Abstract 15025: Visceral Adiposity and Muscle Composition in Heart Failure With Preserved Ejection Fraction and Association With Exercise Tolerance

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Wendy Ying ◽  
Kavita Sharma ◽  
Lisa R Yanek ◽  
Dhananjay Vaidya ◽  
Michael Schar ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Ejection Fraction ◽  
Exercise Tolerance ◽  
Nyha Class ◽  
Well Being ◽  
Liver Fat ◽  
Exercise Intolerance ◽  
Preserved Ejection Fraction ◽  
Intermuscular Fat

Introduction: Visceral adipose tissue (AT) promotes inflammation and adverse metabolic changes that mediate disease progression in heart failure with preserved ejection fraction (HFpEF). Exercise intolerance is a hallmark of HFpEF, but little is known about its relation to the extent and distribution of AT. We characterized regional AT distribution in HFpEF patients and controls and analyzed associations with comorbidities and exercise tolerance. Methods: MRI was performed to quantify epicardial, liver, abdominal and thigh skeletal muscle AT. We assessed NYHA class, 6-minute walk distance (6MWD), and global well-being score (GWBS). Multivariable linear and logistic regression models were used, adjusted for age, sex, and body surface area. Results: We studied 55 HFpEF patients (41 women, mean age 67) and 33 controls (21 women, mean age 57). Epicardial AT (4.6 vs 3.2mm, p = 0.03), thigh intermuscular fat (11.0 vs 5.0cm 2 , p < 0.01) and liver fat fraction (FF) (6.4% vs 4.1%, p = 0.04) were higher in HFpEF patients than controls. Women with HFpEF had higher abdominal (443.9 vs 297.3 cm 2 , p = 0.03) and thigh (228.6 vs 112.3 cm 2 , p < 0.001) subcutaneous AT than men. Higher thigh intermuscular fat was associated with higher blood pressure (β [SE] 14.1 [3.3], p < 0.001) and diabetes (β [SE] 2.6 [1.1], p = 0.02), and liver FF was associated with chronic kidney disease (β [SE] 1.6 [0.6], p = 0.01). Higher thigh intramuscular fat was associated with both higher NYHA class and shorter 6MWD, and higher thigh intermuscular AT FF was associated with higher NYHA class ( Table ). Higher epicardial AT and liver FF were associated with lower GWBS. Conclusions: HFpEF patients have increased epicardial, liver, and skeletal muscle fat compared to controls out of proportion to their body size, and adiposity was associated with worse exercise intolerance in HFpEF. These results provide the basis for further investigation into regional AT distribution in relation to HFpEF symptoms and pathophysiology.

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 Determinants of exercise intolerance in patients with heart failure and reduced or preserved ejection fraction

2015 ◽  
Vol 119 (6) ◽  
pp. 739-744 ◽  
Author(s):  
Mark J. Haykowsky ◽  
Corey R. Tomczak ◽  
Jessica M. Scott ◽  
D. Ian Paterson ◽  
Dalane W. Kitzman
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Ejection Fraction ◽  
Muscle Blood Flow ◽  
Exercise Intolerance ◽  
Healthy Controls ◽  
Preserved Ejection Fraction ◽  
Skeletal Muscle Function ◽  
Skeletal Morphology ◽  
Patients With Heart Failure

This mini-review summarizes the literature regarding the mechanisms of exercise intolerance in patients with heart failure and reduced or preserved ejection fraction (HFREF and HFPEF, respectively). Evidence to date suggests that the reduced peak pulmonary oxygen uptake (pulm V̇o2) in patients with HFREF compared with healthy controls is due to both central (reduced convective O2 transport) and peripheral factors (impaired skeletal muscle blood flow, decreased diffusive O2 transport coupled with abnormal skeletal morphology, and metabolism). Although central and peripheral impairments also limit peak pulm V̇o2 in HFPEF patients compared with healthy controls, emerging data suggest that the latter may play a relatively greater role in limiting exercise performance in these patients. Unlike HFREF, currently there is limited evidence-based therapies that improve exercise capacity in HFPEF patients, therefore future studies are required to determine whether interventions targeted to improve peripheral vascular and skeletal muscle function result in favorable improvements in peak pulm and leg V̇o2 and their determinants in HFPEF patients.

From diastolic dysfunction to exercise intolerance: an in silico simulation study on the phenotypic markers of heart failure with preserved ejection fraction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Van Loon ◽  
C Knackstedt ◽  
T Delhaas ◽  
K.D Reesink ◽  
H.P Brunner-La Rocca ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
In Silico ◽  
Exercise Tolerance ◽  
Exercise Intolerance ◽  
Funding Source ◽  
Preserved Ejection Fraction ◽  
Filling Pattern ◽  
Lv Diastolic Dysfunction

Abstract Background Left ventricular (LV) diastolic dysfunction, i.e. impaired LV relaxation function and/or increased LV stiffness, has been hypothesized to be responsible for at least part of the exercise intolerance in heart failure with preserved ejection fraction (HFpEF). Yet the mechanisms remain largely unknown. Purpose To determine in silico if and how abnormal LV diastolic function causes reduction in maximum cardiac output (COmax), i.e. exercise intolerance. Methods We used a cardiovascular model (CircAdapt) to simulate the effects of impaired LV relaxation and increased LV myocardial stiffness on cardiac hemodynamics. The model was initialized using a reference simulation with hypertension (systolic blood pressure: 150 mmHg) and concentric LV hypertrophy (LV wall mass: +25%). Impaired LV relaxation was introduced by increasing tau from 35 ms to 65 ms. LV stiffness was increased by increasing LV end-diastolic elastance from 0.15 mmHg/ml to 0.60 mmHg/ml and 2.00 mmHg/ml (moderate and severe LV stiffness, respectively). In each simulation, LV ejection fraction (LVEF), E/A ratio and mean left atrial (LA) pressure (mLAP) was assessed. To evaluate the effect on exercise tolerance, COmax was determined by gradually increasing cardiac output and heart rate in a predefined manner until mLAP exceeded 35 mmHg. Results In all simulations, LVEF remained unchanged and preserved (i.e. 60%). In rest, impaired LV relaxation decreased E/A ratio from 1.1 to 0.8 (impaired filling pattern) and increased mLAP from 7.2 mmHg to 8.0 mmHg (Figure top: gray vs. orange). Total LV filling time was reduced at rest, reducing diastolic reserve capacity and thereby of COmax, by 15% compared to the reference (Figure bottom: gray vs. orange). Moderate LV stiffness increased E/A ratio to 1.1 (pseudo-normal filling pattern) and mLAP to 15.0 mmHg (Figure top: gray vs. red). COmax was reduced by 40% due to a steep increase of mLAP with exercise intensity. Severe LV stiffness increased E/A ratio to 2.2 (i.e. restrictive filling pattern), but resulted in a non-physiological mLAP of 40 mmHg at rest. However, when combining moderate LV stiffness with LA dysfunction (i.e. reduced LA contractility and increased LA stiffness) also led to restrictive filling pattern (E/A ratio &gt;2.0) with mLAP 19 mmHg (Figure top: red vs. dashed blue). COmax reduced most severely by 53%, emphasizing the importance of LA function in LV diastolic dysfunction (Figure bottom: gray vs. dashed blue). Conclusions Through variations in LV and LA function, we linked the progression of LV diastolic dysfunction to LV and LA properties. Increased LV stiffness, more than impaired LV relaxation, is associated with substantially reduced exercise tolerance. The combination of LV and LA dysfunction led to the most severe exercise intolerance. Our unique in silico framework enables future studies to investigate other potential cardiac and vascular mechanisms underlying exercise intolerance in HFpEF. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was funded by the Netherlands Organisation for Scientific Research and the Dutch Heart Foundation.

Skeletal myopathy in a rat model of postmenopausal heart failure with preserved ejection fraction

2021 ◽  
Author(s):  
Rachel C. Kelley ◽  
Lauren Betancourt ◽  
Andrea M. Noriega ◽  
Suzanne C. Brinson ◽  
Nuria Curbello-Bermudez ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Ejection Fraction ◽  
Strain Difference ◽  
Exercise Intolerance ◽  
Preserved Ejection Fraction ◽  
Cross Sectional ◽  
Skeletal Myopathy ◽  
Key Features ◽  
Wistar Kyoto

Heart failure with preserved ejection fraction (HFpEF) accounts for ~50% of all patients with heart failure and frequently affects postmenopausal women. The HFpEF condition is phenotype-specific, with skeletal myopathy that is crucial for disease development and progression. However, most of the current preclinical models of HFpEF have not addressed the postmenopausal phenotype. We sought to advance a rodent model of postmenopausal HFpEF and examine skeletal muscle abnormalities therein. Female, ovariectomized, spontaneously hypertensive rats (SHR) were fed a high fat, high sucrose diet to induce HFpEF. Controls were female sham-operated Wistar-Kyoto rats on a lean diet. In a complementary, longer-term cohort, controls were female sham-operated SHRs on a lean diet to evaluate the effect of strain difference in the model. Our model developed key features of HFpEF that included increased body weight, glucose intolerance, hypertension, cardiac hypertrophy, diastolic dysfunction, exercise intolerance, and elevated plasma cytokines. In limb skeletal muscle, HFpEF decreased specific force by 15-30% (p < 0.05) and maximal mitochondrial respiration by 40-55% (p < 0.05), increased oxidized glutathione by ~2-fold (p < 0.05), and tended to increase mitochondrial H2O2 emission (p = 0.10). Muscle fiber cross-sectional area, markers of mitochondrial content, and indices of capillarity were not different between control and HFpEF in our short-term cohort. Overall, our model of postmenopausal HFpEF recapitulates several key features of the disease. This new model reveals contractile and mitochondrial dysfunction and redox imbalance that are potential contributors to abnormal metabolism, exercise intolerance, and diminished quality of life in patients with postmenopausal HFpEF.

scholarly journals Mechanisms of exercise intolerance in patients with heart failure and preserved ejection fraction. Part II: The role of right heart chambers, vascular system and skeletal muscles

Kardiologiia ◽  
2019 ◽  
Vol 59 (8S) ◽  
pp. 4-14
Author(s):  
A. G. Ovchinnikov ◽  
A. V. Potekhina ◽  
N. M. Ibragimova ◽  
E. A. Barabanova ◽  
E. N. Yushchyuk ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Exercise Tolerance ◽  
Vascular System ◽  
Exercise Intolerance ◽  
Preserved Ejection Fraction ◽  
Right Heart ◽  
Patients With Heart Failure ◽  
The Right

The main clinical manifestation of heart failure with preserved ejection fraction is poor exercise tolerance. In addi-tion to the dysfunction of the left heart chambers, which were presented in the first part of this review, many other disorders are involved in poor exercise tolerance in such patients: impairments of the right heart, vascular system and skeletal muscle. The second part of this review presents the mechanisms for the development of these disorders, as well as possible ways to correct them.

Abstract 16734: Oral Nitrite Supplementation Improves Skeletal Muscle Mitochondrial Respiration and Cardiorespiratory Fitness in Older Adults With Heart Failure With Preserved Ejection Fraction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Rohan Shah ◽  
Paul Coen ◽  
Mark T Gladwin ◽  
Daniel E Forman
Keyword(s):  
Heart Failure ◽  
Older Adults ◽  
Skeletal Muscle ◽  
Steady State ◽  
Ejection Fraction ◽  
Cardiorespiratory Fitness ◽  
Mitochondrial Respiration ◽  
Perceived Exertion ◽  
Exercise Intolerance ◽  
Preserved Ejection Fraction

Introduction: Prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing, especially among older adults. HFpEF is commonly associated with exercise intolerance and skeletal muscle weakening which likely contribute to functional decline. We studied the utility of nitrite (NO 2 ) supplementation with the aim to augment skeletal muscle mitochondrial respiration. Hypothesis: NO 2 administered via oral supplements would be associated with improved mitochondrial respiration. Whereas prior studies with other oral and inhaled nitrate and NO 2 therapy in HFpEF patients have been inconsistent, we used novel NO 2 capsules that we hypothesized would achieve higher serum levels of nitrite and nitrate, and greater cellular and clinical benefits. Methods: A randomized, placebo-controlled pilot trial to study the utility of oral sodium (Na) NO 2 over 4 weeks in an older population (≥70 years) was done. Participants received 20 or 40 mg Na-NO 2 supplements 3 times daily based on their hemodynamic responses. Pre- and post-NO 2 intervention participants underwent biopsies of the vastus lateralis muscle with associated assessments of mitochondrial respiration in permeabilized fibers and also completed cardiopulmonary exercise test. Results: 15 participants were randomized and 13 completed the interventions (n=6 on NO 2 , n=7 on placebo, 69% men, mean age 75.7 years, range 70-91). Post-intervention serum NO 2 level increased (+0.61±0.67 μmol on NO 2, +0.25±0.15 on placebo). Ex-vivo analysis of mitochondrial respiration showed increased O 2 consumption in muscle (+27.1±27.4 pmol/(s*mg) on NO 2 , -11.7±11.3 on placebo). Rated perceived exertion during steady-state walking decreased (-1.2±2.0 on NO 2, +0.2±1.6 on placebo). Peak oxygen uptake (VO 2 ) increased (+1.4±5.2 ml/kg/min on NO2, -3.4±5.2 on placebo). Conclusion: Our study demonstrated efficacy and potential clinical utility of oral NO 2 supplementation in older HFpEF patients with an internally consistent physiologic composite of improved skeletal muscle mitochondrial respiration in association with improved cardiorespiratory fitness and diminished perceived exertion during steady-state walking. Clinical implications are auspicious and further research is indicated.

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