Withdrawal of drug therapy in responders to cardiac resynchronization therapy: rationale and design of the REMOVE trial.

Introduction and objectives Cardiac resynchronization therapy (CRT) is an effective treatment for patients with nonischemic dilated cardiomyopathy associated with left bundle branch block (LBBB). In these patients, the device can normalize left ventricular ejection fraction (LVEF). Nevertheless, it remains unclear whether CRT responders still require neurohormonal blockers. The aim of this study is to determine the long-term safety of withdrawing drug therapy in these patients. Methods The REMOVE trial (NCT05151861) is a prospective, multicenter, open-label and randomized 1:1 study designed to assess the effect of withdrawing neurohormonal blockers in patients with nonischemic dilated cardiomyopathy associated with left bundle branch block who recovered LVEF after CRT. The study will include a 12-month follow-up with the option to continue into the follow-up extension phase for up to 24 months. The primary endpoint is the recurrence of cardiomyopathy defined as any of the following criteria: a) a reduction in LVEF > 10% (provided the LVEF is < 50%); b) a reduction in LVEF > 10% accompanied by an increase > 15% in the indexed end-systolic volume relative to the previous value and in a range higher than the normal values, or c) decompensated heart failure requiring intravenous diuretic administration. In patients meeting the primary endpoint, drug therapy will be restarted. Conclusions The results of this study will help to enhance our understanding of CRT superresponders, a specific group of patients.

Levosimendán ambulatorio repetitivo como puente al trasplante cardiaco / Repetitive ambulatory levosimendan as a bridge to heart transplantation

Introducción y objetivos:El levosimendán ambulatorio repetitivo es una opción como puente al trasplante cardiaco (TxC), aunque la evidencia sobre su eficacia y su seguridad es escasa. El objetivo del registro LEVO-T es describir a los pacientes en lista de TxC que reciben levosimendán, sus pautas y los eventos clínicos durante el seguimiento, en comparación con los que no lo reciben. Métodos: Se revisó en retrospectiva a los pacientes en lista de espera para TxC electivo de 14 centros españoles desde 2015 hasta 2020. Resultados: Se incluyó a 1.015 pacientes consecutivos; los 238 (23,4%) que recibieron levosimendán mostraron más ingresos por insuficiencia cardiaca (IC) el año anterior y peor perfil clínico. Las dosis fijas por necesidades clínicas fueron la pauta más frecuente. Dos pacientes (0,8%) presentaron arritmias ventriculares no mortales. No hubo diferencias en hospitalizaciones por IC entre los que comenzaron levosimendán en los primeros 30 días después de inclusión y los que no (el 33,6 frente al 34,5%; p=0,848). De estos últimos, 102 (32,9%) pasaron a levosimendán después de un ingreso por IC, y la tasa de ingresos por IC/mes varió de 0,57 antes del levosimendán a 0,21 después. El análisis mediante emparejamiento por puntuación de propensión no mostró diferencias entre los pacientes con y sin levosimendán en la supervivencia a 1 año tras la inclusión en lista (HR=1,03; IC95%, 0,36-2,97; p=0,958) ni en la supervivencia tras el TxC (HR=0,97; IC95%, 0,60-1,56; p=0,958). Conclusiones: El levosimendán ambulatorio repetitivo como puente al trasplante cardiaco es un tratamiento frecuente y seguro que podría reducir ingresos por IC. (AU)

Introduction and objectives: Repetitive ambulatory doses of levosimendan are an option as a bridge to heart transplantation (HT), but evidence regarding the safety and efficacy of this treatment is scarce. The objective of the LEVO-T Registry is to describe the profile of patients on the HT list receiving levosimendan, prescription patterns, and clinical outcomes compared with patients not on levosimendan. Methods: We retrospectively reviewed all patients listed for elective HT from 2015 to 2020 from 14 centers in Spain. Results: A total of 1015 consecutive patients were included, of whom 238 patients (23.4%) received levosimendan. Patients treated with levosimendan had more heart failure (HF) admissions in the previous year and a worse clinical profile. The most frequent prescription pattern were fixed doses triggered by the patients’ clinical needs. Nonfatal ventricular arrhythmias occurred in 2 patients (0.8%). No differences in HF hospitalizations were found between patients who started levosimendan in the first 30 days after listing and those who did not (33.6% vs 34.5%; P=.848). Among those who did not, 102 patients (32.9%) crossed over to levosimendan after an HF admission. These patients had a rate of 0.57 HF admissions per month before starting levosimendan and 0.21 afterwards. Propensity score matching analysis showed no differences in survival at 1 year after listing between patients receiving levosimendan and those who did not (HR, 1.03; 95%CI, 0.36-2.97; P=.958) or in survival after HT (HR, 0.97; 95%CI, 0.60-1.56; P=.958). Conclusions: Repetitive levosimendan in an ambulatory setting as a bridge to heart transplantation is commonly used, is safe, and may reduce HF hospitalizations. (AU)

Repetitive ambulatory levosimendan as a bridge to heart transplantation.

INTRODUCTION AND OBJECTIVES: Repetitive ambulatory doses of levosimendan are an option as a bridge to heart transplantation (HT), but evidence regarding the safety and efficacy of this treatment is scarce. The objective of the LEVO-T Registry is to describe the profile of patients on the HT list receiving levosimendan, prescription patterns, and clinical outcomes compared with patients not on levosimendan. METHODS: We retrospectively reviewed all patients listed for elective HT from 2015 to 2020 from 14 centers in Spain. RESULTS: A total of 1015 consecutive patients were included, of whom 238 patients (23.4%) received levosimendan. Patients treated with levosimendan had more heart failure (HF) admissions in the previous year and a worse clinical profile. The most frequent prescription pattern were fixed doses triggered by the patients' clinical needs. Nonfatal ventricular arrhythmias occurred in 2 patients (0.8%). No differences in HF hospitalizations were found between patients who started levosimendan in the first 30 days after listing and those who did not (33.6% vs 34.5%; P=.848). Among those who did not, 102 patients (32.9%) crossed over to levosimendan after an HF admission. These patients had a rate of 0.57 HF admissions per month before starting levosimendan and 0.21 afterwards. Propensity score matching analysis showed no differences in survival at 1 year after listing between patients receiving levosimendan and those who did not (HR, 1.03; 95%CI, 0.36-2.97; P=.958) or in survival after HT (HR, 0.97; 95%CI, 0.60-1.56; P=.958). CONCLUSIONS: Repetitive levosimendan in an ambulatory setting as a bridge to heart transplantation is commonly used, is safe, and may reduce HF hospitalizations.

Influence of the medical treatment schedule in new diagnoses patients with heart failure and reduced ejection fraction.

AIMS: Heart failure (HF) guidelines recommend treating all patients with HF and reduced ejection fraction (HFrEF) with quadruple therapy, although they do not establish how to start it. This study aimed to evaluate the implementation of these recommendations, analyzing the efficacy and safety of the different therapeutic schedules. METHODS AND RESULTS: Prospective, observational, and multicenter registry that evaluated the treatment initiated in patients with newly diagnosed HFrEF and its evolution at 3 months. Clinical and analytical data were collected, as well as adverse reactions and events during follow-up. Five hundred and thirty-three patients were included, selecting four hundred and ninety-seven, aged 65.5 ± 12.9 years (72% male). The most frequent etiologies were ischemic (25.5%) and idiopathic (21.1%), with a left ventricular ejection fraction of 28.7 ± 7.4%. Quadruple therapy was started in 314 (63.2%) patients, triple in 120 (24.1%), and double in 63 (12.7%). Follow-up was 112 days [IQI 91; 154], with 10 (2%) patients dying. At 3 months, 78.5% had quadruple therapy (p < 0.001). There were no differences in achieving maximum doses or reducing or withdrawing drugs (< 6%) depending on the starting scheme. Twenty-seven (5.7%) patients had any emergency room visits or admission for HF, less frequent in those with quadruple therapy (p = 0.02). CONCLUSION: It is possible to achieve quadruple therapy in patients with newly diagnosed HFrEF early. This strategy makes it possible to reduce admissions and visits to the emergency room for HF without associating a more significant reduction or withdrawal of drugs or significant difficulty in achieving the target doses.

Lack of improvement in autonomic cardiac tone after sacubitril/valsartan at lower than target doses.

Autonomic regulation plays a role in the progression of heart failure with reduced ejection fraction (HrEF).Twenty-one HFrEF patients, 60.8 ±â€¯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 ±â€¯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.

Impacto de las enfermedades autoinmunitarias en el tratamiento y el pronóstico del síndrome coronario agudo / Impact of autoimmune disease on the management and prognosis of acute coronary syndrome

No disponible

Comparison of the Global Registry of Acute Coronary Events Risk Score Versus the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse outcomes With Early Implementation of the ACC/AHA Guidelines Risk Score to Predict In-Hospital Mortality and Major Bleeding in Acute Coronary Syndromes.

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 <60 ml/min/1.73 m(2) or those treated with new antiplatelets. Reclassification analyses showed GRACE risk score was associated with a significant improvement in the predictive accuracy of CRUSADE risk score for predicting mortality (net reclassification improvement: 22.5%; p <0.001) and MB (net reclassification improvement: 17.6%; p = 0.033) but not for CRUSADE MB. In conclusion, GRACE risk score has a better predictive performance for predicting both in-hospital mortality and BARC MB. In light of these findings, we propose the GRACE score as a single score to predict these in-hospital complications.

Repercusiones en la posología de los anticoagulantes orales no antagonistas de la vitamina K por las variaciones de la función renal de los pacientes con fibrilación auricular e insuficiencia cardiaca aguda reciente / Impact of variations in kidney function on nonvitamin k oral anticoagulant dosing in patients with atrial fibrillation and recent acute heart failure

Introducción y objetivos: El deterioro de la función renal y las fluctuaciones de esta son frecuentes en los pacientes recientemente hospitalizados por insuficiencia cardiaca aguda que presentan fibrilación auricular. El objetivo de este estudio es evaluar la necesidad hipotética de ajustes de dosis (según las fluctuaciones de la función renal) de dabigatrán, rivaroxabán y apixabán durante los 6 meses siguientes al alta hospitalaria a los pacientes con fibrilación auricular e insuficiencia cardiaca concomitantes. Métodos: Se llevó a cabo un estudio observacional en 162 pacientes con fibrilación auricular no valvular después de una hospitalización por insuficiencia cardiaca aguda descompensada a los que se practicaron determinaciones de creatinina durante el seguimiento. Se determinaron las posologías hipotéticas recomendadas de dabigatrán, rivaroxabán y apixabán según la función renal al alta. Se identificaron las variaciones aparecidas en la creatinina sérica y el aclaramiento de creatinina y los consiguientes cambios en las dosis recomendadas de estos fármacos durante 6 meses de seguimiento. Resultados: De la población total del estudio, el 44% de los pacientes habría necesitado un ajuste de la posología de dabigatrán durante el seguimiento; el 35%, la de rivaroxabán y el 29%, la de apixabán. Hubo mayor proporción de pacientes con aclaramiento de creatinina < 60 ml/min o de edad avanzada (≥ 75 años) que habrían necesitado ajuste de la dosis durante el seguimiento. Conclusiones: La necesidad de un ajuste de la posología de los anticoagulantes orales no antagonistas de la vitamina K durante el seguimiento es frecuente en los pacientes con fibrilación auricular después de una insuficiencia cardiaca aguda descompensada, sobre todo los de mayor edad y con deterioro de la función renal. Se necesitan nuevos estudios para esclarecer la importancia clínica de estas necesidades de ajuste de la dosis de los fármacos y la pauta idónea de seguimiento de la función renal de los pacientes con insuficiencia cardiaca y otros subgrupos de pacientes con fibrilación auricular (AU)

Introduction and objectives: 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. Methods: 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. Results: 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 clearance < 60 mL/min or with advanced age (≥ 75 years) would have needed dosage adjustment during follow-up. Conclusions: 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 (AU)

Impact of Variations in Kidney Function on Nonvitamin K Oral Anticoagulant Dosing in Patients With Atrial Fibrillation and Recent Acute Heart Failure.

INTRODUCTION AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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 clearance < 60 mL/min or with advanced age (≥ 75 years) would have needed dosage adjustment during follow-up. CONCLUSIONS: 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.

Cystatin C-based CKD-EPI equations and N-terminal pro-B-type natriuretic peptide for predicting outcomes in acutely decompensated heart failure.

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 <60 mL/min/1.73 m(2) and NT-proBNP >3251 pg/mL were independent predictors of adverse outcomes (P < 0.01). The combination of GFR <60 mL/min/1.73 m(2) and NT-proBNP >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.

Mineralocorticoid receptor antagonists modulate galectin-3 and interleukin-33/ST2 signaling in left ventricular systolic dysfunction after acute myocardial infarction.

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)-ß 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-ß, SMAD3, IL-33, and sST2, as well as higher concentrations of markers of fibrosis and inflammation. Treatment with MRAs down-regulated Gal-3, TGF-ß, 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.

Prognostic significance of long-period heart rate rhythms in chronic heart failure.

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.

Mild kidney disease as a risk factor for major bleeding in patients with atrial fibrillation undergoing percutaneous coronary stenting.

Bleeding risk is increased in patients with atrial fibrillation (AF) and moderate to severe kidney disease (KD); however, the implication of mild KD on bleeding remains unclear. The aim of this study was to determine whether the presence of mild KD increases risk for major bleeding (MB) in patients with AF undergoing percutaneous coronary intervention with stent implantation (PCI-S). Two hundred eighty-five patients were included. Patients were classified into three kidney function groups: moderate to severe KD (n=91; <60 ml/min/1.73 m²), mild KD (n=139; 60-89 ml/min/1.73 m²) and non-KD (n=55; ≥90 ml/min/1.73 m²). Estimated glomerular filtration rate was calculated using the simplified Modification of Diet in Renal Disease equation. Patients were followed for one year, and the occurrence of MB was obtained in all. A total of 28 patients (9.8%) presented MB. MB complications examined as a function of KD groups revealed that there was a graded increase in MB with worsening renal function (non KD=1.8%, mild KD=7.9%, moderate to severe KD=17.6%; p <0.001). Multivariable Cox regression analysis showed that mild KD was associated with nearly a 2.5-fold (2.43 95% confidence interval 1.11-5.34, p=0.039) increase in the risk of MB as compared with non-KD patients. Other independent predictors of MB were moderate-severe KD, anaemia and triple antithrombotic therapy after PCI-S (C-index=0.76). In this population, mild KD confers a significantly increase in the risk for MB complications. Future studies should assess the potential role of incorporating mild KD into the bleeding risk scales to improve the stratification of these patients.

Short-term variability of heart rate turbulence in chronic heart failure.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Anabolic status and functional impairment in men with mild chronic heart failure.

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, p <0.001), 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.

Valor pronóstico comparativo del pro-péptido natriurético tipo B aminoterminal urinario en pacientes con insuficiencia cardiaca aguda descompensada / Comparative Prognostic Value of Plasma and Urinary N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Acute Destabilized Heart Failure

Introducción y objetivos: Se ha sugerido que las concentraciones urinarias de la porción aminoterminal del pro-péptido natriurético tipo B (NT-proBNP) pueden tener valor pronóstico en pacientes con insuficiencia cardiaca estable, pero hasta ahora no se ha realizado una comparación directa con las concentraciones plasmáticas de este marcador en pacientes con una insuficiencia cardiaca aguda descompensada (ICAD). El objetivo de este estudio fue comparar el valor pronóstico de la concentración plasmática de NT-proBNP con el de la concentración urinaria de este marcador en la estratificación del riesgo de los pacientes con ICAD.Métodos: Se estudió prospectivamente a pacientes consecutivos hospitalizados con ICAD. A la llegada al hospital, se obtuvieron simultáneamente muestras de sangre y orina, para determinar las concentraciones de NT-proBNP. Se realizó un seguimiento clínico, y se registraron la mortalidad y la hospitalización por insuficiencia cardiaca.Resultados: Se incluyó un total de 138 pacientes (mediana de edad, 74 años [rango intercuartiles, 67-80]; 54 varones). Durante una mediana de seguimiento de 387 días [rango intercuartiles, 161-559], 65 pacientes (47%) presentaron eventos clínicos adversos. La concentración plasmática de NT-proBNP fue más alta en los pacientes que presentaron eventos clínicos 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 concentración urinaria de NT-proBNP fue similar en ambos grupos (p=0,62). En los análisis de regresión de Cox multivariable, la concentración plasmática de NT-proBNP se asoció a un mayor riesgo de eventos clínicos adversos, tanto como variable continua (por 100 pg/ml; razón de riesgos [HR]=1,004; intervalo de confianza [IC] del 95%, 1,001-1,007; p=0,003) o categórica (≥3.345 pg/ml; HR; IC del 95%, 1,41-3,93; p=0,001). En cambio, la concentración urinaria de NT-proBNP no se asoció a una evolución clínica adversa.Conclusiones: La concentración plasmática de NT-proBNP es superior a la concentración urinaria de este marcador en la predicción de los resultados clínicos adversos en pacientes con ICAD (AU)

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 (AU)

[Comparative prognostic value of plasma and urinary N-terminal pro-B-type natriuretic peptide in patients with acute destabilized heart failure]. / Valor pronóstico comparativo del pro-péptido natriurético tipo B aminoterminal urinario en pacientes con insuficiencia cardiaca aguda descompensada.

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.