The role of the mineralocorticoid receptor and mineralocorticoid-receptor-directed therapies in heart failure

Endocrinology ◽  
2021 ◽  
Author(s):  
Morag J Young ◽  
Monica Kanki ◽  
Nikshay Karthigan ◽  
Penny Konstandopoulos
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Mineralocorticoid Receptor ◽  
Epithelial Tissue ◽  
Distal Nephron ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Electrolyte Homeostasis ◽  
The Impact

Abstract Mineralocorticoid receptor (MR) antagonists (MRA), also referred to as aldosterone blockers, are now well recognised for their clinical benefit in patients with heart failure with reduced ejection fraction (HFrEF). Recent studies have also shown MRA can improve outcomes in patients with ‘HFpEF’, where the ejection fraction is preserved but left ventriclar filling is reduced. While the MR is a steroid hormone receptor best known for anti-natriuretic actions on electrolyte homeostasis in the distal nephron, it is now estalished that the MR has many physiological and pathophysiological roles in the heart, vasculature and other non-epithelial tissue types. It is the impact of MR activation on these tissues that underpins the use of MRA in cardiovascular disease, in particular heart failure. This minireview will discuss the origins and the development of MRA and highlight how their use has evolved from the ‘potassium-sparing diuretics’ spironolactone and canrenone over 60 years ago, to the more receptor-selective eplerenone and most recently the emergence of new non-steroidal receptor antagonists esaxerenone and finerenone.

Prognostic role of myocardial work in patients with heart failure and reduced ejection fraction treated by sacubitril/valsartan

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Galli ◽  
Y Bouali ◽  
C Laurin ◽  
A Gallard ◽  
A Hubert ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Rank Test ◽  
Reduced Ejection Fraction ◽  
Non Invasive ◽  
Patients With Heart Failure ◽  
Increase Risk ◽  
Echocardiographic Examination ◽  
Constructive Work

Abstract Background The non-invasive assessment of myocardial work (MW) by pressure-strain loops analysis (PSL) is a relative new tool for the evaluation of myocardial performance. Sacubitril/Valsartan is a treatment for heart failure with reduced ejection fraction (HFrEF) which has a spectacular effect on the reduction of cardiovascular events (MACEs). Purposes of this study were to evaluate 1) the short and medium term effect of Sacubitril/Valsartan treatment on MW parameters; 2) the prognostic value of MW in this specific group of patients. Methods 79 patients with HFrEF (mean age: 66±12 years; LV ejection fraction: 28±9%) were prospectively included in the study and treated with Sacubitril/Valsartan. Echocardiographic examination was performed at baseline, and after 6- and 12-month of therapy with Sacubitril/Valsartan. Results Sacubitril/Valsartan significantly increased global myocardial constructive work (CW) (1023±449 vs 1424±484 mmHg%, p<0.0001) and myocardial work efficiency (WE) [87 (78–90) vs 90 (86–95), p<0.0001]. During FU (2.6±0.9 years), MACEs occurred in 13 (16%) patients. After correction for LV size, LVEF and WE, CW was the only predictor of MACEs (Table 1). A CW<910 mmHg (AUC=0.81, p<0.0001, Figure 1A) identified patients at particularly increase risk of MACEs [HR 11.09 (1.45–98.94), p=0.002, log-rank test p<0.0001] (Figure 1 B). Conclusions In patients with HFrEF who receive a comprehensive background beta-blocker and mineral-corticoid receptor antagonist therapy, Sacubitril/Valsartan induces a significant improvement of myocardial CW and WE. In this population, the estimation of CW before the initiation of Sacubitril/Valsartan therapy allows the prediction of MACEs. Funding Acknowledgement Type of funding source: None

Abstract 040: Mineralocorticoid Receptor Antagonists After Hospitalization of Patients With Heart Failure With a Reduced Ejection Fraction

2017 ◽  
Vol 10 (suppl_3) ◽  
Author(s):  
Matthew S Durstenfeld ◽  
Stuart D Katz ◽  
Hannah Park ◽  
Saul Blecker
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Mineralocorticoid Receptor ◽  
Secondary Diagnosis ◽  
Mineralocorticoid Receptor Antagonists ◽  
Principal Diagnosis ◽  
Receptor Antagonists ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Before And After

Background: Mineralocorticoid receptor antagonists (MRAs) are an important component of guideline-directed therapy for patients with heart failure with a reduced ejection fraction (HFrEF) but are underutilized in clinical practice. Hospitalization is a quality-improvement opportunity to increase appropriate use of MRAs, particularly as this therapy is associated with reduced readmission following both hospitalizations with a principal and secondary diagnosis of heart failure. We studied MRA prescription for heart failure patients before and after hospitalization. Methods: We performed a retrospective cohort study of adults hospitalized within an academic tertiary-care hospital system in 2013-2015 with a principal or secondary discharge diagnosis of heart failure. We included patients with ejection fraction ≤35%, systolic blood pressure ≥100 mm Hg, estimated glomerular filtration rate >30 ml/min/1.73 m 2 , and potassium <5.0 mEq/L. We recorded MRA prescription before and after hospitalization. We used McNemar’s test to compare MRA prescription before and after hospitalization, with pre-specified principal and secondary diagnosis subgroups. We used the chi-square test to compare prescriptions between groups. Results: Among 1176 hospitalizations of patients who met the inclusion criteria, the mean age was 72.7±13.4 years and 366 (31%) were female. Of these patients, 303 (25.8%) were prescribed MRAs prior to hospitalization and 331 (28.2%) were prescribed them at discharge, a small but statistically significant increase (p=0.02). Among patients previously prescribed MRAs, 241 (79.5%) continued them at discharge. Among 873 patients not previously prescribed MRAs, 90 (10.3%) had MRAs initiated at discharge. Among 347 patients with a principal diagnosis of heart failure, 95 had MRAs continued, 27 had MRAs discontinued, and 39 had MRAs initiated, a non-significant increase of 12 patients (+3.6%, p=0.14). Among 829 patients with a secondary diagnosis, 146 had MRAs continued, 35 had MRAs discontinued, and 51 had MRAs initiated, a non-significant increase of 16 patients (+1.9%, p=0.08). More patients with a principal diagnosis received MRAs at discharge: 134/347 (38.6%) compared to 197/829 (23.7%) patients discharged with a secondary diagnosis of HFrEF, p<0.0001; similarly, patients with a principal diagnosis of HFrEF had higher rates of MRA initiation at discharge: 39/225 (17.3%) versus 51/648 (7.9%), p=0.0004. Conclusions: Over 70% of hospitalized HFrEF patients did not receive MRAs before or after hospitalization. Although more patients with a principal diagnosis than secondary diagnosis of heart failure received MRAs and had them initiated, over 80% of eligible patients not on MRAs were not initiated on them at discharge. Hospitalization remains an opportunity to identify patients indicated for MRAs and initiate guideline-directed heart failure pharmacotherapy.

Abstract 12849: Changes in N-terminal Pro Brain Natriuretic Peptide Levels Predicts Mortality and Heart Failure Hospitalization in Patients With Heart Failure and Preserved Ejection Fraction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Gianluigi Savarese ◽  
Camilla Hage ◽  
Ulf Dahlström ◽  
Pasquale Perrone-Filardi ◽  
Lars H Lund
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Total Mortality ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
The Impact

Introduction: Changes in N-terminal pro brain natriuretic peptide (NT-proBNP) have been demonstrated to correlate with outcomes in patients with heart failure (HF) and reduced ejection fraction (EF). However the prognostic value of a change in NT-proBNP in patients with heart failure and preserved ejection fraction (HFPEF) is unknown. Hypothesis: To assess the impact of changes in NT-proBNP on all-cause mortality, HF hospitalization and their composite in an unselected population of patients with HFPEF. Methods: 643 outpatients (age 72+12 years; 41% females) with HFPEF (ejection fraction ≥40%) enrolled in the Swedish Heart Failure Registry between 2005 and 2012 and reporting NT-proBNP levels assessment at initial registration and at follow-up were prospectively studied. Patients were divided into 2 groups according the median value of NT-proBNP absolute change that was 0 pg/ml. Median follow-up from first measurement was 2.25 years (IQR: 1.43 to 3.81). Adjusted Cox’s regression models were performed using total mortality, HF hospitalization (with censoring at death) and their composite as outcomes. Results: After adjustments for 19 baseline variables including baseline NT-proBNP, as compared with an increase in NT-proBNP levels at 6 months (NT-proBNP change>0 pg/ml), a reduction in NT-proBNP levels (NT-proBNP change<0 pg/ml) was associated with a 45.2% reduction in risk of all-cause death (HR: 0.548; 95% CI: 0.378 to 0.796; p:0.002), a 50.1% reduction in risk of HF hospitalization (HR: 0.49; 95% CI: 0.362 to 0.689; p<0.001) and a 42.6% reduction in risk of the composite outcome (HR: 0.574; 95% CI: 0.435 to 0.758; p<0.001)(Figure). Conclusions: Reductions in NT-proBNP levels over time are independently associated with an improved prognosis in HFPEF patients. Changes in NT-proBNP could represent a surrogate outcome in phase 2 HFPEF trials.

scholarly journals Clinical Utility of Exercise Training in Heart Failure with Reduced and Preserved Ejection Fraction

2015 ◽  
Vol 9 ◽  
pp. CMC.S21372 ◽  
Author(s):  
Muhammad Asrar Ul Haq ◽  
Cheng Yee Goh ◽  
Itamar Levinger ◽  
Chiew Wong ◽  
David L. Hare
Keyword(s):  
Heart Failure ◽  
Exercise Training ◽  
Ejection Fraction ◽  
Exercise Tolerance ◽  
Exercise Intolerance ◽  
Sufficient Evidence ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure

Reduced exercise tolerance is an independent predictor of hospital readmission and mortality in patients with heart failure (HF). Exercise training for HF patients is well established as an adjunct therapy, and there is sufficient evidence to support the favorable role of exercise training programs for HF patients over and above the optimal medical therapy. Some of the documented benefits include improved functional capacity, quality of life (QoL), fatigue, and dyspnea. Major trials to assess exercise training in HF have, however, focused on heart failure with reduced ejection fraction (HFREF). At least half of the patients presenting with HF have heart failure with preserved ejection fraction (HFPEF) and experience similar symptoms of exercise intolerance, dyspnea, and early fatigue, and similar mortality risk and rehospitalization rates. The role of exercise training in the management of HFPEF remains less clear. This article provides a brief overview of pathophysiology of reduced exercise tolerance in HFREF and heart failure with preserved ejection fraction (HFPEF), and summarizes the evidence and mechanisms by which exercise training can improve symptoms and HF. Clinical and practical aspects of exercise training prescription are also discussed.

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