Consensus on the approach to hydrosaline overload in acute heart failure. SEMI/SEC/S.E.N. recommendations.

Most of the signs and symptoms of heart failure can be explained by fluid overload, which is also related to disease progression. Fluid overload is a complex phenomenon that extends beyond increased intravascular pressures and poses challenges for accurate diagnosis and effective treatment. Current recommendations advise a multiparametric approach, including clinical data (symptoms/signs), imaging tests, and biomarkers. This article proposes a practical therapeutic approach to managing hydrosaline overload in heart failure in both inpatient and outpatient settings. This document is an initiative of the Spanish Society of Internal Medicine (SEMI) in collaboration with the Spanish Society of Cardiology (SEC) and the Spanish Society of Nephrology (S.E.N.).

Morbimortalidad no cardiovascular en función de la fracción de eyección del ventrículo izquierdo tras una hospitalización por insuficiencia cardiaca / Noncardiovascular morbidity and mortality across left ventricular ejection fraction categories following hospitalization for heart failure

Introducción y objetivos Los eventos no cardiovasculares son una importante causa de morbimortalidad en pacientes con insuficiencia cardiaca (IC), pero parece que su riesgo difiere en función de la fracción de eyección del ventrículo izquierdo (FEVI). Nuestro objetivo es evaluar el riesgo de mortalidad y hospitalizaciones no cardiovasculares totales en función de la FEVI tras una hospitalización por IC. Métodos Se evaluó en retrospectiva a una cohorte multicéntrica de 4.595 pacientes tras una hospitalización por IC. Se evaluó la FEVI como variable continua y estratificada en 4 categorías (FEVI ≤ 40%, 41%-49%, 50-59% y ≥ 60%). Los objetivos fueron los riesgos de muerte no cardiovascular y de hospitalizaciones recurrentes por causas no cardiovasculares según la FEVI. Resultados Tras una mediana de seguimiento de 2,2 [intervalo intercuartílico, 0,76-4,8] años, se registraron 646 muertes y 4.014 episodios de rehospitalización por causas no cardiovasculares. En el análisis multivariante, que incluía el riesgo de evento cardiovascular como evento adverso competitivo, se halló relación directa entre la FEVI y el riesgo de muerte o rehospitalización no cardiovascular (p<0,001). En comparación con la FEVI ≤ 40%, la FEVI del 51-59% y especialmente la ≥ 60% se asociaron de manera significativa con un mayor riesgo de muerte no cardiovascular (respectivamente, HR=1,31; IC95%, 1,02-1,68; p=0,032; y HR=1,47; IC95%, 1,15-1,86; p=0,002) y de rehospitalizaciones no cardiovasculares (IRR=1,17; IC95%, 1,02-1,35; p=0,024; IRR=1,26; IC95%, 1,11-1,45; p=0,001). Conclusiones Tras una hospitalización por IC, la FEVI tiene relación directa con el riesgo de morbimortalidad no cardiovascular. Los pacientes con FEVI conservada tienen un riesgo significativamente mayor de muerte y hospitalizaciones por causas no cardiovasculares, fundamentalmente si la FEVI es ≥ 60%. (AU)

Introduction and objectives Noncardiovascular events represent a significant proportion of the morbidity and mortality burden in patients with heart failure (HF). However, the risk of these events appears to differ by left ventricular ejection fraction (LVEF) status. In this study, we sought to evaluate the risk of noncardiovascular death and recurrent noncardiovascular readmission by LVEF status following an admission for acute HF. Methods We retrospectively assessed a cohort of 4595 patients discharged after acute HF in a multicenter registry. We evaluated LVEF as a continuum, stratified in 4 categories (LVEF ≤ 40%, 41%-49%, 50%-59%, and ≥ 60%). Study endpoints were the risks of noncardiovascular mortality and recurrent noncardiovascular admissions during follow-up. Results At a median follow-up of 2.2 [interquartile range, 0.76-4.8] years, we registered 646 noncardiovascular deaths and 4014 noncardiovascular readmissions. After multivariable adjustment including cardiovascular events as a competing event, LVEF status was associated with the risk of noncardiovascular mortality and recurrent noncardiovascular admissions. When compared with patients with LVEF ≤ 40%, those with LVEF 51%-59%, and especially those with LVEF ≥ 60%, were at higher risk of noncardiovascular mortality (HR, 1.31; 95%CI, 1.02-1,68; P=.032; and HR, 1.47; 95%CI, 1.15-1.86; P=.002; respectively), and at higher risk of recurrent noncardiovascular admissions (IRR, 1.17; 95%CI, 1.02-1.35; P=.024; and IRR, 1.26; 95%CI, 1.11-1.45; P=.001; respectively). Conclusions Following an admission for HF, LVEF status was directly associated with the risk of noncardiovascular morbidity and mortality. Patients with HFpEF were at higher risk of noncardiovascular death and total noncardiovascular readmissions, especially those with LVEF ≥ 60%. (AU)

Loop diuretic down-titration at discharge in patients hospitalized for acute heart failure.

AIMS: The current literature provides limited guidance on the best diuretic strategy post-hospitalization for acute heart failure (AHF). It is postulated that the efficacy and safety of the outpatient diuretic regimen may be significantly influenced by the degree of fluid overload (FO) encountered during hospitalization. We hypothesize that in patients with more pronounced FO, reducing their regular oral diuretic dosage might be associated with an elevated risk of unfavourable clinical outcomes. METHODS AND RESULTS: It was a retrospective observational study of 410 patients hospitalized for AHF in which the dose of furosemide at admission and discharge was collected. Patients were categorized across diuretic dose status into two groups: (i) the down-titration group and (ii) the stable/up-titration group. FO status was evaluated by a clinical congestion score and circulating biomarkers. The endpoint of interest was the composite of time to all-cause death and/or heart failure readmission. A multivariable Cox proportional hazard regression model was constructed to analyse the endpoints. The median age was 86 (78-92) years, 256 (62%) were women, and 80% had heart failure with preserved ejection fraction. After multivariate adjustment, the down-titration furosemide equivalent dose remained not associated with the risk of the combined endpoint in the whole sample (hazard ratio 1.34, 95% confidence interval 0.86-2.06, P = 0.184). The risk of the combination of death and/or worsening heart failure associated with the diuretic strategy at discharge was significantly influenced by FO status, including clinical congestion scores and circulating proxies of FO like BNP and cancer antigen 125. CONCLUSIONS: In patients hospitalized for AHF, furosemide down-titration does not imply an increased risk of mortality and/or heart failure readmission. However, FO status modifies the effect of down-titration on the outcome. In patients with severe congestion or residual congestion at discharge, down-titration was associated with an increased risk of mortality and/or heart failure readmission.

Prognosis of acute heart failure in patients followed up in nursing homes in Spain: Results from the RICA registry / Impacto pronóstico en la supervivencia de los pacientes en residencias de ancianos con insuficiencia cardiaca en España: Resultados del Registro RICA

Background: Patients with chronic diseases such as heart failure (HF) are at risk of hospital admission. We evaluated the impact of living in nursing homes (NH) on readmissions and all-cause mortality of HF patients during a one-year follow up. Methods: An observational and multicenter study from the Spanish National Registry of Heart Failure (RICA) was performed. We compared clinical and prognostic characteristics between both groups. Bivariate analyses were performed using Student's t-test and Tukey's method and a Kaplan–Meier survival at one-year follow up. A multivariate proportional hazards analysis of [Cox] regression by the conditional backward method was conducted for the variables being statistically significant related to the probability of death in the univariate. Results: There were 5644 patients included, 462 (8.2%) of whom were nursing home residents. There were 52.7% women and mean age was 79.7±8.8 years. NH residents had lower Barthel (74.07), Charlson (3.27), and Pfeiffer index (2.2), p<0.001). Mean pro-BNP was 6686pg/ml without statistical significance differences between groups. After 1-year follow-up, crude analysis showed no differences in readmissions 74.7% vs. 72.3%, p=0.292, or mortality 63.9% vs. 61.1%, p=0.239 between groups. However, after controlling for confounding variables, NH residents had a higher 1-year all-cause mortality (HR 1.153; 95% CI 1.011–1.317; p=0.034). Kaplan–Meier analysis showed worse survival in nursing home residents (log-rank of 7.12, p=0.008). Conclusions: Nursing home residents with heart failure showed higher one-year mortality which could be due to worse functional status, higher comorbidity, and cognitive deterioration.(AU)

Introducción: Los pacientes con enfermedades crónicas como la insuficiencia cardiaca (IC) presentan mayor riesgo de ingreso. Se evaluó el impacto sobre los reingresos y la mortalidad por todas las causas de los pacientes con IC respecto a vivir o no en residencias de ancianos durante un año de seguimiento. Métodos: Estudio observacional y multicéntrico a partir del Registro Nacional de Insuficiencia Cardiaca (RICA). Se compararon las características clínicas y pronósticas entre ambos grupos. Se realizó un análisis bivariante mediante el método de t de Student y Tukey y un análisis de supervivencia mediante Kaplan-Meier al año de seguimiento, así como un análisis multivariante de riesgos proporcionales de regresión (Cox) por el método de retroceso condicional para las variables que se relacionaban de forma estadísticamente significativa con la probabilidad de muerte en el univariante. Resultados: Fueron incluidos 5.644 pacientes; 462 (8,2%) de ellos estaban en residencias, el 52,7% eran mujeres y la edad media era de 79,7±8,8 años. Los pacientes en residencias tenían menor Barthel (74,07), Charlson (3,27) y Pfeiffer (2,2) (p<0,001). El pro-BNP medio era de 6.686 pg/ml sin diferencias significativas. Tras un año de seguimiento, el análisis bruto no mostró diferencias en los reingresos (74,7 vs. 72,3%; p=0,292) ni en mortalidad (63,9 vs. 61,1%; p=0,239) entre ambos grupos. Tras controlar las variables de confusión, los pacientes en residencias presentaron una mayor mortalidad por todas las causas a un año (hazard ratio 1,153; IC 95%: 1,011-1,317; p=0,034) así como peor supervivencia en el análisis de Kaplan-Meier (log-rank 7,12; p=0,008). Conclusiones: Los pacientes con IC en residencias de ancianos mostraron una mayor mortalidad a un año, que podría deberse a un peor estado funcional, a mayor deterioro cognitivo y a más comorbilidad.(AU)

Trajectory of Urine Albumin-Creatinine Ratio in Patients with Acute Heart Failure.

INTRODUCTION: Albuminuria is prevalent in patients with chronic heart failure and is a risk factor for disease progression. However, its clinical meaning in acute heart failure remains elusive. This study analyzed the trajectory of urine albumin to creatinine ratio (UACR) between admission and discharge and its association with decongestion. METHODS: In this prospective observational study, 63 patients were enrolled. UACR, B-type natriuretic peptide (BNP), and clinical congestion score (CCS) were obtained at admission and discharge. We used linear mixed regression analysis to compare changes in the natural logarithm of UACR (logUACR) and its association with changes in markers of decongestion. Estimates were reported as least squares mean with their respective 95% CIs. RESULTS: The median age of the study population was 87 years, 68.5% were women, and 69.8% had a left ventricular ejection fraction >50%. LogUACR at discharge significantly decreased in the overall population compared to admission (Δ -0.47, 95% CI: -0.78 to -0.15, p value = 0.003). The magnitude of UACR drop at discharge was associated with changes in surrogate markers of decongestion. Patients who showed a greater reduction in BNP at discharge exhibited a greater reduction in UACR (p = 0.016). The same trend was also found with clinical decongestion, as assessed by changes in CCS, however, without achieving statistical significance (p = 0.171). UACR change at discharge was not associated with changes in serum creatinine (p value = 0.923). CONCLUSION: In elderly patients with AHF and volume overload, the level of UACR significantly decreased upon discharge compared to admission. This reduction in UACR was closely linked to decreases in BNP.

Noncardiovascular morbidity and mortality across left ventricular ejection fraction categories following hospitalization for heart failure.

INTRODUCTION AND OBJECTIVES: Noncardiovascular events represent a significant proportion of the morbidity and mortality burden in patients with heart failure (HF). However, the risk of these events appears to differ by left ventricular ejection fraction (LVEF) status. In this study, we sought to evaluate the risk of noncardiovascular death and recurrent noncardiovascular readmission by LVEF status following an admission for acute HF. METHODS: We retrospectively assessed a cohort of 4595 patients discharged after acute HF in a multicenter registry. We evaluated LVEF as a continuum, stratified in 4 categories (LVEF ≤ 40%, 41%-49%, 50%-59%, and ≥ 60%). Study endpoints were the risks of noncardiovascular mortality and recurrent noncardiovascular admissions during follow-up. RESULTS: At a median follow-up of 2.2 [interquartile range, 0.76-4.8] years, we registered 646 noncardiovascular deaths and 4014 noncardiovascular readmissions. After multivariable adjustment including cardiovascular events as a competing event, LVEF status was associated with the risk of noncardiovascular mortality and recurrent noncardiovascular admissions. When compared with patients with LVEF ≤ 40%, those with LVEF 51%-59%, and especially those with LVEF ≥ 60%, were at higher risk of noncardiovascular mortality (HR, 1.31; 95%CI, 1.02-1,68; P=.032; and HR, 1.47; 95%CI, 1.15-1.86; P=.002; respectively), and at higher risk of recurrent noncardiovascular admissions (IRR, 1.17; 95%CI, 1.02-1.35; P=.024; and IRR, 1.26; 95%CI, 1.11-1.45; P=.001; respectively). CONCLUSIONS: Following an admission for HF, LVEF status was directly associated with the risk of noncardiovascular morbidity and mortality. Patients with HFpEF were at higher risk of noncardiovascular death and total noncardiovascular readmissions, especially those with LVEF ≥ 60%.

Intrarenal Venous Flow Pattern Changes Do Relate With Renal Function Alterations in Acute Heart Failure.

BACKGROUND: There is scarce evidence supporting the clinical utility of congestive intrarenal venous flow (IRVF) patterns in patients with acute heart failure. OBJECTIVES: This study aims to: 1) investigate the association between IRVF patterns and the odds of worsening renal function (WRF); 2) track the longitudinal changes of serum creatinine (sCr) across IRVF at predetermined points and its association with decongestion; and 3) explore the relationship between IRVF/WRF categories and patient outcomes. METHODS: IRVF was assessed at baseline (pre-decongestive therapy), 72 hours, and 30 and 90 days postdischarge. Changes in sCr trajectories across dynamic IRVF variations and parameters of decongestion were assessed using linear mixed effect models. The association between IRVF/WRF categories and outcomes was evaluated using univariable/multivariable models. RESULTS: In this prospective, multicenter study with 188 participants, discontinuous IRVF patterns indicated higher odds of WRF (OR: 3.90 [95% CI: 1.24-12.20]; P = 0.020 at 72 hours; and OR: 5.76 [95% CI: 1.67-19.86]; P = 0.006 at 30 days) and an increase in sCr (Δ-72 hours 0.14 mg/dL [95% CI: 0.06-0.22]; P = 0.001; Δ-discharge 0.13 mg/dL [95% CI: 0.03-0.23]; P = 0.007). However, the diuretic response and decongestion significantly influenced the magnitude of these changes. Patients exhibiting both WRF and discontinuous IRVF at 30 days experienced an increased hazard of adverse events (HR: 5.96 [95% CI: 2.63-13.52]; P < 0.001). CONCLUSIONS: Discontinuous IRVF identifies patients with higher odds of WRF during admission and postdischarge periods. Nonetheless, adequate diuretic response and decongestion could modify this association. Patients showing both WRF and discontinuous IRVF at 30 days had increased rates of adverse events.

Prognosis of acute heart failure in patients followed up in nursing homes in Spain: Results from the RICA registry.

BACKGROUND: Patients with chronic diseases such as heart failure (HF) are at risk of hospital admission. We evaluated the impact of living in nursing homes (NH) on readmissions and all-cause mortality of HF patients during a one-year follow up. METHODS: An observational and multicenter study from the Spanish National Registry of Heart Failure (RICA) was performed. We compared clinical and prognostic characteristics between both groups. Bivariate analyses were performed using Student's t-test and Tukey's method and a Kaplan-Meier survival at one-year follow up. A multivariate proportional hazards analysis of [Cox] regression by the conditional backward method was conducted for the variables being statistically significant related to the probability of death in the univariate. RESULTS: There were 5644 patients included, 462 (8.2%) of whom were nursing home residents. There were 52.7% women and mean age was 79.7±8.8 years. NH residents had lower Barthel (74.07), Charlson (3.27), and Pfeiffer index (2.2), p<0.001). Mean pro-BNP was 6686pg/ml without statistical significance differences between groups. After 1-year follow-up, crude analysis showed no differences in readmissions 74.7% vs. 72.3%, p=0.292, or mortality 63.9% vs. 61.1%, p=0.239 between groups. However, after controlling for confounding variables, NH residents had a higher 1-year all-cause mortality (HR 1.153; 95% CI 1.011-1.317; p=0.034). Kaplan-Meier analysis showed worse survival in nursing home residents (log-rank of 7.12, p=0.008). CONCLUSIONS: Nursing home residents with heart failure showed higher one-year mortality which could be due to worse functional status, higher comorbidity, and cognitive deterioration.

Prevalence and clinical profile of kidney disease in patients with chronic heart failure. Insights from the Spanish cardiorenal registry.

INTRODUCTION AND OBJECTIVES: Patients with combined heart failure (HF) and chronic kidney disease (CKD) have been underrepresented in clinical trials. The prevalence of CKD in these patients and their clinical profile require constant evaluation. This study aimed to analyze the prevalence of CKD, its clinical profile, and patterns of use of evidence-based medical therapies in HF across CKD stages in a contemporary cohort of ambulatory patients with HF. METHODS: From October 2021 to February 2022, the CARDIOREN registry included 1107 ambulatory HF patients from 13 HF clinics in Spain. RESULTS: The median age was 75 years, 63% were male, and 48% had heart failure with reduced left ventricular ejection fraction (HFrEF). A total of 654 (59.1%) had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, and 122 (11%) patients with eGFR ≥ 60 mL/min/1.73 m2 had a urine albumin-creatinin ratio ≥ 30 mg/g. The most important variables associated with lower eGFR were age (R2=61%) and furosemide dose (R2=21%). The proportion of patients receiving an angiotensin-converting enzyme inhibitor (ACEI)/ angiotensin II receptor blockers (ARB), an angiotensin receptor-neprilysin inhibitor (ARNi), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), or a mineralocorticoid receptor antagonist (MRA) progressively decreased with lower eGFR categories. Notably, 32% of the patients with HFrEF and an eGFR <30 mL/min/1.73 m2 received the combination of ACEI/ARB/ARNi+beta-blockers+MRA+SGLT2i. CONCLUSIONS: In this contemporary HF registry, 70% of patients had kidney disease. Although this population is less likely to receive evidence-based therapies, structured and specialized follow-up approaches within HF clinics may facilitate the adoption of these life-saving drugs.

Improvement in left atrial strain following ferric carboxymaltose in heart failure: an analysis of the Myocardial-IRON trial.

AIMS: Iron deficiency (ID) is associated with an impaired cardiac function and remodelling in heart failure (HF). Treatment with ferric carboxymaltose (FCM) has been showed recently to improve biventricular systolic function and ventricular strain parameters in patients with HF with reduced ejection fraction and ID, but there is no evidence on the benefit of FCM on the left atrium (LA). In this study, we aimed to evaluate the effect of FCM on LA longitudinal strain (LA-LS). METHODS AND RESULTS: This is a post hoc subanalysis of a double-blind, placebo-controlled, randomized clinical trial that enrolled 53 ambulatory patients with HF, left ventricular ejection fraction (LVEF) < 50%, and ID [Myocardial-IRON trial (NCT03398681)], treated with FCM or placebo. Cardiac magnetic resonance-featured tracking (CMR-FT) strain changes were evaluated before and 7 and 30 days after randomization using linear mixed regression analysis. The median age of the sample was 68 years (interquartile range: 64-76), and 20 (69%) were men. Mean ± standard deviation of LVEF was 39 ± 11%, and most (97%) were in stable New York Heart Association class II. At baseline, mean LA-LS was -8.9 ± 3.5%. At 30 days, and compared with placebo, LA-LS significantly improved in those allocated to FCM treatment arm (LA-LS = -12.0 ± 0.5 and -8.5 ± 0.6, respectively; - ∆ 3.55%, P < 0.001). CONCLUSIONS: In patients with stable HF, LVEF < 50%, and ID, treatment with FCM was associated with short-term improvements in LA-LS assessed by CMR-FT. Future works should assess the potential benefit of iron repletion on LA function.

Combining loop and thiazide diuretics for acute heart failure across the estimated glomerular filtration rate spectrum: A post-hoc analysis of the CLOROTIC trial.

AIMS: In patients with acute heart failure (AHF), the addition of hydrochlorothiazide (HCTZ) to furosemide improved diuretic response in the CLOROTIC trial. This work aimed to evaluate if these effects differ across the estimated glomerular filtration rate (eGFR) spectrum. METHODS AND RESULTS: This post-hoc analysis of the CLOROTIC trial analysed 230 patients with AHF and explored the influence of eGFR on primary and secondary endpoints. The median eGFR was 43 ml/min/1.73 m2 (range 14-109) and 23% had eGFR ≥60 ml/min/1.73 m2 (group 1), 24% from 45 to 59 ml/min/1.73 m2 (group 2), and 53% <45 ml/min/1.73 m2 (group 3). Patients treated with HCTZ had greatest weight loss at 72 h in all three groups, but patients in group 1 had a significantly greater response (-2.1 kg [-3.0 to 0.5]), compared to patients in groups 2 (-1.3 kg [-2.3 to 0.2]) and 3 (-0.1 kg [-1.3 to 0.4]) (p-value for interaction = 0.246). At 96 h, the differences in weight were -1.8 kg (-3.0 to -0.3), -1.4 kg (-2.6 to 0.3), and -0.5 kg (-1.3 to -0.1) in groups 1, 2, and 3, respectively (p-value for interaction = 0.256). There were no significant differences observed with the addition of HCTZ in terms of diuretic response, mortality or rehospitalizations, or safety endpoints (impaired renal function, hyponatraemia, and hypokalaemia) among the three eGFR groups (all p-values for interaction were no significant). CONCLUSION: The addition of eGFR-adjusted doses of oral HCTZ to loop diuretics in patients with AHF improved diuretic response across the eGFR spectrum. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT01647932; EudraCT number: 2013-001852-36.

Índice cronotrópico y eventos adversos a largo plazo en insuficiencia cardiaca con fracción de eyección conservada / Chronotropic index and long-term outcomes in heart failure with preserved ejection fraction

Introducción y objetivos: Poco se sabe sobre la utilidad de la respuesta de la frecuencia cardiaca (FC) al ejercicio para la estratificación del riesgo en la insuficiencia cardiaca con fracción de eyección conservada (ICFEc). El objetivo de este estudio fue evaluar la asociación entre la respuesta de la FC al ejercicio y el riesgo de episodios de descompensación por insuficiencia cardiaca (DIC) en pacientes sintomáticos estables con ICFEc. Métodos: Se trata de un estudio unicéntrico que incluyó a un total de 133 pacientes con ICFEc (NYHA II-III) tras la realización de una prueba de esfuerzo cardiopulmonar máxima. La respuesta de la FC al ejercicio se evaluó mediante la fórmula del índice cronotrópico (IxC). Para el análisis se utilizó un método de regresión binomial negativa. Resultados: La edad media fue de 73,2±10,5 años, el 56,4% eran mujeres y el 51,1% estaban en fibrilación auricular. La mediana de IxC fue de 0,4 (0,3-0,55). Tras una mediana de seguimiento de 2,4 (1,6-5,3) años, se registraron un total de 146 DIC en 58 pacientes y 41 (30,8%) muertes. El IxC no se asoció con eventos adversos (muerte, p=0,319, y DIC, p=0,573) cuando se analizó de forma conjunta toda la muestra. Sin embargo, se encontró un efecto diferencial en función del ritmo electrocardiográfico para DIC (p para interacción=0,002). El IxC se asoció inversa y linealmente con el riesgo de DIC en aquellos pacientes con ritmo sinusal y de forma lineal y positiva con aquellos en fibrilación auricular. Conclusiones: En pacientes con ICFEc, el IxC se asoció diferencialmente con el riesgo de DIC en función del ritmo electrocardiográfico. Un Ixc más bajo surgió como un factor de riesgo para predecir un mayor riesgo de DIC en pacientes en ritmo sinusal. Por el contrario, un IxC más alto identificó un mayor riesgo en aquellos pacientes en fibrilación auricular. (AU)

Introduction and objectives: Little is known about the usefulness of heart rate (HR) response to exercise for risk stratification in heart failure with preserved ejection fraction (HFpEF). Therefore, this study aimed to assess the association between HR response to exercise and the risk of total episodes of worsening heart failure (WHF) in symptomatic stable patients with HFpEF. Methods: This single-center study included 133 patients with HFpEF (NYHA II-III) who performed maximal cardiopulmonary exercise testing. HR response to exercise was evaluated using the chronotropic index (CIx) formula. A negative binomial regression method was used. Results: The mean age of the sample was 73.2± 10.5 years; 56.4% were female, and 51.1% were in atrial fibrillation. The median for CIx was 0.4 [0.3-0.55]. At a median follow-up of 2.4 [1.6-5.3] years, a total of 146 WHF events in 58 patients and 41 (30.8%) deaths were registered. In the whole sample, CIx was not associated with adverse outcomes (death, P=.319, and WHF events, P=.573). However, we found a differential effect across electrocardiographic rhythms for WHF events (P for interaction=.002). CIx was inversely and linearly associated with the risk of WHF events in patients with sinus rhythm and was positively and linearly associated with those with atrial fibrillation. Conclusions: In patients with HFpEF, CIx was differentially associated with the risk of total WHF events across rhythm status. Lower CIx emerged as a risk factor for predicting higher risk in patients with sinus rhythm. In contrast, higher CIx identified a higher risk in those with atrial fibrillation. (AU)

Usefulness of urinary potassium to creatinine ratio to predict diuretic response in patients with acute heart failure and preserved ejection fraction.

BACKGROUND: Patients with acute heart failure (AHF) require intensification in the diuretic strategy. However, the optimal diuretic strategy remains unclear. In this work, we aimed to evaluate the role of urinary potassium to creatinine ratio (K/Cr) to predict diuretic and natriuretic response to thiazide or mineralocorticoid receptor antagonists (MRAs) in a cohort of patients with AHF and preserved ejection fraction (AHF-pEF). HYPOTHESIS: Patients with a high urinary K/Cr ratio will have a better diuretic and natriuretic response with spironolactone versus chlorthalidone. METHODS: This is a study of 44 patients with AHF-pEF with suboptimal loop diuretic response. The primary endpoint was the baseline K/Cr associated with natriuretic and diuretic effect of chlorthalidone versus spironolactone at 24 and 72 h. Mixed linear regression models were used to analyze the endpoints. Estimates were reported as least squares mean with their respective 95% confidence interval (CIs). RESULTS: The median age of the study population was 85 years (82.5-88.5), and 30 (68.2%) were women. The inferential multivariate analysis suggested a greater natriuretic and diuretic effect of chlorthalidone across K/Cr levels. In the upper category, chlorthalidone translated into a statistically increase in natriuresis at 24 and 72 h. Chlorthalidone versus spironolactone showed ∆uNa of 25.7 mmol/L at 24 h (95% CI = -3.7 to 55.4, p = .098) and ∆uNa of 24.8 mmol/L at 72 h (95% CI = -4 to 53.6, p = .0106). The omnibus p value is .027. Multivariate analyses revealed a significant increase in 72 h cumulative diuresis irrespective of K/Cr status in those on chlorthalidone. CONCLUSIONS: In patients with AHF-pEF and suboptimal diuretic response, diuresis and natriuresis are higher with the administration of chlorthalidone over spironolactone. These data don't support the hypothesis that the K/Cr ratio can help guide the choice of thiazide diuretic versus MRA in AHF-pEF patients on loop diuretic.

Projected clinical benefits of dapagliflozin in patients with heart failure with preserved ejection fraction.

Aims: To address the projected clinical benefits of dapagliflozin among patients with heart failure (HF) with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF). Methods: A multicenter, prospective, cohort study of patients ≥50 years admitted with HF to Spanish internal medicine departments. The projected clinical benefits of dapagliflozin were calculated from the DELIVER trial. Results: A total of 4049 patients were included; 3271 (80.8%) were eligible for dapagliflozin treatment, according to DELIVER criteria. Within 1 year after discharge, 22.2% were rehospitalized for HF and 21.6% died. Implementation of dapagliflozin would translate into an absolute risk reduction of 1.3% for mortality and 5.1% for HF readmission. Conclusion: HF patients with preserved or mildly reduced ejection fraction have a high risk of events. The use of dapagliflozin could substantially reduce the HF burden.

Heart failure (HF) with preserved ejection fraction is frequent in clinical practice, particularly in the elderly. In HF with preserved ejection fraction, the heart still pumps a similar proportion of blood, but the heart muscle has become thicker. This means there is less space inside the heart to fill with blood, so too little is pumped out each time. Until very recently, no drugs had been shown to provide significant benefits on the outcome of the condition or the chance of recovery for these patients. Fortunately, recent clinical trials have demonstrated that treatment with drugs called SGLT2 inhibitors (e.g., dapagliflozin) could reduce the chance of being admitted to hospital or dying from HF. We investigated the benefits for patients who took dapagliflozin after being admitted to hospital and had HF with mildly reduced or preserved ejection fraction. We saw substantial benefits in this population.

Prognostic significance of plasma chloride in elderly patients hospitalized for acute heart failure.

AIMS: Previous studies demonstrated the relationship between hypochloraemia and poor prognosis in patients hospitalized for acute heart failure (AHF). However, the usefulness of chloride in clinical practice remains uncertain, notably in very old patients with predominantly heart failure (HF) with preserved ejection fraction (HFpEF). We aimed to evaluate the prognostic impact of chloride in a cohort of very aged patients with AHF and the possible existence of different phenotypes of hypochloraemia with distinct clinical significance. METHODS AND RESULTS: It was an observational study of 429 patients hospitalized for AHF in which chloraemia was measured. Two different phenotypes of hypochloraemia were identified by their relationship with estimated plasma volume status (ePVS) as a proxy of intravascular congestion. The endpoint of interest was time to all-cause mortality and the composite of death and/or HF readmission. A multivariable Cox proportional hazard regression model was constructed to analyse the endpoints. The median age was 85 (78-92) years, 266 (62%) were women, and 80% had HFpEF. After multivariable analysis, chloraemia, but not natraemia, was associated with the risk of death and HF readmission in a U-shaped pattern. The phenotype characterized by hypochloraemia and low ePVS (depletional) was associated with an increased risk of mortality when compared with patients with normochloraemia [hazard ratio (HR) 1.86, P = 0.008]. In contrast, hypochloraemia with high ePVS (dilutional) had no prognostic significance (HR 0.94, P = 0.855). CONCLUSIONS: In very old patients hospitalized with AHF, plasma chloride was associated with the risk of death and HF readmission in a U-shaped pattern and could potentially be used for congestion phenotyping.

Sex differences in Cardiorenal Syndrome: Insights from CARDIOREN Registry.

PURPOSE OF THE WORK: Although sex-specific differences in heart failure (HF) or kidney disease (KD) have been analyzed separately, the predominant cardiorenal phenotype by sex has not been described. This study aims to explore the sex-related differences in cardiorenal syndrome (CRS) in a contemporary cohort of outpatients with HF. FINDINGS: An analysis of the Cardiorenal Spanish registry (CARDIOREN) was performed. CARDIOREN Registry is a prospective multicenter observational registry including 1107 chronic ambulatory HF patients (37% females) from 13 Spanish HF clinics. Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73 m2 was present in 59.1% of the overall HF population, being this prevalence higher in the female population (63.2% vs. 56.6%, p = 0.032, median age: 81 years old, IQR:74-86). Among those with kidney dysfunction, women displayed higher odds of showing HF with preserved ejection fraction (HFpEF) (odds ratio [OR] = 4.07; confidence interval [CI] 95%: 2.65-6.25, p < 0.001), prior valvular heart disease (OR = 1.76; CI 95%:1.13-2.75, p = 0.014), anemia (OR: 2.02; CI 95%:1.30-3.14, p = 0.002), more advanced kidney disease (OR for CKD stage 3: 1.81; CI 95%:1.04-3.13, p = 0.034; OR for CKD stage 4: 2.49, CI 95%:1.31-4.70, p = 0.004) and clinical features of congestion (OR:1.51; CI 95%: 1.02-2.25, p = 0.039). On the contrary, males with cardiorenal disease showed higher odds of presenting HF with reduced ejection fraction (HFrEF) (OR:3.13; CI 95%: 1.90-5.16, p < 0.005), ischemic cardiomyopathy (OR:2.17; CI 95%: 1.31-3.61, p = 0.003), hypertension (OR = 2.11; CI 95%:1.18-3.78, p = 0.009), atrial fibrillation (OR:1.71; CI 95%: 1.06-2.75, p = 0.025), and hyperkalemia (OR:2.43, CI 95%: 1.31-4.50, p = 0.005). In this contemporary registry of chronic ambulatory HF patients, we observed sex-related differences in patients with combined heart and kidney disease. The emerging cardiorenal phenotype characterized by advanced CKD, congestion, and HFpEF was predominantly observed in women, whereas HFrEF, ischemic etiology, hypertension, hyperkalemia, and atrial fibrillation were more frequently observed in men.

Safety of benzodiazepines in patients with acute heart failure: A propensity score-matching study.

AIM: Benzodiazepines (BZDs) are one of the most used drugs to control symptoms in patients with acute heart failure (HF). However, the evidence on its safety is inconclusive. The objective was to describe the characteristics of patients admitted for HF and treated with BZDs and to assess the relationship of this treatment and mortality. PATIENTS AND METHODS: We performed a cross-sectional, multicentre (74 Spanish hospitals), cohort study. Patients admitted for HF were divided depending on whether they were treated with BZDs or not. Propensity score analysis matched patients in both groups in a 1:1 manner according to different factors. The primary outcome was mortality at day 7. Secondary outcomes were mortality at days 30 and 180, as well as readmissions and emergency room visits at 180 days. RESULTS: We included 1855 patients: 639 (34.4%) had prescribed BZDs treatment versus 1216 (65.6%) who had not been treated. Patients receiving BZDs had advanced heart disease, severe symptoms, need more HF intensive treatment and higher mortality. After propensity matching 381 balanced paired cases were included in each group. Treatment with BZDs was not associated with greater risk of mortality at day 7 of index hospitalization (7.6% vs 5.2%, adjusted OR 1.49, 95% CI 0.83-2.68, p = 0.186). There were also no differences between groups in terms of mortality at day 30 and 180, readmissions or visits to the emergency room. CONCLUSIONS: Our data support that benzodiazepines could be safely used for improving symptoms. in patients admitted for acute HF in terms of short-medium term mortality.

Oral Sodium Chloride in the Prevention of Contrast-Associated Acute Kidney Injury in Elderly Outpatients: The PNIC-Na Randomized Non-Inferiority Trial.

OBJECTIVE: We aimed to test the non-inferiority of oral versus intravenous hydration in the incidence of contrast-associated acute kidney injury (CA-AKI) in elderly outpatients undergoing a contrast-enhanced computed tomography (CE-CT) scan. METHODS: PNIC-Na (NCT03476460) is a phase-2, single-center, randomized, open-label, non-inferiority trial. We included outpatients undergoing a CE-CT scan, >65 years having at least one risk factor for CA-AKI, such as diabetes, heart failure, or an estimated glomerular filtration rate (eGFR) of 30-59 mL/min/1.73 m². Participants were randomized (1:1) to oral sodium-chloride capsules or intravenous hydration. The primary outcome was an increase in serum creatinine >0.3 mg/dL or a reduction in eGFR >25% within 48 h. The non-inferiority margin was set at 5%. RESULTS: A total of 271 subjects (mean age 74 years, 66% male) were randomized, and 252 were considered for the main analysis (per-protocol). A total of 123 received oral hydration and 129 intravenous. CA-AKI occurred in 9 (3.6%) of 252 patients and 5/123 (4.1%) in the oral-hydration group vs. 4/129 (3.1%) in the intravenous-hydration group. The absolute difference between the groups was 1.0% (95% CI -4.8% to 7.0%), and the upper limit of the 95% CI exceeded the pre-established non-inferiority margin. No major safety concerns were observed. CONCLUSION: The incidence of CA-AKI was lower than expected. Although both regimens showed similar incidences of CA-AKI, the non-inferiority was not shown.

Estimating the Prevalence of Cardiac Amyloidosis in Old Patients with Heart Failure-Barriers and Opportunities for Improvement: The PREVAMIC Study.

BACKGROUND: Cardiac amyloidosis (CA) could be a common cause of heart failure (HF). The objective of the study was to estimate the prevalence of CA in patients with HF. METHODS: Observational, prospective, and multicenter study involving 30 Spanish hospitals. A total of 453 patients ≥ 65 years with HF and an interventricular septum or posterior wall thickness > 12 mm were included. All patients underwent a 99mTc-DPD/PYP/HMDP scintigraphy and monoclonal bands were studied, following the current criteria for non-invasive diagnosis. In inconclusive cases, biopsies were performed. RESULTS: The vast majority of CA were diagnosed non-invasively. The prevalence was 20.1%. Most of the CA were transthyretin (ATTR-CM, 84.6%), with a minority of cardiac light-chain amyloidosis (AL-CM, 2.2%). The remaining (13.2%) was untyped. The prevalence was significantly higher in men (60.1% vs 39.9%, p = 0.019). Of the patients with CA, 26.5% had a left ventricular ejection fraction less than 50%. CONCLUSIONS: CA was the cause of HF in one out of five patients and should be screened in the elderly with HF and myocardial thickening, regardless of sex and LVEF. Few transthyretin-gene-sequencing studies were performed in older patients. In many patients, it was not possible to determine the amyloid subtype.

Chronotropic index and long-term outcomes in heart failure with preserved ejection fraction.

INTRODUCTION AND OBJECTIVES: Little is known about the usefulness of heart rate (HR) response to exercise for risk stratification in heart failure with preserved ejection fraction (HFpEF). Therefore, this study aimed to assess the association between HR response to exercise and the risk of total episodes of worsening heart failure (WHF) in symptomatic stable patients with HFpEF. METHODS: This single-center study included 133 patients with HFpEF (NYHA II-III) who performed maximal cardiopulmonary exercise testing. HR response to exercise was evaluated using the chronotropic index (CIx) formula. A negative binomial regression method was used. RESULTS: The mean age of the sample was 73.2± 10.5 years; 56.4% were female, and 51.1% were in atrial fibrillation. The median for CIx was 0.4 [0.3-0.55]. At a median follow-up of 2.4 [1.6-5.3] years, a total of 146 WHF events in 58 patients and 41 (30.8%) deaths were registered. In the whole sample, CIx was not associated with adverse outcomes (death, P=.319, and WHF events, P=.573). However, we found a differential effect across electrocardiographic rhythms for WHF events (P for interaction=.002). CIx was inversely and linearly associated with the risk of WHF events in patients with sinus rhythm and was positively and linearly associated with those with atrial fibrillation. CONCLUSIONS: In patients with HFpEF, CIx was differentially associated with the risk of total WHF events across rhythm status. Lower CIx emerged as a risk factor for predicting higher risk in patients with sinus rhythm. In contrast, higher CIx identified a higher risk in those with atrial fibrillation.