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Resumen Introduccion y objetivos Se presentan las caracteristicas clinicas y los resultados de los trasplantes cardiacos realizados en Espana con la actualizacion correspondiente a 2019. Metodos Se describen las caracteristicas clinicas y los resultados de los trasplantes cardiacos realizados en 2019, asi como las tendencias de estos en el periodo 2010-2018. Resultados En 2019 se realizaron 300 trasplantes (8.794 desde 1984; 2.745 entre 2010 y 2019). Respecto a anos previos, los cambios mas llamativos son el descenso hasta el 38% de los trasplantes realizados en codigo urgente, y la consolidacion en el cambio de asistencia circulatoria pretrasplante, con la practica desaparicion del balon de contrapulsacion (0,7%), la estabilizacion del uso del oxigenador extracorporeo de membrana (9,6%) y el aumento de los dispositivos de asistencia ventricular (29%). La supervivencia en el trienio 2016-2018 es similar a la del trienio 2013-2015 (p = 0,34), y ambas mejores que la del trienio 2010-2012 (p = 0,002 y p = 0,01 respectivamente). Conclusiones Se mantienen estables tanto la actividad del trasplante cardiaco en Espana como los resultados en supervivencia en los ultimos 2 trienios. Hay una tendencia a realizar menos trasplantes urgentes, la mayoria con dispositivos de asistencia ventricular.

Introducción y objetivos Se presentan las características clínicas y los resultados de los trasplantes cardiacos realizados en España con la actualización correspondiente a 2019. Métodos Se describen las características clínicas y los resultados de los trasplantes cardiacos realizados en 2019, así como las tendencias de estos en el periodo 2010-2018. Resultados En 2019 se realizaron 300 trasplantes (8.794 desde 1984; 2.745 entre 2010 y 2019). Respecto a años previos, los cambios más llamativos son el descenso hasta el 38% de los trasplantes realizados en código urgente, y la consolidación en el cambio de asistencia circulatoria pretrasplante, con la práctica desaparición del balón de contrapulsación (0, 7%), la estabilización del uso del oxigenador extracorpóreo de membrana (9, 6%) y el aumento de los dispositivos de asistencia ventricular (29%). La supervivencia en el trienio 2016-2018 es similar a la del trienio 2013-2015 (p = 0, 34), y ambas mejores que la del trienio 2010-2012 (p = 0, 002 y p = 0, 01 respectivamente). Conclusiones Se mantienen estables tanto la actividad del trasplante cardiaco en España como los resultados en supervivencia en los últimos 2 trienios. Hay una tendencia a realizar menos trasplantes urgentes, la mayoría con dispositivos de asistencia ventricular. Introduction and objectives: The present report describes the clinical characteristics and outcomes of heart transplants in Spain and updates the data to 2019. Methods: We describe the clinical characteristics and outcomes of heart transplants performed in Spain in 2019, as well as trends in this procedure from 2010 to 2018. Results: In 2019, 300 transplants were performed (8794 since 1984; 2745 between 2010 and 2019). Compared with previous years, the most notable findings were the decreasing rate of urgent transplants (38%), and the consolidation of the type of circulatory support prior to transplant, with an almost complete disappearance of counterpulsation balloon (0.7%), stabilization in the use of extracorporeal membrane oxygenation (9.6%), and an increase in the use of ventricular assist devices (29.0%). Survival from 2016 to 2018 was similar to that from 2013 to 2015 (P = .34). Survival in both these periods was better than that from 2010 to 2012 (P = .002 and P = .01, respectively). Conclusions: Heart transplant activity has remained stable during the last few years, as have outcomes (in terms of survival). There has been a trend to a lower rate of urgent transplants and to a higher use of ventricular assist devices prior to transplant.

Background Cardiac resynchronization therapy (CRT) with biventricular pacing has demonstrated clinical benefits in heart failure patients with left bundle branch block (LBBB) and ventricular dysfunction. Left bundle branch area pacing (LBBAP) results in a relatively short QRS duration (QRSd) with fast left ventricular activation and could be considered as an alternative to conventional CRT. Purpose The aim of the present study was to evaluate the feasibility and outcomes of LBBAP in patients with indications for CRT. Methods Consecutive patients with indications for CRT were included. LBBAP was performed via transventricular septal approach (1–3). We aimed to achieve a paced QRS with right bundle branch conduction delay morphology, a stimulus to peak left ventricular activation time (S-LVAT) Results LBBAP was achieved in 19 of 21 (90.5%) patients with indication for CRT. Indications were heart failure with LBBB and left ventricular ejection fraction (LVEF) ≤35% in 8 (42%), AV node ablation or AV block with LVEF The mean follow-up was 4.6±1.7 months and the percentage of ventricular pacing was 93.4±13.9%. There were no device-related complications during this period. LBBA capture threshold was 0.6±0.3V at 0.4ms at the implantation, and remained stable (0.7±0.1 V, p=0.17). The lead impedance and R-wave amplitude at implantation were 636±106 ohms and 13.4±6.8 mV, and 541±88 ohms and 13.0±5.1 mV during the follow-up (p Mean S-LVAT was 85.5±13.9 ms, and mean QRSd was 122±9 ms, that remained stable during follow-up (122 vs 124 ms, p=0.21). In patients with LBBB, a significant narrowing of paced QRSd was achieved (160.9±16.7 vs. 123.9±9.7 ms, p Mean LVEF increased by 15.9%, from 35.4±8.9% at baseline to 51.3±9.8% at follow-up (p After one month, estimated time for elective replacement was 11.9±0.4 years. Conclusions LBBPA was successfully achieved in 90.5% of the patients with indication for CRT, with good and stable pacing electrical parameters, long estimated battery longevity and relatively narrow QRS, and was associated with improvement in cardiac function. LBBAP may be considered as a first-line option for patients with indications for CRT. Funding Acknowledgement Type of funding sources: None.

Introduction and objectives The present report describes the clinical characteristics and outcomes of heart transplants in Spain and updates the data to 2019. Methods We describe the clinical characteristics and outcomes of heart transplants performed in Spain in 2019, as well as trends in this procedure from 2010 to 2018. Results In 2019, 300 transplants were performed (8794 since 1984; 2745 between 2010 and 2019). Compared with previous years, the most notable findings were the decreasing rate of urgent transplants (38%), and the consolidation of the type of circulatory support prior to transplant, with an almost complete disappearance of counterpulsation balloon (0.7%), stabilization in the use of extracorporeal membrane oxygenation (9.6%), and an increase in the use of ventricular assist devices (29.0%). Survival from 2016 to 2018 was similar to that from 2013 to 2015 (P=.34). Survival in both these periods was better than that from 2010 to 2012 (P=.002 and P=.01, respectively). Conclusions Heart transplant activity has remained stable during the last few years, as have outcomes (in terms of survival). There has been a trend to a lower rate of urgent transplants and to a higher use of ventricular assist devices prior to transplant.

Acute kidney injury (AKI) is a serious complication in patients hospitalized for decompensated heart failure (HF). Currently, AKI definitions consider creatinine levels at admission as reference of baseline renal function (RF). However, renal impairment may already be present at admission. We aimed to study the impact on AKI detection of considering outpatient RF as reference.In a cohort of 458 patients hospitalized for decompensated HF, we studied the occurrence of AKI using the standardized KDIGO criteria and grading (stages: 1, 2, 3), and considering two different definitions according to the RF used as reference or baseline: the latest outpatient measurement prior to admission vs. the first measurement at admission. We compared the prevalence, timing and prognostic value for both AKI definitions.The definition based on outpatient RF was associated with an increase in overall AKI detection from 20.1% to 33.8% (p 0.001), and from 3.1% to 5.0% for advanced stages (2-3) (p 0.001); additionally, 12.5% of patients already had criteria of AKI at admission (36.8% of AKI cases). Both definitions were associated with longer hospital stay. However, only AKI already present at admission, as based on pre-hospital creatinine, was independently associated with all-cause death, in-hospital and after discharge, and death or HF readmission in the follow-up: 1 stage (HR 2.72, 95%CI 1.83-4.06, p 0.001) and 2-3 stage (HR 7.29, 95%CI, 3.02-17.64, p 0.001).Evaluation of AKI in patients admitted with HF should consider pre-hospital RF, since it improves early identification of AKI and has implications for risk assessment.

BACKGROUND: Soluble ST2 (sST2), which is the soluble form of interleukin (IL)-1 receptor-like 1, identifies risk in acutely decompensated heart failure (ADHF). IL-1β is an inflammatory cytokine that has deleterious effects in myocardial remodeling and function. IL-1β inhibition has beneficial effects after acute myocardial infarction. However, the role of IL-1β in ADHF and its relationship to ST2 remain unclear. OBJECTIVES: This study sought to investigate the relationship between IL-1β and sST2, and the prognostic impact of such a relationship in patients with ADHF. METHODS: This study examined 316 consecutive patients who were hospitalized with ADHF (72 ± 12 years of age, 57% male, and left ventricular ejection fraction 45 ± 17%). Blood samples were collected at presentation, and IL-1β and sST2 levels were measured. All-cause mortality was obtained for all patients at 1 year. RESULTS: The IL-1β concentration at presentation was associated with prior HF hospitalizations, functional impairment, and higher N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T concentrations. IL-1β was higher in patients who died during the year after hospitalization (n = 52, 16.5%) (p = 0.005), and the optimal threshold was identified with levels over 49.1 pg/ml (hazard ratio: 2.5; 95% confidence interval: 1.43 to 4.49; p = 0.0014). Circulating IL-1β positively correlated with sST2 (ρ = 0.65; p < 0.001). Considering the prognostic thresholds of IL-1β (≥49.1 pg/ml) and sST2 (≥35.0 ng/ml) concentrations: all patients with low sST2 also presented with low IL-1β; among patients with high sST2, only those with also high IL-1β had a significantly higher risk of death (30% vs. 14%; hazard ratio: 2.52; 95% confidence interval: 1.40 to 4.56; p = 0.002). CONCLUSIONS: Circulating IL-1β concentrations are clinically meaningful in ADHF patients and interplay with the predictive ability of sST2. IL-1 axis-related inflammation signaling may represent a therapeutic target in ADHF. This work has been supported by grants PI14/01637 and PI17/01742 from "Instituto de Salud Carlos III," Madrid, Spain, and grant PI14/19334 from "Fundacion Seneca de Ciencia y Tecnologia de la Region de Murcia," Murcia, Spain. Dr. Pascual-Figal has received grant support from Roche Diagnostics; and has received educational fees from Novartis. Dr. Bayes-Genis has received speaker fees from Novartis, Roche, and Critical Diagnostics. Dr. Diez has received educational fees from Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Sí

Risk assessment plays a major role in the management of acute coronary syndrome. The aim was to compare the performance of the Global Registry of Acute Coronary Events (GRACE) and the Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the American College of Cardiology/American Heart Asociation guidelines (CRUSADE) risk scores to predict in-hospital mortality and major bleeding (MB) in 1,587 consecutive patients with acute coronary syndrome. In-hospital deaths and bleeding complications were prospectively collected. Bleeding complications were defined according to CRUSADE and Bleeding Academic Research Consortium (BARC) criteria. During the hospitalization, 71 patients (4.5%) died, 37 patients (2.3%) had BARC MB and 34 patients (2.1%) had CRUSADE MB. Receiver operating characteristic curves analyses showed GRACE risk score has better discrimination capacity than CRUSADE risk score for both, mortality (0.86 vs 0.79; p = 0.018) and BARC MB (0.80 vs 0.73; p = 0.028), but similar for CRUSADE MB (0.79 vs 0.79; p = 0.921). Both scores had low discrimination for predicting MB in the elderly (>75 years) and patients with atrial fibrillation, whereas CRUSADE risk score was especially poor for predicting MB in patients with

Renal impairment and fluctuations in renal function are common in patients recently hospitalized for acute heart failure and in those with atrial fibrillation. The aim of the present study was to evaluate the hypothetical need for dosage adjustment (based on fluctuations in kidney function) of dabigatran, rivaroxaban and apixaban during the first 6 months after hospital discharge in patients with concomitant atrial fibrillation and heart failure.An observational study was conducted in 162 patients with nonvalvular atrial fibrillation after hospitalization for acute decompensated heart failure who underwent creatinine determinations during follow-up. The hypothetical recommended dosage of dabigatran, rivaroxaban and apixaban according to renal function was determined at discharge. Variations in serum creatinine and creatinine clearance and consequent changes in the recommended dosage of these drugs were identified during 6 months of follow-up.Among the overall study population, 44% of patients would have needed dabigatran dosage adjustment during follow-up, 35% would have needed rivaroxaban adjustment, and 29% would have needed apixaban dosage adjustment. A higher proportion of patients with creatinine clearance60 mL/min or with advanced age (≥ 75 years) would have needed dosage adjustment during follow-up.The need for dosage adjustment of nonvitamin K oral anticoagulants during follow-up is frequent in patients with atrial fibrillation after acute decompensated heart failure, especially among older patients and those with renal impairment. Further studies are needed to clarify the clinical importance of these needs for drug dosing adjustment and the ideal renal function monitoring regime in heart failure and other subgroups of patients with atrial fibrillation.

Autonomic regulation plays a role in the progression of heart failure with reduced ejection fraction (HrEF).Twenty-one HFrEF patients, 60.8 ± 13.1 years, receiving angiotensin inhibition, were replaced by angiotensin receptor-neprilysin inhibitor (ARNI). A 24-hour Holter recording was performed before and after 3 months of the maximum tolerated dose of ARNi. We evaluated changes in autonomic tone using heart rate variability (SDNN, rMSSD, pNN50, LF, HF, LF/HF, α1, α2), and heart rate turbulence (TO and TS). ARNI was up-titrated to a maximum daily dose of 190 ± 102 mg, 47.5% of the target dose. ARNI therapy was not associated with any improvement in any of the parameters related with heart rate variability or heart rate turbulence (p > 0.05 for all). ARNI use at lower than target doses did not improve autonomic cardiac tone as evaluated by 24-hour Holter monitoring.

Background In patients with acute decompensated heart failure (ADHF), both natriuretic peptides and renal impairment predict adverse outcomes. Our aim was to evaluate the complementary prognosis role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the newly developed Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on cystatin C (CysC) for glomerular filtration rate (GFR) estimation in ADHF patients. Hypothesis Renal impairment assessed by CysC-based CKD-EPI equations and natriuretic peptides have complementary prognostic value in ADHF patients. Methods The study included 613 consecutive patients presenting with ADHF. At admission, plasma levels of NT-proBNP and CysC were determined. The GFR was estimated using CysC-based CKD-EPI equations. The primary endpoint was death from any cause and heart failure readmission. Results During the median follow-up of 365 days (interquartile range, 227–441 days), 323 patients (0.65 %patient-year) died or were readmitted for heart failure. After multivariate adjustment, estimated GFR 3251 pg/mL were independent predictors of adverse outcomes (P 3251 pg/mL was associated with the highest risk of adverse outcomes. Furthermore, reclassification analyses demonstrated that use of both NT-proBNP and CysC-based CKD-EPI equations resulted in improving the accuracy for adverse outcomes prediction. Conclusions In patients with ADHF, the combination of NT-proBNP with estimated GFR using CysC-based CKD-EPI equations better predicts outcomes than either parameter alone and adds valuable complementary prognosis information to other established risk factors.

Objectives This study aimed to evaluate the specific role of the 2 available mineralocorticoid receptor antagonists (MRAs), eplerenone and spironolactone, on the modulation of galectin-3 (Gal-3) and interleukin (IL)-33/ST2 signaling in an experimental model of left ventricular systolic dysfunction after acute myocardial infarction (MI). Background The molecular mechanisms of benefits of MRAs in patients with left ventricular systolic dysfunction after MI not well understood. Methods MI and left ventricular systolic dysfunction were induced by permanent ligation of the anterior coronary artery in 45 male Wistar rats, randomly assigned to no therapy (MI group, n = 15) or to receive MRAs (100 mg/kg/day) for 4 weeks; either eplerenone (n = 15) or spironolactone (n = 15) was used. A sham group was used as a control (n = 8). Elements of the pathway for Gal-3 including transforming growth factor (TGF)-β and SMAD3, as well as that for IL-33/ST2 (including IL-33 and soluble ST2 [sST2]) were analyzed in the infarcted and noninfarcted myocardium by quantitative real-time reverse transcription polymerase chain reaction. Expression of markers of fibrosis (collagen types I and III, tissue inhibitor of metalloproteinase-1) and inflammation (IL-6, tumor necrosis factor-α, monocyte chemotactic protein-1) was also examined. Results In the infarcted myocardium, compared with sham animals, the MI group had higher concentrations of Gal-3, TGF-β, SMAD3, IL-33, and sST2, as well as higher concentrations of markers of fibrosis and inflammation. Treatment with MRAs down-regulated Gal-3, TGF-β, and SMAD3 and enhanced IL-33/ST2 signaling with lower expression of sST2; protective IL-33 up-regulation was unaffected by MRAs. Modulation of Gal-3 and IL-33/ST2 signaling induced by MRAs correlated with lower expression levels of fibrosis and inflammatory markers. No differences were found between eplerenone and spironolactone. In the noninfarcted myocardium, compared with sham animals, the MI group exhibited a higher expression of Gal-3 and IL-33, but no signs of inflammation or fibrosis were observed; in the presence of MRAs, IL-33 expression was significantly up-regulated, but Gal-3 was unaffected. Conclusions MRAs play a pivotal role in the Gal-3 and IL-33/ST2 modulation in post-MI cardiac remodeling.

Introduccion y objetivos El ancho de distribucion eritrocitaria ha surgido como un marcador biologico con valor pronostico en enfermedades cardiovasculares. Su valor adicional en la estratificacion de riesgo de pacientes con insuficiencia cardiaca cronica no se encuentra establecido. Metodos Se estudio consecutivamente a 698 pacientes ambulatorios con insuficiencia cardiaca cronica (edad, 71 anos [intervalo intercuartilico, 62-77]; el 63% varones; fraccion de eyeccion del ventriculo izquierdo, 40±14%). A su inclusion, se midio el ancho de distribucion eritrocitaria y se registraron variables clinicas, bioquimicas y ecocardiograficas. La mediana de seguimiento fue 2,5 anos [1,2-3,7]. Resultados En total, fallecieron 211 pacientes y 206 precisaron hospitalizacion por insuficiencia cardiaca descompensada. El analisis de Kaplan-Meier mostro un incremento tanto de la probabilidad de muerte como de ingreso por insuficiencia cardiaca a traves de cuartiles de ancho de distribucion eritrocitaria (log rank, p

Introduction and objectives Red blood cell distribution width has emerged as a new prognostic biomarker in cardiovascular diseases. Its additional value in risk stratification of patients with chronic heart failure has not yet been established. Methods A total of 698 consecutive outpatients with chronic heart failure were studied (median age 71 years [interquartile range, 62-77], 63% male, left ventricular ejection fraction 40 [14]%). On inclusion, the red cell distribution width was measured and clinical, biochemical, and echocardiographic variables were recorded. The median follow-up period was 2.5 years [interquartile range, 1.2-3.7]. Results A total of 211 patients died and 206 required hospitalization for decompensated heart failure. Kaplan-Meier analysis showed an increase in the probability of death and hospitalization for heart failure with red cell distribution width quartiles (log rank, P P P P P =.001). Conclusions Red cell distribution width is an independent risk marker and adds prognostic information in outpatients with chronic heart failure. These findings suggest that this biological measurement should be included in the management of these patients.

Objectives: To determine whether serial measures of the interleukin receptor family member soluble ST2 (sST2) provide additional prognostic information to baseline measures for long-term risk stratification of acutely decompensated heart failure (ADHF) patients. Methods: We prospectively enrolled 72 ADHF patients. Blood samples were collected to measure sST2 concentrations at presentation and on day 4 of hospitalization. All patients were clinically followed, and vital status was registered. Results: Between presentation and day 4, sST2 concentrations decreased from 62 ng/ml (interquartile range 38–105) to 44 ng/ml (interquartile range 26–72; p < 0.001). Both sST2 concentrations at presentation [hazard ratio (HR) 1.011, 95% confidence interval (CI) 1.005–1.016; p < 0.001] and on day 4 (HR 1.015, 95% CI 1.005–1.024; p = 0.003) were independent predictors of mortality. Patients with sST2 ≤76 ng/ml at presentation and ≤46 ng/ml on day 4 had the lowest mortality rates (3%), whereas those with both sST2 values above these cutoff points had the highest mortality (50%). C index and reclassification analyses demonstrated that the use of serial sST2 measures resulted in an improvement in the accuracy of mortality prediction. Conclusions: Among ADHF patients, sST2 concentrations tend to decrease following initiation of treatment and are prognostic both at presentation and during hospitalization. Serial sampling of sST2 adds prognostic information and may provide a basis for enhanced clinical decision making.

BACKGROUND Abnormalities in autonomic control are a feature of neuroendocrine activation in HF and are responsible for dysregulation of biological rhythms. The purpose was to investigate the presence and the prognostic significance of long-period heart rate (HR) rhythms in heart failure (HF) patients. METHODS AND RESULTS In the study, 92 HF patients were enrolled (age 53 ± 14 years and left ventricular ejection fraction [LVEF] 37 ± 10%). A rhythmometric analysis was used to assess the HR rhythms in 7-days (7D) Holter recordings. Rhythms properties were quantified by mesor and amplitude, in beats/min and by acrophase, in hours. Cardiac death or HF decompensation were registered. All patients had 24-h rhythm, 61 patients (77%) had 8-h rhythm, and 66 patients (83%) had 7D rhythm. Twelve patients (15%) experienced events. Among rhythm parameters only 7D median amplitude was different between patients with or without events: 1.1 beats/min [0.5-1.5] vs. 2.0 beats/min [0.0-3.9], P=0.049 respectively. After multivariate adjustment, LVEF (per 1%, hazard ratio 0.92, 95% confidence interval (CI) 0.87 to 0.98, P=0.01), N-terminal portion of pro-natriuretic hormone type B (per 100 pg/ml, hazard ratio 1.036, 95% CI 1.005-1.069, P=0.022), and 7D amplitude of the HR ≤1.71 beats/min (hazard ratio 5.4, 95% CI 1.2-34.4, P=0.047) were independent predictors of events. CONCLUSIONS A 7D HR rhythm is present in most patients with HF, and has prognostic significance.

Introduccion y objetivos La deteccion del rechazo agudo en pacientes trasplantados cardiacos mediante metodos no invasivos representa un reto. La disponibilidad de un nuevo metodo de alta sensibilidad para la determinacion de troponina T podria ayudar a su deteccion. Metodos Estudio case-crossover, en el que cada paciente sirvio como control de si mismo, mediante la seleccion de muestras obtenidas en episodios de rechazo agudo tratados (29 casos) y muestras sin rechazo obtenidas inmediatamente antes y/o despues (38 controles). La determinacion de alta sensibilidad de troponina T se realizo mediante un nuevo test precomercial (Elecsys Troponina T HS). Resultados La troponina T fue detectable en todas las muestras: mediana, 0,068 [intervalo intercuartilico, 0,030-0,300] ng/l. Sus concentraciones se correlacionaron con la presion auricular derecha (r=0,37; p=0,002), la fraccion aminoterminal del propeptido natriuretico cerebral (r=0,67; p

Introduction and objectives Urinary concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP) may be prognostically meaningful; however, direct comparison to plasma concentrations of this marker have not been performed in patients with acutely decompensated heart failure (ADHF). The aims of this study were to compare the prognostic value of plasma versus urinary NT-proBNP concentration for the risk stratification of patients with ADHF. Methods Consecutive hospitalized patients with ADHF were prospectively studied. Blood and urine samples were simultaneously collected on hospital arrival to determine NT-proBNP concentrations. Clinical follow-up was obtained, and the occurrence of mortality and heart failure hospitalization was registered. Results The study included 138 patients (median, 74 years [interquartile range, 67-80]; 54% men). During a median follow-up period of 387 days [interquartile range, 161-559], 65 patients (47%) suffered adverse clinical events. Plasma NT-proBNP concentration was higher among patients who presented adverse events (4561 pg/mL [2191-8631] vs 2906 pg/mL [1643-5823]; P = .03), whereas urinary NT-proBNP was similar in both groups (P = .62). After multivariable Cox regression analyses, plasma NT-proBNP concentration was associated with a higher risk of adverse events, whether considered continuously (per 100 pg/mL; hazard ratio [HR] = 1.004; 95% confidence interval [CI], 1.001-1.007; P = .003) or categorically (≥3345 pg/mL; HR = 2.35; 95% CI, 1.41-3.93; P = .001). In contrast, urinary NT-proBNP concentration was not associated with adverse outcomes . Conclusions Plasma NT-proBNP concentration is superior to urinary NT-proBNP concentration for the prediction of adverse clinical outcomes among unselected patients with ADHF.

Resumen Introduccion y objetivos Se ha sugerido que las concentraciones urinarias de la porcion aminoterminal del pro-peptido natriuretico tipo B (NT-proBNP) pueden tener valor pronostico en pacientes con insuficiencia cardiaca estable, pero hasta ahora no se ha realizado una comparacion directa con las concentraciones plasmaticas de este marcador en pacientes con una insuficiencia cardiaca aguda descompensada (ICAD). El objetivo de este estudio fue comparar el valor pronostico de la concentracion plasmatica de NT-proBNP con el de la concentracion urinaria de este marcador en la estratificacion del riesgo de los pacientes con ICAD. Metodos Se estudio prospectivamente a pacientes consecutivos hospitalizados con ICAD. A la llegada al hospital, se obtuvieron simultaneamente muestras de sangre y orina, para determinar las concentraciones de NT-proBNP. Se realizo un seguimiento clinico, y se registraron la mortalidad y la hospitalizacion por insuficiencia cardiaca. Resultados Se incluyo un total de 138 pacientes (mediana de edad, 74 anos [rango intercuartiles, 67-80]; 54 varones). Durante una mediana de seguimiento de 387 dias [rango intercuartiles, 161-559], 65 pacientes (47%) presentaron eventos clinicos adversos. La concentracion plasmatica de NT-proBNP fue mas alta en los pacientes que presentaron eventos clinicos adversos (4.561 pg/ml [2.191-8.631] frente a 2.906 pg/ml [1.643-5.823]; p = 0,03), mientras que la concentracion urinaria de NT-proBNP fue similar en ambos grupos (p = 0,62). En los analisis de regresion de Cox multivariable, la concentracion plasmatica de NT-proBNP se asocio a un mayor riesgo de eventos clinicos adversos, tanto como variable continua (por 100 pg/ml; razon de riesgos [HR] = 1,004; intervalo de confianza [IC] del 95%, 1,001-1,007; p = 0,003) o categorica (≥3.345 pg/ml; HR; IC del 95%, 1,41-3,93; p = 0,001). En cambio, la concentracion urinaria de NT-proBNP no se asocio a una evolucion clinica adversa. Conclusiones La concentracion plasmatica de NT-proBNP es superior a la concentracion urinaria de este marcador en la prediccion de los resultados clinicos adversos en pacientes con ICAD.

Heart rate variability (HRV) markers have been widely used to characterize the autonomous regulation state of the heart from 24-h Holter monitoring, but long-term evolution of HRV indexes is mostly unknown. A dataset of 7-day Holter recordings of 22 patients with congestive heart failure was studied. A rhythmometric procedure was designed to characterize the infradian, circadian, and ultradian components for each patient, as well as circadian and ultradian fluctuations. Furthermore, a bootstrap test yielded automatically the rhythmometric model for each patient. We analyzed the temporal evolution of relevant time-domain (AVNN, SDNN, and NN50), frequency-domain (LF, HF, HFn, and LF/HF), and nonlinear (alpha(1) and SampEn) HRV indexes. Circadian components were the most significant for all HRV indexes, but the infradian ones were also strongly present in NN50, HFn, LF/HF, alpha(1), and SampEn indexes. Among ultradian components that one corresponding to 12 h, was the most relevant. Long-term monitoring of HRV conveys new potentially relevant rhythmometric information, which can be analyzed by using the proposed automatic procedure.

The aims of this study were to compare the prognostic value of cystatin C over creatinine and the Modification of Diet in Renal Disease (MDRD) equation and to evaluate whether it provides complementary information to cardiac biomarkers in the risk stratification of an unselected cohort of patients with acute heart failure. Consecutive hospitalized patients with established diagnoses of acute heart failure were prospectively studied. Blood samples were collected on hospital arrival to determine cystatin C, cardiac troponin T, and N-terminal-pro-brain natriuretic peptide. Clinical follow-up was obtained, and the occurrence of mortality and/or heart failure readmission was registered. One hundred thirty-eight patients (median age 74 years, interquartile range 67 to 80; 54% men) were studied. During a median follow-up period of 261 days (interquartile range 161 to 449), 60 patients (43.5%) presented with adverse events. After multivariate adjustment, cystatin C, N-terminal-pro-brain natriuretic peptide, cardiac troponin T, New York Heart Association functional class III or IV, and diabetes mellitus were identified as independent predictors of mortality and/or heart failure readmission. In contrast to creatinine and the MDRD equation, the highest cystatin C tertile (>1.50 mg/L) was a significant independent risk factor for adverse events (hazard ratio 3.08, 95% confidence interval 1.54 to 6.14, p = 0.004). A multimarker approach combining cardiac troponin T, N-terminal-pro-brain natriuretic peptide, and cystatin C improved risk stratification further, showing that patients with 2 (hazard ratio 2.37, 95% confidence interval 1.10 to 5.71) or 3 (hazard ratio 3.64, 95% confidence interval 1.55 to 8.56) elevated biomarkers had a higher risk for adverse events than patients with no elevated biomarkers (p for trend = 0.015). In conclusion, in this unselected cohort, cystatin C was a stronger predictor of adverse events than conventional measures of kidney function. In addition, cystatin C offered complementary prognostic information to cardiac biomarkers and could help clinicians perform more accurate risk stratification of patients with acute heart failure.

Background Patients with indications for oral anticoagulation (OAC) undergoing percutaneous coronary artery stenting (PCI-S) represent a high-risk population for major bleeding complications. Chronic kidney disease (CKD) is also associated with poor outcome after PCI-S. Limited data are available regarding the impact of CKD on the frequency of major bleeding and mortality in this population. Methods We investigated the influence of CKD on major bleeding and all-cause mortality in patients with indication for OAC who undergo PCI-S. Patients were grouped according to calculated creatinine clearance (CrCl): CrCl > 60 mL/min, (n = 98) and CrCl ≤ 60 mL/min, (n = 68). Major bleeding and major adverse vascular events (all-cause mortality, myocardial infarction, repeat revascularization, stent thrombosis, or stroke) were collected during follow-up. Results We analyzed 166 consecutive patients with indication(s) for OAC (77% men; mean age, 71 years; range, 66 to 76 years) after undergoing PCI-S. CKD was associated with higher risk for major bleeding (hazard ratio [HR], 3.44; 95% confidence interval [CI], 1.50 to 7.93; p = 0.004) and all-cause mortality (HR, 3.50; 95% CI, 1.53 to 7.99; p = 0.003). In multivariate analyses, age > 75 years (HR, 2.75; 95% CI, 1.15 to 6.56; p = 0.023), CKD (HR, 2.59; 95% CI, 1.00 to 6.95; p = 0.049), anemia (HR, 2.36; 95% CI, 1.00 to 5.54; p = 0.049), and triple antithrombotic therapy (HR, 3.29; 95% CI, 1.23 to 8.84; p = 0.018) were independent predictors for major bleeding, whereas age > 75 years (HR, 2.38; 95% CI, 1.03 to 5.59; p = 0.046) and CKD (HR, 2.44; 95% CI, 1.03 to 5.82; p = 0.044) were predictors for all-cause mortality. Conclusion In this high-risk population, CKD is independently associated with increased major bleeding and all-cause mortality following PCI-S.

Introduction and objectives. Anemia is a common finding in outpatients with heart failure (HF) and is associated with increased mortality. The aims of this study were to identify determinants of the hemoglobin level in a large group of hospitalized patients with systolic HF and to investigate the medium-term prognostic value of the hemoglobin level. Methods. The study included 460 consecutive patients (age 68.3 [12.3] years, 74% male) who were hospitalized with a diagnosis of HF and left ventricular systolic dysfunction (i.e., a left ventricular ejection fraction

☆ Funding: This work was supported by Research Proj and by Research Grants TEC2010-19263 and URJC-CM Government. ⁎ Corresponding author at: Department of Cardiology, Arrixaca, Ctra. Madrid-Cartagena s/n, 30120 Murcia, S fax: +34 968 369662. E-mail address: franpastor79@hotmail.com (F.J. Pastor 1 This author takes responsibility for all aspects of the r of the data presented and their discussed interpretation.

Background Patients with autoimmune diseases (AID) have a high burden of cardiovascular disease leading to premature morbidity and mortality 1 . But it is unclear if it is due to a higher prevalence of cardiovascular disease, to a worse case fatality or to a different management after an index event. Objectives The aim of the study is to assess the prevalence of AID in patients with acute coronary syndrome (ACS), the management and prognostic implications. Methods The study included consecutive patients admitted after ACS from January 2011 to May 2014. For AID patients, in-hospital management and ACS presentation was compared to non-AID patients. We also compared in-hospital and 1-year major adverse events (MACE): death, recurrent myocardial infarction, stroke and major bleeding, between groups. The percentage lost to follow-up was Results Of 964 patients, 53 had AID (5.5%): 11 rheumatoid arthritis, 9 inflammatory bowel disease, 7 ankylosing spondylitis, 7 psoriatic arthritis, 5 polymyalgia rheumatica, 4 systemic lupuserythematosus and 10 miscellanea. Mean evolution of the disease was 14±3 years. No significant differences were found in clinical and demographics characteristics between groups except for a higher percentage of previous stable coronary heart disease in non-AID patients. Compared to non-AID patients, AID patients had similar clinical ACS presentation and no differences were found with respect to revascularization strategies or medical treatment at discharge. Overall there were 207 MACE (69% during hospitalization): 108 deaths, 52 recurrent myocardial infarctions, 19 ischemic strokes and 28 major bleedings. The two groups had comparable rates of MACE both during hospitalization (9.6% vs 12.2%, p=0.58) and at 1 year (26.4% vs 19.1%, p=0.19), AID vs non-AID respectively. The presence of AID was not associated with increased in-hospital mortality (OR 1.1, 95% CI 0.4 to 3.3) but it was a risk factor for higher 1-year crude mortality (OR 2.2, 95% CI 1.1 to 4.4), with a trend to higher 1-year mortality after multivariable adjusting (OR 1.7, 95%CI 0.8 to 3.9). Conclusions The presence of AID did not change ACS presentation and clinical management. Moreover it is not independently associated with worse outcomes during hospitalization although there is a trend to higher 1-year mortality. References Symmons DP, Gabriel SE. Epidemiology of CVD in rheumatic disease, with a focus on RA and SLE. Nat Rev Rheumatol. 2011 May 31;7(7):399–408 Disclosure of Interest None declared

Cardiac allograft vasculopathy (CAV) is a major impediment to long-term graft survival after heart transplantation. Intravascular ultrasound (IVUS) is more sensitive than coronary angiography for diagnosis, but the identification of specific plaque components or plaque composition is limited. In addition, there is an evident need for other noninvasive tools for diagnosing CAV. The aim of this study was to assess the utility of 2 new techniques for evaluating CAV: optical coherence tomography (OCT), and new high-sensitivity troponin T (hsTnT) assays. In 21 heart transplantation patients, coronary arteriography with IVUS and OCT were performed. Maximal intimal thickness (MIT) and luminal area at the most severe site were measured using the 2 techniques. Immediately before cardiac catheterization, blood samples were obtained and hsTnT levels measured. The evaluation of CAV by OCT showed a good correlation with IVUS measurements, with a mean difference in MIT of 0.0033 (95% confidence interval -0.049 to 0.043), taking advantage of lower interobserver variability (r = 0.94 for OCT vs r = 0.78 for IVUS) and better plaque characterization. When independent predictors of MIT were assessed in a multiple linear regression model, time after transplantation (β = 0.488, p = 0.004) and hsTnT (β = 0.392, p = 0.011) were the only independent predictors of MIT (R(2) = 0.591). In conclusion, this study is the first to evaluate 2 new techniques, OCT and hsTnT, in the challenging setting of CAV. The findings suggest that OCT provides lower interobserver variability and better plaque characterization than IVUS. Also, hsTnT could become a useful tool for ruling out CAV.

Aim To investigate the use of biomarkers providing independent information regarding physiology in acutely decompensated heart failure (ADHF) for assessment of risk. Methods and results This was a prospective study of 107 patients hospitalized with ADHF (mean age 72 ± 13 years, 44% male, left ventricular ejection fraction 47 ± 15%). Blood samples were collected on presentation to measure soluble (s)ST2, high-sensitivity troponin T (hsTnT), and amino-terminal pro-B type natriuretic peptide (NT-proBNP) levels. Clinical follow-up was obtained for all patients over a median period of 739 days, and all-cause mortality was registered. Concentrations of sST2 [per 10 ng/mL, hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.04–1.13; P< 0.001], hsTnT (per 0.1 ng/mL, HR 1.16, 95% CI 1.09–1.24; P< 0.001), and NT-proBNP (per 100 pg/mL, HR 1.01, 95% CI 1.003–1.01; P< 0.001) were each predictive of a higher risk of death. In bootstrapped models, each biomarker retained independent predictive value for mortality. Patients with all three biomarkers below their optimal cut-off at presentation were free of death (0%) during follow-up, whereas 53% of those with elevations of all three biomarkers had died. For each elevated marker (from 0 to 3) adjusted analysis suggested a tripling of the risk of death (for each elevated marker, HR 2.64, 95% CI 1.63–4.28, P< 0.001). Integrated discrimination analyses indicated that the use of these three markers in a multimarker approach uniquely improved prediction of death. Conclusions Biomarkers reflecting remodelling (sST2), myonecrosis (hsTnT), and myocardial stretch (NT-proBNP) provide complementary prognostic information in patients with ADHF. When used together, these novel markers provide superior risk stratification.

A B S T R A C T Introduction and objectives: Detection of acute allograft rejection in heart transplant recipients by noninvasive methods is a challenge in the management of these patients. In this study, the usefulness of a new highly sensitive method for the measurement of troponin T is evaluated. Methods: We designed a case-crossover study, in which each patient served as his or her own control, by selecting samples from treated acute rejection episodes (29 cases) and samples obtained immediately before and/or after rejection (38 controls). The highly sensitive troponin T was measured by a new pre- commercial test (Elecsys Troponin T HS). Results: In all samples, highly sensitive troponin was detectable, with a median of 0.068 ng/mL (IQR, 0.030-0.300 ng/mL). The levels correlated with right atrial pressure (r = 0.37; P = .002), N-terminal pro- brain natriuretic peptide concentration (r = 0.67; P < .001), and time since transplantation (r = -0.81; P < .001). The highly sensitive troponin concentrations were higher in patients with rejection (0.155 ng/mL vs 0.047 ng/mL; P = .006). In the receiver operating characteristic analysis, the area under the curve was 0.67 (95% confidence interval, 0.53-0.77) and the best cutoff was 0.035 ng/mL, which was associated with rejection (odds ratio = 3.7; 95% confidence interval, 1.2-11.9; P = .02). By restricting the analysis to the first 2 months, the area under the curve increased to 0.86 (95% confidence interval 0.66-0.97), with an optimal cutoff of 1.10 ng/mL (S = 58% (28%-85%); E = 100% (74%-100%)). Conclusions: Troponin T was detectable in all samples when a new highly sensitive assay was used, and at higher concentrations in the presence of acute rejection; however, the usefulness of this test in patient management is limited to support for clinical or histological suspicion of rejection, especially in the early post-transplant period.

The purpose of this study was to establish the role of hormonal anabolic deficiencies in exercise intolerance in patients with chronic heart failure One hundred four consecutive men (mean age 53.1 ± 10.6 years) with established diagnoses of chronic heart failure were included. At enrollment, blood samples were taken, and echocardiography and cardiopulmonary exercise testing were carried out. Exercise capacity was expressed as peak oxygen consumption (Vo₂), predicted peak Vo₂, and the ventilatory response to exercise (VE/Vco₂) slope. The mean left ventricular ejection fraction was 29.7 ± 11.9%, and most patients (86%) were in New York Heart Association class I or II, with a mean peak Vo₂ of 18 ml/min/kg. According to the age-adjusted reference values, hormonal deficiencies were present in 29% for total testosterone, 39% for estimated free testosterone, 34% for insulin-like growth factor-1, and 61% for dehydroepiandrosterone sulfate. Dehydroepiandrosterone sulfate showed a significant correlation with peak Vo₂ (r = 0.29, p = 0.007), predicted peak Vo₂ (r = 0.28, p = 0.006), and VE/Vco₂ slope (r = -0.39, p0.001), whereas total testosterone, estimated free testosterone, and insulin-like growth factor-1 were not significantly correlated. After adjusting in a multivariable model, dehydroepiandrosterone sulfate remained an independent predictor of each exercise parameter. In conclusion, in a cohort of patients with mild chronic heart failure, exercise capacity objectively measured using cardiopulmonary exercise testing was related to anabolic impairment of the adrenal rather than the somatotropic or peripheral axis.

Hematologic abnormalities such as elevated red blood cell distribution width (RDW) as well as anemia are prognostically meaningful among heart failure (HF) patients. The inter-relationship between these hematologic abnormalities in HF is unclear, however. We therefore aimed to assess whether RDW is predicting changes in hemoglobin concentrations as well as onset of anemia.268 consecutive non-anemic patients with acutely decompensated HF (ADHF) were enrolled at hospital discharge and RDW was measured. At 6 month follow-up, change in hemoglobin as well as new-onset anemia was studied as a function of RDW at discharge.RDW at discharge correlated negatively with hemoglobin values at 6 months (r=-0.220; p0.001); a greater decrease in hemoglobin concentration occurred in those with higher values of RDW at discharge (p=0.004), independently of baseline hemoglobin concentration and other risk factors. At 6 months, 54 patients (20%) developed new-onset anemia. RDW values at discharge were significantly higher among patients who developed new-onset anemia (15.1 ± 2.2 vs. 14.2 ± 1.4, p=0.005). In integrated discrimination improvement analyses, the addition of RDW measurement improved the ability to predict new-onset anemia (IDI 0.0531, p0.001), beyond known risk factors as hemoglobin, renal function, age, diabetes mellitus, sex and HF symptom severity. In adjusted analyses, patients with RDW15% (derived from receiver operating characteristic analysis) had a tripling of the risk of new-onset anemia (OR=3.1, 95% CI 1.5-5.1, p=0.002).Among non-anemic patients with ADHF, RDW measurement at the time of hospital discharge independently predicts lower hemoglobin concentrations and new-onset anemia over a 6-month follow up period.

Heart rate turbulence (HRT) is associated with risk in chronic heart failure (CHF). The objective of this study was to assess the short-term variability of HRT and to compare the diagnostic yield of 7-day (7DH) versus 24-hour (1DH) Holter monitoring for calculating HRT in a CHF population.Forty-nine consecutive patients with CHF were studied. At inclusion, 7DH was performed to evaluate the variability of HRT parameters. For categorized analyses, turbulence onset (TO) ≥0% and turbulence slope (TS) ≤2.5 ms/RR were defined as abnormal, and patients were classified into subgroups based on the number of abnormal HRT parameters.The cumulative percentage of patients with calculable HRT increased from 69.4% with 1DH to 93.9% with 7DH. The intraclass correlation coefficients across the 7-day monitoring were 0.81 (95% confidence interval [CI] 0.70-0.89) for TO and 0.90 (95% CI 0.84-0.95) for TS. When comparing 2 randomly selected days, TO and TS values were similar (P.1) and showed a strong correlation (TO: r = 0.79; TS: r = 0.84: P.001). Bland-Altman plots showed a mean difference of 0.31% (95% CI -0.07 to 0.70) for TO and 0.44 ms/RR (95% CI -1.37 to 0.48) for TS. In contrast, categorized analyses showed that up to 16% of patients changed their HRT subgroup score from day 1 to day 2 of comparison.In this population, 7DH significantly increased the percentage of patients with calculable HRT parameters. The short-term variability of the quantitative HRT values was good, but when patients were categorized into the established HRT subgroups, the concordance was suboptimal.

Acute heart failure (AHF) represents a major burden in developed countries. However, pharmacological approaches have remained almost the same for 30 years and are still based on consensus rather than evidence, given that no medical therapy has been shown to positively affect clinical outcomes. Current pharmacological approaches are still based on decongestion by using diuretics in almost all patients, plus either vasodilators or inotropic agents to improve hemodynamics according to perfusion status. The role of loop diuretics (furosemide) and nitrates (nitroglycerin and nitroprusside) is well established, but new agents such as vasopressin and adenosine antagonists, as well as nesiritide, have failed to show any additional value. In the presence of hypoperfusion, the use of inotropics must be considered despite the lack of benefit in terms of survival, and the use of phosphodiesterase inhibitors and levosimendan has not shown any significant advantages over catecholamines (dobutamine). AHF involves a wide spectrum of patients and syndromes, and this probably accounts for the failure of trials set up to evaluate new therapeutic approaches for improving outcomes: therapies need to be tailored to specific patients. At this time, serelaxin represents a promising new agent which has a multifaceted effect, including organ protection, and has shown encouraging results when tailored for a well defined population. In addition, the role of ularitide, a synthetic form of the natriuretic peptide urodilatin, and the new cardiac myosin activators, as a new class of inotropic agents, will be established in the near future by ongoing trials. Therefore, AHF continues to be an unsolved problem and, in light of the lessons learned, new pharmacological approaches should be tai- lored to well defined AHF populations, incorporating concepts such as "the sooner the better", "improve and stabilize", and "prevent organ damage", in order to be able to improve clinical outcomes, including both mortality and readmission rates.

We have read with interest the recent article,1 in which the authors aimed to compare four test to assess inhibition of platelet function by clopidogrel in stable coronary disease patients. They demonstrate that the results of each test are not equivalent, being highly test-specific. The identification of patients with insufficient platelet inhibition varied greatly and correlations between the tests were poor. The idea of tailoring antiplatelet therapy is a promising tool to improve the outcomes of patients but we must not forget that …

We thank Dr Pastor-Perez et al. for raising an important discussion point related to our article.1 We agree with their proposal regarding treatment strategy after percutaneous coronary intervention (PCI). As the addition of anticoagulant treatment to dual antiplatelet therapy has the potential to increase bleeding complications,2,3 routine supplementation of anticoagulant therapy after PCI should be avoided. The lack of patient safety data means that the risks of bleeding are likely to weigh more heavily in decision-making than any benefits. However, some particular clinical situations involving a hypercoagulability state (e.g. impaired cardiac function and/or atrial fibrillation) might be …