Early glomerular filtration rate decline is associated with hemoglobin rise following dapagliflozin initiation in heart failure with reduced ejection fraction.

INTRODUCTION AND OBJECTIVES: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) induce short-term changes in renal function and hemoglobin. Their pathophysiology is incompletely understood. We aimed to evaluate the relationship between 1- and 3-month estimated glomerular filtration rate (eGFR) and hemoglobin changes following initiation of dapagliflozin in patients with stable heart failure with reduced ejection fraction (HFrEF). METHODS: This is a post hoc analysis of a randomized clinical trial that evaluated the effect of dapagliflozin on 1- and 3-month peak oxygen consumption in outpatients with stable HFrEF (DAPA-VO2 trial, NCT04197635). We used linear mixed regression analysis to assess the relationship between eGFR and hemoglobin changes across treatment arms. RESULTS: A total of 87 patients were evaluated in this substudy. The mean age was 67.0± 10.5 years, and 21 (24.1%) were women. The mean baseline eGFR and hemoglobin were 66.9±20.7mL/min/1.73m2 and 14.3±1.7g/dL, respectively. Compared with placebo, eGFR did not significantly change at either time points in the dapagliflozin group, but hemoglobin significantly increased at 1 and 3 months. At 1 month, the hemoglobin increase was related to decreases in eGFR only in the dapagliflozin arm (P <.001). At 3 months, there was no significant association in either treatment arms (P=.123). Changes in eGFR were not associated with changes in peak oxygen consumption, quality of life, or natriuretic peptides. CONCLUSIONS: In patients with stable HFrEF, 1-month changes in eGFR induced by dapagliflozin are inversely related to changes in hemoglobin. This association was no longer significant at 3 months.

Epidemiology and treatment of heart failure in Spain: the HF-PATHWAYS study.

INTRODUCTION AND OBJECTIVES: To describe the epidemiology and treatment of a large contemporary cohort of patients with heart failure (HF). METHODS: Observational, retrospective, population-based study using the BIG-PAC database, which includes people aged ≥ 18 years seeking care for HF between 2017 and 2019. The main variables were the prevalence/annual incidence rate, comorbidities, clinical variables, and medication administered. RESULTS: We identified 19 762 patients with HF from a total of 1 189 003 persons seeking medical attention from 2017 to 2019 (2019: mean age, 78.3 years; 53.0% men). Distribution by type of left ventricular ejection fraction (LVEF) was as follows: 51.7% reduced, 40.2% preserved, and 8.1% mid-range. In 2019, the prevalence was 1.89% (95%CI, 1.70-2.08), with an incidence rate of 2.78 new cases per 1000 persons/y. No statistically significant differences were observed in prevalence and/or incidence from 2017 to 2019. Among patients with HF with reduced ejection fraction (HFrEF), 64% received beta-blockers, 80.5% angiotensin-converting enzyme inhibitor/angiotensin receptor blockers or sacubitril-valsartan, and 29.8% an aldosterone antagonist. In addition, from the diagnosis (baseline) to 24 months of follow-up, there was discreet treatment optimization, which was notable in the first 3 to 6 months. CONCLUSIONS: Epidemiological data on HF remained stable during the study period, with a lower prevalence than that reported in non-population-based studies. There is wide room for improvement in the optimization of medical treatment of HFrEF.

[Dapagliflozin in the prevention and treatment of heart failure]. / Dapagliflozina en la prevención y tratamiento de la insuficiencia cardiaca.

To substantially reduce the risk of hospitalization and death among subjects with heart failure (HF) and reduced left ventricular ejection fraction, it is necessary to make a comprehensive approach of the different neurohormonal systems that are implied in its etiopathogenesis, including not only sympathetic nervous system, and renin-angiotensin system, but also vasoactive peptides and sodium-glucose transport protein 2. The DAPA-HF trial demonstrated that the addition of dapagliflozin to the standard treatment in HF with reduced left ventricular ejection fraction, markedly decreases the risk of cardiovascular death, HF hospitalization and overall death. In addition, dapagliflozin improves functional class and quality of life. Importantly, the prognostic benefit starts early after initiating treatment with dapagliflozin, regardless baseline therapy or the presence of diabetes. All these evidences make dapagliflozin as one of the mainstays of treatment for the management of HF with reduced left ventricular ejection fraction.

[Practical approach of dapagliflozin for the treatment of heart failure. Role of primary care physician]. / Abordaje práctico de dapagliflozina en el tratamiento de la insuficiencia cardíaca. Papel del médico de atención primaria.

Despite traditional treatments, morbidity and mortality of patients with heart failure (HF) and reduced left ventricular ejection fraction remains unacceptably high. Traditionally, guidelines recommended a step by step approach in the management of this population. However, this approach could delay the prescription of some drugs with proven efficacy on morbidity and prognosis. As current HF guidelines recommend, an initial comprehensive approach with the aim of targeting all neurohormonal systems that are implied in the etiopathogenesis of HF seems necessary. The DAPA-HF trial demonstrated that dapagliflozin markedly reduces the risk of HF hospitalization, and also improves prognosis. Consequently, dapagliflozin should be considered as a first-line therapy in the management of these patients. On the other hand, primary care physicians are essential for the prevention and treatment of patients with HF and reduced left ventricular ejection fraction. As a result, it is mandatory that they know when and how dapagliflozin should be used. In this review, a practical approach for an appropriate use of this drug is provided.

Changes in causes of death and influence of therapeutic improvement over time in patients with heart failure and reduced ejection fraction.

INTRODUCTION AND OBJECTIVES: In patients with heart failure and reduced ejection fraction (HFrEF), several therapies have been proven to reduce mortality in clinical trials. However, there are few data on the effect of the use of evidence-based therapies on causes of death in clinical practice. METHODS: This study included 2351 outpatients with HFrEF (< 40%) from 2 multicenter prospective registries: MUSIC (n=641, period: 2003-2004) and REDINSCOR I (n=1710, period: 2007-2011). Variables were recorded at inclusion and all patients were followed-up for 4 years. Causes of death were validated by an independent committee. RESULTS: Patients in REDINSCOR I more frequently received beta-blockers (85% vs 71%; P <.001), mineralocorticoid antagonists (64% vs 44%; P <.001), implantable cardioverter-defibrillators (19% vs 2%; P <.001), and resynchronization therapy (7.2% vs 4.8%; P=.04). In these patients, sudden cardiac death was less frequent than in those in MUSIC (6.8% vs 11.4%; P <.001). After propensity score matching, we obtained 2 comparable populations differing only in treatments (575 vs 575 patients). In patients in REDINSCOR I, we found a lower risk of total mortality (HR, 0.70; 95%CI, 0.57-0.87; P=.001) and sudden cardiac death (sHR, 0.46; 95%CI, 0.30-0.70; P <.001), and a trend toward lower mortality due to end-stage HF (sHR, 0.73; 95%CI, 0.53-1.01; P=.059), without differences in other causes of death (sHR, 1.17; 95%CI, 0.78-1.75; P=.445), regardless of functional class. CONCLUSIONS: In ambulatory patients with HFrEF, implementation of evidence-based therapies was associated with a lower risk of death, mainly due to a significant reduction in sudden cardiac death.

Long-term and clinical profile of heart failure with recovered ejection fraction in a non-tertiary hospital. / Características y evolución de la insuficiencia cardiaca con función sistólica recuperada en un hospital no terciario.

INTRODUCTION: Heart failure (HF) with recovered ejection fraction (EF) is emerging as a different HF subtype. There is little information about his clinical profile in hospitals that are not a reference. METHODS: We analysed characteristics and prognosis in patients with recovered HF followed prospectively in the HF Unit of a non-tertiary hospital. RESULTS: A total of 431 patients with HF with reduced EF were followed (median 50 months, 79.3% males, mean age 70.3±12.2years). Of the patients, 26.9% (N 116) recovered EF, mainly in the first year of follow-up (76.7%). Compared with patients that did not recovered EF in the follow-up, they were younger, rate of ischemic origin of cardiomyopathy was less frequent and presented less comorbidity. Mortality was lower in patients with recovered HF (survival median of 85.2±2.1 vs. 74.2±1.9 months [log-rank χ2 11.5, P=0.001], hazard ratio 0.37, 95% confidence interval [CI]: 0.21-0.67, P=0.002). Aetiology of deaths was not mainly secondary to HF. Younger age of 68 years (odds ratio [OR] 0-98, 95% CI: 0.96-0,99; P=0.025), ischemic origin (OR 1.12, 95% CI: 1.01-1.21; P=0.003) and use of aldosterone antagonists (OR 1.89, 95% CI: 1.09-3.26; P=0.023) were the variables independently associated to normalisation of EF. CONCLUSION: HF with recovered EF is a frequent phenomenon. It has a more favourable clinical course, prognosis and basal characteristics than HF with persistent reduced EF. Further studies are needed to identify natural history and optimal medications for HF-recovered patients.

Obesidad en la mortalidad de pacientes con insuficiencia cardiaca y fracción de eyección reducida / Obesity in the mortality of patients with heart failure and reduced ejection fraction

Introducción: La asociación entre obesidad y menor mortalidad en pacientes con insuficiencia cardiaca y fracción de eyección del ventrículo izquierdo es controversial. Objetivo: Evaluar la asociación entre obesidad y mortalidad en pacientes con insuficiencia cardiaca y fracción de eyección reducida. Métodos: Se realizó un estudio observacional de cohorte prospectivo en pacientes con insuficiencia cardiaca y fracción de eyección reducida en el período comprendido entre enero del 2010 y diciembre de 2020. La muestra quedó conformada por 173 pacientes. Se evaluó la supervivencia mediante el método de Kaplan-Meier, para estimar el efecto del pronóstico de la variable obesidad sobre la mortalidad. Se utilizó el modelo de regresión de Cox. Resultados: Se observó que los pacientes obesos al año de seguimiento tuvieron mejor supervivencia que los que presentaron normopeso (0,6 versus 0,8) a los cinco años presentaron similar supervivencia los tres subgrupos de índice masa corporal (0,6), la mayor mortalidad la presentaron los pacientes bajo peso. La curva de éstos últimos, se distancia del resto de las categorías de IMC, Log Rank p= 0,001. En el modelo de regresión de Cox la obesidad presentó un odd ration OR=´1,159 p=0,648 (intervalo de confianza de 0,615-2,181). Conclusiones: En los pacientes con insuficiencia cardiaca con fracción de eyección reducida no se observó el fenómeno de obesidad paradójica en relación a la mortalidad(AU)

Introduction: The association between obesity and lower mortality in patients with heart failure and left ventricular ejection fraction is controversial. Objective: To evaluate the association between obesity and mortality in patients with heart failure and reduced ejection fraction. Methods: An observational prospective cohort study was carried out, from January 2010 to December 2020, in patients with heart failure and reduced ejection fraction. The sample was made up of 173 patients. Survival was evaluated using Kaplan-Meier method to estimate the prognostic effect of the obesity variable on mortality. Cox regression model was used. Results: It was observed that obese patients at one year of follow-up had better survival than those with normal weight (0.6 versus 0.8). At five years, the three subgroups of body mass index (0.6) showed similar survival and the highest mortality was observed by low weight patients. The curve of the latter differs from the rest of the BMI categories, Log Rank p=0.001. In the Cox regression model, obesity had an odds ratio OR=´1.159 p=0.648 (confidence interval 0.615-2.181). Conclusions: In patients with heart failure with reduced ejection fraction, the phenomenon of paradoxical obesity was not observed in relation to mortality(AU)

La tercera cara de la moneda en el manejo de la falla cardíaca / The third side of the coin in the management of heart failure

Resumen En las últimas décadas, el manejo de la insuficiencia cardíaca ha tenido avances significativos nunca antes vistos en la historia de la cardiología, lo cual ha elevado el pronóstico de vida de los pacientes con falla cardíaca, a niveles cercanos a los de un individuo sano. Para ello se han empleado múltiples alternativas farmacológicas, como los inhibidores de la enzima convertidora de angiotensina (IECA), los antagonistas de los receptores de angiotensina (ARA II), los bloqueadores de los receptores mineralocorticoides, los bloqueadores de los receptores IF I, los inhibidores de la neprilisina y los betabloqueadores, asociadas al desarrollo de la cardiología intervencionista y la cirugía cardiovascular a nivel coronario, valvular, remodelado cardíaco y dispositivos de estimulación, asistencia, resincronización y cardioversión miocárdica. Sin embargo, hay un importante escenario en el manejo de la falla cardíaca que, en ocasiones, por diversas circunstancias, se deja de lado o se pospone como terapia de primera línea concomitante a las ya expuestas. Este artículo intenta describir la importancia que tienen dichas terapias -a las que hemos llamado la tercera cara de la moneda en el manejo de la falla cardíaca- a la luz de la evidencia actual.

Abstract In the last decades the management of heart failure has seen significant advance as never before in the history of cardiology, raising the life expectancy of patients with heart failure to levels close to those of healthy individuals. For such a task, multiple pharmacological alternatives have been employed: angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor antagonists (ARB), mineralocorticoid receptor antagonists, I-F channel antagonists, neprilysin inhibitors, beta blockers, associated to the development of interventionist cardiology and cardiac surgery at coronary level, valvular level, cardiac remodeling, and devices for stimulation, assistance, resynchronization and myocardial cardioversion. However, there is an important stage in the management of heart failure that occasionally, due to varied circumstances, is set aside or put off as a front-line therapy accompanying the ones already mentioned. This article attempts to describe the importance that said therapies have in light of current evidence, which we have called: the third side of the coin in the management of heart failure.

Función renal en pacientes ambulatorios con insuficiencia cardíaca con fracción de eyección reducida; análisis de su evolución e implicancia pronóstica. Seguimiento a 4 años en una Unidad Multidisciplinaria de Insuficiencia Cardíaca / Renal function in outpatients with heart failure with reduced ejection fraction; analysis of its evolution and forecast implications. A 4 year follow up in a Multidisciplinary Unit of Heart Failure / Função renal em pacientes ambulatoriais com insuficiência cardíaca com fração de ejeção reduzida; análise de sua evolução e implicações prognósticas. Acompanhamento de até 4 anos em uma Unidade Multidisciplinar de Insuficiência Cardíaca

Resumen: Introducción: El deterioro de la función renal está asociado a un aumento de la mortalidad en los pacientes con insuficiencia cardíaca (IC). El objetivo de este estudio fue evaluar si la progresión de la enfermedad renal en pacientes estables portadores de IC con fracción de eyección reducida (ICFEr) y enfermedad renal crónica (ERC) se asocia a eventos cardiovasculares (ECV), hospitalización por IC y muerte. Metodología: Estudio de cohorte de seguimiento a 4 años, con análisis en dos etapas: tiempo 1 (inicio del estudio); y tiempo 2 (fin del estudio o muerte). Se definió ICFEr estable como IC con una fracción de eyección del ventrículo izquierdo (FEVI)<40% sin elementos de descompensación. Se definió ERC con la presencia de un filtrado glomerular estimado (FGe) < 60 ml/min/1,73 y ERC estable en ausencia de fracaso renal agudo. Resultados: Se incluyeron 94 pacientes con media de seguimiento de 37,2 meses; la edad media fue 69,5 años, 71.3% de sexo masculino. La cardiomiopatía era isquémica en 48% y la nefropatía vascular fue la predominante (62%). Se diagnosticó síndrome cardio-renal tipo 2 en 76 (81%) pacientes. Se evidenció descenso significativo del FGe entre los tiempos de análisis (tiempo 1: 45 ± 10 ml/min.; tiempo 2: 38 ± 15 ml/min.; p < 0,001) y 50% de los pacientes tuvieron peoría del estadio de ERC (p = 0,027). Se halló asociación entre progresión de la ERC con mayor frecuencia de ECV (P=0,002), ingresos por IC (OR 3,3;IC95% 1,9-11,2; p = 0.044) y muerte cardiovascular (OR 10,9;IC95% 2,9-40,1; p < 0.001). Conclusiones: La progresión de la ERC en pacientes con ICFEr ambulatorios se asocia a un peor pronóstico en términos de mortalidad cardiovascular, ingresos por IC y ECV.

Abstract: Introduction: Deterioration of renal function is associated with increased mortality in patients with heart failure (HF). The objective of the present study was to assess whether the progression of kidney disease is associated with the appearance of cardiovascular events (CVE), hospitalization for HF and death in a cohort of stable outpatients with chronic kidney disease (CKD) and Heart failure with reduced ejection fraction (HFrEF). Methodology: A 4 years follow-up cohort study, with a two stage analysis: time 1 (start of the study); and time 2 (end of study or death). Stable HFrEF was defined as HF with an ejection fraction of the left ventricle (LVEF)<40% without elements of decompensation. An estimated glomerular filtration less than 60 ml / min / 1.73 was used as diagnostic criterion for CKD and stable CKD in the absence of acute renal failure. Results: A total of 94 patients were included with a follow up mean of 37.2 months; the mean age was 69.5 years ± 9 years, 71.3% were male. Cardiomyopathy was ischemic in 48% and vascular nephropathy was predominant (62%). Cardio-renal syndrome type 2 was diagnosed in 76 (81%) patients. There was a significant decrease in eGFR between the time of analysis (time 1: 45 ± 10 ml/min, time 2: 38 ± 15 ml/min, p <0.001) and 50% of patients worsened their stage of CKD (p = 0.027). An association was found between progression of CKD with a higher frequency of CVD (P = 0.002), hospitalization for HF (OR 3.3, 95% CI 1.9-11.2, p = 0.044) and cardiovascular death (OR 10.9, 95% CI 2.9-40.1, p <0.001). Conclusions: The progression of CKD is associated with a worse prognosis in not hospitalized HF patients in terms of cardiovascular mortality, admissions for HF and CVE.

Resumo: Introdução: A deterioração da função renal está associada ao aumento da mortalidade em pacientes com insuficiência cardíaca (IC). O objectivo deste estudo foi avaliar se a progressão da doença renal em pacientes com IC estáveis ​​com fracção de ejecção reduzida (ICFER) e doença renal crónica (IRC) está associada com eventos cardiovasculares (DCV), HF hospitalização e morte. Metodologia: Estudo de coorte de acompanhamento aos 4 anos, com análise em duas etapas: tempo 1 (início do estudo); e tempo 2 (fim do estudo ou morte). O rEFFE estável foi definido como IC com fração de ejeção do ventrículo esquerdo (FEVE) <40% sem elementos de descompensação. DRC foi definida na presença de uma taxa de filtração glomerular estimada (EGFR) <60 ml / min / 1,73 CEI e estável na ausência de insuficiência renal aguda. Resultados: Foram incluídos 94 pacientes com seguimento médio de 37,2 meses; a idade média foi de 69,5 anos, 71,3% do sexo masculino. A cardiomiopatia era isquêmica em 48% e a nefropatia vascular era predominante (62%). Síndrome Cardio-renal tipo 2 foi diagnosticada em 76 (81%) pacientes. diminuição significativa da taxa de filtração glomerular entre os tempos de verificação (45 ± 10 ml / min; cerca de 2 cerca de 1 38 ± 15 ml / min; p <0,001) foi evidenciado e 50% dos pacientes tiveram a fase de Peoria DRC (p = 0,027). e morte cardiovascular (OU 10,9 associação entre a progressão DRC de DCV com maior frequência (P = 0,002), o rendimento de IC (OR 3.3, 95 % CI 1.9-11.2 p = 0,044), verificou-se IC 95% 2,9-40,1, p <0,001). Conclusões: A progressão da DRC em pacientes com HFrR ambulatorial está associada a um pior prognóstico em termos de mortalidade cardiovascular, IC e DCV