scholarly journals Exercise limitations in heart failure with reduced and preserved ejection fraction

2018 ◽  
Vol 124 (1) ◽  
pp. 208-224 ◽  
Author(s):  
David C. Poole ◽  
Russell S. Richardson ◽  
Mark J. Haykowsky ◽  
Daniel M. Hirai ◽  
Timothy I. Musch
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Ejection Fraction ◽  
Clinical Intervention ◽  
Exercise Intolerance ◽  
Transport Pathway ◽  
Phosphorescence Quenching ◽  
Reduced Ejection Fraction ◽  
Emerging Therapies ◽  
Underlying Mechanisms

The hallmark symptom of chronic heart failure (HF) is severe exercise intolerance. Impaired perfusive and diffusive O2 transport are two of the major determinants of reduced physical capacity and lowered maximal O2 uptake in patients with HF. It has now become evident that this syndrome manifests at least two different phenotypic variations: heart failure with preserved or reduced ejection fraction (HFpEF and HFrEF, respectively). Unlike HFrEF, however, there is currently limited understanding of HFpEF pathophysiology, leading to a lack of effective pharmacological treatments for this subpopulation. This brief review focuses on the disturbances within the O2 transport pathway resulting in limited exercise capacity in both HFpEF and HFrEF. Evidence from human and animal research reveals HF-induced impairments in both perfusive and diffusive O2 conductances identifying potential targets for clinical intervention. Specifically, utilization of different experimental approaches in humans (e.g., small vs. large muscle mass exercise) and animals (e.g., intravital microscopy and phosphorescence quenching) has provided important clues to elucidating these pathophysiological mechanisms. Adaptations within the skeletal muscle O2 delivery-utilization system following established and emerging therapies (e.g., exercise training and inorganic nitrate supplementation, respectively) are discussed. Resolution of the underlying mechanisms of skeletal muscle dysfunction and exercise intolerance is essential for the development and refinement of the most effective treatments for patients with HF.

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.

Abstract 12549: Circulating Irisin is a Novel Biomarker Providing Prognostic Information in Patients With Heart Failure With Reduced Ejection Fraction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Shinsuke Hanatani ◽  
Yasuhiro Izumiya ◽  
Yuichi Kimura ◽  
Yoshiro Onoue ◽  
Satoshi Araki ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Ejection Fraction ◽  
Disease Severity ◽  
Cardiovascular Events ◽  
Roc Analysis ◽  
Left Ventricular Ejection ◽  
Prognostic Information ◽  
Reduced Ejection Fraction ◽  
One Year

Introduction: Reduced skeletal muscle function link to poor prognosis in patients with chronic heart failure (HF). Irisin is a newly identified muscle-derived protein found in human serum. The gene expression of irisin precursor fibronectin domain containing protein 5 in skeletal muscle is associated with exercise tolerance in HF patients. Hypothesis: Irisin could be a useful biomarker for disease severity and future adverse cardiovascular events in patients with HF with reduced ejection fraction (HFrEF). Methods and results: We measured serum irisin levels in 84 patients with HFrEF. HFrEF was defined as left ventricular ejection fraction≦50% and meet the Framingham criteria of HF. Serum irisin concentrations were measured by ELISA. The endpoint of this study was a composite of total mortality, cardiovascular hospitalization and coronary revascularization. Serum irisin levels were negatively correlated with serum high sensitive troponin T levels (r=-0.24, p=0.048). Right heart catheterization revealed that serum irisin levels had significant negative correlation with pulmonary capillary wedge pressure (r=-0.23, p=0.044). In receiver operating characteristic (ROC) analysis, cut-off values of irisin and BNP for prediction of one-year events were 55.548 ng/mL and 324.8 pg/mL, respectively. Kaplan Meier curve demonstrated that the event-free rate was decreased in the low irisin (≦cut-off value) group (log-rank test p=0.024). The combination of low irisin and high BNP (≧cut-off value) identified patients with a significantly higher probability of adverse events (p=0.008). Multivariate Cox hazard analysis identified low levels of irisin (≦cut-off value) (hazard ratio [HR]: 3.08; 95% confidence interval [CI]: 1.31-7.21, p=0.01) and ischemic etiology (HR: 3.32; 95% CI: 1.50-7.35, p=0.003) as independent predictors of mortality and cardiovascular events. ROC analysis revealed that irisin achieved an area under the curve (AUC) of 0.67 for one-year events (p=0.031), and that the AUC increased when irisin was added to BNP level (alone: 0.64, BNP+irisin: 0.74). Conclusions: Irisin could be a useful biomarker for evaluating disease severity and providing incremental prognostic information in patients with HFrEF.

Chronic heart failure diagnosis: HFpEF

ESC CardioMed ◽  
2018 ◽  
pp. 1762-1768
Author(s):  
Daniel N. Silverman ◽  
Sanjiv J. Shah
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiopulmonary Exercise Testing ◽  
Clinical History ◽  
Right Heart Catheterization ◽  
Clinical Syndrome ◽  
Exercise Intolerance ◽  
Heart Catheterization ◽  
Reduced Ejection Fraction ◽  
Treatment Measures

Heart failure (HF) with preserved ejection fraction (HFpEF) is a very common clinical syndrome that is often misdiagnosed or overlooked due to diagnostic challenges with the lack of a specific imaging test or biomarker to make a conclusive diagnosis. Unlike HF with reduced ejection fraction, neither a reduced ejection fraction nor a dilated left ventricle is available to easily make the diagnosis of HFpEF. Furthermore, while echocardiographic evidence of diastolic dysfunction is common in patients with HFpEF, it is not a universal phenomenon. Even natriuretic peptides, which are generally thought to have good negative predictive value for the diagnosis of HF, are frequently not elevated in HFpEF patients. Finally, the cardinal symptoms of HFpEF such as dyspnoea and exercise intolerance are non-specific and may be due to many of the co-morbidities present in patients in whom the HFpEF diagnosis is entertained. This chapter presents a step-wise approach utilizing a careful clinical history, physical examination, natriuretic peptide testing, and echocardiography, which can reliably provide appropriate information to rule in or rule out the HFpEF diagnosis in the majority of patients. If there is still a question about the diagnosis, or if initial general treatment measures for the HF syndrome do not result in clinical improvement, additional testing such as right heart catheterization or cardiopulmonary exercise testing can be performed to further confirm the diagnosis. With a systematic approach to the patient with dyspnoea, the accurate diagnosis of HFpEF can be made reliably so that these high-risk patients can be appropriately treated.

scholarly journals Skeletal Muscle Function, Structure, and Metabolism in Patients With Heart Failure With Reduced Ejection Fraction and Heart Failure With Preserved Ejection Fraction

2020 ◽  
Vol 13 (12) ◽  
Author(s):  
Tarek Bekfani ◽  
Mohamed Bekhite Elsaied ◽  
Steffen Derlien ◽  
Jenny Nisser ◽  
Martin Westermann ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Ejection Fraction ◽  
Oral Anticoagulation ◽  
Muscle Function ◽  
Muscle Endurance ◽  
Acid Oxidation ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction

Background: Reduced exercise capacity in patients with heart failure (HF) could be partially explained by skeletal muscle dysfunction. We compared skeletal muscle function, structure, and metabolism among clinically stable outpatients with HF with preserved ejection fraction, HF with reduced ejection fraction, and healthy controls (HC). Furthermore, the molecular, metabolic, and clinical profile of patients with reduced muscle endurance was described. Methods: Fifty-five participants were recruited prospectively at the University Hospital Jena (17 HF with preserved ejection fraction, 18 HF with reduced ejection fraction, and 20 HC). All participants underwent echocardiography, cardiopulmonary exercise testing, 6-minute walking test, isokinetic muscle function, and skeletal muscle biopsies. Expression levels of fatty acid oxidation, glucose metabolism, atrophy genes, and proteins as well as inflammatory biomarkers were assessed. Mitochondria were evaluated using electron microscopy. Results: Patients with HF with preserved ejection fraction showed compared with HF with reduced ejection fraction and HC reduced muscle strength (eccentric extension: 13.3±5.0 versus 18.0±5.9 versus 17.9±5.1 Nm/kg, P =0.04), elevated levels of MSTN-2 (myostatin-2), FBXO-32 (F-box only protein 32 [Atrogin1]) gene and protein, and smaller mitochondrial size ( P <0.05). Mitochondrial function and fatty acid and glucose metabolism were impaired in HF-patients compared with HC ( P <0.05). In a multiple regression analysis, GDF-15 (growth and differentiation factor 15), CPT1B (carnitine palmitoyltransferase IB)-protein and oral anticoagulation were independent factors for predicting reduced muscle endurance after adjusting for age (log10 GDF-15 [pg/mL] [B, −54.3 (95% CI, −106 to −2.00), P =0.043], log10 CPT1B per fold increase [B, 49.3 (95% CI, 1.90–96.77), P =0.042]; oral anticoagulation present [B, 44.8 (95% CI, 27.90–61.78), P <0.001]). Conclusions: Patients with HF with preserved ejection fraction have worse muscle function and predominant muscle atrophy compared with those with HF with reduced ejection fraction and HC. Inflammatory biomarkers, fatty acid oxidation, and oral anticoagulation were independent factors for predicting reduced muscle endurance.

scholarly journals Clinical Response to Personalized Exercise Therapy in Heart Failure Patients with Reduced Ejection Fraction Is Accompanied by Skeletal Muscle Histological Alterations

2019 ◽  
Vol 20 (21) ◽  
pp. 5514 ◽  
Author(s):  
Tatiana Lelyavina ◽  
Victoria Galenko ◽  
Oksana Ivanova ◽  
Margarita Komarova ◽  
Elena Ignatieva ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Ejection Fraction ◽  
Clinical Response ◽  
Exercise Therapy ◽  
Left Ventricular ◽  
Exercise Intolerance ◽  
Left Ventricular Ejection ◽  
Histological Alterations ◽  
Before And After

Heart failure (HF) is associated with skeletal muscle wasting and exercise intolerance. This study aimed to evaluate the exercise-induced clinical response and histological alterations. One hundred and forty-four HF patients were enrolled. The individual training program was determined as a workload at or close to the lactate threshold (LT1); clinical data were collected before and after 12 weeks/6 months of training. The muscle biopsies from eight patients were taken before and after 12 weeks of training: histology analysis was used to evaluate muscle morphology. Most of the patients demonstrated a positive response after 12 weeks of the physical rehabilitation program in one or several parameters tested, and 30% of those showed improvement in all four of the following parameters: oxygen uptake (VO2) peak, left ventricular ejection fraction (LVEF), exercise tolerance (ET), and quality of life (QOL); the walking speed at LT1 after six months of training showed a significant rise. Along with clinical response, the histological analysis detected a small but significant decrease in both fiber and endomysium thickness after the exercise training course indicating the stabilization of muscle mechanotransduction system. Together, our data show that the beneficial effect of personalized exercise therapy in HF patients depends, at least in part, on the improvement in skeletal muscle physiological and biochemical performance.

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.

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 α-Adrenergic receptor regulation of skeletal muscle blood flow during exercise in heart failure patients with reduced ejection fraction

2019 ◽  
Vol 316 (5) ◽  
pp. R512-R524 ◽  
Author(s):  
Zachary Barrett-O’Keefe ◽  
Joshua F. Lee ◽  
Stephen J. Ives ◽  
Joel D. Trinity ◽  
Melissa A. H. Witman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Ejection Fraction ◽  
Adrenergic Receptor ◽  
Muscle Blood Flow ◽  
Skeletal Muscle Blood Flow ◽  
Reduced Ejection Fraction ◽  
Leg Blood Flow ◽  
Related Increase

Patients suffering from heart failure with reduced ejection fraction (HFrEF) experience impaired limb blood flow during exercise, which may be due to a disease-related increase in α-adrenergic receptor vasoconstriction. Thus, in eight patients with HFrEF (63 ± 4 yr) and eight well-matched controls (63 ± 2 yr), we examined changes in leg blood flow (Doppler ultrasound) during intra-arterial infusion of phenylephrine (PE; an α1-adrenergic receptor agonist) and phentolamine (Phen; a nonspecific α-adrenergic receptor antagonist) at rest and during dynamic single-leg knee-extensor exercise (0, 5, and 10 W). At rest, the PE-induced reduction in blood flow was significantly attenuated in patients with HFrEF (−15 ± 7%) compared with controls (−36 ± 5%). During exercise, the controls exhibited a blunted reduction in blood flow induced by PE (−12 ± 4, −10 ± 4, and −9 ± 2% at 0, 5, and 10 W, respectively) compared with rest, while the PE-induced change in blood flow was unchanged compared with rest in the HFrEF group (−8 ± 5, −10 ± 3, and −14 ± 3%, respectively). Phen administration increased leg blood flow to a greater extent in the HFrEF group at rest (+178 ± 34% vs. +114 ± 28%, HFrEF vs. control) and during exercise (36 ± 6, 37 ± 7, and 39 ± 6% vs. 13 ± 3, 14 ± 1, and 8 ± 3% at 0, 5, and 10 W, respectively, in HFrEF vs. control). Together, these findings imply that a HFrEF-related increase in α-adrenergic vasoconstriction restrains exercising skeletal muscle blood flow, potentially contributing to diminished exercise capacity in this population.

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