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 Large Animal Models of Heart Failure With Reduced Ejection Fraction (HFrEF)

2019 ◽  
Vol 6 ◽  
Author(s):  
Andreas Spannbauer ◽  
Denise Traxler ◽  
Katrin Zlabinger ◽  
Alfred Gugerell ◽  
Johannes Winkler ◽  
...  
Keyword(s):  
Heart Failure ◽  
Animal Models ◽  
Ejection Fraction ◽  
Large Animal ◽  
Reduced Ejection Fraction ◽  
Large Animal Models

Large animal models of heart failure with preserved ejection fraction

2021 ◽  
Author(s):  
Chihiro Miyagi ◽  
Takuma Miyamoto ◽  
Taiyo Kuroda ◽  
Jamshid H. Karimov ◽  
Randall C. Starling ◽  
...  
Keyword(s):  
Heart Failure ◽  
Animal Models ◽  
Ejection Fraction ◽  
Large Animal ◽  
Preserved Ejection Fraction ◽  
Large Animal Models

Echocardiography Evaluation of a Novel Stable Ovine Heart Failure Model Suitable for Cardiovascular Device Testing

2011 ◽  
Author(s):  
Peter W. Walsh ◽  
Craig S. McLachlan ◽  
Leigh Ladd ◽  
Arie Blitz ◽  
R. Mark Gillies ◽  
...  
Keyword(s):  
Heart Failure ◽  
Animal Models ◽  
Large Animal ◽  
Failure Model ◽  
Large Animal Models ◽  
Surgical Model ◽  
Coronary Ligation ◽  
Rapid Ventricular Pacing ◽  
Heart Failure Model ◽  
Underlying Pathology

Numerous large animal models of chronic cardiac ischemia have been developed to explore either pathological mechanisms and or device interventions in developed heart failure models. Traditionally chronic heart failure in large animal models such as sheep or pigs has been induced by either coronary ligation with or without reperfusion. Coronary ligation is often attempted in the open chest surgical model or more recently in the closed chest animal via angiography [1]. Both techniques can be challenging and also induce high mortality with the risk of myocardial stunning and resultant shock and or lethal arrhythmias. There is also difficulty in developing stable heart failure across cases where infarct sizes can be variable. One strategy to over come this variability has been via rapid ventricular pacing, however inducing heart failure does not induce sustained heart failure in many cases if the pacing is switched off, and additionally pacing does not induce some of the underlying pathology seen in the development of heart failure [1].

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.

scholarly journals Treatment of Atrial Fibrillation in Patients with Co-existing Heart Failure and Reduced Ejection Fraction: Time to Revisit the Management Guidelines?

2018 ◽  
Vol 7 (2) ◽  
pp. 91 ◽  
Author(s):  
Alex Baher ◽  
Nassir F Marrouche ◽  
◽  
◽  
◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Trials ◽  
Catheter Ablation ◽  
Ejection Fraction ◽  
Rhythm Control ◽  
Pharmacological Interventions ◽  
Reduced Ejection Fraction ◽  
Increased Risk ◽  
Patients With Heart Failure ◽  
Heart Failure Hospitalisation

AF in patients with heart failure and reduced ejection fraction (HFrEF) is common and is associated with an increased risk of stroke, heart failure hospitalisation and all-cause mortality. Rhythm control of AF in this population has been traditionally limited to the use of antiarrhythmic drugs. Clinical trials assessing superiority of pharmacological rhythm control over rate control have been largely disappointing. Catheter ablation has emerged as a viable alternative to pharmacological rhythm control in symptomatic AF and has enjoyed significant technological advancements over the past decade. Recent clinical trials have suggested that catheter ablation is superior to pharmacological interventions in patients with co-existing AF and HFrEF. In this article, we will review the therapeutic options for AF in patients with HFrEF in the context of the latest clinical trials beyond the current established guidelines.

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 Large Animal Models of Heart Failure

2009 ◽  
Vol 2 (3) ◽  
pp. 262-271 ◽  
Author(s):  
Jennifer A. Dixon ◽  
Francis G. Spinale
Keyword(s):  
Heart Failure ◽  
Animal Models ◽  
Large Animal ◽  
Large Animal Models

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.

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