RESUMEN
Importance: Accurate risk prediction of morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF) may help clinicians risk stratify and inform care decisions. Objective: To develop and validate a novel prediction model for clinical outcomes in patients with HFpEF using routinely collected variables and to compare it with a biomarker-driven approach. Design, Setting, and Participants: Data were used from the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial to derive the prediction model, and data from the Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction (PARAGON-HF) and the Irbesartan in Heart Failure With Preserved Ejection Fraction Study (I-PRESERVE) trials were used to validate it. The outcomes were the composite of HF hospitalization (HFH) or cardiovascular death, cardiovascular death, and all-cause death. A total of 30 baseline candidate variables were selected in a stepwise fashion using multivariable analyses to create the models. Data were analyzed from January 2023 to June 2023. Exposures: Models to estimate the 1-year and 2-year risk of cardiovascular death or hospitalization for heart failure, cardiovascular death, and all-cause death. Results: Data from 6263 individuals in the DELIVER trial were used to derive the prediction model and data from 4796 individuals in the PARAGON-HF trial and 4128 individuals in the I-PRESERVE trial were used to validate it. The final prediction model for the composite outcome included 11 variables: N-terminal pro-brain natriuretic peptide (NT-proBNP) level, HFH within the past 6 months, creatinine level, diabetes, geographic region, HF duration, treatment with a sodium-glucose cotransporter 2 inhibitor, chronic obstructive pulmonary disease, transient ischemic attack/stroke, any previous HFH, and heart rate. This model showed good discrimination (C statistic at 1 year, 0.73; 95% CI, 0.71-0.75) in both validation cohorts (C statistic at 1 year, 0.71; 95% CI, 0.69-0.74 in PARAGON-HF and 0.75; 95% CI, 0.73-0.78 in I-PRESERVE) and calibration. The model showed similar discrimination to a biomarker-driven model including high-sensitivity cardiac troponin T and significantly better discrimination than the Meta-Analysis Global Group in Chronic (MAGGIC) risk score (C statistic at 1 year, 0.60; 95% CI, 0.58-0.63; delta C statistic, 0.13; 95% CI, 0.10-0.15; P < .001) and NT-proBNP level alone (C statistic at 1 year, 0.66; 95% CI, 0.64-0.68; delta C statistic, 0.07; 95% CI, 0.05-0.08; P < .001). Models derived for the prediction of all-cause and cardiovascular death also performed well. An online calculator was created to allow calculation of an individual's risk. Conclusions and Relevance: In this prognostic study, a robust prediction model for clinical outcomes in HFpEF was developed and validated using routinely collected variables. The model performed better than NT-proBNP level alone. The model may help clinicians to identify high-risk patients and guide treatment decisions in HFpEF.
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Causas de Muerte , Insuficiencia Cardíaca Diastólica , Modelos Cardiovasculares , Humanos , Masculino , Insuficiencia Cardíaca Diastólica/diagnóstico , Insuficiencia Cardíaca Diastólica/mortalidad , Modelos de Riesgos Proporcionales , PronósticoRESUMEN
AIMS: This study aimed to identify the impact of increased epicardial adipose tissue (EAT) and its regional distribution on cardiac function in patients with diastolic dysfunction. METHODS AND RESULTS: Sixty-eight patients with exertional dyspnoea (New York Heart Association ≥II), preserved ejection fraction (≥50%), and diastolic dysfunction (E/e' ≥ 8) underwent rest and stress right heart catheterization, transthoracic echocardiography, and cardiovascular magnetic resonance (CMR). EAT volumes were depicted from CMR short-axis stacks. First, the impact of increased EAT above the median was investigated. Second, the association of ventricular and atrial EAT with myocardial deformation at rest and during exercise stress was analysed in a multivariable regression analysis. Patients with high EAT had higher HFA-PEFF and H2FPEFF scores as well as N-terminal prohormone of brain natriuretic peptide levels (all P < 0.048). They were diagnosed with manifest heart failure with preserved ejection fraction (HFpEF) more frequently (low EAT: 37% vs. high EAT: 64%; P = 0.029) and had signs of adverse remodelling indicated by higher T1 times (P < 0.001). No differences in biventricular volumetry and left ventricular mass (all P > 0.074) were observed. Patients with high EAT had impaired atrial strain at rest and during exercise stress, and impaired ventricular strain during exercise stress. Regionally increased EAT was independently associated with functional impairment of the adjacent chambers. CONCLUSIONS: Patients with diastolic dysfunction and increased EAT show more pronounced signs of diastolic functional failure and adverse structural remodelling. Despite similar morphological characteristics, patients with high EAT show significant cardiac functional impairment, in particular in the atria. Our results indicate that regionally increased EAT directly induces atrial functional failure, which represents a distinct pathophysiological feature in HFpEF.
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Tejido Adiposo , Diástole , Imagen por Resonancia Cinemagnética , Pericardio , Volumen Sistólico , Humanos , Masculino , Femenino , Pericardio/diagnóstico por imagen , Pericardio/fisiopatología , Tejido Adiposo/fisiopatología , Tejido Adiposo/diagnóstico por imagen , Imagen por Resonancia Cinemagnética/métodos , Volumen Sistólico/fisiología , Persona de Mediana Edad , Anciano , Función Ventricular Izquierda/fisiología , Ecocardiografía , Insuficiencia Cardíaca Diastólica/fisiopatología , Insuficiencia Cardíaca Diastólica/diagnóstico , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagen , Estudios de Seguimiento , Cateterismo Cardíaco , Tejido Adiposo EpicárdicoAsunto(s)
Insuficiencia Cardíaca Diastólica , Defectos del Tabique Interatrial , Hipertensión Arterial Pulmonar , Humanos , Insuficiencia Cardíaca Diastólica/fisiopatología , Insuficiencia Cardíaca Diastólica/diagnóstico , Defectos del Tabique Interatrial/complicaciones , Defectos del Tabique Interatrial/fisiopatología , Defectos del Tabique Interatrial/diagnóstico , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/diagnóstico , Femenino , Persona de Mediana EdadRESUMEN
Diastolic heart failure (DHF), in which impaired ventricular filling leads to typical heart failure symptoms, represents over 50% of all heart failure cases and is linked with risk factors, including metabolic syndrome, hypertension, diabetes, and aging. A substantial proportion of patients with this disorder maintain normal left ventricular systolic function, as assessed by ejection fraction. Despite the high prevalence of DHF, no effective therapeutic agents are available to treat this condition, partially because the molecular mechanisms of diastolic dysfunction remain poorly understood. As such, by focusing on the underlying molecular and cellular processes contributing to DHF can yield new insights that can represent an exciting new avenue and propose a novel therapeutic approach for DHF treatment. This review discusses new developments from basic and clinical/translational research to highlight current knowledge gaps, help define molecular determinants of diastolic dysfunction, and clarify new targets for treatment.
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Insuficiencia Cardíaca Diastólica , Insuficiencia Cardíaca , Hipertensión , Disfunción Ventricular Izquierda , Humanos , Insuficiencia Cardíaca Diastólica/diagnóstico , Miofibrillas , Hipertensión/complicaciones , Factores de Riesgo , Diástole , Volumen SistólicoRESUMEN
La insuficiencia cardíaca con fracción de eyección preservada (ICFEp) y reducida presentan marcadas diferencias. Mientras que la última tiene un algoritmo diagnóstico y terapéutico desde hace años, con guías y fármacos que mejoran su pronóstico, la ICFEp no solo presenta dificultades para llegar al diagnóstico, sino que tampoco hay fármacos que hayan demostrado disminuir la mortalidad. En esta revisión se hace un abordaje amplio de la ICFEp, comenzando por definirla y distinguirla de la disfunción diastólica. Se describe el gold standard para su diagnóstico invasivo y se analizan los scores no invasivos recientemente desarrollados que estiman la probabilidad de tener la enfermedad. A través del análisis de las comorbilidades frecuentemente asociadas, se describen los mecanismos fisiopatológicos implicados. Asimismo, se detallan los fenotipos propuestos para agrupar pacientes y diseñar ensayos clínicos con fármacos que prueben disminuir la mortalidad. Por último, se reseñan las medidas terapéuticas no farmacológicas y farmacológicas recomendadas.
Heart failure with preserved and reduced ejection fraction have significant differences. While the latter has had a diagnostic and therapeutic algorithm for years, with guidelines and drugs that improve its prognosis, heart failure with preserved ejection fraction (HFpEF) not only presents difficulties in reaching a diagnosis, but also there are no drugs that have been proven to be effective in reducing mortality. In this review, a broad approach to HFpEF is made, beginning by defining it and distinguishing it from diastolic dysfunction. The gold standard for its invasive diagnosis is described and recently developed non-invasive scores that estimate the probability of having the disease are analyzed. Through the analysis of the frequently associated comorbidities, the pathophysiological mechanisms involved are described. Likewise, the phenotypes proposed to group patients and design clinical trials with drugs that try to reduce mortality are detailed. Finally, the recommended non-pharmacological and pharmacological therapeutic measures are outlined.
A insuficiência cardíaca com fração de ejeção preservada (ICFEp) e reduzida apresentam diferenças marcantes. Enquanto esta última conta com um algoritmo diagnóstico e terapêutico há anos, com diretrizes e medicamentos que melhoram seu prognóstico, a ICFEp não só apresenta dificuldades no diagnóstico, mas nenhum há medicamentos que tenham demonstrado reduzir a mortalidade. Nesta revisão, é feita uma abordagem ampla da ICFEp, começando por defini-la e distinguindo-a da disfunção diastólica. O padrão ouro para seu diagnóstico invasivo é descrito e são analisados os escores não invasivos recentemente desenvolvidos que estimam a probabilidade de ter a doença. Através da análise de comorbidades frequentemente associadas, são descritos os mecanismos fisiopatológicos envolvidos. Da mesma forma, são detalhados os fenótipos propostos para agrupar pacientes e desenhar ensaios clínicos com medicamentos que podem ser mostradas para reduzir a mortalidade. Por fim, são delineadas as medidas terapêuticas não farmacológicas e farmacológicas recomendadas.
Asunto(s)
Humanos , Insuficiencia Cardíaca Diastólica/fisiopatología , Factores de Riesgo , Insuficiencia Cardíaca Diastólica/diagnóstico , Insuficiencia Cardíaca Diastólica/terapiaRESUMEN
In August 2021, an update of the European Society of Cardiology-Heart Failure Association guideline for the diagnosis and treatment of heart failure was released. To review the changes implied by current guidelines regarding the diagnosis and treatment of patients with heart failure and preserved left ventricular ejection fraction (HFpEF). The diagnosis of HFpEF requires the combined presence of clinical signs, left ventricular ejection fraction ≥â¯50%, elevated natriuretic peptides, and elevated left ventricular filling pressure. If the diagnosis remains equivocal, a stress test is recommended. The targeted identification and treatment of comorbid conditions is key for a holistic therapeutic approach to HFpEF. Diuretics are recommended in congested patients with HFpEF in order to alleviate signs and symptoms. The treatment of diabetic patients with heart failure should include a sodium glucose co-transporter2 (SGLT2) inhibitor. All patients with HFpEF should be enrolled in a multidisciplinary heart failure management program aiming to improve self-care strategies and offer participation in an exercise program. It was recently shown for the first time in a randomized trial that hard clinical endpoints could be reduced in patients with HFpEF using the SGLT2 inhibitor empagliflozin. It is expected that this finding will become part of updated treatment recommendations in the near future. Although challenging, the early diagnosis of HFpEF is key to averting the poor prognosis associated with this frequent condition. Multidisciplinary care and innovative pharmacologic and non-pharmacologic therapies, however, can improve quality of life, exercise tolerance, and prognosis.
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Insuficiencia Cardíaca Diastólica , Insuficiencia Cardíaca , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca Diastólica/diagnóstico , Humanos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
BACKGROUND Heart failure (HF) most commonly occurs due to ischemic heart disease from stenotic coronary artery disease (CAD). HF is classified into 3 groups based on the percentage of the ejection fraction (EF): reduced (HFrEF), mid-range (HFmrEF), and preserved (HFpEF). This retrospective study included 573 patients who presented with HF based on the evaluation of EF and were evaluated for CAD by coronary angiography before undergoing coronary angioplasty at a single center in Toulouse, France. MATERIAL AND METHODS This retrospective observational study included patients recently diagnosed with HF or acute decompensation of chronic HF and referred for coronary angiography at Toulouse University Hospital between January 2019 and May 2020. RESULTS Significant CAD was found in 55.8%, 55%, and 55% of the whole population, HFpEF, and HFrEF groups, respectively. Older age, male sex, and diabetes mellitus were the main risk factors for ischemic HF. Except for age and sex, patients with ischemic HFpEF were comparable to those with non-ischemic HFpEF, unlike the ischemic HFrEF group, which had more common cardiovascular risk factors than the non-ischemic HFrEF group. The ischemic HFpEF group had an older age and higher rate of dyslipidemia than the ischemic HFrEF group. CONCLUSIONS At our center, CAD was diagnosed in more than half of patients who presented with heart failure with preserved or reduced EF. Older age and male sex were the common risk factors in patients with HFpEF and HFrEF.
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Angioplastia Coronaria con Balón , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Insuficiencia Cardíaca Diastólica , Insuficiencia Cardíaca Sistólica , Factores de Edad , Anciano , Angioplastia Coronaria con Balón/métodos , Angioplastia Coronaria con Balón/estadística & datos numéricos , Angiografía Coronaria/métodos , Angiografía Coronaria/estadística & datos numéricos , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/cirugía , Femenino , Francia/epidemiología , Factores de Riesgo de Enfermedad Cardiaca , Insuficiencia Cardíaca Diastólica/diagnóstico , Insuficiencia Cardíaca Diastólica/etiología , Insuficiencia Cardíaca Diastólica/fisiopatología , Insuficiencia Cardíaca Sistólica/diagnóstico , Insuficiencia Cardíaca Sistólica/etiología , Insuficiencia Cardíaca Sistólica/fisiopatología , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Volumen SistólicoRESUMEN
AIMS: Left ventricular diastolic dysfunction (LVDD) and LV systolic dysfunction (LVSD) are prevalent in CKD, but their prognostic relevance is debatable. We intent to verify whether LVDD and LVSD are independently predictive of all-cause mortality and if they have comparable or different effects on outcomes. METHODS: A retrospective analysis was conducted of the echocardiographic data of 1285 haemodialysis patients followed up until death or transplantation. LVDD was classified into 4 grades of severity. Endpoint was all-cause mortality. RESULTS: During a follow-up of 30 months, 419/1285 (33%) patients died, 224 (53%) due to CV events. LVDD occurred in 75% of patients, grade 1 DD was the prevalent diastolic abnormality, and pseudonormal pattern was the predominant form of moderate-severe DD. Moderate-severe LVDD (HR 1.379, CI% 1.074-1.770) and LVSD (HR 1.814, CI% 1.265-2.576) independently predicted death; a graded, progressive association was found between LVDD categories and the risk of death; and the impact of isolated severe-moderate LVDD on the risk of death was comparable to that exercised by isolated compromised LV systolic function. CONCLUSION: Moderate-severe LVDD and LVSD were independently associated with a higher probability of death and had a similar impact on survival. A progressive association was observed between LVDD grades and mortality.
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Insuficiencia Cardíaca Diastólica , Insuficiencia Cardíaca Sistólica , Diálisis Renal , Insuficiencia Renal Crónica , Disfunción Ventricular Izquierda , Anciano , Brasil/epidemiología , Ecocardiografía Doppler/métodos , Femenino , Insuficiencia Cardíaca Diastólica/diagnóstico , Insuficiencia Cardíaca Diastólica/epidemiología , Insuficiencia Cardíaca Diastólica/fisiopatología , Insuficiencia Cardíaca Sistólica/diagnóstico , Insuficiencia Cardíaca Sistólica/epidemiología , Insuficiencia Cardíaca Sistólica/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Mortalidad , Diálisis Renal/métodos , Diálisis Renal/estadística & datos numéricos , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia , Estudios Retrospectivos , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/mortalidad , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
BACKGROUND: Transient pulmonary congestion during exercise is emerging as an important determinant of reduced exercise capacity in heart failure with preserved ejection fraction (HFpEF). We sought to determine whether an abnormal cardiac energetic state underpins this process. METHODS: We recruited patients across the spectrum of diastolic dysfunction and HFpEF (controls, n=11; type 2 diabetes, n=9; HFpEF, n=14; and severe diastolic dysfunction attributable to cardiac amyloidosis, n=9). Cardiac energetics were measured using phosphorus spectroscopy to define the myocardial phosphocreatine to ATP ratio. Cardiac function was assessed by cardiovascular magnetic resonance cine imaging and echocardiography and lung water using magnetic resonance proton density mapping. Studies were performed at rest and during submaximal exercise using a magnetic resonance imaging ergometer. RESULTS: Paralleling the stepwise decline in diastolic function across the groups (E/e' ratio; P<0.001) was an increase in NT-proBNP (N-terminal pro-brain natriuretic peptide; P<0.001) and a reduction in phosphocreatine/ATP ratio (control, 2.15 [2.09, 2.29]; type 2 diabetes, 1.71 [1.61, 1.91]; HFpEF, 1.66 [1.44, 1.89]; cardiac amyloidosis, 1.30 [1.16, 1.53]; P<0.001). During 20-W exercise, lower left ventricular diastolic filling rates (r=0.58; P<0.001), lower left ventricular diastolic reserve (r=0.55; P<0.001), left atrial dilatation (r=-0.52; P<0.001), lower right ventricular contractile reserve (right ventricular ejection fraction change, r=0.57; P<0.001), and right atrial dilation (r=-0.71; P<0.001) were all linked to lower phosphocreatine/ATP ratio. Along with these changes, pulmonary proton density mapping revealed transient pulmonary congestion in patients with HFpEF (+4.4% [0.5, 6.4]; P=0.002) and cardiac amyloidosis (+6.4% [3.3, 10.0]; P=0.004), which was not seen in healthy controls (-0.1% [-1.9, 2.1]; P=0.89) or type 2 diabetes without HFpEF (+0.8% [-1.7, 1.9]; P=0.82). The development of exercise-induced pulmonary congestion was associated with lower phosphocreatine/ATP ratio (r=-0.43; P=0.004). CONCLUSIONS: A gradient of myocardial energetic deficit exists across the spectrum of HFpEF. Even at low workload, this energetic deficit is related to markedly abnormal exercise responses in all 4 cardiac chambers, which is associated with detectable pulmonary congestion. The findings support an energetic basis for transient pulmonary congestion in HFpEF.
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Ejercicio Físico/efectos adversos , Insuficiencia Cardíaca Diastólica/diagnóstico , Insuficiencia Cardíaca Diastólica/etiología , Hiperemia/complicaciones , Hiperemia/fisiopatología , Circulación Pulmonar , Anciano , Biomarcadores , Susceptibilidad a Enfermedades , Ecocardiografía , Prueba de Esfuerzo , Femenino , Pruebas de Función Cardíaca , Humanos , Hiperemia/diagnóstico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Edema Pulmonar/diagnóstico , Índice de Severidad de la Enfermedad , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
OBJECTIVE: The study aimed to investigate the functional capacity and hemodynamics at rest and during exercise in patients with chronic atrial fibrillation and severe functional symptomatic tricuspid regurgitation (AF-FTR). BACKGROUND: Symptoms and clinical performance of severe AF-FTR mimic the population of patients with heart failure with preserved ejection fraction (HFpEF). Severe AF-FTR is known to be associated with an adverse prognosis whereas less is reported about the clinical performance including exercise capacity and hemodynamics in patients symptomatic AF-FTR. METHODS: Right heart catheterization (RHC) at rest and during exercise was conducted in a group of patients with stable chronic AF-TR and compared with a group of patients with HFpEF diagnosed with cardiac amyloid cardiomyopathy (CA). All patients had preserved ejection fraction and no significant left-sided disease. RESULTS: Patients with AF-FTR demonstrated a low exercise capacity that was comparable to CA patients (TR 4.9 ± 1.2 METS vs. CA 4. 7 ± 1.5 METS; P = 0.78) with an average peak maximal oxygen consumption of 15 mL/min/kg. Right atrium pressure increased significantly more in the AF-FTR patients as compared to CA patients at peak exercise (25 ± 8 vs 19 ± 9, p < 0.01) whereas PCWP increased significantly to a similar extent in both groups (31 ± 4 vs 31 ± 8 mmHg, p = 0.88). Cardiac output (CO) was significantly lower among AF-FTR at rest as compared to CA patients (3.6 ± 0.9 vs 4.4 ± 1.3 l/min; p < 0.05) whereas both groups demonstrated a poor but comparable CO reserve at peak exercise (7.3 ± 2.9 vs 7.9 ± 3.8 l/min, p = 0.59). CONCLUSIONS: AF-FTR contributes to the development of advanced heart failure symptoms and poor exercise capacity reflected in increased atrial filling pressures, reduced cardiac output at rest and during exercise sharing common features seen in HFpEF patients with other etiologies.
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Fibrilación Atrial/fisiopatología , Tolerancia al Ejercicio , Insuficiencia Cardíaca Diastólica/fisiopatología , Hemodinámica , Insuficiencia de la Válvula Tricúspide/fisiopatología , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Cateterismo Cardíaco , Estudios de Casos y Controles , Enfermedad Crónica , Prueba de Esfuerzo , Femenino , Estado Funcional , Insuficiencia Cardíaca Diastólica/diagnóstico , Insuficiencia Cardíaca Diastólica/etiología , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Insuficiencia de la Válvula Tricúspide/diagnóstico , Insuficiencia de la Válvula Tricúspide/etiologíaRESUMEN
BACKGROUND: Complicated pathophysiology makes it difficult to identify the prognosis of heart failure with preserved ejection fraction (HFpEF). While plasma osmolality has been reported to have prognostic importance, mainly in heart failure with reduced ejection fraction (HFrEF), its prognostic meaning for HFpEF has not been elucidated. METHODS: We prospectively studied 960 patients in PURSUIT-HFpEF, a multicenter observational study of acute decompensated HFpEF inpatients. We divided patients into three groups according to the quantile values of plasma osmolality on admission. During a follow-up averaging 366 days, we examined the primary composite endpoint of cardiac mortality or heart failure re-admission using Kaplan-Meier curve analysis and Cox proportional hazard testing. RESULTS: 216 (22.5%) patients reached the primary endpoint. Kaplan-Meier curve analysis revealed that the highest quantile of plasma osmolality on admission (higher than 300.3 mOsm/kg) was significantly associated with adverse outcomes (Log-rank P = 0.0095). Univariable analysis in the Cox proportional hazard model also revealed significantly higher rates of adverse outcomes in the higher plasma osmolality on admission (hazard ratio [HR] 7.29; 95% confidence interval [CI] 2.25-23.92, P = 0.0009). Multivariable analysis in the Cox proportional hazard model also showed that higher plasma osmolality on admission was significantly associated with adverse outcomes (HR 5.47; 95% CI 1.46-21.56, P = 0.0113) independently from other confounding factors such as age, gender, comorbid of atrial fibrillation, hypertension history, diabetes, anemia, malnutrition, E/e', and N-terminal pro-B-type natriuretic peptide elevation. CONCLUSIONS: Higher plasma osmolality on admission was prognostically important for acute decompensated HFpEF inpatients.
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Insuficiencia Cardíaca Diastólica/sangre , Admisión del Paciente , Volumen Sistólico , Función Ventricular Izquierda , Anciano , Anciano de 80 o más Años , Causas de Muerte , Femenino , Insuficiencia Cardíaca Diastólica/diagnóstico , Insuficiencia Cardíaca Diastólica/mortalidad , Insuficiencia Cardíaca Diastólica/fisiopatología , Humanos , Japón , Masculino , Concentración Osmolar , Readmisión del Paciente , Pronóstico , Estudios Prospectivos , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
INTRODUCTION: Diastolic heart failure (DHF) is an important pathological type of heart failure, that involves multiple organ dysfunction and multiple complications. The prevalence of DHF is high, and effective treatments are lacking. Chinese herbs are an alternative therapy for DHF. Shen'ge formula (SGF) is a classical formula from which patients can benefit, but convincing evidence of its efficacy is lacking. Therefore, we designed this randomized controlled trial protocol. METHODS/DESIGN: This randomized, double-blind, placebo-controlled clinical trial will evaluate the efficacy and safety of SGF in the treatment of DHF. A total of 130 patients with DHF will be enrolled in the trial and treated with SGF granules or placebo for 12âweeks and followed up for 12âweeks. The primary outcome measurement will be to changes in plasma N-terminal brain natriuretic peptide precursor before versus after treatment, while the second primary outcome measurement will be changes in heart function before versus after treatment and the 12-week follow-up period. It will also include echocardiography, a cardiopulmonary exercise test, cardiac function grading, traditional Chinese medicine syndrome score, and the Minnesota Heart Failure Quality of Life Scale. Adverse events will be evaluated throughout the trial. DISCUSSION: The results of this trial will demonstrate whether SGF could alleviate symptoms, improve cardiac function, reduce readmission rates, and improve quality of life of patients with DHF. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2000036533, registered on August 24, 2020.
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Medicamentos Herbarios Chinos/administración & dosificación , Insuficiencia Cardíaca Diastólica/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Medicamentos Herbarios Chinos/efectos adversos , Ecocardiografía , Prueba de Esfuerzo , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca Diastólica/sangre , Insuficiencia Cardíaca Diastólica/complicaciones , Insuficiencia Cardíaca Diastólica/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Placebos/administración & dosificación , Placebos/efectos adversos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Heart failure (HF) is associated with highly significant morbidity, mortality, and health care costs. Despite the significant advances in therapies and prevention, HF remains associated with poor clinical outcomes. Understanding the contractile force and kinetic changes at the level of cardiac muscle during end-stage HF in consideration of underlying etiology would be beneficial in developing targeted therapies that can help improve cardiac performance. OBJECTIVE: Investigate the impact of the primary etiology of HF (ischemic or non-ischemic) on left ventricular (LV) human myocardium force and kinetics of contraction and relaxation under near-physiological conditions. METHODS AND RESULTS: Contractile and kinetic parameters were assessed in LV intact trabeculae isolated from control non-failing (NF; n = 58) and end-stage failing ischemic (FI; n = 16) and non-ischemic (FNI; n = 38) human myocardium under baseline conditions, length-dependent activation, frequency-dependent activation, and response to the ß-adrenergic stimulation. At baseline, there were no significant differences in contractile force between the three groups; however, kinetics were impaired in failing myocardium with significant slowing down of relaxation kinetics in FNI compared to NF myocardium. Length-dependent activation was preserved and virtually identical in all groups. Frequency-dependent activation was clearly seen in NF myocardium (positive force frequency relationship [FFR]), while significantly impaired in both FI and FNI myocardium (negative FFR). Likewise, ß-adrenergic regulation of contraction was significantly impaired in both HF groups. CONCLUSIONS: End-stage failing myocardium exhibited impaired kinetics under baseline conditions as well as with the three contractile regulatory mechanisms. The pattern of these kinetic impairments in relation to NF myocardium was mainly impacted by etiology with a marked slowing down of kinetics in FNI myocardium. These findings suggest that not only force development, but also kinetics should be considered as a therapeutic target for improving cardiac performance and thus treatment of HF.
Asunto(s)
Susceptibilidad a Enfermedades , Insuficiencia Cardíaca Diastólica/etiología , Insuficiencia Cardíaca Diastólica/fisiopatología , Miocardio/metabolismo , Disfunción Ventricular Izquierda/complicaciones , Disfunción Ventricular Izquierda/metabolismo , Biomarcadores , Análisis de Datos , Femenino , Insuficiencia Cardíaca , Insuficiencia Cardíaca Diastólica/diagnóstico , Insuficiencia Cardíaca Diastólica/tratamiento farmacológico , Pruebas de Función Cardíaca , Frecuencia Cardíaca , Humanos , Isoproterenol/farmacología , Isoproterenol/uso terapéutico , Cinética , Masculino , Contracción Miocárdica , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/tratamiento farmacológicoRESUMEN
Abstract Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome, which accounts for about 50% of patients with heart failure (HF). The morbidity and mortality associated with HFpEF is similar to HFrEF. Clinical trials to date have failed to show a benefit of medical therapy for HFpEF, which may due to lack of uniform phenotypes and heterogeneous population. In addition, medical therapy proven for HFrEF may not address the pathophysiologic basis for HFpEF. Left atrial remodeling and dysfunction is central to HFpEF and accounts for secondary pulmonary hypertension and pulmonary vascular congestion that frequently occurs with exertion. Interatrial shunts represent a novel treatment modality for HFpEF. These shunts allow for left atrial decongestion and a reduction in pulmonary venous hypertension during exercise leading to improvements in hemodynamics, functional status and quality of life. Trials to date have demonstrated safety and short-term efficacy of these devices for HFpEF. The long-term benefits are currently being evaluated in ongoing trials. If effective, the use of interatrial shunts may be a new therapeutic paradigm for the treatment of HFpEF.
Asunto(s)
Insuficiencia Cardíaca Diastólica/cirugía , Reemplazo de la Válvula Aórtica Transcatéter , Equipos y Suministros , Insuficiencia Cardíaca Diastólica/diagnóstico , Insuficiencia Cardíaca Diastólica/fisiopatología , Insuficiencia Cardíaca Diastólica/mortalidad , Remodelación AtrialAsunto(s)
Compuestos de Bencidrilo/uso terapéutico , Glucósidos/uso terapéutico , Insuficiencia Cardíaca Diastólica/tratamiento farmacológico , Insuficiencia Cardíaca Sistólica/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Volumen Sistólico/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacos , Compuestos de Bencidrilo/efectos adversos , Glucósidos/efectos adversos , Insuficiencia Cardíaca Diastólica/diagnóstico , Insuficiencia Cardíaca Diastólica/fisiopatología , Insuficiencia Cardíaca Sistólica/diagnóstico , Insuficiencia Cardíaca Sistólica/fisiopatología , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Resultado del TratamientoRESUMEN
Background Myocardial fibrosis is an important contributor for development of diastolic dysfunction. We investigated the impact of sirolimus as primary immunosuppression on diastolic dysfunction and fibrosis progression among heart transplantation recipients. Methods and Results In 100 heart transplantation recipients who were either treated with a calcineurin inhibitor (CNI) (n=51) or converted from CNI to sirolimus (n=49), diastolic function parameters were assessed using serial echocardiograms and right heart catheterizations. Myocardial fibrosis was quantified on serial myocardial biopsies. After 3 years, lateral e' increased within the sirolimus group but decreased in the CNI group (0.02±0.04 versus -0.02±0.04 m/s delta change; P=0.003, respectively). Both pulmonary capillary wedge pressure and diastolic pulmonary artery pressure significantly decreased in the sirolimus group but remained unchanged in the CNI group (-1.50±2.59 versus 0.20±2.20 mm Hg/year; P=0.02; and -1.72±3.39 versus 0.82±2.59 mm Hg/year; P=0.005, respectively). A trend for increased percentage of fibrosis was seen in the sirolimus group (8.48±3.17 to 10.10±3.0%; P=0.07) as compared with marginally significant progression in the CNI group (8.76±3.87 to 10.56±4.34%; P=0.04). The percent change in fibrosis did not differ significantly between the groups (1.62±4.67 versus 1.80±5.31%, respectively; P=0.88). Conclusions Early conversion to sirolimus is associated with improvement in diastolic dysfunction and filling pressures as compared with CNI therapy. Whether this could be attributed to attenuation of myocardial fibrosis progression with sirolimus treatment warrants further investigation.
Asunto(s)
Inhibidores de la Calcineurina , Cardiomiopatías , Trasplante de Corazón , Miocardio/patología , Sirolimus , Biopsia/métodos , Inhibidores de la Calcineurina/administración & dosificación , Inhibidores de la Calcineurina/efectos adversos , Cateterismo Cardíaco/métodos , Cardiomiopatías/etiología , Cardiomiopatías/patología , Cardiomiopatías/fisiopatología , Ecocardiografía/métodos , Femenino , Fibrosis/etiología , Fibrosis/patología , Fibrosis/prevención & control , Insuficiencia Cardíaca Diastólica/diagnóstico , Insuficiencia Cardíaca Diastólica/etiología , Insuficiencia Cardíaca Diastólica/prevención & control , Trasplante de Corazón/efectos adversos , Trasplante de Corazón/métodos , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sirolimus/administración & dosificación , Sirolimus/efectos adversosRESUMEN
Heart failure with preserved ejection fraction (HFpEF), often referred to as diastolic heart failure, remains one of the more challenging forms of heart failure to treat. This is a condition in which patients may or may not have signs and symptoms of heart failure, and retain a left ventricular ejection fraction greater than 50%. The challenge to treating HFpEF is due to the paucity of clinical trials with specific therapies, and those that have been completed have yielded relatively neutral results. This has resulted in treatments that are aimed more towards associated conditions, such as hypertension, rather than the underlying pathophysiology. This article will review the epidemiology and pathophysiology of HFpEF, and discuss the current therapeutic modalities, and clinical trials. In addition, we will discuss an ongoing clinical trial and the impact it may hold on future treatment options.
Asunto(s)
Insuficiencia Cardíaca Diastólica , Insuficiencia Cardíaca , Hipertensión , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca Diastólica/diagnóstico , Insuficiencia Cardíaca Diastólica/tratamiento farmacológico , Insuficiencia Cardíaca Diastólica/epidemiología , Humanos , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Interleukin (IL)-17 and its related cytokines have been shown to be involved in myocardial fibrosis and irreversible ventricular remodelling, which have predictive values in the development of left ventricular diastolic dysfunction (LVDD). This study aimed to assess the correlation between IL-17 and LVDD, and investigate the prognostic value of IL-17 among patients with normal left ventricular ejection fraction (LVEF). METHODS: A total of 120 patients with normal LVEF underwent left ventricular (LV) catheterisation for LV end-diastolic pressure (LVEDP) measurement and routine echocardiography. The follow-up period was 30 (18, 35) months. RESULTS: The levels of IL-17 and IL-6 from the systemic blood were significantly increased in non-heart failure (HF) patients with LVDD (p<0.001). Receiver operating characteristic (ROC) revealed that the combination of IL-17 and IL-6 showed the highest diagnostic accuracy in predicting LVDD (AUC, 0.890; 95% CI, 0.835-0.945; p<0.001), and the cut-off value was 41.5 pg/mL. On logistic regression analysis, the increment of the combination of IL-17 and IL-6 was an independent predictor for the prognosis of LVDD (odds ratio, 1.25; 95% CI, 1.01-1.12; p<0.05). According to the cut-off value of the combination of IL-17 and IL-6, the patients with lower levels of IL-17 and IL-6 (<41.5 pg/mL group) had a better prognosis. The increased levels of IL17 and IL-6 were significantly correlated with the levels of fibrotic parameters. CONCLUSIONS: Assessment of LVDD by measuring the combination of IL-17 and IL-6 might provide valuable prognostic significance for non-HF patients with LVDD.