scholarly journals The Molecular and Cellular Mechanisms Associated with a Microvascular Inflammation in the Pathogenesis of Heart Failure with Preserved Ejection Fraction

Acta Naturae ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 40-51
Author(s):  
A. G. Ovchinnikov ◽  
T. I. Arefieva ◽  
A. V. Potekhina ◽  
A. Yu. Filatova ◽  
F. T. Ageev ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Severe Disease ◽  
Treatment Options ◽  
Cellular Mechanisms ◽  
Reduced Ejection Fraction ◽  
Hypertrophied Myocardium ◽  
Microvascular Inflammation ◽  
Novel Strategy ◽  
Current Paradigm

Heart failure withpreserved ejection fraction (HFpEF) is a severe disease with an often unfavorable outcome. The prevalence of HFpEF continues to increase, while effective treatment options remain elusive. All the medical strategies used toimprove the outcome in a heart failure with reduced ejection fraction proved ineffective in HFpEF, which was probably due to the different mechanisms ofdevelopment of these two types of heart failure and the diversity of the HFpEF phenotypes. According to the current paradigm of HFpEF development, a chronic mild pro-inflammatory statecauses a coronary microvascular endothelial inflammation, with further myocardial fibrosis and diastolic dysfunction progression. This inflammatory paradigm of HFpEF has been confirmed with someevidence, and suppressing the inflammation may become a novel strategy for treating and managing HFpEF. This review summarizes current concepts about a microvascular inflammation in hypertrophied myocardium and provides a translational perspective of the anti-inflammatory and immunomodulatory approaches in HFpEF.

scholarly journals The Molecular and Cellular Mechanisms Associated with a Microvascular Inflammation in the Pathogenesis of Heart Failure with Preserved Ejection Fraction

Acta Naturae ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 40-51
Author(s):  
A. G. Ovchinnikov ◽  
T. I. Arefieva ◽  
A. V. Potekhina ◽  
A. Yu. Filatova ◽  
F. T. Ageev ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Severe Disease ◽  
Treatment Options ◽  
Cellular Mechanisms ◽  
Reduced Ejection Fraction ◽  
Hypertrophied Myocardium ◽  
Microvascular Inflammation ◽  
Novel Strategy ◽  
Current Paradigm

Heart failure withpreserved ejection fraction (HFpEF) is a severe disease with an often unfavorable outcome. The prevalence of HFpEF continues to increase, while effective treatment options remain elusive. All the medical strategies used toimprove the outcome in a heart failure with reduced ejection fraction proved ineffective in HFpEF, which was probably due to the different mechanisms ofdevelopment of these two types of heart failure and the diversity of the HFpEF phenotypes. According to the current paradigm of HFpEF development, a chronic mild pro-inflammatory statecauses a coronary microvascular endothelial inflammation, with further myocardial fibrosis and diastolic dysfunction progression. This inflammatory paradigm of HFpEF has been confirmed with someevidence, and suppressing the inflammation may become a novel strategy for treating and managing HFpEF. This review summarizes current concepts about a microvascular inflammation in hypertrophied myocardium and provides a translational perspective of the anti-inflammatory and immunomodulatory approaches in HFpEF.

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.

Nocturnal Hypertension and Heart Failure: Mechanisms, Evidence, and New Treatments

Hypertension ◽  
2021 ◽  
Author(s):  
Kazuomi Kario ◽  
Bryan Williams
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiovascular Events ◽  
Treatment Options ◽  
Left Ventricular ◽  
Nocturnal Hypertension ◽  
Reduced Ejection Fraction ◽  
Nighttime Blood Pressure ◽  
Evidence Based Treatments ◽  
New Treatments

Heart failure (HF) is a common condition with an increasing prevalence. Despite a variety of evidence-based treatments for patients with HF with reduced ejection fraction, morbidity and mortality rates remain high. Furthermore, there are currently no treatments that have yet been shown to reduce complication and death rates in patients who have HF with preserved ejection fraction. Hypertension is a common comorbidity in patients with HF, contributing to disease development and prognosis. For example, hypertension is closely associated with the development of left ventricular hypertrophy, which an important precursor of HF. In particular, nighttime blood pressure (BP) appears to be an important, modifiable risk factor. Both nighttime BP and an abnormal circadian pattern of nighttime BP dipping have been shown to predict development of HF and the occurrence of cardiovascular events, independent of office BP. Key mechanisms for this association include sodium handling/salt sensitivity and increased sympathetic activation. These pathogenic mechanisms are targeted by several new treatment options, including sodium-glucose cotransporter 2 inhibitors, angiotensin receptor neprilysin inhibitors, mineralocorticoid receptor antagonists, and renal denervation. All of these could form part of antihypertensive strategies designed to control nighttime BP and contribute to the goal of achieving perfect 24-hour BP management. Nevertheless, additional research is needed to determine the effects of reducing nighttime BP and improving the circadian BP profile on the rate of HF, other cardiovascular events, and mortality.

New Novel Treatment Approaches for Heart Failure With Reduced Ejection Fraction

2016 ◽  
Vol 30 (5) ◽  
pp. 541-548
Author(s):  
Shreya Patel ◽  
Keith Veltri
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Hospital Readmission ◽  
Treatment Options ◽  
Poor Quality ◽  
Pharmacological Agents ◽  
Reduced Ejection Fraction ◽  
New Novel ◽  
Novel Treatment

Despite availability of standardized drug therapies with proven beneficial outcomes, heart failure is associated with poor quality of life, increased hospital readmission, and high mortality rate. In the recent years, comprehensive understanding of the pathophysiological mechanisms of heart failure has led to the development and approval of 2 new pharmacological agents, sacubitril–valsartan and ivabradine. These agents are currently approved for use in heart failure with reduced ejection fraction (HFrEF) and present as novel approaches to further improve prognosis and outcomes in patients with HF. They offer alternative treatment options for patients who are intolerant or continue to be symptomatic despite utilization of standard HF drug therapies at optimally tolerated dosages. A review of these 2 novel agents in HFrEF, including information on pivotal trials that led to its approval and its place in therapy for HFrEF, is presented.

scholarly journals Secondary valve regurgitation in patients with heart failure with preserved ejection fraction, heart failure with mid-range ejection fraction, and heart failure with reduced ejection fraction

2020 ◽  
Vol 41 (29) ◽  
pp. 2799-2810 ◽  
Author(s):  
Philipp E Bartko ◽  
Martin Hülsmann ◽  
Judy Hung ◽  
Noemi Pavo ◽  
Robert A Levine ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Treatment Options ◽  
Valve Regurgitation ◽  
Future Directions ◽  
Reduced Ejection Fraction ◽  
Public Health Burden ◽  
Patients With Heart Failure ◽  
Scientific Approach

Abstract Secondary mitral regurgitation and secondary tricuspid regurgitation due to heart failure (HF) remain challenging in almost every aspect: increasing prevalence, poor prognosis, notoriously elusive in diagnosis, and complexity of therapeutic management. Recently, defined HF subgroups according to three ejection fraction (EF) ranges (reduced, mid-range, and preserved) have stimulated a structured understanding of the HF syndrome but the role of secondary valve regurgitation (SVR) across the spectrum of EF remains undefined. This review expands this structured understanding by consolidating the underlying phenotype of myocardial impairment with each type of SVR. Specifically, the current understanding, epidemiological considerations, impact, public health burden, mechanisms, and treatment options of SVR are discussed separately for each lesion across the HF spectrum. Furthermore, this review identifies important gaps in knowledge, future directions for research, and provides potential solutions for diagnosis and treatment. Mastering the challenge of SVR requires a multidisciplinary collaborative effort, both, in clinical practice and scientific approach to optimize patient outcomes.

scholarly journals Large Animal Models of Heart Failure: Reduced vs. Preserved Ejection Fraction

Animals ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1906 ◽  
Author(s):  
Christopher J. Charles ◽  
Miriam T. Rademaker ◽  
Nicola J. A. Scott ◽  
A. Mark Richards
Keyword(s):  
Heart Failure ◽  
Clinical Trials ◽  
Animal Models ◽  
Ejection Fraction ◽  
Treatment Options ◽  
Large Animal ◽  
Reduced Ejection Fraction ◽  
Large Animal Models ◽  
Sampling Protocols ◽  
Underlying Mechanisms

Heart failure (HF) is the final common end point of multiple metabolic and cardiovascular diseases and imposes a significant health care burden worldwide. Despite significant improvements in clinical management and outcomes, morbidity and mortality remain high and there remains an indisputable need for improved treatment options. The pathophysiology of HF is complex and covers a spectrum of clinical presentations from HF with reduced ejection fraction (HFrEF) (≤40% EF) through to HF with preserved EF (HFpEF), with HFpEF patients demonstrating a reduced ability of the heart to relax despite an EF maintained above 50%. Prior to the last decade, the majority of clinical trials and animal models addressed HFrEF. Despite growing efforts recently to understand underlying mechanisms of HFpEF and find effective therapies for its treatment, clinical trials in patients with HFpEF have failed to demonstrate improvements in mortality. A significant obstacle to therapeutic innovation in HFpEF is the absence of preclinical models including large animal models which, unlike rodents, permit detailed instrumentation and extensive imaging and sampling protocols. Although several large animal models of HFpEF have been reported, none fulfil all the features present in human disease and few demonstrate progression to frank decompensated HF. This review summarizes well-established models of HFrEF in pigs, dogs and sheep and discusses attempts to date to model HFpEF in these species.

scholarly journals Central sleep apnoea and periodic breathing in heart failure: prognostic significance and treatment options

2019 ◽  
Vol 28 (153) ◽  
pp. 190084 ◽  
Author(s):  
Winfried Randerath ◽  
Oana Deleanu ◽  
Sofia Schiza ◽  
Jean-Louis Pepin
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Failure ◽  
Treatment Options ◽  
Randomised Trial ◽  
Prognostic Significance ◽  
Periodic Breathing ◽  
Sleep Apnoea ◽  
Reduced Ejection Fraction ◽  
Central Sleep Apnoea

Central sleep apnoea (CSA) including periodic breathing is prevalent in more than one-third of patients with heart failure and is highly and independently associated with poor outcomes. Optimal treatment is still debated and well-conducted studies regarding efficacy and impact on outcomes of available treatment options are limited, particularly in cardiac failure with preserved ejection fraction. While continuous positive airway pressure and oxygen reduce breathing disturbances by 50%, adaptive servoventilation (ASV) normalises breathing disturbances by to controlling the underlying mechanism of CSA. Results are contradictory regarding impact of ASV on hard outcomes. Cohorts and registry studies show survival improvement under ASV, while secondary analyses of the large SERVE-HF randomised trial showed an excess mortality in cardiac failure with reduced ejection fraction. The current priority is to understand which phenotypes of cardiac failure patients may benefit from treatment guiding individualised and personalised management.

scholarly journals Healthcare resource utilisation and costs associated with a heart failure diagnosis: a retrospective, population-based cohort study in Sweden

BMJ Open ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. e053806
Author(s):  
Kurt Boman ◽  
Krister Lindmark ◽  
Jan Stålhammar ◽  
Mona Olofsson ◽  
Madlaina Costa-Scharplatz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cohort Study ◽  
Ejection Fraction ◽  
Secondary Care ◽  
Healthcare Resource ◽  
Severe Disease ◽  
Resource Utilisation ◽  
First Year ◽  
Reduced Ejection Fraction ◽  
Care Costs

ObjectivesTo examine healthcare resource use (HRU) and costs among heart failure (HF) patients using population data from Sweden.DesignRetrospective, non-interventional cohort study.SettingTwo cohorts were identified from linked national health registers (cohort 1, 2005–2014) and electronic medical records (cohort 2, 2010–2012; primary/secondary care patients from Uppsala and Västerbotten).ParticipantsPatients (aged ≥18 years) with primary or secondary diagnoses of HF (≥2 International Classification of Diseases and Related Health Problems, 10th revision classification) during the identification period of January 2005 to March 2015 were included.Outcome measuresHRU across the HF phenotypes was assessed with logistic regression. Costs were estimated based on diagnosis-related group codes and general price lists.ResultsTotal annual costs of secondary care of prevalent HF increased from SEK 6.23 (€0.60) to 8.86 (€0.85) billion between 2005 and 2014. Of 4648 incident patients, HF phenotype was known for 1715: reduced ejection fraction (HFrEF): 64.5%, preserved ejection fraction (HFpEF): 35.5%. Within 1 year of HF diagnosis, the proportion of patients hospitalised was only marginally higher for HFrEF versus HFpEF (all-cause (95% CI): 64.7% (60.8 to 68.4) vs 63.7% (60.8 to 66.5), HR 0.91, p=0.14; cardiovascular disease related (95% CI): 61.1% (57.1 to 64.8) vs 60.9% (58.0 to 63.7), HR 0.93, p=0.28). Frequency of hospitalisations and outpatient visits per patient declined after the first year. All-cause secondary care costs in the first year were SEK 122 758 (€12 890)/patient/year, with HF-specific care accounting for 69% of the costs. Overall, 10% of the most expensive population (younger; predominantly male; more likely to have comorbidities) incurred ~40% of total secondary care costs.ConclusionsHF-associated costs and HRU are high, especially during the first year of diagnosis. This is driven by high hospitalisations rates. Understanding the profile of resource-intensive patients being at younger age, male sex and high Charlson comorbidity index scores at the time of the HF diagnosis is most likely a sign of more severe disease.

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