Heart Failure With Reduced Ejection Fraction in a Patient With Erdheim-Chester Disease on Dabrafenib.

A 54-year-old woman with a diagnosis of Erdheim-Chester disease under therapy with dabrafenib presents with clinical signs of heart failure. After discontinuing the offending medication and initiating guideline-directed medical therapy for heart failure with reduced ejection fraction, the clinical picture improved.

Is the obesity paradox in outpatients with heart failure reduced ejection fraction real?

Background: The obesity occurrence has achieved epidemic levels worldwide and several studies indicate a paradoxical similarity among obesity and the prognosis in heart failure (HF). The primary objective was to understand the association between body mass index (BMI) and heart failure with reduced ejection fraction (HFREF) of ischemic etiology in outpatients, using mortality as a parameter. The secondary objectives were to determine the differences in HF functional class, pharmacological therapy and evaluate the prognostic value of MAGGIC Score in this population. Methods: We analyzed 1,556 medical records from the HF outpatient clinic of a quaternary hospital and 242 were selected according to the criteria. Most were male, average age 62.6 (56-70), BMI 18.5-24.9 = 35.1%, 25-29.9 = 37.2%, 30-34.9 = 17.8%, 35-39.9 = 7%; BMI <18.5 and >40 groups were eliminated from the central analyzes because of scarce testing. Results: BMI 30-34.9 and BMI 18.5-24.9 had the best prognosis, BMI 25-29.9 had an average performance, and BMI -39.9 group provided the worst outcome (p = 0.123). In the subcategory analysis, BMI 30-34.9 group had a better prognosis compared to the BMI 35-39.9 group (p = 0.033). In the multivariate analysis The MAGGIC score was not able to foretell mortality in this population according to BMI. Conclusion: In not hospitalized patients with HFREF of ischemic etiology, obesity was not a protective factor.

From End-of-Life Care to Improved Quality of Life and Better Prognosis by Using Vericiguat: A Case Report From Costa Rica.

In this case report, we present the evolution of a heart failure with reduced ejection fraction (HFrEF) patient who was set to receive end-of-life care but demonstrated improvement following treatment with vericiguat in combination with foundational therapy. Vericiguat is a novel soluble guanylate cyclase stimulant that has been proven helpful for treating decompensated heart failure with HFrEF, decreasing hospitalization rates and mortality of cardiovascular causes. This medication is currently indicated in patients who require IV diuretics administration or hospitalization due to decompensated heart failure. This is a case study of a 62-year-old woman with dilated heart failure and reduced left ventricular ejection fraction (LVEF), who was a wheelchair user due to severe cardiovascular symptoms and various comorbidities, who was referred to our heart failure program for treatment. Despite previous treatment, the patient experienced persistent cardiovascular symptoms and required palliative care. After optimizing the foundational therapy, the patient's condition improved but continued to require hospitalization. Vericiguat was initiated as an add-on. After six months, the patient's LVEF improved by 9%, and she is now asymptomatic with a considerable decrease in pro-B-type natriuretic peptide levels and is wheelchair independent due to enhance exercise resistance. However, the echocardiogram revealed a progression in the dysfunction of both the mitral and aortic valves. The patient's renal function and quality of life scores also changed over time. Vericiguat therapy, as an adjunct to foundational therapy, improved exercise tolerance and symptom relief. However, further investigation is necessary to assess the effects of vericiguat on renal function and disease progression in individuals with HFrEF.

Exertional Cardiac and Pulmonary Vascular Hemodynamics in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Exertional dyspnea is a cardinal manifestation of heart failure with reduced ejection fraction (HFrEF), but quantitative data regarding exertional hemodynamics are lacking. OBJECTIVES: We sought to characterize exertional cardiopulmonary hemodynamics in patients with HFrEF. METHODS: We studied 35 patients with HFrEF (59 ± 12 years old, 30 males) who completed invasive cardiopulmonary exercise testing. Data were collected at rest, at submaximal exercise and at peak effort on upright cycle ergometry. Cardiovascular and pulmonary vascular hemodynamics were recorded. Fick cardiac output (Qc) was determined. Hemodynamic predictors of peak oxygen uptake (VO2) were identified. RESULTS: Left ventricular ejection fraction and cardiac index were 23% ± 8% and 2.9 ± 1.1 L/min/m2, respectively. Peak VO2 was 11.8 ± 3.3 mL/kg/min, and the ventilatory efficiency slope was 53 ± 13. Right atrial pressure increased from rest to peak exercise (4 ± 5 vs 7 ± 6 mmHg,). Mean pulmonary arterial pressure increased from rest to peak exercise (27 ± 13 vs 38 ± 14 mmHg). Pulmonary artery pulsatility index increased from rest to peak exercise, while pulmonary arterial capacitance and pulmonary vascular resistance declined. CONCLUSIONS: Patients with HFrEF suffer from marked increases in filling pressures during exercise. These findings provide new insight into cardiopulmonary abnormalities contributing to impairments in exercise capacity in this population. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT03078972.

Inter-American Society of Cardiology (CIFACAH-ELECTROSIAC) and Latin-American Heart Rhythm Society (LAHRS): multidisciplinary review on the appropriate use of implantable cardiodefibrillator in heart failure with reduced ejection fraction.

BACKGROUND: Our main objective was to present a multidisciplinary review on the epidemiology of sudden cardiac death (SCD) and the tools that could be used to identify malignant ventricular arrhythmias (VAs) and to perform risk stratification. In addition, indications and contraindications for the use of implantable cardioverter defibrillator (ICD) in general and in special populations including the elderly and patients with chronic kidney disease (CKD) are also given. METHODS: An expert group from the Inter American Society of Cardiology (IASC), through their HF Council (CIFACAH) and Electrocardiology Council (ElectroSIAC), together with the Latin American Heart Rhythm Society (LAHRS), reviewed and discussed the literature regarding the appropriate use of an ICD in people with heart failure (HF) with reduced ejection fraction (HFpEF). Indications and contraindications for the use of ICD are presented in this multidisciplinary review. RESULTS: Numerous clinical studies have demonstrated the usefulness of ICD in both primary and secondary prevention of SCD in HFpEF. There are currently precise indications and contraindications for the use of these devices. CONCLUSIONS: In some Latin American countries, a low rate of implantation is correlated with low incomes, but this is not the case for all Latin America. Determinants of the low rates of ICD implantation in many Latin American countries are still a matter of research. VA remains one of the most common causes of cardiovascular death associated with HFrEF and different tools are available for stratifying the risk of SCD in this population.

Long-term mortality after acute coronary syndromes among patients with normal, mildly reduced, or reduced ejection fraction.

AIMS: Left ventricular ejection fraction (LVEF) ≤ 40% is a well-established risk factor for mortality after acute coronary syndromes (ACS). However, the long-term prognostic impact of mildly reduced ejection fraction (EF) (LVEF 41-49%) after ACS remains less clear. METHODS AND RESULTS: This was a retrospective study enrolling patients admitted with ACS included in a single-centre databank. LVEF was assessed by echocardiography during index hospitalization. Patients were divided in the following categories according to LVEF: normal (LVEF ≥ 50%), mildly reduced (LVEF 41-49%), and reduced (LVEF ≤ 40%). The endpoint of interest was all-cause death after hospital discharge. A multivariable Cox model was used to adjust for confounders. A total of 3200 patients were included (1952 with normal EF, 375 with mildly reduced EF, and 873 with reduced EF). The estimated cumulative incidence rates of mortality at 10 years for patients with normal, mildly reduced, and reduced EF were 24.8%, 33.5%, and 41.3%, respectively. After adjustments, the presence of reduced EF was associated with higher mortality compared with normal EF [adjusted hazard ratio (HR) 1.64; 95% confidence interval (CI) 1.36-1.96; P < 0.001], as was mildly reduced EF compared with normal EF (adjusted HR 1.33; 95% CI 1.05-1.68; P = 0.019). The presence of reduced EF was not associated with a statistically significantly higher mortality compared with mildly reduced EF (adjusted HR 1.23; 95% CI 0.96-1.57; P = 0.095). CONCLUSIONS: In patients with ACS, mildly reduced EF measured in the acute phase was associated with higher long-term mortality compared with patients with normal EF. These data emphasize the importance of anti-remodelling therapies for ACS patients who have LVEF in the mildly reduced range.

Neuromodulação Vagal Auricular e sua Aplicabilidade em Pacientes com Insuficiência Cardíaca e Fração de Ejeção Reduzida / Auricular Vagal Neuromodulation and its Application in Patients with Heart Failure and Reduced Ejection Fraction

Resumo Fundamento O desequilíbrio do sistema nervoso autônomo (SNA) na insuficiência cardíaca (IC) cria um ciclo vicioso, o excesso de atividade simpática e a diminuição da atividade vagal contribuindo para a piora da IC. A estimulação elétrica transcutânea de baixa intensidade do ramo auricular do nervo vago (taVNS) é bem tolerada e abre novas possibilidades terapêuticas. Objetivos Gerar hipótese da aplicabilidade e benefício da taVNS na IC através da comparação intergrupos de parâmetros ecocardiográficos, teste de caminhada de 6 min, variabilidade da frequência cardíaca pelo Holter (SDNN e rMSSD), questionário de qualidade de vida de Minnesota e classe funcional pela New York Heart Association. Métodos Estudo clínico prospectivo, duplo cego, randomizado com metodologia sham, unicêntrico. Avaliados 43 pacientes e alocados em 2 grupos: o Grupo 1 recebeu taVNS (frequências 2/15 Hz) e Grupo 2 recebeu sham. Nas comparações, valores de p<0,05 foram considerados significativos. Resultados Na fase pós-intervenção, observou-se que o Grupo 1 se manteve com melhor rMSSD (31 x 21; p = 0,046) e atingiu melhor SDNN (110 vs. 84, p = 0,033). Ao compararmos os parâmetros intragrupos, antes e após intervenção, observou-se que todos melhoraram significativamente no grupo 1 e não houve diferenças no grupo 2. Conclusão A taVNS é uma intervenção segura, de fácil execução e que sugere provável benefício na IC pela melhora na variabilidade da frequência cardíaca, o que indica melhor equilíbrio autonômico. Novos estudos com maior número de pacientes são necessários para responder às questões levantadas por esse estudo.

Abstract Background The autonomic nervous system (ANS) imbalance in heart failure (HF) creates a vicious cycle, excess sympathetic activity, and decreased vagal activity contributing to the worsening of HF. Low-intensity transcutaneous electrical stimulation of the auricular branch of the vagus nerve (taVNS) is well tolerated and opens new therapeutic possibilities. Objectives To hypothesize the applicability and benefit of taVNS in HF through intergroup comparison of echocardiography parameters, 6-minute walk test, Holter heart rate variability (SDNN and rMSSD), Minnesota quality of life questionnaire, and functional class by the New York Heart Association. In comparisons, p values <0.05 were considered significant. Methods Prospective, double-blind, randomized clinical study with sham methodology, unicentric. Forty-three patients were evaluated and divided into 2 groups: Group 1 received taVNS (frequencies 2/15 Hz), and Group 2 received sham. In comparisons, p values <0.05 were considered significant. Results In the post-intervention phase, it was observed that Group 1 had better rMSSD (31 x 21; p = 0.046) and achieved better SDNN (110 vs. 84, p = 0.033). When comparing intragroup parameters before and after the intervention, it was observed that all of them improved significantly in group 1, and there were no differences in group 2. Conclusion taVNS is a safe to perform and easy intervention and suggests a probable benefit in HF by improving heart rate variability, which indicates better autonomic balance. New studies with more patients are needed to answer the questions raised by this study.

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.

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)

Vagal Neuromodulation in Chronic Heart Failure With Reduced Ejection Fraction: A Systematic Review and Meta-Analysis.

Objectives: The aim of this study was to evaluate the effects of invasive vagal nerve stimulation (VNS) in patients with chronic heart failure (HF) and reduced ejection fraction (HFrEF). Background: Heart failure is characterized by autonomic nervous system imbalance and electrical events that can lead to sudden death. The effects of parasympathetic (vagal) stimulation in patients with HF are not well-established. Methods: From May 1994 to July 2020, a systematic review was performed using PubMed, Embase, and Cochrane Library for clinical trials, comparing VNS with medical therapy for the management of chronic HFrEF (EF ≤ 40%). A meta-analysis of several outcomes and adverse effects was completed, and GRADE was used to assess the level of evidence. Results: Four randomized controlled trials (RCT) and three prospective studies, totalizing 1,263 patients were identified; 756 treated with VNS and 507 with medical therapy. RCT data were included in the meta-analysis (fixed-effect distribution). Adverse effects related to VNS were observed in only 11% of patients. VNS was associated with significant improvement (GRADE = High) in the New York Heart Association (NYHA) functional class (OR, 2.72, 95% CI: 2.07-3.57, p < 0.0001), quality of life (MD -14.18, 95% CI: -18.09 to -10.28, p < 0.0001), a 6-min walk test (MD, 55.46, 95% CI: 39.11-71.81, p < 0.0001) and NT-proBNP levels (MD -144.25, 95% CI: -238.31 to -50.18, p = 0.003). There was no difference in mortality (OR, 1.24; 95% CI: 0.82-1.89, p = 0.43). Conclusions: A high grade of evidence demonstrated that vagal nerve stimulation improves NYHA functional class, a 6-min walk test, quality of life, and NT-proBNP levels in patients with chronic HFrEF, with no differences in mortality.

Heart Failure and Diabetes: Perspective of a Dangerous Association.

The relationship between diabetes and risk of heart failure has been described in previous trials, releasing the importance of the hyperglycemic state that, added to other risk factors, favors the development of coronary heart disease. The mechanism by which, in the absence of hypertension, obesity and/or dyslipidemia, diabetic patients develop cardiomyopathy has been less studied. Recently, the Sodium Glucose Co-transporter type 2 inhibitors (SGLT2 inhibitors) used for the treatment of heart failure patients with or without diabetes has been a breakthrough in the field of medicine. This review describes the established pathophysiology of diabetic cardiomyopathy and SGLT2 inhibitors, their mechanisms of action, and benefits in this group of patients.

Revisiting heart failure assessment based on objective measures in NYHA functional classes I and II.

OBJECTIVE: New York Heart Association (NYHA) functional class plays a central role in heart failure (HF) assessment but might be unreliable in mild presentations. We compared objective measures of HF functional evaluation between patients classified as NYHA I and II in the Rede Brasileira de Estudos em Insuficiência Cardíaca (ReBIC)-1 Trial. METHODS: The ReBIC-1 Trial included outpatients with stable HF with reduced ejection fraction. All patients had simultaneous protocol-defined assessment of NYHA class, 6 min walk test (6MWT), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and patient's self-perception of dyspnoea using a Visual Analogue Scale (VAS, range 0-100). RESULTS: Of 188 included patients with HF, 122 (65%) were classified as NYHA I and 66 (35%) as NYHA II at baseline. Although NYHA class I patients had lower dyspnoea VAS Scores (median 16 (IQR, 4-30) for class I vs 27.5 (11-49) for class II, p=0.001), overlap between classes was substantial (density overlap=60%). A similar profile was observed for NT-proBNP levels (620 pg/mL (248-1333) vs 778 (421-1737), p=0.015; overlap=78%) and for 6MWT distance (400 m (330-466) vs 351 m (286-408), p=0.028; overlap=64%). Among NYHA class I patients, 19%-34% had one marker of HF severity (VAS Score >30 points, 6MWT <300 m or NT-proBNP levels >1000 pg/mL) and 6%-10% had two of them. Temporal change in functional class was not accompanied by variation on dyspnoea VAS (p=0.14). CONCLUSIONS: Most patients classified as NYHA classes I and II had similar self-perception of their limitation, objective physical capabilities and levels of natriuretic peptides. These results suggest the NYHA classification poorly discriminates patients with mild HF.

What Is the Role of the Inflammation in the Pathogenesis of Heart Failure?

PURPOSE OF REVIEW: In heart failure, whether it is associated with reduced or preserved ejection fraction, the immune system is activated and contributes to heart remodeling and impaired function. RECENT FINDINGS: Studies indicate that cells of the immune system not only play a role in the pathology but are also critical regulators of heart function. Knowledge about the role of the immune system driving heart failure will lead to the development of new targets to this system, particularly in those patients that, despite the apparent wellness, relapse and worsen. In this review, we will address the diverse mechanisms that trigger inflammation and their impact on heart failure progression.

Recently Approved and Under Investigation Drugs for Treating Patients with Heart Failure.

Heart Failure (HF) represents a leading cause of morbidity and mortality worldwide. Despite the recent advances in the treatment of this condition, patients´ prognosis remains unfavorable in most cases. Sacubitril/valsartan and ivabradine have been recently approved to improve clinical outcomes in patients with HF with reduced ejection fraction. Drugs under investigation for treating patients with HF encompass many novel mechanisms including vasoactive peptides, blocking inflammatory- mediators, natriuretic peptides, selective non-steroidal mineralocorticoid-receptor antagonists, myocardial ß3 adrenoreceptor agonists, inhibiting the cytochrome C/cardiolipin peroxidase complex, neuregulin-1/ErbB signaling and inhibiting late inward sodium current. The aim of this manuscript is to review the main drugs under investigation for the treatment of patients with HF and give perspectives for their implementation into clinical practice.

Heart failure with preserved ejection fraction: an update on pathophysiology, diagnosis, treatment, and prognosis

Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome in which patients have symptoms and signs of HF with normal or near-normal left ventricular ejection fraction (LVEF ≥50%). Roughly half of all patients with HF worldwide have an LVEF ≥50% and nearly half have an LVEF <50%. Thanks to the increased scientific attention about the condition and improved characterization and diagnostic tools, the incidence of HF with reduced ejection fraction (HFrEF) dropped while that of HFpEF has increased by 45%. HFpEF has no single guideline for diagnosis or treatment, the patient population is heterogeneously and inconsistently described, and longitudinal studies are lacking. To better understand and overcome the disease, in this review, we updated the latest knowledge of HFpEF pathophysiology, introduced the existing promising diagnostic methods and treatments, and summarized its prognosis by reviewing the most recent cohort studies.

Un novedoso agente en el tratamiento de la insuficiencia cardiaca con función sistólica deprimida / A novel agent in the treatment of heart failure with depressed systolic function

Resumen Introducción: Se revisará la evolución del tratamiento farmacológico de la insuficiencia cardiaca (IC) en los últimos 25 an˜os, desde el concepto de tratamiento con vasodilatadores, pasando por el bloqueo o inhibición del sistema renina-angiotensina-aldosterona y la inhibición betaadrenérgica y su importante contribución en la disminución de la morbimortalidad por IC, el papel de los péptidos natriuréticos y, finalmente, se conocerá uno de los estudios más importantes en el área cardiológica y específicamente en el manejo de la IC, en el cual se demuestra un enfoque modulador de los sistemas neuro humorales que se activan en estos pacientes. Objetivos: La IC constituye la etapa final de la mayoría de las enfermedades cardiovasculares, con una alta tasa de hospitalización y de morbimortalidad cardiovascular, siendo, por lo tanto, de interés constante la necesidad de encontrar un agente terapéutico innovador que disminuya significativamente estas complicaciones y también que mejore la calidad de vida de los que la presentan. Metodología: Se realizará una descripción del PARADIGM-HF Clinical Trial, que utilizó un compuesto sacubitrilo/valsartán para el manejo de la IC con un mecanismo modulador diferente del concepto de bloqueador de sistemas deletéreos que se activan cuando un paciente presenta síntomas y signos de IC. Conclusiones: La muerte por causas cardiovasculares u hospitalización por IC (el punto final primario) se produjo en 914 pacientes (21.8%) en el grupo sacubitrilo/valsartán y 1,117 pacientes (26.5%) en el grupo de enalapril (razón de riesgo en el grupo sacubitrilo/valsartán, 0.80; intervalo de confianza (IC) del 95%: 0.73 a 0.87; p < 0.001 (exacta p = 4.0 × 10 - 7)). De los pacientes que recibieron sacubitrilo/valsartán, 537 (12.8%) fueron hospitalizados por IC, en comparación con los 658 pacientes (15.6%) que recibieron enalapril (razón de riesgo, 0.79; IC del 95%, 0.71 a 0.89; p < 0.001). Un total de 711 pacientes (17.0%) en el grupo sacubitrilo/valsartán y 835 pacientes (19.8%) en el grupo de enalapril murió (razón de riesgo de muerte por cualquier causa, 0.84; IC del 95%, 0.76 a la 0.93; p < 0.001).

Abstract Introduction: A review is presented on the evolution of the pharmacological treatment of heart failure (HF) in the last 25 years, from the concept of treatment with vasodilators to the blocking or inhibition of the renin angiotensin aldosterone system. Beta-adrenergic inhibition and its important contribution in the reduction of morbidity and mortality due to HF will be discussed along with the role of the natriuretic peptides. One of the most important studies in the cardiology area, and specifically in the management of HF, is presented, in which an approach is demonstrated of the modulator of the neurohumoral systems that are activated in these patients. Objectives: HF is the final stage of most cardiovascular diseases, and has a high rate of hospital admission, as well as cardiovascular morbidity and mortality. Therefore, there is constant interest in the need to find an innovative therapeutic agent that significantly reduces these complications and that improves the quality of life of those who suffer from it. Methods: A description will be presented of the PARADIGM-HF Clinical Trial using a sacubitril/valsartán compound for the management of HF with a modulating mechanism different from the concept of a deleterious system blocker that is activated when a patient has symptoms and signs of heart failure. Conclusions: Death due to cardiovascular causes, or hospital admission due to heart failure (the primary endpoint) occurred in 914 patients (21.8%) in the Sacubitril / valsartán group, and 1117 patients (26.5%) in the enalapril group (risk ratio in the sacubitril / valsartán group, 0.80, with a 95% confidence interval [CI]: 0.73 to 0.87, P<0.001 ;exact P= 4.0 × 10 --7;). Of the patients receiving sacubitril / valsartán, 537 (12.8%) were hospitalised due to heart failure, compared with 658 patients (15.6%) receiving enalapril (hazard ratio 0.79, 95% CI: 0.71 to 0.89, P<.001). A total of 711 patients (17.0%) in the sacubitril / valsartán group, and 835 patients (19.8%) in the enalapril group, died (all-cause death rate, 0.84, 95% CI: 0.76 to 0.93, P<.001)

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