Skeletal Muscle Composition and Its Relation to Exercise Intolerance in Older Patients With Heart Failure and Preserved Ejection Fraction

doi:10.1016/j.amjcard.2013.12.031

The American Journal of Cardiology

Volume 113, Issue 7, 1 April 2014, Pages 1211-1216

https://doi.org/10.1016/j.amjcard.2013.12.031 Get rights and content

Exercise intolerance is the primary chronic symptom in heart failure with preserved ejection fraction (HFpEF), the most common form of heart failure in older patients; however its pathophysiology is not well understood. Recent data suggest that peripheral factors such as skeletal muscle (SM) dysfunction may be important contributors. Therefore, 38 participants, 23 patients with HFpEF (69 ± 7 years) and 15 age-matched healthy controls (HCs), underwent magnetic resonance imaging and cardiopulmonary exercise testing to assess for SM, intermuscular fat (IMF), subcutaneous fat, total thigh, and thigh compartment (TC) areas and peak exercise oxygen consumption (peak VO₂). There were no significant intergroup differences in total thigh area, TC, subcutaneous fat, or SM. However, in the HFpEF versus HC group, IMF area (35.6 ± 11.5 vs 22.3 ± 7.6 cm², p = 0.01), percent IMF/TC (26 ± 5 vs 20 ± 5%, p = 0.005), and the ratio of IMF/SM (0.38 ± 0.10 vs 0.28 ± 0.09, p = 0.007) were significantly increased, whereas percent SM/TC was significantly reduced (70 ± 5 vs 75 ± 5, p = 0.009). In multivariate analyses, IMF area (partial r = −0.51, p = 0.002) and IMF/SM ratio (partial r = −0.45, p = 0.006) were independent predictors of peak VO₂ whereas SM area was not (partial r = −0.14, p = 0.43). Thus, older patients with HFpEF have greater thigh IMF and IMF/SM ratio compared with HCs, and these are significantly related to their severely reduced peak VO₂. These data suggest that abnormalities in SM composition may contribute to the severely reduced exercise capacity in older patients with HFpEF. This implicates potential targets for novel therapeutic strategies in this common debilitating disorder of older persons.

Section snippets

Methods

As previously described in studies reported from our laboratory,1, 2, 5, 6, 7, 8 HFpEF was defined as symptoms and signs of HF according to the National Health and Nutrition Examination Survey HF clinical score of ≥3 and the criteria of Rich et al.9, 10 Age-matched sedentary HCs were recruited and screened and excluded if they had any chronic medical illness, were on any long-term medication, had current complaints or an abnormal physical examination (including blood pressure ≥140/90 mm Hg),

Results

The patients were clinically stable (New York Heart Association class II and III) with typical characteristics of HFpEF, including advanced age, female preponderance, abnormal left ventricular diastolic filling, left ventricular hypertrophy, increased left atrial size, and severely reduced peak exercise VO₂ (Table 1). HFpEF and HC groups were well matched for age and gender. Body weight, body mass index (BMI), and body surface area were higher for HFpEF than HCs (Table 1); however, the mean

Discussion

Multiple lines of evidence suggest that in addition to cardiac dysfunction, abnormalities in noncardiac peripheral factors may be important contributors to the severe exercise intolerance observed in older patients with HFpEF.2, 4, 5, 7, 16 The major novel finding is that compared with age-matched healthy adults, older patients with HFpEF have increased thigh IMF, whether expressed as absolute area or as a proportion of the TC, and this occurs despite similar amount of SCF. Furthermore, the

Disclosures

The authors have no conflicts of interest to declare.

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Cited by (186)

Impact of Structured Resistance Training on Locomotor Muscle Composition in Patients with HFpEF
2024, Journal of Cardiac Failure
Body Composition, Coronary Microvascular Dysfunction, and Future Risk of Cardiovascular Events Including Heart Failure
2024, JACC: Cardiovascular Imaging
Body mass index (BMI) is a controversial marker of cardiovascular prognosis, especially in women. Coronary microvascular dysfunction (CMD) is prevalent in obese patients and a better discriminator of risk than BMI, but its association with body composition is unknown.
The authors used a deep learning model for body composition analysis to investigate the relationship between CMD, skeletal muscle (SM), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT), and their contribution to adverse outcomes in patients referred for evaluation of coronary artery disease.
Consecutive patients (n = 400) with normal perfusion and preserved left ventricular ejection fraction on cardiac stress positron emission tomography were followed (median, 6.0 years) for major adverse events, including death and hospitalization for myocardial infarction or heart failure. Coronary flow reserve (CFR) was quantified as stress/rest myocardial blood flow from positron emission tomography. SM, SAT, and VAT cross-sectional areas were extracted from abdominal computed tomography at the third lumbar vertebra using a validated automated algorithm.
Median age was 63, 71% were female, 50% non-White, and 50% obese. Compared with the nonobese, patients with obesity (BMI: 30.0-68.4 kg/m²) had higher SAT, VAT, and SM, and lower CFR (all P < 0.001). In adjusted analyses, decreased SM but not increased SAT or VAT was significantly associated with CMD (CFR <2; OR: 1.38; 95% CI: 1.08-1.75 per –10 cm²/m² SM index; P < 0.01). Both lower CFR and SM, but not higher SAT or VAT, were independently associated with adverse events (HR: 1.83; 95% CI: 1.25-2.68 per –1 U CFR and HR: 1.53; 95% CI: 1.20-1.96 per −10 cm²/m² SM index, respectively; P < 0.002 for both), especially heart failure hospitalization (HR: 2.36; 95% CI: 1.31-4.24 per –1 U CFR and HR: 1.87; 95% CI: 1.30-2.69 per –10 cm²/m² SM index; P < 0.004 for both). There was a significant interaction between CFR and SM (adjusted P = 0.026), such that patients with CMD and sarcopenia demonstrated the highest rate of adverse events, especially among young, female, and obese patients (all P < 0.005).
In a predominantly female cohort of patients without flow-limiting coronary artery disease, deficient muscularity, not excess adiposity, was independently associated with CMD and future adverse outcomes, especially heart failure. In patients with suspected ischemia and no obstructive coronary artery disease, characterization of lean body mass and coronary microvascular function may help to distinguish obese phenotypes at risk for cardiovascular events.
Contribution of reduced skeletal muscle perfusion reserve to exercise intolerance in heart failure with preserved ejection fraction
2024, International Journal of Cardiology
Skeletal muscle (SM)-associated mechanisms of exercise intolerance in HFpEF are insufficiently defined, and inadequate augmentation of SM blood flow during physical effort may be one of the contributors. Therefore, we sought to investigate the association of SM perfusion response to exertion with exercise capacity in this clinical condition.
Echocardiography and SM microvascular perfusion by contrast-enhanced ultrasound were performed at rest and immediately post-exercise test in 77 HFpEF patients in NYHA class II and III, and in 25 subjects with normal exercise tolerance (stage B). Exercise reserve of cardiac function and SM perfusion was calculated by subtracting resting value from exercise value.
In addition to decreased cardiac functional reserve, HFpEF patients demonstrated significantly reduced SM perfusion reserve as compared to HF stage B, with the degree of impairment being greater in the subgroup with more profound left ventricular (LV) diastolic abnormalities (E/e’ > 15 and TRV > 2.8 m/s).
SM perfusion reserve was significantly associated with exercise capacity (beta = 0.33; SE 0.11; p = 0.003), cardiac output reserve (beta = 0.24; SE 0.12; p = 0.039), resting E/e’ (beta = −0.33; SE 0.11; p = 0.006), and patient frailty expressed by the PRISMA 7 score (beta = −0.30; SE 0.11; p = 0.008). In multivariable analysis including clinical, demographic and cardiac functional variables, SM perfusion reserve was in addition to patient frailty, sex and LV longitudinal strain reserve among the independent correlates of exercise capacity.
SM perfusion reserve is impaired in HFpEF, and is associated with reduced exercise capacity independent of clinical, demographic and “central” cardiac factors. This supports the need to consider the SM domain in patient management strategies in HFpEF.
Skeletal muscle quality, measured via phase angle, and cardiorespiratory fitness in patients with obesity and heart failure with preserved ejection fraction
2023, Nutrition
Cardiorespiratory fitness (CRF) is influenced by body composition quantity and quality in heart failure with preserved ejection fraction (HFpEF) and obesity. Bioelectrical impedance analysis (BIA) provides a noninvasive quantitative and qualitative body composition assessment. The aim of this study was to determine the role of phase angle (PhA), a BIA-measure of skeletal muscle quality and body cell mass, on CRF in patients with obesity and HFpEF.
Fifty-nine consecutive outpatients with HFpEF underwent cardiopulmonary exercise testing to measure CRF. Single-frequency segmental BIA was used to measure PhA and body composition quantity. Resting Doppler echocardiography and biomarkers were measured to assess cardiac function and systemic inflammation.
Compared with patients with lower PhA, patients with higher PhA (above mean 5.8°) presented a greater absolute peak oxygen consumption (VO₂; 1.83 [1.3–2.1] versus 1.39 [1.1–1.6] L/min, P = 0.003), VO_{2 peak} adjusted for body weight (17.5 [12.3–18.1] versus 13.3 [12.7–15.2] mL/kg/min, P = 0.040), and a lower edema index (48.7 [2.9] versus 51.4% [2.7], P < 0.001) and N-terminal pro-B-type natriuretic peptide (NT-proBNP; 64 [50–121] versus 183 [68–343.5] pg/dL, P < 0.001). In the overall sample, PhA was correlated with absolute VO_{2 peak} (r = 0.468, P < 0.001), VO_{2 peak} adjusted for body weight (r = 0.368, P = 0.004), VO_{2 peak} adjusted for fat-free mass (r = 0.315, P = 0.015), edema index (r = –0.508, P < 0.001), and NT-proBNP (r = –0.579, P < 0.001). PhA remained a significant predictor for CRF even after adjustment for potential confounders and HFpEF severity.
In patients with obesity and HFpEF, a greater PhA is an independent predictor for favorable CRF.
Modulation of the nitric oxide/cGMP pathway in cardiac contraction and relaxation: Potential role in heart failure treatment
2023, Pharmacological Research
Evidence exists that heart failure (HF) has an overall impact of 1–2 % in the global population being often associated with comorbidities that contribute to increased disease prevalence, hospitalization, and mortality. Recent advances in pharmacological approaches have significantly improved clinical outcomes for patients with vascular injury and HF. Nevertheless, there remains an unmet need to clarify the crucial role of nitric oxide/cyclic guanosine 3',5'-monophosphate (NO/cGMP) signalling in cardiac contraction and relaxation, to better identify the key mechanisms involved in the pathophysiology of myocardial dysfunction both with reduced (HFrEF) as well as preserved ejection fraction (HFpEF). Indeed, NO signalling plays a crucial role in cardiovascular homeostasis and its dysregulation induces a significant increase in oxidative and nitrosative stress, producing anatomical and physiological cardiac alterations that can lead to heart failure. The present review aims to examine the molecular mechanisms involved in the bioavailability of NO and its modulation of downstream pathways. In particular, we focus on the main therapeutic targets and emphasize the recent evidence of preclinical and clinical studies, describing the different emerging therapeutic strategies developed to counteract NO impaired signalling and cardiovascular disease (CVD) development.
Supervised Exercise Training for Chronic Heart Failure With Preserved Ejection Fraction: A Scientific Statement From the American Heart Association and American College of Cardiology
2023, Journal of the American College of Cardiology
Heart failure with preserved ejection fraction (HFpEF) is one of the most common forms of heart failure; its prevalence is increasing, and outcomes are worsening. Affected patients often experience severe exertional dyspnea and debilitating fatigue, as well as poor quality of life, frequent hospitalizations, and a high mortality rate. Until recently, most pharmacological intervention trials for HFpEF yielded neutral primary outcomes. In contrast, trials of exercise-based interventions have consistently demonstrated large, significant, clinically meaningful improvements in symptoms, objectively determined exercise capacity, and usually quality of life. This success may be attributed, at least in part, to the pleiotropic effects of exercise, which may favorably affect the full range of abnormalities—peripheral vascular, skeletal muscle, and cardiovascular—that contribute to exercise intolerance in HFpEF. Accordingly, this scientific statement critically examines the currently available literature on the effects of exercise-based therapies for chronic stable HFpEF, potential mechanisms for improvement of exercise capacity and symptoms, and how these data compare with exercise therapy for other cardiovascular conditions. Specifically, data reviewed herein demonstrate a comparable or larger magnitude of improvement in exercise capacity from supervised exercise training in patients with chronic HFpEF compared with those with heart failure with reduced ejection fraction, although Medicare reimbursement is available only for the latter group. Finally, critical gaps in implementation of exercise-based therapies for patients with HFpEF, including exercise setting, training modalities, combinations with other strategies such as diet and medications, long-term adherence, incorporation of innovative and more accessible delivery methods, and management of recently hospitalized patients are highlighted to provide guidance for future research.

View all citing articles on Scopus

: This study was supported by grants R37AG18915 and R01 HL093713 from the National Institutes of Health (NIH) and the NIH grant P30AG021332 from The Claude D. Pepper Older Americans Independence Center of Wake Forest University.

: See page 1215 for disclosure information.

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Heart FailureSkeletal Muscle Composition and Its Relation to Exercise Intolerance in Older Patients With Heart Failure and Preserved Ejection Fraction

Section snippets

Methods

Results

Discussion

Disclosures

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Neurol Sci

Am J Cardiol

J Am Coll Cardiol

Am J Clin Nutr

Am J Clin Nutr

Am J Clin Nutr

Contemp Clin Trials

Am J Cardiol

Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure

JAMA

Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction

Circulation

Abnormal haemodynamic response to exercise in heart failure with preserved ejection fraction

Eur J Heart Fail

Heart Failure
Skeletal Muscle Composition and Its Relation to Exercise Intolerance in Older Patients With Heart Failure and Preserved Ejection Fraction