RESUMO
BACKGROUND: Obesity and type 2 diabetes are prevalent in patients with heart failure with preserved ejection fraction and are characterized by a high symptom burden. No approved therapies specifically target obesity-related heart failure with preserved ejection fraction in persons with type 2 diabetes. METHODS: We randomly assigned patients who had heart failure with preserved ejection fraction, a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or more, and type 2 diabetes to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level. RESULTS: A total of 616 participants underwent randomization. The mean change in the KCCQ-CSS was 13.7 points with semaglutide and 6.4 points with placebo (estimated difference, 7.3 points; 95% confidence interval [CI], 4.1 to 10.4; P<0.001), and the mean percentage change in body weight was -9.8% with semaglutide and -3.4% with placebo (estimated difference, -6.4 percentage points; 95% CI, -7.6 to -5.2; P<0.001). The results for the confirmatory secondary end points favored semaglutide over placebo (estimated between-group difference in change in 6-minute walk distance, 14.3 m [95% CI, 3.7 to 24.9; P = 0.008]; win ratio for hierarchical composite end point, 1.58 [95% CI, 1.29 to 1.94; P<0.001]; and estimated treatment ratio for change in CRP level, 0.67 [95% CI, 0.55 to 0.80; P<0.001]). Serious adverse events were reported in 55 participants (17.7%) in the semaglutide group and 88 (28.8%) in the placebo group. CONCLUSIONS: Among patients with obesity-related heart failure with preserved ejection fraction and type 2 diabetes, semaglutide led to larger reductions in heart failure-related symptoms and physical limitations and greater weight loss than placebo at 1 year. (Funded by Novo Nordisk; STEP-HFpEF DM ClinicalTrials.gov number, NCT04916470.).
Assuntos
Diabetes Mellitus Tipo 2 , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Peptídeos Semelhantes ao Glucagon , Insuficiência Cardíaca , Obesidade , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/etiologia , Método Duplo-Cego , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Obesidade/complicações , Obesidade/tratamento farmacológico , Volume Sistólico , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon/efeitos adversos , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon/uso terapêuticoRESUMO
BACKGROUND: Heart failure with preserved ejection fraction is increasing in prevalence and is associated with a high symptom burden and functional impairment, especially in persons with obesity. No therapies have been approved to target obesity-related heart failure with preserved ejection fraction. METHODS: We randomly assigned 529 patients who had heart failure with preserved ejection fraction and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or higher to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The dual primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in the 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level. RESULTS: The mean change in the KCCQ-CSS was 16.6 points with semaglutide and 8.7 points with placebo (estimated difference, 7.8 points; 95% confidence interval [CI], 4.8 to 10.9; P<0.001), and the mean percentage change in body weight was -13.3% with semaglutide and -2.6% with placebo (estimated difference, -10.7 percentage points; 95% CI, -11.9 to -9.4; P<0.001). The mean change in the 6-minute walk distance was 21.5 m with semaglutide and 1.2 m with placebo (estimated difference, 20.3 m; 95% CI, 8.6 to 32.1; P<0.001). In the analysis of the hierarchical composite end point, semaglutide produced more wins than placebo (win ratio, 1.72; 95% CI, 1.37 to 2.15; P<0.001). The mean percentage change in the CRP level was -43.5% with semaglutide and -7.3% with placebo (estimated treatment ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). Serious adverse events were reported in 35 participants (13.3%) in the semaglutide group and 71 (26.7%) in the placebo group. CONCLUSIONS: In patients with heart failure with preserved ejection fraction and obesity, treatment with semaglutide (2.4 mg) led to larger reductions in symptoms and physical limitations, greater improvements in exercise function, and greater weight loss than placebo. (Funded by Novo Nordisk; STEP-HFpEF ClinicalTrials.gov number, NCT04788511.).
Assuntos
Peptídeos Semelhantes ao Glucagon , Insuficiência Cardíaca , Obesidade , Humanos , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Obesidade/complicações , Volume SistólicoRESUMO
BACKGROUND: In the STEP-HFpEF (NCT04788511) and STEP-HFpEF DM (NCT04916470) trials, the GLP-1 receptor agonist semaglutide improved symptoms, physical limitations, bodyweight, and exercise function in people with obesity-related heart failure with preserved ejection fraction. In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, we aimed to provide a more definitive assessment of the effects of semaglutide across a range of outcomes and to test whether these effects were consistent across key patient subgroups. METHODS: We conducted a prespecified pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM, randomised, double-blind, placebo-controlled trials at 129 clinical research sites in 18 countries. In both trials, eligible participants were aged 18 years or older, had heart failure with a left ventricular ejection fraction of at least 45%, a BMI of at least 30 kg/m2, New York Heart Association class II-IV symptoms, and a Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; a measure of heart failure-related symptoms and physical limitations) of less than 90 points. In STEP-HFpEF, people with diabetes or glycated haemoglobin A1c concentrations of at least 6·5% were excluded, whereas for inclusion in STEP-HFpEF DM participants had to have been diagnosed with type 2 diabetes at least 90 days before screening and to have an HbA1c of 10% or lower. In both trials, participants were randomly assigned to either 2·4 mg semaglutide once weekly or matched placebo for 52 weeks. The dual primary endpoints were change from baseline to week 52 in KCCQ-CSS and bodyweight in all randomly assigned participants. Confirmatory secondary endpoints included change from baseline to week 52 in 6-min walk distance, a hierarchical composite endpoint (all-cause death, heart failure events, and differences in changes in KCCQ-CSS and 6-min walk distance); and C-reactive protein (CRP) concentrations. Heterogeneity in treatment effects was assessed across subgroups of interest. We assessed safety in all participants who received at least one dose of study drug. FINDINGS: Between March 19, 2021 and March 9, 2022, 529 people were randomly assigned in STEP-HFpEF, and between June 27, 2021 and Sept 2, 2022, 616 were randomly assigned in STEP-HFpEF DM. Overall, 1145 were included in our pooled analysis, 573 in the semaglutide group and 572 in the placebo group. Improvements in KCCQ-CSS and reductions in bodyweight between baseline and week 52 were significantly greater in the semaglutide group than in the placebo group (mean between-group difference for the change from baseline to week 52 in KCCQ-CSS 7·5 points [95% CI 5·3 to 9·8]; p<0·0001; mean between-group difference in bodyweight at week 52 -8·4% [-9·2 to -7·5]; p<0·0001). For the confirmatory secondary endpoints, 6-min walk distance (mean between-group difference at week 52 17·1 metres [9·2 to 25·0]) and the hierarchical composite endpoint (win ratio 1·65 [1·42 to 1·91]) were significantly improved, and CRP concentrations (treatment ratio 0·64 [0·56 to 0·72]) were significantly reduced, in the semaglutide group compared with the placebo group (p<0·0001 for all comparisons). For the dual primary endpoints, the efficacy of semaglutide was largely consistent across multiple subgroups, including those defined by age, race, sex, BMI, systolic blood pressure, baseline CRP, and left ventricular ejection fraction. 161 serious adverse events were reported in the semaglutide group compared with 301 in the placebo group. INTERPRETATION: In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide was superior to placebo in improving heart failure-related symptoms and physical limitations, and reducing bodyweight in participants with obesity-related heart failure with preserved ejection fraction. These effects were largely consistent across patient demographic and clinical characteristics. Semaglutide was well tolerated. FUNDING: Novo Nordisk.
Assuntos
Peptídeos Semelhantes ao Glucagon , Insuficiência Cardíaca , Obesidade , Volume Sistólico , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Masculino , Volume Sistólico/efeitos dos fármacos , Feminino , Idoso , Pessoa de Meia-Idade , Método Duplo-Cego , Obesidade/complicações , Obesidade/tratamento farmacológico , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: The angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear. METHODS: We randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Primary outcome components, secondary outcomes (including NYHA class change, worsening renal function, and change in Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary score [scale, 0 to 100, with higher scores indicating fewer symptoms and physical limitations]), and safety were also assessed. RESULTS: There were 894 primary events in 526 patients in the sacubitril-valsartan group and 1009 primary events in 557 patients in the valsartan group (rate ratio, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P = 0.06). The incidence of death from cardiovascular causes was 8.5% in the sacubitril-valsartan group and 8.9% in the valsartan group (hazard ratio, 0.95; 95% CI, 0.79 to 1.16); there were 690 and 797 total hospitalizations for heart failure, respectively (rate ratio, 0.85; 95% CI, 0.72 to 1.00). NYHA class improved in 15.0% of the patients in the sacubitril-valsartan group and in 12.6% of those in the valsartan group (odds ratio, 1.45; 95% CI, 1.13 to 1.86); renal function worsened in 1.4% and 2.7%, respectively (hazard ratio, 0.50; 95% CI, 0.33 to 0.77). The mean change in the KCCQ clinical summary score at 8 months was 1.0 point (95% CI, 0.0 to 2.1) higher in the sacubitril-valsartan group. Patients in the sacubitril-valsartan group had a higher incidence of hypotension and angioedema and a lower incidence of hyperkalemia. Among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women. CONCLUSIONS: Sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failure and an ejection fraction of 45% or higher. (Funded by Novartis; PARAGON-HF ClinicalTrials.gov number, NCT01920711.).
Assuntos
Aminobutiratos/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Doenças Cardiovasculares/mortalidade , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Neprilisina/antagonistas & inibidores , Tetrazóis/administração & dosagem , Valsartana/administração & dosagem , Idoso , Aminobutiratos/efeitos adversos , Angioedema/induzido quimicamente , Antagonistas de Receptores de Angiotensina/efeitos adversos , Compostos de Bifenilo , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipotensão/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Fatores Sexuais , Método Simples-Cego , Volume Sistólico , Tetrazóis/efeitos adversos , Valsartana/efeitos adversosRESUMO
Guideline-directed optimal medical therapy is a well-established therapy in treating patients with heart failure with reduced ejection fraction (HFrEF). Despite clear recommendations, the prognosis in this group of patients is still poor with high mortality. After publishing results of the PARADIGM-HF trial (Prospective Comparison of ARNI-Angiotensin Receptor/Neprilysin Inhibitors-with ACEI-Angiotensin-Converting Enzyme Inhibitor-to Determine Impact on Global Mortality and Morbidity in Heart Failure) clinical investigators accelerated their research. Recently, many new trials have been designed to evaluate the efficacy and safety of promising management, taking into account heterogeneity of population with chronic HFrEF. Determining target doses still poses the biggest problem in standard pharmacotherapy. Implementation of new substances for the HFrEF therapy makes it possible to formulate simple rules of treatment-in most cases, administering a dose of drug in one tablet provides a faster therapeutic effect. The aim of this article is to summarize current knowledge on recently announced findings on novel molecules and to propose a new revolutionary and individualised approach to treatment of HFrEF patients.
Assuntos
Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Antagonistas de Receptores de Angiotensina/uso terapêutico , Ensaios Clínicos como Assunto , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Motivação , Estudos Prospectivos , Volume SistólicoRESUMO
BACKGROUND: Unlike heart failure with reduced ejection fraction, there is no approved treatment for heart failure with preserved ejection fraction, the predominant phenotype in women. Therefore, there is a greater heart failure therapeutic deficit in women compared with men. METHODS: In a prespecified subgroup analysis, we examined outcomes according to sex in the PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction), which compared sacubitril-valsartan and valsartan in patients with heart failure with preserved ejection fraction. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and death from cardiovascular causes. We also report secondary efficacy and safety outcomes. RESULTS: Overall, 2479 women (51.7%) and 2317 men (48.3%) were randomized. Women were older and had more obesity, less coronary disease, and lower estimated glomerular filtration rate and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels than men. For the primary outcome, the rate ratio for sacubitril-valsartan versus valsartan was 0.73 (95% CI, 0.59-0.90) in women and 1.03 (95% CI, 0.84-1.25) in men (P interaction = 0.017). The benefit from sacubitril-valsartan was attributable to reduction in heart failure hospitalization. The improvement in New York Heart Association class and renal function with sacubitril-valsartan was similar in women and men, whereas the improvement in Kansas City Cardiomyopathy Questionnaire clinical summary score was less in women than in men. The difference in adverse events between sacubitril-valsartan and valsartan was similar in women and men. CONCLUSIONS: As compared with valsartan, sacubitril-valsartan seemed to reduce the risk of heart failure hospitalization more in women than in men. Whereas the possible sex-related modification of the effect of treatment has several potential explanations, the present study does not provide a definite mechanistic basis for this finding. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov. Unique identifier: NCT01920711.
Assuntos
Aminobutiratos/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Fatores Sexuais , Tetrazóis/farmacologia , Valsartana/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Aminobutiratos/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Compostos de Bifenilo , Combinação de Medicamentos , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico/efeitos dos fármacos , Tetrazóis/efeitos adversos , Valsartana/efeitos adversosRESUMO
It is over 4 years since the Prospective Comparison of angiotensin receptor/neprilysin inhibitor (ARNI) with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial was published in New England Journal of Medicine. The PARADIGM-HF trial was the one that contributed to the official approval to use ARNI simultaneously with cardiac resynchronisation therapy (CRT) or implantable cardioverter-defibrillator (ICD) in patients who receive optimal medical treatment and still presented NYHA II-IV class symptoms according to the 2016 European Society of Cardiology Guidelines for the diagnosis and treatment of acute and chronic heart failure. The aim of this article is to summarise current knowledge on the activity of ARNI in a selected group of patients with heart failure with reduced ejection fraction (HFrEF) based on a recent PARADIGM-HF subanalysis in the field of renal function in patients with and without chronic kidney disease, glycaemia control in patients with diabetes, ventricular arrhythmias and sudden cardiac death and health-related quality of life. This article includes also recently announced findings on the TRANSITION study which revealed that HFrEF therapy with ARNI might be safely initiated after an acute decompensated heart failure episode, including patients with heart failure de novo and ACEI/ARB naïve, both hospitalised or shortly after discharge, in contrary to the PARADIGM-HF trial, where patients had to be administered a stable dose of an ACEI/ARB equivalent to enalapril 10 mg a day for at least 4 weeks before the screening.
Assuntos
Aminobutiratos/uso terapêutico , Ensaios Clínicos como Assunto , Enalapril/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Neprilisina/antagonistas & inibidores , Volume Sistólico/fisiologia , Tetrazóis/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Humanos , ValsartanaRESUMO
BACKGROUND: Pregnant women with a mechanical heart valve (MHV) are at a heightened risk of a thrombotic event, and their absolute need for adequate anticoagulation puts them at considerable risk of bleeding and, with some anticoagulants, fetotoxicity. METHODS AND RESULTS: Within the prospective, observational, contemporary, worldwide Registry of Pregnancy and Cardiac disease (ROPAC), we describe the pregnancy outcome of 212 patients with an MHV. We compare them with 134 patients with a tissue heart valve and 2620 other patients without a prosthetic valve. Maternal mortality occurred in 1.4% of the patients with an MHV, in 1.5% of patients with a tissue heart valve (P=1.000), and in 0.2% of patients without a prosthetic valve (P=0.025). Mechanical valve thrombosis complicated pregnancy in 10 patients with an MHV (4.7%). In 5 of these patients, the valve thrombosis occurred in the first trimester, and all 5 patients had been switched to some form of heparin. Hemorrhagic events occurred in 23.1% of patients with an MHV, in 5.1% of patients with a tissue heart valve (P<0.001), and in 4.9% of patients without a prosthetic valve (P<0.001). Only 58% of the patients with an MHV had a pregnancy free of serious adverse events compared with 79% of patients with a tissue heart valve (P<0.001) and 78% of patients without a prosthetic valve (P<0.001). Vitamin K antagonist use in the first trimester compared with heparin was associated with a higher rate of miscarriage (28.6% versus 9.2%; P<0.001) and late fetal death (7.1% versus 0.7%; P=0.016). CONCLUSIONS: Women with an MHV have only a 58% chance of experiencing an uncomplicated pregnancy with a live birth. The markedly increased mortality and morbidity warrant extensive prepregnancy counseling and centralization of care.
Assuntos
Cardiologia , Próteses Valvulares Cardíacas , Complicações Cardiovasculares na Gravidez/diagnóstico , Complicações Cardiovasculares na Gravidez/mortalidade , Sistema de Registros , Sociedades Médicas , Adulto , Cardiologia/tendências , Bases de Dados Factuais/tendências , Europa (Continente)/epidemiologia , Feminino , Cardiopatias/diagnóstico , Cardiopatias/mortalidade , Próteses Valvulares Cardíacas/tendências , Humanos , Mortalidade/tendências , Gravidez , Estudos Prospectivos , Sociedades Médicas/tendências , Adulto JovemRESUMO
INTRODUCTION: It is well known that the prevalence of atrial fibrillation (AF) increases with age. The purpose was to evaluate the impact of AF at the 1-year outcome of patients aged 80? who suffered from chronic heart failure (CHF). MATERIALS AND METHODS: The study included 220 consecutive patients at age 8092 (mean 82.8 years, 45.5 % men) hospitalized for heart failure. The prospective analysis contains demographic and clinical data, basic laboratory tests with hsTnT and NT-proBNP, 12-lead resting electrocardiogram, echocardiography and coronary angiography results and the number of deaths at the 1-year followup. Patients were analyzed depending on AF in the resting electrocardiogram at hospital entry. RESULTS: AF was recorded in 52 patients (24 %). The relationship with AF was found for more advanced NYHA class III and IV (p\0.001), higher concentrations of hsCRP (p = 0.0005), hsTnT (p = 0.007) and NT-proBNP (p = 0.0098), higher heart rate in the electrocardiogram (p = 0.000) and longer hospitalization (p = 0.025), older age (p = 0.003) and lower left ventricular ejection fraction (p = 0.006). Annual mortality was 13 % and was higher if AF occurred (17 %). However, there was no association between deaths and AF (p = 0.3297). From the multivariate stepwise analysis, independent risk factors for annual mortality were male gender (OR = 3.432; p = 0.043), left ventricular systolic dimension (OR = 1.871; p = 0.004) and dyslipidemia (OR = 0.252; p = 0.043). CONCLUSIONS: In the oldest patients aged 80? who suffered from CHF, the incidence of atrial fibrillation and annual mortality was high. The independent variables, which enhanced the risk of death at the 1-year follow-up, were male sex and left ventricular systolic dimension, but not atrial fibrillation.
Assuntos
Fibrilação Atrial/diagnóstico , Fibrilação Atrial/patologia , Idoso de 80 Anos ou mais , Fibrilação Atrial/fisiopatologia , Doença Crônica , Ecocardiografia/métodos , Eletrocardiografia/métodos , Feminino , Insuficiência Cardíaca/patologia , Frequência Cardíaca/fisiologia , Hospitalização , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Função Ventricular Esquerda/fisiologiaRESUMO
Quality of life (QoL) is a therapeutic goal in heart failure. There are many EBM therapies for improving QoL. In this study, data is presented on new pharmacotherapies and devices that impact QoL in the heart failure population.
Assuntos
Insuficiência Cardíaca , Qualidade de Vida , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológicoRESUMO
Diagnosis of heart failure with preserved ejection fraction (HFpEF) may be challenging owing to the heterogeneous clinical presentation and comorbidities in this population of patients, along with the limited availability of standard diagnostic tools, including natriuretic peptide tests and functional testing. This expert opinion summarizes the current state of knowledge on the identification and therapy for patients with HFpEF based on recent European and American recommendations. This expert opinion aims to aid clinicians in HFpEF management.
Assuntos
Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/tratamento farmacológico , Prova Pericial , Polônia , Volume Sistólico , ComorbidadeRESUMO
BACKGROUND: The glucagon-like peptide-1 receptor agonist, semaglutide, improved health status and reduced body weight in patients with obesity-related heart failure (HF) with preserved ejection fraction (HFpEF) in the STEP-HFpEF (Semaglutide Treatment Effect in People with Obesity and HFpEF) program. Whether benefits were due to mechanical unloading or effects on HF pathobiology is uncertain. OBJECTIVES: This study sought to determine if semaglutide 2.4 mg reduced N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with obesity-related HFpEF and compare treatment responses by baseline NT-proBNP. METHODS: This was a prespecified secondary analysis of pooled data from 2 double-blind, placebo-controlled, randomized trials (STEP-HFpEF [Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity] and STEP-HFpEF DM [Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes]) testing effects of semaglutide in patients with obesity-related HFpEF. The main outcomes were change in NT-proBNP at 52 weeks and change in the dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score and body weight by baseline NT-proBNP. RESULTS: In total, 1,145 patients were randomized. Semaglutide compared with placebo reduced NT-proBNP at 52 weeks (estimated treatment ratio: 0.82; 95% CI: 0.74-0.91; P = 0.0002). Improvements in health status were more pronounced in those with higher vs lower baseline NT-proBNP (estimated difference: tertile 1: 4.5 points, 95% CI: 0.8-8.2; tertile 2: 6.2 points, 95% CI: 2.4-10.0; tertile 3: 11.9 points, 95% CI: 8.1-15.7; P interaction = 0.02; baseline NT-proBNP as a continuous variable: P interaction = 0.004). Reductions in body weight were consistent across baseline NT-proBNP levels (P interaction = 0.21). CONCLUSIONS: In patients with obesity-related HFpEF, semaglutide reduced NT-proBNP. Participants with higher baseline NT-proBNP had a similar degree of weight loss but experienced larger reductions in HF-related symptoms and physical limitations with semaglutide than those with lower NT-proBNP.
Assuntos
Peptídeos Semelhantes ao Glucagon , Insuficiência Cardíaca , Peptídeo Natriurético Encefálico , Obesidade , Fragmentos de Peptídeos , Volume Sistólico , Humanos , Peptídeo Natriurético Encefálico/sangue , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Fragmentos de Peptídeos/sangue , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Masculino , Feminino , Método Duplo-Cego , Idoso , Obesidade/sangue , Obesidade/complicações , Obesidade/tratamento farmacológico , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/fisiologia , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: The use of urinary sodium to guide diuretics in acute heart failure is recommended by experts and the most recent European Society of Cardiology guidelines. However, there are limited data to support this recommendation. The ENACT-HF study (Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure) investigated the feasibility and efficacy of a standardized natriuresis-guided diuretic protocol in patients with acute heart failure and signs of volume overload. METHODS: ENACT-HF was an international, multicenter, open-label, pragmatic, 2-phase study, comparing the current standard of care of each center with a standardized diuretic protocol, including urinary sodium to guide therapy. The primary end point was natriuresis after 1 day. Secondary end points included cumulative natriuresis and diuresis after 2 days of treatment, length of stay, and in-hospital mortality. All end points were adjusted for baseline differences between both treatment arms. RESULTS: Four hundred one patients from 29 centers in 18 countries worldwide were included in the study. The natriuresis after 1 day was significantly higher in the protocol arm compared with the standard of care arm (282 versus 174 mmol; adjusted mean ratio, 1.64; P<0.001). After 2 days, the natriuresis remained higher in the protocol arm (538 versus 365 mmol; adjusted mean ratio, 1.52; P<0.001), with a significantly higher diuresis (5776 versus 4381 mL; adjusted mean ratio, 1.33; P<0.001). The protocol arm had a shorter length of stay (5.8 versus 7.0 days; adjusted mean ratio, 0.87; P=0.036). In-hospital mortality was low and did not significantly differ between the 2 arms (1.4% versus 2.0%; P=0.852). CONCLUSIONS: A standardized natriuresis-guided diuretic protocol to guide decongestion in acute heart failure was feasible, safe, and resulted in higher natriuresis and diuresis, as well as a shorter length of stay.
Assuntos
Diuréticos , Insuficiência Cardíaca , Humanos , Diuréticos/uso terapêutico , Natriurese , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Diurese , Sódio , Inibidores de Simportadores de Cloreto de Sódio e Potássio/efeitos adversosRESUMO
BACKGROUND: Early repolarization variant (ERV) was recently described as an electrocardiogram (ECG) pattern associated with increased risk of sudden cardiac death (SCD) in some populations. We decided to establish the significance of ERV in syncopal patients referred to tilt testing due to suspected reflex syncope. METHODS: From 160 consecutive patients (mean age 36.6 ± 15 years) history of syncopal episodes and resting ECG were collected. ERV was diagnosed if elevation of point J ≥ 0.1 mV was in ≥ 2 ECG leads II, III, aVF and/or I, aVL, V4-V6. Analysis was performed in regard to ERV and degree of J-point elevation (JPE; ≥ 2 mV vs <2 mV). Patients were at 2 years follow-up. RESULTS: ERV was present in 31% of patients. The most frequent was the ascending ST elevation variant (84%) and lateral ECG locations (74%). The degree of JPE did not differentiate the studied patients. Male sex was associated with the higher risk of ERV (odds ratio [OR] = 2.84; P = 0.003). ERV in inferior ECG leads enhanced the risk of positive tilt testing (OR = 3.57; P = 0.048). There was no relationship between ERV and injuries or syncopal history. No deaths were observed in follow-up. CONCLUSIONS: Among middle-aged people referred to tilt testing due to suspected reflex syncope the ascending ST elevation type was the most frequent variant of ERV and in midterm follow-up there were no deaths. In this population ERV was frequent and associated with positive tilt testing. According to recently described higher risk of SCD among people with ERV, we need further studies and longer follow-up to establish the clinical importance of ERV in patients with reflex syncope.
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Arritmias Cardíacas/fisiopatologia , Síncope/fisiopatologia , Teste da Mesa Inclinada , Adulto , Idoso , Arritmias Cardíacas/complicações , Distribuição de Qui-Quadrado , Morte Súbita Cardíaca/etiologia , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Síncope/complicaçõesRESUMO
This study investigates the potential role of 17 chosen polymorphisms in 15 candidate genes and the risk of myocardial infarction in patients under 45 years of age. The study consists of 271 patients with myocardial infarction and 141 controls. The analysis of genetic polymorphisms was performed using the PCR-RFLP method. Of the chosen polymorphisms, two (Leu125Val PECAM1 and A1/A2 FVII) are related to myocardial infarction and two (C677T MTHFR and 5A/6A MMP3) to advanced stenosis in arterial vessels (> 75%). We also found that the frequency of some combinations among the analyzed genes and environmental factors varied between the patient and control groups.
Assuntos
Infarto do Miocárdio/genética , Polimorfismo Genético , Adulto , Fatores Etários , Aterosclerose/etiologia , Aterosclerose/genética , Feminino , Triagem de Portadores Genéticos , Humanos , Hipertensão/genética , Masculino , Metaloproteinase 3 da Matriz/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Fatores de Risco , Fumar/genéticaRESUMO
According to the 2021 European Society of Cardiology guidelines, the four pillars of medical therapy in heart failure with reduced ejection fraction (HFrEF) include sodium-glucose co-transporter-2 inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and angiotensin-converting enzyme inhibitors or angiotensin receptor-neprilysin inhibitors. However, in clinical practice, concomitant use of all four drug groups in target doses is often limited by their intolerance or fear of potential complications. Herein, we present strategies to initiate or modify HFrEF therapy in frequent but challenging clinical scenarios (symptomatic hypotension, atrial fibrillation, kidney disease or worsening renal function, hyperkalemia) in a way that does not lead to unnecessary reduction or cessation of life-saving treatment.
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Insuficiência Cardíaca , Nefropatias , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Volume Sistólico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêuticoRESUMO
According to the 2021 European Society of Cardiology guidelines, the four pillars of medical therapy in heart failure with reduced ejection fraction (HFrEF) include sodium-glucose co-transporter-2 inhibitors, beta-blockers, mineralocorticoid receptor antagonists and angiotensin-converting enzyme inhibitors or angiotensin receptor-nephrilysin inhibitors. However, in clinical practice, concomitant use of all four drug groups in target doses is often limited by their intolerance or fear of potential complications. Herein, we present strategies to initiate or modify HFrEF therapy in frequent but challenging clinical scenarios (symptomatic hypotension, atrial fibrillation, kidney disease or worsening renal function, hyperkalemia) in a way that does not lead to unnecessary reduction or cessation of life-saving medications.
RESUMO
INTRODUCTION: Heart failure (HF) patients discharged from a hospital are at a high risk of death and rehospitalization. Scarce data are available on the use of sacubitril / valsartan in this population in Poland. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of sacubitril / valsartan in the group of Polish patients who participated in the TRANSITION study with the patients recruited at other sites. PATIENTS AND METHODS: This is a post hoc secondary analysis of the TRANSITION study comparing sacubitril / valsartan initiation pre- vs postdischarge in 991 patients hospitalized for acute decompensated HF with reduced ejection fraction (HFrEF). The Polish subgroup consisted of 104 patients. RESULTS: Significant differences were identified in the characteristics of Polish vs nonPolish populations. At baseline, the Polish population showed higher proportion of men, higher body mass index, lower heart rate, Nterminal pro-Btype natriuretic peptide and highsensitivity troponin T levels, and significantly lower New York Heart Association class. The Polish patients were better managed in terms of implanted electrotherapy devices, percutaneous coronary interventions, and drug therapy, and were more often hospitalized. The primary end point of achieving the target dose of sacubitril / valsartan at treatment week 10 was met by 45.6% of the Polish patients and 48.4% of the nonPolish population (P = 0.61). Approximately 90% of the Polish patients received and maintained any sacubitril / valsartan dose for 2 weeks over 10week treatment vs 87.5% of the nonPolish patients (P = 0.36). The rate of permanent sacubitril / valsartan treatment discontinuation was low in both Polish (3.9%) and nonPolish populations (6.4%) (P = 0.33). CONCLUSIONS: Sacubitril / valsartan can be used safely in the early period after an episode of acute HF both in the Polish and nonPolish patients with HFrEF, and the likelihood to achieve the maximum dose is the same despite significant differences between the studied populations.
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Insuficiência Cardíaca , Masculino , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Tetrazóis , Polônia , Assistência ao Convalescente , Volume Sistólico/fisiologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Alta do Paciente , Valsartana/uso terapêuticoRESUMO
Despite advances in the treatment of heart failure (HF), the rate of hospitalisation for exacerbations of the disease remains high. One of the underlying reasons is that recommended guidelines for the management of HF are still too rarely followed in daily practice. Disease exacerbation requiring inpatient treatment is always afactor that worsens the prognosis, and thus signals disease progression. This is also akey moment when therapy should be modified for HF exacerbation, or initiated in the case of newly diagnosed disease. Inpatient treatment and the peridischarge period is the time when the aetiology and mechanism of HF decompensation should be established. Therapy should be individualised based on aetiology, HF phenotype, and comorbidities; it should take into account the possibilities of modern treatment. According to the recommendations of the European Society of Cardiology (ESC), patients with HF should receive multidisciplinary management. Cooperation between the various members of the multidisciplinary team taking care of patients with HF improves the efficiency and quality of treatment. This document expands and details the information on the peridischarge management of HF contained in the 2021 ESC guidelines and the 2022 American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Failure Society of America (HFSA) guidelines.
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Cardiologia , Insuficiência Cardíaca , Humanos , Estados Unidos , Polônia , Medicina de Família e Comunidade , Médicos de Família , Alta do Paciente , Prova Pericial , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/diagnósticoRESUMO
Heart failure (HF) remains one of the most common causes of hospitalization and mortality among Polish patients. The position of the Section of Cardiovascular Pharmacotherapy presents the currently applicable options for pharmacological treatment of HF based on the latest European and American guidelines from 2021-2022 in relation to Polish healthcare conditions. Treatment of HF varies depending on its clinical presentation (acute/chronic) or left ventricular ejection fraction. Initial treatment of symptomatic patients with features of volume overload is based on diuretics, especially loop drugs. Treatment aimed at reducing mortality and hospitalization should include drugs blocking the renin-angiotensin-aldosterone system, preferably angiotensin receptor antagonist/neprilysin inhibitor, i.e. sacubitril/valsartan, selected beta-blockers (no class effect - options include bisoprolol, metoprolol succinate, or vasodilatory beta-blockers - carvedilol and nebivolol), mineralocorticoid receptor antagonist, and sodium-glucose cotransporter type 2 inhibitor (flozin), constituting the 4 pillars of pharmacotherapy. Their effectiveness has been confirmed in numerous prospective randomized trials. The current HF treatment strategy is based on the fastest possible implementation of all four mentioned classes of drugs due to their independent additive action. It is also important to individualize therapy according to comorbidities, blood pressure, resting heart rate, or the presence of arrhythmias. This article emphasizes the cardio- and nephroprotective role of flozins in HF therapy, regardless of ejection fraction value. We propose practical guidelines for the use of medicines, profile of adverse reactions, drug interactions, as well as pharmacoeconomic aspects. The principles of treatment with ivabradine, digoxin, vericiguat, iron supplementation, or antiplatelet and anticoagulant therapy are also discussed, along with recent novel drugs including omecamtiv mecarbil, tolvaptan, or coenzyme Q10 as well as progress in the prevention and treatment of hyperkalemia. Based on the latest recommendations, treatment regimens for different types of HF are discussed.