The Role of Mineralocorticoid Receptor Antagonists in the Management of Heart Failure with Preserved Ejection Fraction

2019 ◽  
Vol 24 (46) ◽  
pp. 5525-5527 ◽  
Author(s):  
Achilleas Papagiannis ◽  
Stelina Alkagiet ◽  
Konstantinos Tziomalos
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Mineralocorticoid Receptor ◽  
Therapeutic Potential ◽  
Preserved Ejection Fraction ◽  
Mineralocorticoid Receptor Antagonists ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Definition Of

Background: Heart failure with preserved ejection fraction (HFpEF) is associated with increased risk for hospitalization and all-cause mortality. Currently, there is no established treatment to improve the survival of these patients. Aldosterone appears to play a role in the pathogenesis of HFpEF. Objective: To discuss the findings of studies that evaluated the effects of mineralocorticoid receptor (MR) antagonists on the outcome of patients with HFpEF. Methods: PubMed was searched for relevant papers. References of retrieved articles were also evaluated for pertinent material. Results: Accumulating data suggest that MR antagonists might be useful in the management of patients with HFpEF. However, existing evidence is limited and conflicting. Conclusions: More studies are needed to clearly define the therapeutic potential of MR antagonists in HFpEF. Given the heterogeneity of this disease and the low specificity of the criteria used for its diagnosis, it is also important to improve the definition of HFpEF and include appropriately selected patients in these studies.

Effect of Mineralocorticoid Receptor Antagonists in Heart Failure with Preserved Ejection Fraction and with Reduced Ejection Fraction - A Narrative Review

2021 ◽  
Vol 19 ◽  
Author(s):  
Adriana Mares ◽  
Tayana Rodriguez ◽  
Abhizith Deoker ◽  
Angelica Lehker ◽  
Debabrata Mukherjee
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Mineralocorticoid Receptor ◽  
Narrative Review ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Mineralocorticoid Receptor Antagonists ◽  
Receptor Antagonists ◽  
Reduced Ejection Fraction

Background: Heart failure is a major cause of morbidity and mortality globally. By end of this decade, ~8 million Americans will have heart failure, with an expenditure of $69.8 billion. Objective: In this narrative review, we evaluate the benefits, potential risks, and role of Mineralocorticoid Receptor Antagonists (MRAs) in the management of both Heart Failure with Preserved Ejection Fraction (HFpEF) and Heart Failure with Reduced Ejection Fraction (HFrEF). Methods: We performed a comprehensive literature review to assess the available evidence on the role of MRAs in heart failure using the online databases (PubMed, Embase, Scopus, CINAHL, and Google Scholar). Results: Clinical evidence shows that MRAs, such as spironolactone and eplerenone, reduce mortality and readmissions for patients with HFrEF compared with placebo. Furthermore, one trial has reported that MRAs minimize heart failure hospitalization in patients with HFpEF. The American College of Cardiology/American Heart Association Guidelines strongly recommend using MRA in patients with reduced left ventricular ejection fraction (LVEF) with Class II-IV symptoms, estimated glomerular filtration rate >30 ml/min/1.73 m2, and absence of hyperkalemia. Despite this, MRAs are underutilized in the management of heart failure. Conclusions: MRAs improve outcomes in patients with both HFpEF and HFrEF but remain underutilized.

scholarly journals MR-proANP and incident cardiovascular disease in patients with type 2 diabetes with and without heart failure with preserved ejection fraction

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Jesper Jensen ◽  
Morten Schou ◽  
Caroline Kistorp ◽  
Jens Faber ◽  
Tine W. Hansen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ejection Fraction ◽  
Natriuretic Peptides ◽  
Continuous Variable ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Increased Risk ◽  
Definition Of

Abstract Background Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a useful biomarker in outpatients with type 2 diabetes (T2D) to diagnose heart failure (HF). Elevated B-type natriuretic peptides are included in the definition of HF with preserved ejection fraction (HFpEF) but little is known about the prognostic value of including A-type natriuretic peptides (MR-proANP) in the evaluation of patients with T2D. Methods We prospectively evaluated the risk of incident cardiovascular (CV) events in outpatients with T2D (n = 806, mean ± standard deviation age 64 ± 10 years, 65% male, median [interquartile range] duration of diabetes 12 [6–17] years, 17.5% with symptomatic HFpEF) according to MR-proANP levels and stratified according to HF-status including further stratification according to a prespecified cut-off level of MR-proANP. Results A total of 126 CV events occurred (median follow-up 4.8 [4.1–5.3] years). An elevated MR-proANP, with a cut-off of 60 pmol/l or as a continuous variable, was associated with incident CV events (p < 0.001). Compared to patients without HF, patients with HFpEF and high MR-proANP (≥ 60 pmol/l; median 124 [89–202] pmol/l) and patients with HF and reduced ejection fraction (HFrEF) had a higher risk of CV events (multivariable model; hazard ratio (HR) 2.56 [95% CI 1.64–4.00] and 3.32 [1.64–6.74], respectively). Conversely, patients with HFpEF and low MR-proANP (< 60 pmol/l; median 46 [32–56] pmol/l) did not have an increased risk (HR 2.18 [0.78–6.14]). Conclusions Patients with T2D and HFpEF with high MR-proANP levels had an increased risk for CV events compared to patients with HFpEF without elevated MR-proANP and compared to patients without HF, supporting the use of MR-proANP in the definition of HFpEF from a prognostic point-of-view.

scholarly journals Cardiac Tissue Factor Regulates Inflammation, Hypertrophy and Heart Failure in Mouse Model of Type 1 Diabetes

2021 ◽  
Author(s):  
Dasan Mary Cibi ◽  
Reddemma Sandireddy ◽  
Hanumakumar Bogireddy ◽  
Nicole Tee ◽  
Siti Aishah Binte Abdul Ghani ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Tissue Factor ◽  
Cardiac Tissue ◽  
Immune Cell ◽  
Preserved Ejection Fraction ◽  
Cardiac Inflammation ◽  
Protein Levels ◽  
Increased Risk

Diabetes patients have an increased risk of heart failure (HF). Diabetes is highly prevalent in HF with preserved ejection fraction (HFpEF), which is on the rise worldwide. The role of diabetes in HF is less established and available treatments of HF are not effective in HFpEF patients. Tissue factor (TF), a transmembrane receptor, plays an important role in immune-cell inflammation and atherothrombosis in diabetes. However, its role in diabetes-induced cardiac inflammation, hypertrophy, and HF has not been studied. Here, we have utilized Wildtype (WT), heterozygous, and Low-TF (with 1% human TF) mice to determine TF’s role in <i>Type1 diabetes</i>-induced HF. We found significant upregulation of cardiac TF mRNA and protein levels in diabetic WT hearts compared to non-diabetic controls. WT diabetic hearts also exhibited increased inflammation and cardiac hypertrophy versus controls. However, these changes in cardiac inflammation and hypertrophy were not found in diabetic Low-TF mice compared to their non-diabetic controls. TF deficiency was also associated with improved cardiac function parameters suggestive of HFpEF, which was evident in diabetic WT mice. The TF regulation of inflammation and cardiac remodeling was further dependent on downstream ERK1/2 and STAT3 pathways. In summary, our study demonstrated an important role of TF in regulating diabetes-induced inflammation, hypertrophy, and remodeling of the heart leading to HF with preserved ejection fraction.

Abstract 12936: Impact of Mitral Regurgitation on Heart Failure Hospitalization and Mortality in Older Age Adults With a Preserved Ejection Fraction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ginger Y Jiang ◽  
Warren J Manning ◽  
Lawrence Markson ◽  
A. R Garan ◽  
Marwa A Sabe ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mitral Regurgitation ◽  
Ejection Fraction ◽  
Primary Outcome ◽  
Secondary Outcome ◽  
P Value ◽  
Preserved Ejection Fraction ◽  
Risk Of Death ◽  
Increased Risk ◽  
All Cause Mortality

Background: The effect of mitral regurgitation (MR) severity on heart failure (HF) hospitalization and mortality in individuals with a preserved ejection fraction (LVEF) and no prior HF history is uncertain. Methods: Transthoracic echocardiogram (TTE) reports from patients with an LVEF > 50% at our institution were linked to complete Medicare inpatient claims, 2003-2017. Patients with HF hospitalization within the 12 months prior to TTE were excluded. We evaluated the relationship of baseline MR severity and time to the composite of all-cause mortality or HF hospitalization using the Kaplan-Meier technique. Secondary outcomes included the individual components of all-cause mortality and HF hospitalization, adjusting for the competing risk of death with Fine-Gray methods. Results: A total of 18,315 individuals met inclusion criteria (77.6 ±7.7 years, 54.3% female). Over a median follow-up time of 6.5 (IQR 3.0 to 10.2) years, the primary endpoint occurred in 7566 individuals (50.6%) of whom 6,927 (37.8%) died and 1703 (13.9%) were admitted for HF at a median of 1.4 (IQR 0.2 to 4.3) years and 1.6 (IQR 0.2 to 4.3) years respectively ( Figure ). After multivariable adjustment, MR severity was not associated with the primary or secondary outcome at 1-, 3-, 5-, or 10-years after TTE (p > 0.05 for all). Mitral valve prolapse (MVP) was associated with decreased risk of the primary outcome at 1-year and 3-years (interaction p-value = 0.04 for both). Jet eccentricity did not impact the observed relationship (interaction p-value > 0.05). Conclusions: In this large, single institution echocardiographic study of individuals with preserved ejection fraction and no prior history of HF, MR severity was not associated with an increased risk of all-cause mortality or HF hospitalization. Presence of MVP was associated with decreased risk of the primary outcome with increasing MR severity.

The Role of Mineralocorticoid Receptor Antagonists in Heart Failure with Reduced Ejection Fraction

2019 ◽  
Vol 24 (46) ◽  
pp. 5517-5524 ◽  
Author(s):  
Vasilios Papademetriou ◽  
Maria Toumpourleka ◽  
Konstantinos P. Imprialos ◽  
Sofia Alataki ◽  
Alexandros Manafis ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Mineralocorticoid Receptor ◽  
Morbidity And Mortality ◽  
Current Evidence ◽  
Mineralocorticoid Receptor Antagonists ◽  
Receptor Antagonists ◽  
Level Of Evidence ◽  
Reduced Ejection Fraction

Background: Heart failure (HF) is a worldwide modern epidemic, associated with significant morbidity and mortality. Several causes have been identified for the syndrome, most of which share common pathophysiologic pathways, including neurohormonal activation. Central to the latter lies activation of the reninangiotensin- aldosterone system, and its effects on cardiovascular disease progression. Objectives: The aim of this review is to summarize the pathophysiology of aldosterone and the effects of its blockage in the failing heart, as well as to provide state-of-the-art evidence, and address future perspectives regarding the use of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction. Method: Literature was reviewed for studies that assess the pathophysiology of aldosterone in HF with reduced ejection fraction (HFrEF), and the effects of mineralocorticoid receptor antagonists (MRAs) in this condition. Results: Several major society guidelines have synthesized the available evidence on HFrEF management, and drugs that block the renin-angiotensin-aldosterone system at different levels continue to form the key component of standard of care for these patients. Mineralocorticoid receptor antagonists are an important part of HFrEF pharmacologic treatment, and their use is supported by a high level of evidence studies. This class of drugs demonstrated significant benefits for morbidity and mortality, across the spectrum oh HFrEF, including patients after acute myocardial infarction. Conclusion: Current evidence supports the central role of aldosterone in HFrEF progression, and the significant benefits on outcomes with the use of MRAs.

Mineralocorticoid receptor antagonists in heart failure with preserved ejection fraction (HFpEF)

2015 ◽  
Vol 200 ◽  
pp. 15-19 ◽  
Author(s):  
Annalisa Capuano ◽  
Cristina Scavone ◽  
Cristiana Vitale ◽  
Liberata Sportiello ◽  
Francesco Rossi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Mineralocorticoid Receptor ◽  
Preserved Ejection Fraction ◽  
Mineralocorticoid Receptor Antagonists ◽  
Receptor Antagonists

Abstract 12813: Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Mohan Satish ◽  
Raviteja Guddeti ◽  
Florian Wenzl ◽  
Ryan Walters ◽  
Venkata M Alla
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Systematic Review ◽  
Ejection Fraction ◽  
Meta Analysis ◽  
Excess Risk ◽  
Mortality Data ◽  
Preserved Ejection Fraction ◽  
Increased Risk ◽  
All Cause Mortality

Introduction: Due to shared risk factors and pathophysiology, atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) frequently coexist. However, the prognostic implications of AF in HFpEF are unclear with conflicting data. Herein, we conducted a systematic review and meta-analysis to assess the impact of concomitant AF on cardiovascular outcomes in patients with HFpEF. Methods: PubMed, Scopus, and Google Scholar were comprehensively searched through May 7th, 2020 for studies comparing outcomes of HFpEF patients with and without AF. Outcomes assessed were all-cause mortality and a composite of HF hospitalization or cardiovascular (CV) mortality. Data from selected studies were abstracted and pooled using a random-effects meta-analysis to calculate odds ratios (ORs) and 95% confidence intervals [CIs] for each of the outcomes. Results: Our final analysis included 10 studies with 27,440 HFpEF patients (43.2% with AF). AF was associated with significantly increased risk of all-cause mortality (OR 1.37 [1.17-1.61], p < 0.001, Fig. 1A), HF hospitalization or CV mortality (OR 1.66 [1.16-2.36], p = 0.005, Fig. 1B), and HF hospitalization alone (OR 1.34 [1.03-1.76], p = 0.03, Fig. 1C). However, AF was not associated with excess risk of CV mortality alone (OR 1.10 [0.79-1.52], p = 0.57, Fig. 1D). Conclusions: In patients with HFpEF, concomitant AF is associated with an increased risk of all-cause mortality and HF hospitalization. Further research into the mechanisms and interventions to mitigate this excess risk is necessary.

scholarly journals The clinical and prognostic value of late Gadolinium enhancement imaging in heart failure with mid-range and preserved ejection fraction

2021 ◽  
Author(s):  
Gijs van Woerden ◽  
Dirk J. van Veldhuisen ◽  
Thomas M. Gorter ◽  
Tineke P. Willems ◽  
Vanessa P. M. van Empel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Late Gadolinium Enhancement ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Regression Analyses ◽  
Gadolinium Enhancement ◽  
Increased Risk ◽  
All Cause Mortality

AbstractHeart failure (HF) with mid-range or preserved ejection fraction (HFmrEF; HFpEF) is a heterogeneous disorder that could benefit from strategies to identify subpopulations at increased risk. We tested the hypothesis that HFmrEF and HFpEF patients with myocardial scars detected with late gadolinium enhancement (LGE) are at increased risk for all-cause mortality. Symptomatic HF patients with left ventricular ejection fraction (LVEF) > 40%, who underwent cardiac magnetic resonance (CMR) imaging were included. The presence of myocardial LGE lesions was visually assessed. T1 mapping was performed to calculate extracellular volume (ECV). Multivariable logistic regression analyses were used to determine associations between clinical characteristics and LGE. Cox regression analyses were used to assess the association between LGE and all-cause mortality. A total of 110 consecutive patients were included (mean age 71 ± 10 years, 49% women, median N-terminal brain natriuretic peptide (NT-proBNP) 1259 pg/ml). LGE lesions were detected in 37 (34%) patients. Previous myocardial infarction and increased LV mass index were strong and independent predictors for the presence of LGE (odds ratio 6.32, 95% confidence interval (CI) 2.07–19.31, p = 0.001 and 1.68 (1.03–2.73), p = 0.04, respectively). ECV was increased in patients with LGE lesions compared to those without (28.6 vs. 26.6%, p = 0.04). The presence of LGE lesions was associated with a fivefold increase in the incidence of all-cause mortality (hazards ratio 5.3, CI 1.5–18.1, p = 0.009), independent of age, sex, New York Heart Association (NYHA) functional class, NT-proBNP, LGE mass and LVEF. Myocardial scarring on CMR is associated with increased mortality in HF patients with LVEF > 40% and may aid in selecting a subpopulation at increased risk.

Effect of Mineralocorticoid Receptor Antagonists in Individuals With Heart Failure With Preserved Ejection Fraction: A Systematic Review

2018 ◽  
Vol 24 (9) ◽  
pp. 618-621 ◽  
Author(s):  
Bárbara Pereira Fernandes ◽  
Lino Sergio Rocha Conceição ◽  
Paulo Ricardo Saquete Martins-Filho ◽  
Douglas Rafanelle Moura de Santana Motta ◽  
Vitor Oliveira Carvalho
Keyword(s):  
Heart Failure ◽  
Systematic Review ◽  
Ejection Fraction ◽  
Mineralocorticoid Receptor ◽  
Preserved Ejection Fraction ◽  
Mineralocorticoid Receptor Antagonists ◽  
Receptor Antagonists
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