The Sarcopenia Study

Official title

The Imaging Assessment of Sarcopenia Across the Heart Failure Spectrum

Overview

The goal of this cross-sectional study is to investigate the prevalence of sarcopenia in patients with Heart Failure. The main question it aims to answer is: Whether there is a difference in the prevalence of sarcopenia across the spectrum of HFpEF (Heart failure with preserved ejection fraction) and HFrEF (heart failure with reduced ejection fraction). This is an observational study. The participant population involves patients with heart failure with preserved ejection fraction and heart failure with reduced ejection fraction. Healthy volunteers will be recruited as controls in addition to adults with asymptomatic Type 2 Diabetes. Participants will undergo the following: 1. Skeletal muscle mass, quality and body composition assessments using magnetic resonance imaging (MRI) and bioelectrical impedance analysis (BIA) 2. Skeletal muscle strength assessments (Dynamometer, FysioMeter, handgrip strength) 3. Skeletal muscle energetics assessment (31p-Spectroscopy pre/post-exercise recovery) Researchers will compare Heart failure groups with healthy controls and adults with asymptomatic type 2 Diabetes to see if there are significant differences in the strength, mass and quality of skeletal muscle.

Detailed description

Heart failure is a complex condition which affects the hearts' ability to pump blood around the body properly. Due to this complexity, it often affects multiple systems in the body and can impact the quality of life. A proportion of heart failure patients also have muscle weakness, where one can feel fatigued, and weak, and may have trouble balancing and standing. To characterise muscle weakness, it is important to look at skeletal muscle mass, strength, and function. The study will focus on the prevalence of reduced muscle strength or function, using a variety of assessments within patients with heart failure. The prevalence of muscle weakness will be investigated by running assessments to look into muscle strength, a series of simple exercise tests will be run of the calf and thigh, in addition to a walking test, a balance test and a standing test to assess whole body performance. To look at the quality of skeletal muscle, a magnetic resonance imaging (MRI) and spectroscopy session will allow us to investigate the quality of the thigh muscle and the energetics in the calf. Finally, a muscle biopsy will be performed to understand differences in muscle tissue in people with different types of heart failure.

Overall, this study will provide us with unique information on skeletal muscle strength, composition and energetics within patients with heart failure, by looking at the main factors which characterise muscle weakness.

Primary outcome measures

• Volumetric quadriceps skeletal muscle mass (cm^3) [Time frame: Through study completion, an average of 3 years]

Secondary outcome measures (12)

• HF symptoms and quality of life [Time frame: Baseline]
• Frailty assessment [Time frame: Baseline]
• Comparison of Body composition [Time frame: Baseline]
• The difference in Muscle fat fraction (percent) [Time frame: Baseline]
• quadriceps Skeletal muscle strength (N) [Time frame: Baseline]
• Calf plantar flexor strength (N) [Time frame: Baseline]
• Handgrip strength (N) [Time frame: Baseline]
• A comparison of post-exercise recovery metabolites [Time frame: Baseline]
• A comparison in distance (metres) walked during 6MWT [Time frame: Baseline]
• A comparison of daily physical activity [Time frame: Baseline]
• The Short Physical Performance Battery (SPPB) performance [Time frame: Baseline]
• Sarcopenia assessment [Time frame: Baseline]

Eligibility criteria

Inclusion criteria

Heart Failure (HF) Patients: Stage A/B HFpEF

• Established clinical diagnosis of HFpEF (EF>50%)
• Clinically stable for ≥ 3 months (no admissions to hospital)
• Age ≥65
• Willing to provide written consent for participation in the study.

HF Patients: Stage C/D HFpEF and HFrEF

• Established clinical diagnosis of HFpEF (EF>50%) OR HFrEF (EF<40%)
• Clinically stable for ≥ 3 months (no admissions to hospital)
• Age ≥65
• Willing to provide written consent for participation in the study. Healthy volunteers

1\. Age >18 2. Able to provide written informed consent Asymptomatic T2D

• Male or female, aged ≥18 and ≤75 years.
• Diagnosis of stable T2D (determined by i) formal diagnosis in primary care physician case records, ii) a record of diagnostic oral glucose tolerance test OR glycated haemoglobin level ≥6.5%).

Exclusion criteria

Heart failure

• Absolute contraindication to MRI
• Inability to walk/undertake the 6-Minute Walk Test (6MWT)
• Neuromuscular disorders that may impact skeletal muscle assessment, such as motor neurone disease, multiple sclerosis, skeletal muscle myopathies and myositis
• Regular or intermittent oral corticosteroid use
• Untreated hyper or hypothyroidism
• Heart failure-related hospitalisations in the last 3 months

Healthy volunteers

• Previous or current signs of HF
• Risk factors for the development of HF, such as hypertension, diabetes Mellitus or coronary artery disease

Asymptomatic Type 2 Diabetes Mellitus (T2D)

• Angina pectoris or limiting dyspnoea (>NYHA II)
• Major atherosclerotic disease: Symptomatic CAD, history of MI, previous revascularisation, stroke/transient ischaemic attack or symptomatic peripheral vascular disease.
• Atrial fibrillation or flutter.
• Moderate to severe valvular heart disease.
• History of heart failure or cardiomyopathy.
• Type 1 diabetes mellitus (T1DM).
• Low fasting C-peptide levels suggestive of adult-onset T1DM.
• Stage III-V renal disease (estimated glomerular filtration rate ≤30ml/min/1.73m2).
• Absolute contraindications to MRI.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

United Kingdom · 1 center

• University Hospitals of Leicester NHS Trust — Leicester

Publications

• Redfield MM, Borlaug BA. Heart Failure With Preserved Ejection Fraction: A Review. JAMA. 2023 Mar 14;329(10):827-838. doi: 10.1001/jama.2023.2020. PMID 36917048
• Murphy SP, Ibrahim NE, Januzzi JL Jr. Heart Failure With Reduced Ejection Fraction: A Review. JAMA. 2020 Aug 4;324(5):488-504. doi: 10.1001/jama.2020.10262. PMID 32749493
• Del Buono MG, Arena R, Borlaug BA, Carbone S, Canada JM, Kirkman DL, Garten R, Rodriguez-Miguelez P, Guazzi M, Lavie CJ, Abbate A. Exercise Intolerance in Patients With Heart Failure: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019 May 7;73(17):2209-2225. doi: 10.1016/j.jacc.2019.01.072. PMID 31047010
• Pandey A, Shah SJ, Butler J, Kellogg DL Jr, Lewis GD, Forman DE, Mentz RJ, Borlaug BA, Simon MA, Chirinos JA, Fielding RA, Volpi E, Molina AJA, Haykowsky MJ, Sam F, Goodpaster BH, Bertoni AG, Justice JN, White JP, Ding J, Hummel SL, LeBrasseur NK, Taffet GE, Pipinos II, Kitzman D. Exercise Intolerance in Older Adults With Heart Failure With Preserved Ejection Fraction: JACC State-of-the-Art Review PMID 34503685
• Salmon T, Essa H, Tajik B, Isanejad M, Akpan A, Sankaranarayanan R. The Impact of Frailty and Comorbidities on Heart Failure Outcomes. Card Fail Rev. 2022 Mar 21;8:e07. doi: 10.15420/cfr.2021.29. eCollection 2022 Jan. PMID 35399550
• Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M; Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019 Jan 1;48( PMID 30312372
• Tucker WJ, Haykowsky MJ, Seo Y, Stehling E, Forman DE. Impaired Exercise Tolerance in Heart Failure: Role of Skeletal Muscle Morphology and Function. Curr Heart Fail Rep. 2018 Dec;15(6):323-331. doi: 10.1007/s11897-018-0408-6. PMID 30178183
• Uchmanowicz I, Mlynarska A, Lisiak M, Kaluzna-Oleksy M, Wleklik M, Chudiak A, Dudek M, Migaj J, Hinterbuchner L, Gobbens R. Heart Failure and Problems with Frailty Syndrome: Why it is Time to Care About Frailty Syndrome in Heart Failure. Card Fail Rev. 2019 Feb;5(1):37-43. doi: 10.15420/cfr.2018.37.1. PMID 30847244

Identifiers

NCT: NCT05888688 · 0916

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗