scholarly journals Suppression of Tumourigenicity 2 in Heart Failure With Preserved Ejection Fraction

2020 ◽  
Vol 6 ◽  
Author(s):  
Veronika Zach ◽  
Felix Lucas Bähr ◽  
Frank Edelmann
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Incidence Rates ◽  
Current Evidence ◽  
Ageing Population ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Novel Biomarkers ◽  
Underlying Mechanisms ◽  
Receptor Family

Heart failure (HF), with steadily increasing incidence rates and mortality in an ageing population, represents a major challenge. Evidence suggests that more than half of all patients with a diagnosis of HF suffer from HF with preserved ejection fraction (HFpEF). Emerging novel biomarkers to improve and potentially guide the treatment of HFpEF are the subject of discussion. One of these biomarkers is suppression of tumourigenicity 2 (ST2), a member of the interleukin (IL)-1 receptor family, binding to IL-33. Its two main isoforms – soluble ST2 (sST2) and transmembrane ST2 (ST2L) – show opposite effects in cardiovascular diseases. While the ST2L/IL-33 interaction is considered as being cardioprotective, sST2 antagonises this beneficial effect by competing for binding to IL-33. Recent studies show that elevated levels of sST2 are associated with increased mortality in HF with reduced ejection fraction. Nevertheless, the significance of sST2 in HFpEF remains uncertain. This article aims to give an overview of the current evidence on sST2 in HFpEF with an emphasis on prognostic value, clinical association and interaction with HF treatment. The authors conclude that sST2 is a promising biomarker in HFpEF. However, further research is needed to fully understand underlying mechanisms and ultimately assess its full value.

scholarly journals Therapeutic implications of statins in heart failure with reduced ejection fraction and heart failure with preserved ejection fraction: a review of current literature

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 16
Author(s):  
Chol Techorueangwiwat ◽  
Chanavuth Kanitsoraphan ◽  
Panupong Hansrivijit
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cohort Studies ◽  
Clinical Outcomes ◽  
Lipid Lowering ◽  
Current Evidence ◽  
Controlled Trials ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Meta Analyses

Statins are one of the standard treatments to prevent cardiovascular events such as coronary artery disease and heart failure (HF). However, data on the use of statins to improve clinical outcomes in patients with established HF remains controversial. We summarized available clinical studies which investigated the effects of statins on clinical outcomes in patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Statins possess many pleiotropic effects in addition to lipid-lowering properties that positively affect the pathophysiology of HF. In HFrEF, data from two large randomized placebo-controlled trials did not show benefits of statins on mortality of patients with HFrEF. However, more recent prospective cohort studies and meta-analyses have shown decreased risk of mortality as well as cardiovascular hospitalization with statins treatment. In HFpEF, most prospective and retrospective cohort studies as well as meta analyses have consistently reported positive effects of statins, including reducing mortality and improving other clinical outcomes. Current evidence also suggests better outcomes with lipophilic statins in patients with HF. In summary, statins might be effective in improving survival and other clinical outcomes in patients with HF, especially for patients with HFpEF. Lipophilic statins might also be more beneficial for HF patients. Based on current evidence, statins did not cause harm and should be continued in HF patients who are already taking the medication. Further randomized controlled trials are needed to clarify the benefits of statins in HF patients.

scholarly journals Hospitalisation in Patients With Heart Failure With Preserved Ejection Fraction

2018 ◽  
Vol 12 ◽  
pp. 117954681775160 ◽  
Author(s):  
Shane Nanayakkara ◽  
Hitesh C Patel ◽  
David M Kaye
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Ageing Population ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
The Impact ◽  
Overall Mortality

Heart failure is highly prevalent with more than 50% of cases being patients with a preserved ejection fraction (HFPEF), a figure that is projected to increase due to the changing risk factor landscape, in particular the ageing population. Overall mortality is similar to patients with heart failure with reduced ejection fraction (HFREF), as are the rates of hospitalisation. Patients with HFPEF have more comorbid conditions with fewer therapeutic options available. In this review, we explore the epidemiology of hospitalisation of HFPEF, the impact of current treatment modalities, and the potential of future therapies.

scholarly journals Heart Failure and Diabetes Mellitus: Biomarkers in Risk Stratification and Prognostication

2021 ◽  
Vol 11 (10) ◽  
pp. 4397
Author(s):  
Michael Lichtenauer ◽  
Peter Jirak ◽  
Vera Paar ◽  
Brigitte Sipos ◽  
Kristen Kopp ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Risk Stratification ◽  
Natriuretic Peptides ◽  
Predictive Ability ◽  
High Sensitivity ◽  
Routine Practice ◽  
Reduced Ejection Fraction ◽  
Novel Biomarkers

Heart failure (HF) and type 2 diabetes mellitus (T2DM) have a synergistic effect on cardiovascular (CV) morbidity and mortality in patients with established CV disease (CVD). The aim of this review is to summarize the knowledge regarding the discriminative abilities of conventional and novel biomarkers in T2DM patients with established HF or at higher risk of developing HF. While conventional biomarkers, such as natriuretic peptides and high-sensitivity troponins demonstrate high predictive ability in HF with reduced ejection fraction (HFrEF), this is not the case for HF with preserved ejection fraction (HFpEF). HFpEF is a heterogeneous disease with a high variability of CVD and conventional risk factors including T2DM, hypertension, renal disease, older age, and female sex; therefore, the extrapolation of predictive abilities of traditional biomarkers on this population is constrained. New biomarker-based approaches are disputed to be sufficient for improving risk stratification and the prediction of poor clinical outcomes in patients with HFpEF. Novel biomarkers of biomechanical stress, fibrosis, inflammation, oxidative stress, and collagen turn-over have shown potential benefits in determining prognosis in T2DM patients with HF regardless of natriuretic peptides, but their role in point-to-care and in routine practice requires elucidation in large clinical trials.

scholarly journals Chamber-enriched gene expression profiles in failing human hearts with reduced ejection fraction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin Luo ◽  
Jun Yin ◽  
Denise Dwyer ◽  
Tracy Yamawaki ◽  
Hong Zhou ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Human Genetics ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Left Heart ◽  
Reduced Ejection Fraction ◽  
Cell Type Composition ◽  
Type Composition ◽  
Underlying Mechanisms

AbstractHeart failure with reduced ejection fraction (HFrEF) constitutes 50% of HF hospitalizations and is characterized by high rates of mortality. To explore the underlying mechanisms of HFrEF etiology and progression, we studied the molecular and cellular differences in four chambers of non-failing (NF, n = 10) and HFrEF (n = 12) human hearts. We identified 333 genes enriched within NF heart subregions and often associated with cardiovascular disease GWAS variants. Expression analysis of HFrEF tissues revealed extensive disease-associated transcriptional and signaling alterations in left atrium (LA) and left ventricle (LV). Common left heart HFrEF pathologies included mitochondrial dysfunction, cardiac hypertrophy and fibrosis. Oxidative stress and cardiac necrosis pathways were prominent within LV, whereas TGF-beta signaling was evident within LA. Cell type composition was estimated by deconvolution and revealed that HFrEF samples had smaller percentage of cardiomyocytes within the left heart, higher representation of fibroblasts within LA and perivascular cells within the left heart relative to NF samples. We identified essential modules associated with HFrEF pathology and linked transcriptome discoveries with human genetics findings. This study contributes to a growing body of knowledge describing chamber-specific transcriptomics and revealed genes and pathways that are associated with heart failure pathophysiology, which may aid in therapeutic target discovery.

Heart Failure with Preserved Ejection Fraction: Mechanisms and Treatment Strategies

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Kazunori Omote ◽  
Frederik H. Verbrugge ◽  
Barry A. Borlaug
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Treatment Strategies ◽  
Annual Review ◽  
Publication Date ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Prevalence Of Obesity

Approximately half of all patients with heart failure (HF) have a preserved ejection fraction, and the prevalence is growing rapidly given the aging population in many countries and the rising prevalence of obesity, diabetes, and hypertension. Functional capacity and quality of life are severely impaired in heart failure with preserved ejection fraction (HFpEF), and morbidity and mortality are high. In striking contrast to HF with reduced ejection fraction, there are few effective treatments currently identified for HFpEF, and these are limited to decongestion by diuretics, promotion of a healthy active lifestyle, and management of comorbidities. Improved phenotyping of subgroups within the overall HFpEF population might enhance individualization of treatment. This review focuses on the current understanding of the pathophysiologic mechanisms underlying HFpEF and treatment strategies for this complex syndrome. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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 Targeting Endothelial Function to Treat Heart Failure with Preserved Ejection Fraction: The Promise of Exercise Training

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Andreas B. Gevaert ◽  
Katrien Lemmens ◽  
Christiaan J. Vrints ◽  
Emeline M. Van Craenenbroeck
Keyword(s):  
Heart Failure ◽  
Endothelial Dysfunction ◽  
Exercise Training ◽  
Ejection Fraction ◽  
Current Knowledge ◽  
Beta Blockers ◽  
Preserved Ejection Fraction ◽  
Cellular Mechanisms ◽  
Converting Enzyme Inhibitors ◽  
Reduced Ejection Fraction

Although the burden of heart failure with preserved ejection fraction (HFpEF) is increasing, there is no therapy available that improves prognosis. Clinical trials using beta blockers and angiotensin converting enzyme inhibitors, cardiac-targeting drugs that reduce mortality in heart failure with reduced ejection fraction (HFrEF), have had disappointing results in HFpEF patients. A new “whole-systems” approach has been proposed for designing future HFpEF therapies, moving focus from the cardiomyocyte to the endothelium. Indeed, dysfunction of endothelial cells throughout the entire cardiovascular system is suggested as a central mechanism in HFpEF pathophysiology. The objective of this review is to provide an overview of current knowledge regarding endothelial dysfunction in HFpEF. We discuss the molecular and cellular mechanisms leading to endothelial dysfunction and the extent, presence, and prognostic importance of clinical endothelial dysfunction in different vascular beds. We also consider implications towards exercise training, a promising therapy targeting system-wide endothelial dysfunction in HFpEF.

Abstract 19228: Cost-effectiveness of the CardioMems Implantable Pulmonary Artery Pressure Monitoring System in Patients With Chronic Heart Failure

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Alexander T Sandhu ◽  
Jeremy D Goldhaber-Fiebert ◽  
Mintu P Turakhia ◽  
Daniel W Kaiser ◽  
Paul A Heidenreich
Keyword(s):  
Heart Failure ◽  
Cost Effectiveness ◽  
Ejection Fraction ◽  
Nyha Class ◽  
Case Analysis ◽  
Preserved Ejection Fraction ◽  
Heart Failure Hospitalization ◽  
Reduced Ejection Fraction ◽  
Life Years ◽  
The Cost

Background: For management of heart failure, the value of the CardioMems device remains uncertain. We assessed the cost-effectiveness of the CardioMems device. Methods: We developed a Markov model to determine quality-adjusted life-years (QALYs), cost, and cost-effectiveness of patients with heart failure receiving CardioMems implantation compared to those with routine care. In the main case analysis, we modeled the intervention in the CHAMPION trial cohort, which included patients with NYHA Class III heart failure with a heart failure hospitalization within the past twelve months. We also performed subgroup analyses of patients with preserved ejection fraction or reduced ejection fraction, and a scenario analysis of a second cohort of patients from the CHARM trials with a previous heart failure hospitalization. We obtained event rates and utilities from published trial data; we used costs from literature estimates and Medicare payment data. The main case analysis was calibrated to the hospitalization and survival rates of the CHAMPION trial. Results: In the CHAMPION trial main case analysis, CardioMems reduced lifetime hospitalizations (2.37 versus 3.27), increased months of survival (67 versus 62), increased QALYs (2.66 versus 2.38) and increased costs ($171,132 versus $154,084), yielding a cost of $59,520 per QALY gained or $40,301 per life-year gained. The cost per QALY gained was $71,964 in patients with reduced ejection fraction compared to $34,899 in those with preserved ejection fraction. In less ill patients from the CHARM trials, which included patients with NYHA Class II heart failure, the device cost increased to $110,565 per QALY gained. If the device cost decreased from $17,500 in the main case analysis to $15,000, the intervention would cost less than $50,000 per QALY gained. The duration of effectiveness was initially assumed to be lifelong; if less than 29 months, CardioMems would cost more than $150,000 per QALY gained. Conclusion: The CardioMems device is cost-effective in populations similar to the CHAMPION trial, with a cost of less than $100,000 per QALY gained, if durability of device effectiveness is sustained. Post-marketing surveillance data on the device’s durability will further clarify its value.

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