Spironolactone and preserved heart failure

Background and Objectives: Inhibitors of sodium-glucose cotransporter 2 (SGLT2i) reduce the risk of hospitalization for heart failure (HF). We aimed to examine the effect of empagliflozin on change of diuretics dose in outpatient HF patients. Methods: We retrospectively reviewed the medical records of 612 patients who were treated using both empagliflozin and diuretics. We excluded patients who did not meet the criteria for HF. Dose and duration of empagliflozin and diuretics were measured...

It remains unclear whether cumulative blood pressure (BP) exposure is associated with adverse outcomes in heart failure with preserved ejection fraction (HFpEF). The aim was to investigate the associations of adverse health outcomes with cumulative BP exposure as captured by weighted BP, cumulative BP and trends in BP over a 1-year timespan from baseline to a 12-month visit among 1303 patients with HFpEF (49.5% women; mean age, 71.5 years) enrolled in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial...

Epicardial adipose tissue (EAT) is a metabolically active organ which generates inflammatory cytokines. Thickness of EAT is associated with onset and development of heart failure with preserved ejection fraction (HFpEF). However, it is still unclear the specific mechanisms and pharmacological targets on EAT induced inflammation in HFpEF. A two-hit protocol with western diet and Nω -nitrol-arginine methyl ester (L-NAME) was used to establish HFpEF mouse model. In HFpEF mice, inflammatory biomarkers, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and von willebrand factor (vWF) elevated in myocardium compared to control...

AIMS: Spironolactone is currently used in a large proportion of patients with heart failure and preserved ejection fraction (HFpEF), yet its effect on cardiac structure and function in a large population has not been well established. The aim of this study was to evaluate the impact of spironolactone on key echocardiographic parameters in HFpEF. METHODS AND RESULTS: An individual-patient-data meta-analysis of three randomized trials (HOMAGE, Aldo-DHF, and TOPCAT) was performed comparing spironolactone (9-12 month exposure) to placebo (or control) for the changes in left atrial volume index (LAVi), left ventricular mass index (LVMi), interventricular septum (IVS) thickness, E/e' ratio, and left ventricular ejection fraction (LVEF) among patients with stage B (HOMAGE) or C (Aldo-DHF and TOPCAT) HFpEF...

INTRODUCTION: Mineralocorticoid receptor antagonists (MRAs) improve cardiovascular outcomes in patients with heart failure. These benefits of MRAs vary in different heart failure populations based on left ventricular ejection fraction and associated comorbidities. AREAS COVERED: We define the pharmacologic properties of MRAs and the pathophysiological rationale for their utility in heart failure. We outline the current literature on the use of MRAs in different heart failure populations, including reduced and preserved ejection fraction (HFrEF/HFpEF) and acute heart failure decompensation...

Heart failure with preserved left ventricular ejection fraction (HFpEF) is a serious condition with a constantly increasing prevalence which is in correlation with the increase of this disease's risk factors incidence (obesity, arterial hypertension, diabetes, etc.) and the aging of the population. The first challenge is the diagnosis of HFpEF. Two score-based algorithms have been proposed by the European (ESC HFA-PEFF score) and the American (ACC/AHA H2FpEF score) Cardiology Societies to help the clinician in the differential diagnosis of exertional dyspnea; these scores include the association of various signs of elevated ventricular filling pressures at rest and/or during exercise...

AIMS: We aimed to explore the heterogeneous treatment effects (HTEs) for spironolactone treatment in patients with Heart failure with preserved ejection fraction (HFpEF) and examine the efficacy and safety of spironolactone medication, ensuring a better individualized therapy. METHODS AND RESULTS: We used the causal forest algorithm to discover the heterogeneous treatment effects (HTEs) from patients in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial...

Background: Heart failure with preserved ejection fraction (HFpEF) patients varied by left ventricular ejection fraction (LVEF) have different clinical characteristics, prognosis, and treatment response. With data from our prospective HFpEF cohort, we assessed the possible relationship between clinical characteristics, outcome as well as treatment response and LVEF. Methods: We compared differences in baseline characteristics and clinical outcomes across LVEF categories (50%≤LVEF <60% vs...

BACKGROUND: The TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) suggested clinical benefits of spironolactone treatment among patients with heart failure with preserved ejection fraction enrolled in the Americas. However, a comprehensive assessment of biologic pathways impacted by spironolactone therapy in heart failure with preserved ejection fraction has not been performed. METHODS: We conducted aptamer-based proteomic analysis utilizing 5284 modified aptamers to 4928 unique proteins on plasma samples from TOPCAT participants from the Americas (n=164 subjects with paired samples at baseline and 1 year) to identify proteins and pathways impacted by spironolactone therapy in heart failure with preserved ejection fraction...

Heart failure with preserved ejection fraction (HFpEF) accounts for 15-20% of patients with heart failure (HF) in India. Diagnosis is by clinical features supported by biomarkers and echocardiography. Lifestyle modifications, control of risk factors to optimum levels, and treatment of comorbidities are essential in the management of HFpEF. Spironolactone and sacubitril-valsartan [angiotensin receptor neprilysin inhibitor (ARNI)] are beneficial in subsets of HFpEF, especially with lower range of ejection fraction (EF)...

OBJECTIVE: To determine whether time-averaged cumulative blood pressure (cumBP) is associated with the risk of cardiovascular outcomes among patients with heart failure with preserved ejection fraction. METHOD: Three thousand, three hundred and thirty participants from Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial were included in this analysis with a median follow-up of 3 years. CumBP, expressed as mmHg-years, was the sum of mean BP for each pair of successive examinations multiplied by the time...

The article discusses the problem of improving the effectiveness of treatment of heart failure with preserved left ventricular ejection fraction (HFpEF). The relative "failure" of early studies with renin-angiotensin-aldosterone system inhibitors was largely due to the lack of understanding that patients with HFpEF represent a heterogeneous group with various etiological factors and pathogenetic mechanisms of the disease. Therefore, the so-called personalized approach should be used in the treatment of these patients...

This phase Ib study compared the effects of AZD9977, a selective mineralocorticoid receptor modulator with predicted low hyperkalemia risk, with spironolactone on serum potassium (sK+ ) in patients with heart failure (HF) with preserved or mildly reduced EF (≥ 40%), and renal impairment. HF patients with EF ≥ 40% and estimated glomerular filtration rate of 40-70 mL/min/1.73 m2 were randomized to once-daily AZD9977 100 mg or spironolactone 25 mg for 14 days, up-titrated to AZD9977 200 mg or spironolactone 50 mg for another 14 days...

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BACKGROUND: Patients with heart failure (HF) with preserved ejection fraction are commonly admitted to the hospital for both cardiovascular (CV) and noncardiovascular (non-CV) reasons. The prognostic implications of non-CV hospitalizations in this population are not well understood. In this study, we aimed to examine the prognostic implications of hospitalizations owing to CV and non-CV reasons in a HF with preserved ejection fraction population. METHODS AND RESULTS: The Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial (TOPCAT) randomized 3445 stable outpatients with chronic HF with a left ventricular ejection fraction of 45% or greater and either prior hospitalization for HF or elevated natriuretic peptides to treatment with spironolactone or placebo...

AIMS: The aims of this study were to explore phenotypes of heart failure with preserved ejection fraction (HFpEF) and evaluate differential effects of spironolactone treatment. METHODS AND RESULTS: A swap-stepwise algorithm was used for variable selection. Latent class analysis based on 10 selected variables was employed in a derivative set of 1540 patients from the TOPCAT trial. Cox proportional hazard models were used to evaluate the prognoses and effects of spironolactone treatment...

BACKGROUND: The impact of the TOPCAT trial publication on spironolactone initiation and subsequent hospitalizations for hyperkalemia among patients with heart failure with preserved ejection fraction (HFpEF) has not been evaluated empirically. METHODS AND RESULTS: We designed a cohort study using US Medicare fee-for-service data. Annual cohorts of patients with HFpEF from 2013 to 2018 were identified based on a validated claims-based phenotyping model. We determined spironolactone initiation in each annual cohort overall and within subgroups with hyperkalemia risk factors of baseline renin-angiotensin system inhibitors use, chronic kidney disease, and diabetes...

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) have poor health-related quality of life (HR-QoL). However, the relationship between HR-QoL measures and the alterations of cardiac structure and function that are present in patients with HFpEF remains unknown. AIMS: To study the associations between HR-QoL and echocardiographic parameters in HFpEF. METHODS: Regression modelling in patients from TOPCAT-Americas who had both HR-QoL questionnaires and a baseline echocardiogram...

Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent syndrome with high cardiovascular and non-cardiovascular morbidity and mortality. Hypertension (HT) is one of its major risk factors and participates in its origin, development, and prognosis. The guidelines do not set out specific treatments, as clinical trials show limitations. Hypertension control is fundamental in the prevention and treatment of HFpEF. The guidelines recommend renin-angiotensin system blockade as the mainstay of hypertension treatment in patients with HFpEF...

AIMS: The HOMAGE randomized trial found that spironolactone reduced left atrial volume index (LAVI), E:A ratio, and a marker of collagen type I synthesis (procollagen type I C-terminal propeptide) in patients at risk of heart failure (HF). Previous trials showed that patients with HF, preserved ejection fraction and low serum collagen type I C-terminal telopeptide to matrix metalloproteinase-1 ratio (CITP:MMP-1), associated with high collagen cross-linking, had less improvement in diastolic function with spironolactone...