (R2). Results: The mean age of the study population was 78 ± 8 years. The median (interquartile range) diuretic efficiency, early spot UNa, aminoterminal pro-brain natriuretic peptide, and eGFR were 747 (490–1,167) mL, 90 mmol/L (65–111), 7,765 pg/mL (3,526–15,369), and 33.7 ± 11.3 mL/min/1.73 m2, respectively. In a multivariate setting, lower UNa was significantly and nonlinearly associated with lower diuretic efficiency (p = 0.001), explaining the 44.4% of the model predictability. Natremia and surrogates of congestion emerged as the main factors related to UNa. Conclusions: In patients with AHF and RD at presentation, early spot UNa was inversely related to 24-h diuretic efficiency.

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.

Resumen Introduccion y objetivos Los pacientes con insuficiencia cardiaca en tratamiento con antagonistas de la vitamina K (AVK) por fibrilacion auricular no valvular (FANV) a menudo presentan valores alterados de la razon internacional normalizada (INR). El objetivo es evaluar la asociacion entre la INR al ingreso por insuficiencia cardiaca y el riesgo de mortalidad en el seguimiento. Metodos Estudio observacional retrospectivo en el que se evaluo la INR al ingreso de 1.137 pacientes consecutivos con insuficiencia cardiaca aguda en tratamiento con AVK por FANV. Esta se categorizo en: INR en rango optimo (INR = 2-3, n = 210), infraterapeutica (INR 3, n = 267). La asociacion independiente entre INR y mortalidad se evaluo mediante calculo restringido de las diferencias en tiempos de supervivencia media, dado que la INR no cumple la condicion de proporcionalidad de riesgos de mortalidad. Resultados Tras una mediana de 2,15 [0,71-4,29] anos, fallecieron 495 pacientes (43,5%). En el analisis multivariable, tanto la INR infraterapeutica como la supraterapeutica se asociaron con un mayor riesgo de mortalidad, con unas diferencias en tiempos de supervivencia media a 5 anos de –0,50 anos (IC95%,–0,77 a –0,23; p Conclusiones La INR fuera de rango optimo al ingreso de los pacientes con insuficiencia cardiaca aguda en tratamiento con AVK por FANV se asocia de manera independiente con un mayor riesgo de mortalidad en el seguimiento a largo plazo.

Introduction and objectives: Heart failure patients with nonvalvular atrial fibrillation (NVAF) on treatment with vitamin K antagonists (VKA) often have suboptimal international normalized ratio (INR) values. Our aim was to evaluate the association between INR values at admission due to acute heart failure and mortality risk during follow-up. Methods: In this observational study, we retrospectively assessed INR on admission in 1137 consecutive patients with acute heart failure and NVAF who were receiving VKA treatment. INR was categorized into optimal values (INR = 2-3, n = 210), subtherapeutic (INR < 2, n = 660), and supratherapeutic (INR > 3, n = 267). Because INR did not meet the proportional hazards assumption for mortality, restricted mean survival time differences were used to evaluate the association among INR categories and the risk of all-cause mortality. Results: During a median [interquartile range] follow-up of 2.15 years [0.71-4.29], 495 (43.5%) patients died. On multivariable analysis, both patients with subtherapeutic and supratherapeutic INR showed higher risks of all-cause mortality, as evidenced by their restricted mean survival time differences at 5 years' follow-up: -0.50; 95%CI, -0.77 to -0.23 years; P < .001; and -0.40; 95%CI, -0.70 to -0.11 years; P = .007, respectively, compared with INR 2-3. Conclusions: In acute heart failure patients on treatment with VKA for NVAF, INR values out of normal range at admission were independently associated with a higher long-term mortality risk. (C) 2018 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.

Resumen Introduccion y objetivos El impacto de la intervencion coronaria percutanea (ICP) sobre oclusiones coronarias cronicas totales (OCT) presenta controversias. Se analizan los resultados agudos y al seguimiento en nuestro entorno. Metodos Registro prospectivo de ICP sobre OCT en 24 centros durante 2 anos. Resultados Se realizaron 1.000 ICP sobre OCT en 952 pacientes. La mayoria tenia sintomas (81,5%) y cardiopatia isquemica previa (59,2%), y hubo intentos de desobstruccion previos en un 15%. El SYNTAX anatomico fue 19,5 ± 10,6 y tenia J-score > 2 el 17,3%. El procedimiento fue retrogrado en 92 pacientes (9,2%). La tasa de exito fue del 74,9%, mayor en aquellos sin ICP previa (el 82,2 frente al 75,2%; p = 0,001), con J-score ≤ 2 (el 80,5 frente al 69,5%; p = 0,002) y con el uso de ecografia intravascular (el 89,9 frente al 76,2%; p = 0,001), que fue predictor independiente del exito. Por el contrario, lesiones calcificadas, > 20 mm o con munon proximal romo lo fueron de fracaso. El 7,1% tuvo complicaciones, como perforacion (3%), infarto (1,3%) o muerte (0,5%). Al ano de seguimiento, el 88,2% mejoro clinicamente en caso de ICP exitosa (frente al 34,8%; p Conclusiones Los pacientes del Registro Iberico con OCT tratados con ICP presentan complejidad clinico-anatomica, tasas de exito y complicaciones similares a los de otros registros nacionales e importante impacto de la recanalizacion exitosa en la mejoria funcional, que a su vez se asocio con menor mortalidad.

Congestion explains many of the signs and symptoms of acute heart failure (AHF) and disease progression. However, accurate quantification of congestion is challenging in daily practice. Antigen carbohydrate 125 (CA125) or mucin 16 (MUC16), a large glycoprotein synthesized by mesothelial cells, has emerged as a reliable proxy of congestion and inflammation in patients with heart failure. In AHF syndromes, CA125 is strongly associated with right-sided heart failure parameters and a higher risk of adverse clinical events beyond standard prognostic factors, including natriuretic peptides. Furthermore, CA125 has the potential for both monitoring and guide HF treatment following a decompensated HF event. The wide availability of CA125 in most clinical laboratories, together with its standardized measurement and reduced cost, makes this marker attractive for routine use in decompensated HF. Further research is required to understand better its biological role and its promising utility as a tool to guide decongestive therapy in HF. This article is protected by copyright. All rights reserved.

This study aimed to evaluate whether glomerular filtration rate (eGFR) during admission modifies the predictive value of plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP) and carbohydrate antigen 125 (CA125) in patients hospitalized for acute heart failure (AHF).We retrospectively evaluated 4595 patients consecutively discharged after admission for AHF at three tertiary-care hospitals from January 2008 through October 2019. To investigate the effect of kidney function on the association of NT-proBNP and CA125 with 1-year mortality (all-cause and cardiovascular mortality), we stratified patients according to four eGFR categories:30 mL•minAt 1-year follow-up, 748 of 4595 (16.3%) patients died after discharge (of all deaths, 575 [12.5%] were cardiovascular). After multivariate adjustment, both NT-proBNP and CA125 remained independently associated with a higher risk of death when modeled as main effects (P0.001). However, we found a differential prognostic effect of NT-proBNP across eGFR categories for both endpoints (all-cause mortality, P-value for interaction=0.002; CV mortality, P-value for interaction=0.001). Whereas NT-proBNP was positively and linearly associated with mortality in the subset of patients with normal or mildly reduced eGFR, its predictive ability progressively decreased at the lower extreme of eGFR (45 mL•minIn patients with AHF and severely reduced eGFR, CA125 outperforms NT-proBNP in predicting 1-year mortality.

Background We 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. Methods Scores 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. Results Mean 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, p Conclusion Procedural 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.

Decision-making is challenging in patients with chest pain and normal high-sensitivity cardiac troponin T (hs-cTnT, &lt, 99th percentile, 14 ng/L) at hospital arrival. Most of these patients might be discharged early. We investigated clinical data and hs-cTnT concentrations for risk stratification. This is a retrospective study including 4476 consecutive patients presenting to the emergency department with chest pain and first normal hs-cTnT. The primary endpoint was one-year death or acute myocardial infarction, and the secondary endpoint added urgent revascularization. The number of primary and secondary endpoints was 173 (3.9%) and 252 (5.6%). Mean hs-cTnT concentrations were 6.9 ± 2.5 ng/L. Undetectable (&lt, 5 ng/L) hs-cTnT (n = 1847, 41%) had optimal negative predictive value (99.1%) but suboptimal sensitivity (90.2%) and discrimination accuracy (AUC = 0.664) for the primary endpoint. Multivariable analysis was used to identify the predictive clinical variables. The clinical model showed good discrimination accuracy (AUC = 0.810). The addition of undetectable hs-cTnT (≥ or &lt, 5 ng/L, HR, hazard ratio = 3.80, 95% CI, confidence interval 2.27–6.35, p = 0.00001) outperformed the clinical model alone (AUC = 0.836, p = 0.002 compared to the clinical model). Measurable hs-cTnT concentrations (between detection limit and 99th percentile, per 0.1 ng/L, HR = 1.13, CI 1.06–1.20, p = 0.0001) provided further predictive information (AUC = 0.844, p = 0.05 compared to the clinical plus undetectable hs-cTnT model). The results were reproducible for the secondary endpoint and 30-day events. Clinical assessment, undetectable hs-cTnT and measurable hs-cTnT concentrations must be considered for decision-making after a single negative hs-cTnT result in patients presenting to the emergency department with acute chest pain.

Background Magnetic resonance imaging (MRI) is the most accurate imaging technique for left ventricular ejection fraction (LVEF) quantification, but as yet the prognostic value of LVEF assessment at any time after ST-segment elevation myocardial infarction (STEMI) for subsequent major adverse cardiac event (MACE) prediction is uncertain. Purpose To explore the prognostic impact of MRI-derived LVEF at any time post-STEMI to predict subsequent MACE (cardiovascular death or re-admission for acute heart failure). Study Type Prospective. Population One thousand thirteen STEMI patients were included in a multicenter registry. Field Strength/Sequence 1.5-T. Balanced steady-state free precession (cine imaging) and segmented inversion recovery steady-state free precession (late gadolinium enhancement) sequences. Assessment Post-infarction MRI-derived LVEF (reduced [r]: = 50%) was sequentially quantified at 1 week and after >3 months of follow-up. Statistical Tests Multi-state Markov model to determine the prognostic value of each LVEF state (r-, mr- or p-) at any time point assessed to predict subsequent MACE. A P-value During a 6.2-year median follow-up, 105 MACE (10%) were registered. Transitions toward improved LVEF predominated and only r-LVEF (at any time assessed) was significantly related to a higher incidence of subsequent MACE. The observed transitions from r-LVEF, mr-LVEF, and p-LVEF states to MACE were: 15.3%, 6%, and 6.7%, respectively. Regarding the adjusted transition intensity ratios, patients in r-LVEF state were 4.52-fold more likely than those in mr-LVEF state and 5.01-fold more likely than those in p-LVEF state to move to MACE state. Nevertheless, no significant differences were found in transitions from mr-LVEF and p-LVEF states to MACE state (P-value = 0.6). Data Conclusion LVEF is an important MRI index for simple and dynamic post-STEMI risk stratification. Detection of r-LVEF by MRI at any time during follow-up identifies a subset of patients at high risk of subsequent events. Level of Evidence 2 Technical Efficacy Stage 2

Aims Iron deficiency (ID) is a frequent finding in patients with chronic and acute heart failure (AHF) along the full spectrum of left ventricular ejection fraction (LVEF). Iron deficiency has been related to ventricular systolic dysfunction, but its role in right ventricular function has not been evaluated. We sought to evaluate whether ID identifies patients with greater right ventricular dysfunction in the setting of AHF. Methods and results We prospectively included 903 patients admitted with AHF. Right systolic function was evaluated by tricuspid annular plane systolic excursion (TAPSE) and the ratio TAPSE/pulmonary artery systolic pressure (TAPSE/PASP). Iron deficiency was defined, according to European Society of Cardiology criteria, as serum ferritin Conclusion In AHF, proxies of ID were associated with right ventricular dysfunction. Further studies should confirm these findings and evaluate the pathophysiological facts behind this association.

BACKGROUND: Right heart dysfunction (RHD) parameters are increasingly important in heart failure (HF). This study aimed to evaluate the association of advanced RHD with the risk of recurrent admissions across the spectrum of left ventricular ejection fraction (LVEF). METHODS AND RESULTS: We included 3383 consecutive patients discharged for acute HF. Of them, in 1435 patients (42.4%), the pulmonary artery systolic pressure could not be measured accurately, leaving a final sample size of 1948 patients. Advanced RHD was defined as the combination of a ratio of tricuspid annular plane systolic excursion/pulmonary artery systolic pressure of less than 0.36 and significant tricuspid regurgitation (n?=?196, 10.2%). Negative binomial regression analyses were used to evaluate the risk of recurrent admissions. At a median follow-up of 2.2 years (interquartile range 0.63-4.71), 3782 readmissions were registered in 1296 patients (66.5%). Patients with advanced RHD showed higher readmission rates, but only if the LVEF was 40% or greater (P < .001). In multivariable analyses, this differential association persisted for cardiovascular and HF recurrent admissions (P value for interaction?=?.015 and P?=?.016; respectively). Advanced RHD was independently associated with the risk of recurrent cardiovascular and HF admissions if HF with an LVEF of 40% or greater (incidence rate ratio 1.64, 95% confidence interval 1.18-2.26, P?=?.003; and incidence rate ratio 1.73; 95% confidence interval 1.25-2.41, P?=?.001;respectively). In contrast, it was not associated with readmission risks if the LVEF was less than 40%. CONCLUSIONS: After an admission for acute HF, advanced RHD was strongly associated with a higher risk of recurrent cardiovascular and HF admissions, but only in patients with an LVEF of 40% or greater.

Background Pulmonary embolism (PE) is globally the third most frequent acute cardiovascular syndrome, ranking high among the causes of cardiovascular mortality. Systemic thrombolytic therapy (STT) permits prompt reperfusion after pulmonary obstruction, nevertheless this treatment carries by itself an inherent risk of major bleeding events. Development of new therapies and interventions that allow us to achieve early lung reperfusion along with a reduced risk of bleeding are necessary. Purpose The aim of this study was to evaluate the safety and efficacy of percutaneous catheter-directed treatment (PCDT) on intermediate-high risk PE patients with high bleeding risk or contraindication for STT. Methods We consecutively included all patients with intermediate-high risk PE undergoing PCDT in two university hospitals. Clinical, echocardiographic and hemodynamic variables (pre and post PCDT) were collected, as well as major adverse cardiac and bleeding events during follow-up. Results Between February 2018 and January 2021, we included 30 consecutive patients admitted with intermediate-high risk PE who underwent PCDT. Median age was 60 years, interquartile range (IQR) 51–72, and 41% were women. 14 patients (46.6%) presented an absolute contraindication for STT, which was the main reason for performing PCDT. Catheter-directed local thrombolysis (CDLT) was performed in 27 (90%) patients and mechanical fragmentation-aspiration was performed in 12 (40%) of them. We observed a significant reduction in mean pulmonary artery pressure (mPAP, mmHg) after PCDT: 40±13 vs. 25±12, p Conclusions PCDT for intermediate-high risk PE is safe and effective, producing an early reduction in mPAP, in prognostic biomarkers such as NT-proBNP, as well as an early improvement of classic echocardiographic parameters of RV dysfunction. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Aims The impact of sex in patients with CAD has been widely reported, but little is known about the influence of sex on the risk of new-onset HF in patients with known or suspected CAD. We aimed to examine sex-related differences and new-onset heart failure (HF) risk in patients with known or suspected coronary artery disease (CAD) undergoing vasodilator stress cardiac magnetic resonance (CMR). Methods and results We prospectively evaluated 5899 consecutive HF-free patients submitted to stress CMR for known or suspected CAD. Ischaemic burden (number of segments with stress-induced perfusion deficit) and left ventricular ejection fraction (LVEF) were assessed by CMR. The association between sex and new-onset HF (including outpatient diagnosis or acute HF hospitalization) was evaluated using a Cox proportional hazards regression model adjusted for competing events [death, myocardial infarction (MI), and revascularization]. A total of 2289 (38.8%) patients were women. During a median follow-up of 4.5 years, 610 (10.3%) patients died, 191 (3.2%) suffered an MI, 905 (15.3%) underwent revascularization, and 314 (5.3%) developed new-onset HF. Unadjusted new-onset HF rates were higher in women than in men (1.25 vs. 0.83 per 100 person-years, P = 0.001). After comprehensive multivariate adjustment, women showed an increased risk of new-onset HF (hazard ratio 1.58, 95% confidence interval 1.18–2.10; P = 0.002). We found a sex-differential effect along the continuum of LVEF (P-value for interaction = 0.007). At lower LVEF, there was an increased risk in both sexes. However, compared with men, the risk of new-onset HF was higher in women with LVEF >55%. Conclusion Women with known or suspected CAD are at a higher risk of new-onset HF. Further studies are needed to unravel the mechanisms behind these sex-related differences.

Introduction and objectives: Urinary sodium (UNa+) has emerged as a useful biomarker of poor clinical outcomes in acute heart failure (AHF). Here, we sought to evaluate: a) the usefulness of a single early determination of UNa+ for predicting adverse outcomes in patients with AHF and renal dysfunction, and b) whether the change in UNa+ at 24 hours (Delta UNa24 h) adds any additional prognostic information over baseline values. Methods: This is a post-hoc analysis of a multicenter, open-label, randomized clinical trial (IMPROVE-HF) (ClinicalTrials.gov NCT02643147) that randomized 160 patients with AHF and renal dysfunction on admission to a) the standard diuretic strategy, or b) a carbohydrate antigen 125-guided diuretic strategy. The primary end point was all-cause mortality and total all-cause readmissions. Results: The mean age was 78 +/- 8 years, and the mean glomerular filtration rate was 34.0 +/- 8.5 mL/min/1.73 m(2). The median UNa+ was 90 (65-111) mmol/L. At a median follow-up of 1.73 years [interquartile range, 0.48-2.35], 83 deaths (51.9%) were registered, as well as 263 all-cause readmissions in 110 patients. UNa+ was independently associated with mortality (HR, 0.75; 95%CI, 0.65-0.87; P 50 mmol/L. Conclusions: In patients with AHF and renal dysfunction, a single early determination of UNa+

BACKGROUND: For patients with heart failure (HF), iron deficiency (ID) is a common therapeutic target. However, little is known about the utility of transferrin saturation (TSAT) or serum ferritin for risk stratification in decompensated HF (DHF) or the European Society of Cardiology's (ESC) current definition of ID (ferritin50%. Medians for NT-proBNP, TSAT, and ferritin were 4067pg/mL (1900-8764), 14.1% (9.0-20.3), and 103 ug/L (54-202), respectively. According to the current ESC definition, 1,246 (73.3%) patients had ID. By day 30, there were 177 (10.4%) events (95 deaths and 85 HF readmission). After multivariable adjustment, lower TSAT was associated with outcome (p=0.009) but serum ferritin was not (HR 1.00; 95% confidence interval 0.99-1.00, p=0.347). CONCLUSIONS: Lower TSAT, but not ferritin, was associated with a higher risk of short-term events in patients with DHF. Further research is needed to confirm these findings and the utility of serum ferritin as a marker of ID in DHF.

Background Intrarenal venous flow (IRVF) measured by Doppler ultrasound has gained interest as a potential surrogate marker of renal congestion and adverse outcomes in heart failure. In this work, we aimed to determine if antigen carbohydrate 125 (CA125) and plasma amino-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with congestive IRVF patterns (i.e., biphasic and monophasic) in acute heart failure (AHF). Methods and results We prospectively enrolled a consecutive cohort of 70 patients hospitalized for AHF. Renal Doppler ultrasound was assessed within the first 24-h of hospital admission. The mean age of the sample was 73.5 ± 12.3 years; 47.1% were female, and 42.9% exhibited heart failure with preserved ejection fraction. The median (interquartile range) for NT-proBNP and CA125 were 6149 (3604–12 330) pg/mL and 64 (37–122) U/mL, respectively. The diagnostic performance of both exposures for identifying congestive IRVF patterns was tested using the receiving operating curve (ROC). The cut-off for CA125 of 63.5 U/mL showed a sensibility and specificity of 67% and 74% and an area under the ROC curve of 0.71. After multivariate adjustment, CA125 remained non-linearly and positively associated with congestive IRVF (P-value = 0.008) and emerged as the most important covariate explaining the variability of the model (R2: 47.5%). Under the same multivariate setting, NT-proBNP did not show to be associated with congestive IRVF patterns (P-value = 0.847). Conclusions CA125 and not NT-proBNP is a useful marker for identifying patients with AHF and congestive IRVF patterns.

Frailty is a marker of poor prognosis in older adults after acute coronary syndrome. We investigated whether cognitive impairment provides additional prognostic information. The study population consisted of a prospective cohort of 342 older (&gt, 65 years) adult survivors after acute coronary syndrome. Frailty (Fried score) and cognitive function (Pfeiffer&rsquo, s Short Portable Mental Status Questionnaire&mdash, SPMSQ) were assessed at discharge. The endpoints were mortality or acute myocardial infarction at 8.7-year median follow-up. Patient distribution according to SPMSQ results was: no cognitive impairment (SPMSQ = 0 errors, n = 248, 73%), mild impairment (SPMSQ = 1&ndash, 2 errors, n = 52, 15%), and moderate to severe impairment (SPMSQ &ge, 3 errors, n = 42, 12%). A total of 245 (72%) patients died or had an acute myocardial infarction, and 216 (63%) patients died. After adjustment for clinical data, comorbidities, and Fried score, the SPMSQ added prognostic value for death or myocardial infarction (per number of errors, HR = 1.11, 95%, CI 1.04&ndash, 1.19, p = 0.002) and death (HR = 1.11, 95% 1.03&ndash, 1.20, p = 0.007). An SPMSQ with &ge, 3 errors identified the highest risk subgroup. Geriatric conditions (SPSMQ and Fried score) explained 19% and 43% of the overall chi-square of the models for predicting death or myocardial infarction and death, respectively. Geriatric assessment after acute coronary syndrome should include both frailty and cognitive function. This is particularly important given that cognitive impairment without dementia can be subclinical and thus remain undetected.

BACKGROUND: The optimal length of stay (LOS) in patients hospitalized for acute heart failure (AHF) remains controversial. Plasma antigen carbohydrate 125 (CA125) has emerged as a reliable proxy of congestion. We aimed to evaluate whether there is a differential impact of LOS on the risk of 6-month AHF readmission across CA125 levels. METHODS: This is a retrospective study that included 1,387 patients discharged for AHF in two third-level centers. CA125 was measured 48±24h after admission. The association between CA125 and LOS with the risk of subsequent AHF readmission at 6 months was analyzed by Cox regression analysis accounting for death as a competing event. RESULTS: The median (IQR) age of the sample was 78 (69-83) years, 625 (41.1%) patients were women, and 832 (60%) exhibited preserved left ventricular ejection fraction. The median LOS and CA125 were 6 (4-9) days and 36 (17-83) U/mL, respectively. A total of 707 (51%) patients displayed high CA125 levels (=35 U/mL). At 6 months, 87 deaths (6,3%) and 304 AHF readmissions (21,9%) were registered, respectively. A multivariate analysis revealed a differential effect of LOS on 6-month AHF readmission across CA125 levels (p-value for interaction=0.010). In those with CA125

[EN] Background Cardiac magnetic resonance (CMR) permits robust risk stratification of discharged ST-segment-elevation myocardial infarction patients, but its indiscriminate use in all cases is not feasible. We evaluated the utility of left ventricular ejection fraction (LVEF) by echocardiography for a selective use of CMR after ST-segment-elevation myocardial infarction. Methods Echocardiography and CMR were performed in 1119 patients discharged for ST-segment-elevation myocardial infarction included in a multicenter registry. The prognostic power of CMR beyond echocardiography-LVEF was assessed using adjusted C statistic, net reclassification improvement index, and integrated discrimination improvement index. Results During a 4.8-year median follow-up, 136 (12%) first major adverse cardiac events (MACE) occurred (47 cardiovascular deaths and 89 readmissions for acute heart failure). In the entire group, CMR-LVEF (but not echocardiography-LVEF) independently predicted MACE occurrence. The MACE rate significantly increased only in patients with CMR-LVEF= 50%: 7%, 40%-49%: 9%, = 50% (629, 56%), and they had a low MACE rate (57/629, 9%). In patients with echocardiography-LVEF= 40% (24/278, 9%) but significantly increased in patients with CMR-LVEF= 50% (C statistic 0.66 versus 0.66; net reclassification improvement index, 0.17; integrated discrimination improvement index, 0.01). Conclusions A straightforward strategy based on a selective use of CMR for risk prediction in ST-segment-elevation myocardial infarction patients with echocardiography-LVEF, This work was supported by Instituto de Salud Carlos III and Fondos Europeos de Desarrollo Regional FEDER (grant numbers PI15/00531, PI17/01836, PI20/00637 and, CIBERCV16/11/00486), Marato TV3 (grant number 20153030-31-32), a grant from the Catalonian Society of Cardiology 2015, and Generalitat Valenciana (grant number GV/2018/116). The study was partially funded by Siemens Healthcare, which provided financial support to conduct CMR studies in 94 subjects of this series. D.M. acknowledges financial support from the Agencia Valenciana de la Innovacion, Generalitat Valenciana (grant number INNCAD00/19/085), and from the Conselleria d'Educacio, Investigacio, Cultura i Esport, Generalitat Valenciana (grant number AEST/2019/037).

En Cardiology Journal. Gdańsk (Polonia) : Via Medica. Vol. 28, n. 4 (01 jul. 2021), pp. 598-606. ISSN 1897-5593. e-ISSN 1898-018X. Este artículo se encuentra disponible en la siguiente URL: https://journals.viamedica.pl/cardiology_journal/article/view/CJ.a2020.0170/52602 En este artículo de investigación también participan: Maria Marco, Teresa García-Ballester, Begoña Zorio, Eduardo Núñez, Francisco J. Chorro, Juan Sanchis y Julio Núñez. Background: There are no well-established predictors of recurrent ischemic coronary events after an acute coronary syndrome (ACS). Higher levels of homocysteine have been reported to be associated with an increased atherosclerotic burden. The primary endpoint was to assess the relationship between homocysteine at discharge and very long-term recurrent myocardial infarction (MI). Methods: 1306 consecutive patients with ACS were evaluated (862 with non-ST-segment elevation ACS [NSTEACS] and 444 with ST-segment elevation myocardial infarction [STEMI]) discharged from October 2000 to June 2003 in a single teaching-center. The relationship between homocysteine at discharge and recurrent MI was evaluated through bivariate negative binomial regression accounting for mortality as a competitive event. Results: The mean age was 66.8 ± 12.4 years, 69.1% were men, and 32.2% showed prior diabetes mellitus. Most of the patients were admitted for an NSTEACS (66.0%). The median (interquartile range) GRACE risk score, Charlson comorbidity index, and homocysteine were 144 (122–175) points, 1 (1–2) points, and 11.9 (9.3–15.6) μmol/L, respectively. In-hospital revascularization was performed in 26.3% of patients. At a median follow-up of 9.7 (4.5–15.1) years, 709 (54.3%) deaths were registered and 779 recurrent MI in 478 (36.6%) patients. The rates of recurrent MI were higher in patients in the upper homocysteine quartiles (p < 0.001). After a multivariate adjustment, homocysteine along its continuum remained almost linearly associated with a higher risk of recurrent MI (p = 0.001) and all-cause mortality (p < 0.001). Conclusions: In patients with ACS, higher homocysteine levels identified those at a higher risk of recurrent MI at very long-term follow-up.

Vasodilator stress cardiac magnetic resonance (stressCMR) has shown robust diagnostic and prognostic value in patients with known or suspected chronic coronary syndrome (CCS). However, it is unknown whether integration of stressCMR with clinical variables in a simple clinical-imaging score can straightforwardly predict all-cause mortality in this population. We included 6187 patients in a large registry that underwent stressCMR for known or suspected CCS. Several clinical and stressCMR variables were collected, such as left ventricular ejection fraction (LVEF) and ischemic burden (number of segments with stress-induced perfusion defects (PD)). During a median follow-up of 5.56 years, we registered 682 (11%) all-cause deaths. The only independent predictors of all-cause mortality in multivariable analysis were age, male sex, diabetes mellitus (DM), LVEF and ischemic burden. Based on the weight of the chi-square increase at each step of the multivariable analysis, we created a simple clinical-stressCMR (C-CMR-10) score that included these variables (age &ge, 65 years = 3 points, LVEF &le, 50% = 3 points, DM = 2 points, male sex = 1 point, and ischemic burden &gt, 5 segments = 1 point). This 0 to 10 points C-CMR-10 score showed good performance to predict all-cause annualized mortality rate ranging from 0.29%/year (score = 0) to &gt, 4.6%/year (score &ge, 7). The goodness of the model and of the C-CMR-10 score was separately confirmed in 2 internal cohorts (n &gt, 3000 each). We conclude that a novel and simple clinical-stressCMR score, which includes clinical and stressCMR variables, can provide robust prediction of the risk of long-term all-cause mortality in a population of patients with known or suspected CCS.