Changes in myocardial iron content following administration of intravenous iron (Myocardial‐IRON): Study design

Treatment with intravenous ferric carboxymaltose (FCM) has been shown to improve symptoms, functional capacity, and quality of life in patients with heart failure and iron deficiency. However, the underlying mechanisms for these beneficial effects remain undetermined. The aim of this study is to quantify cardiac magnetic resonance changes in myocardial iron content after administration of intravenous FCM in patients with heart failure and iron deficiency and contrast them with parameters of heart failure severity. This is a multicenter, double-blind, randomized study. Fifty patients with stable symptomatic heart failure, left ventricular ejection fraction <50%, and iron deficiency will be r…

Short‐term changes in left and right systolic function following ferric carboxymaltose: a substudy of the Myocardial‐IRON trial

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 functio…

Prognostic value of NT-proBNP and CA125 across glomerular filtration rate categories in acute heart failure.

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%)…

Efecto pronóstico de una estrategia terapéutica guiada por los valores del antígeno carbohidrato 125 (CHANCE-HF). Diseño del estudio

Resumen Introduccion y objetivos La morbilidad y la mortalidad despues de un ingreso por insuficiencia cardiaca aguda siguen siendo extremadamente elevadas. En este contexto, se ha demostrado que las concentraciones plasmaticas del antigeno carbohidrato 125 muestran correlacion con la gravedad de la sobrecarga hidrica y el riesgo de muerte y reingreso. Los datos preliminares indican un posible papel del antigeno carbohidrato 125 como guia para el tratamiento. El objetivo de este estudio es evaluar el efecto pronostico de una estrategia de tratamiento guiada por el antigeno carbohidrato 125 comparada con el tratamiento estandar en pacientes dados de alta recientemente tras un ingreso por ins…

Optimal carbohydrate antigen 125 cutpoint for identifying low-risk patients after admission for acute heart failure

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 co…

Punto de corte óptimo del antígeno carbohidrato 125 para la identificación de pacientes con bajo riesgo tras un ingreso por insuficiencia cardiaca aguda

Resumen Introduccion y objetivos El antigeno carbohidrato 125 (CA125) se ha mostrado util para la estratificacion del riesgo de los pacientes ingresados por insuficiencia cardiaca aguda (ICA). Se intenta determinar un punto de corte para identificar a los pacientes con bajo riesgo de muerte y muerte/reingreso por insuficiencia cardiaca 1 mes tras el ingreso por ICA. Metodos La cohorte de derivacion incluyo a 3.231 pacientes con ICA consecutivos. Se identificaron valores de corte de CA125 con un valor predictivo negativo (VPN) del 90% y una sensibilidad de hasta el 85%. La idoneidad de estos puntos de corte y el riesgo de muerte/reingreso al mes se evaluaron mediante el metodo de Royston-Par…

Early Spot Urinary Sodium and Diuretic Efficiency in Acute Heart Failure and Concomitant Renal Dysfunction

&lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; In acute heart failure (AHF), early assessment of spot urinary sodium (U&lt;sub&gt;Na&lt;/sub&gt;) has emerged as a useful biomarker for risk stratification and monitoring. The objective of this study was to investigate (a) whether early spot U&lt;sub&gt;Na&lt;/sub&gt; predicts 24-h diuretic efficiency and (b) the clinical factors associated with early spot U&lt;sub&gt;Na&lt;/sub&gt; in patients with AHF and concomitant renal dysfunction (RD). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; This is a post hoc analysis of the IMPROVE-HF trial, in which 160 patients with AHF and RD (estimated glomerular filtrate rate [eGFR] &amp;#x3c;60 mL/min/1…

Comparación entre CA125 y NT-proBNP para valorar la congestión en insuficiencia cardíaca aguda

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 n…

Carbohydrate Antigen-125–Guided Therapy in Acute Heart Failure

Abstract Objectives This study sought to evaluate the prognostic effect of carbohydrate antigen-125 (CA125)–guided therapy (CA125 strategy) versus standard of care (SOC) after a hospitalization for acute heart failure (AHF). Background CA125 has emerged as a surrogate of fluid overload and inflammatory status in AHF. After an episode of AHF admission, elevated values of this marker at baseline as well as its longitudinal profile relate to adverse outcomes, making it a potential tool for treatment guiding. Methods In a prospective multicenter randomized trial, 380 patients discharged for AHF and high CA125 were randomly assigned to the CA125 strategy (n = 187) or SOC (n = 193). The aim in th…

Noninvasive Imaging Estimation of Myocardial Iron Repletion Following Administration of Intravenous Iron : The Myocardial- Trial

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 eval…

Clinical utility of antigen carbohydrate 125 for planning the optimal length of stay in acute heart failure.

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) a…

Antígeno carbohidrato 125 en insuficiencia cardiaca. Nueva era en la monitorización y control del tratamiento

Resumen Asistimos en los ultimos anos a un gran interes en la busqueda de nuevos biomarcadores en la insuficiencia cardiaca (IC); fundamentalmente, en el ambito del diagnostico, pronostico, monitorizacion y como guia terapeutica. Sin embargo, la mayoria de ellos no cumplen los criterios requeridos para ser utilizados en la practica clinica diaria. El antigeno carbohidrato 125 (CA 125) es el anticuerpo de la glucoproteina mucina 16 (MUC16) y su uso se ha restringido a la monitorizacion terapeutica del cancer de ovario. Sin embargo, se ha constatado su elevacion en otros procesos no tumorales como la IC. En este ultimo contexto, el CA 125 es sintetizado por las celulas serosas epiteliales en …

Diuretic Strategies in Acute Heart Failure and Renal Dysfunction: Conventional vs Carbohydrate Antigen 125-guided Strategy. Clinical Trial Design

Abstract Introduction and objectives The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1. Methods Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4 mg/dL on admission will be randomized to: a) standard diuretic str…

Differential mortality association of loop diuretic dosage according to blood urea nitrogen and carbohydrate antigen 125 following a hospitalization for acute heart failure.

Recent observations in chronic stable heart failure suggest that high-dose loop diuretics (HDLDs) have detrimental prognostic effects in patients with high blood urea nitrogen (BUN), but recent findings have also indicated that diure- tics may improve renal function. Carbohydrate antigen 125 (CA125) has been shown to be a surrogate of systemic congestion. We sought to explore whether BUN and CA125 modulate the mortality risk associated with HDLDs following a hospitalization for acute heart failure (AHF). Methods and results We analysed 1389 consecutive patients discharged for AHF. CA125 and BUN were measured at a mean of 72+12 h after admission. HDLDs (≥120 mg/day in furosemide equivalent d…

Estrategias diuréticas en insuficiencia cardiaca aguda con disfunción renal: terapia convencional frente a guiada por el antígeno carbohidrato 125. Diseño de ensayo clínico

Resumen Introduccion y objetivos El tratamiento optimo de pacientes con insuficiencia cardiaca aguda (ICA) y sindrome cardiorrenal tipo 1 (SCR-1) no esta bien definido. La hipoperfusion arterial y la congestion venosa tienen un papel fundamental en la fisiopatologia del SCR-1. El antigeno carbohidrato 125 (CA125) ha emergido como marcador indirecto de sobrecarga de volumen en la ICA. El objetivo de este estudio es evaluar la utilidad del CA125 para el ajuste del tratamiento diuretico de pacientes con SCR-1. Metodos Ensayo clinico multicentrico, abierto y paralelo, que incluye a pacientes con ICA y creatinina ≥ 1,4 mg/dl al ingreso, aleatorizados a: a)  estrategia convencional: titulacion ba…

Factores clave para modelos de atención a la insuficiencia cardiaca. Una visión integradora y multidisciplinar

[Resumen] Introducción y objetivos. La insuficiencia cardiaca (IC) supone un reto para los sistemas sanitarios que se puede responder a través del desarrollo de modelos integrales de atención. Un grupo multidisciplinar de expertos reflexionó sobre los factores clave para avanzar en el desarrollo de este tipo de modelos, planteando una hoja de ruta dirigida a todos los agentes (administraciones, gestores y profesionales sanitarios). Métodos. Se conformó un panel Delphi multidisciplinar integrado por un comité asesor de 15 expertos y un panel adicional de 31 expertos. A través de una revisión bibliográfica sistemática y entrevistas individuales semiestructuradas se realizó un diagnóstico e id…

Comparison between CA125 and NT-proBNP for evaluating congestion in acute heart failure

Abstract 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). Th…

Soluble ST2 and Diuretic Efficiency in Acute Heart Failure and Concomitant Renal Dysfunction

Abstract 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 …

Digoxin and prognosis of heart failure in older patients with preserved ejection fraction: Importance of heart rate. Results from an observational and multicenter study

Abstract Background The value of digoxin in heart failure (HF) remains controversial, particularly in patients with preserved ejection fraction (HFpEF). This study evaluated the 1-year risk of events after digoxin treatment for acute heart failure (AHF) in patients >70 years old with HFpEF. Methods 1833 patients were included in this analysis (mean age, 82 years). The main endpoints were all-cause death and the composite of death and/or HF re-admission within 1 year. Cox regression analysis was used to evaluate the association between digoxin treatment and prognosis. Results 401 patients received digoxin treatment; of these, 86% had atrial fibrillation. The mean baseline heart rate was 86 ±…

Congestión venosa en insuficiencia cardiaca aguda: mucho más que un epifenómeno

Study design of Heart failure Events reduction with Remote Monitoring and eHealth Support (HERMeS)

Aims: The role of non‐invasive telemedicine (TM) combining telemonitoring and teleintervention by videoconference (VC) in patients recently admitted due to heart failure (HF) (‘vulnerable phase’ HF patients) is not well established. The aim of the Heart failure Events reduction with Remote Monitoring and eHealth Support (HERMeS) trial is to assess the impact on clinical outcomes of implementing a TM service based on mobile health (mHealth), which includes remote daily monitoring of biometric data and symptom reporting (telemonitoring) combined with VC structured, nurse‐based follow‐up (teleintervention). The results will be compared with those of the comprehensive HF usual care (UC) strateg…

Antigen carbohydrate 125 and creatinine on admission for prediction of renal function response following loop diuretic administration in acute heart failure.

The use of loop diuretics in acute heart failure (AHF) is largely empirical and has been associated with renal function impairment by reducing renal perfusion but also renal improvement by decreasing renal venous congestion. Antigen carbohydrate 125 (CA125) has emerged as a proxy for fluid overload. We sought to evaluate whether the early changes in creatinine (ΔCr) induced by intravenous furosemide doses (ivFD) differ among clinical groups defined by overload status (CA125) and creatinine on admission (Cr).We included 526 consecutive patients admitted for AHF. All patients received intravenous furosemide for the first 48 hours. CA125 and Cr were dichotomized at 35 U/ml and 1.4 mg/dl, respe…

Early urinary sodium trajectory and risk of adverse outcomes in acute heart failure and renal dysfunction.

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 carbohydra…

CA125-Guided Diuretic Treatment Versus Usual Care in Patients With Acute Heart Failure and Renal Dysfunction

BACKGROUND: The optimal diuretic treatment strategy for patients with acute heart failure and renal dysfunction remains unclear. Plasma carbohydrate antigen 125 (CA125) is a surrogate of fluid overload and a potentially valuable tool for guiding decongestion therapy. The aim of this study was to determine if a CA125-guided diuretic strategy is superior to usual care in terms of short-term renal function in patients with acute heart failure and renal dysfunction at presentation. METHODS: This multicenter, open-label study randomized 160 patients with acute heart failure and renal dysfunction into 2 groups (1:1). Loop diuretics doses were established according to CA125 levels in the CA125-gui…

Effect of β-Blocker Withdrawal on Functional Capacity in Heart Failure and Preserved Ejection Fraction

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-bloc…

Mid-term Prognostic Implication of hospitalized COVID-19 patients with Prior Heart Failure diagnosis

Trayectoria precoz del sodio urinario y riesgo de eventos adversos en insuficiencia cardiaca aguda y disfunción renal

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 al…

Antigen carbohydrate 125 as a biomarker in heart failure: a narrative review.

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 H…