Oxidative Skeletal Muscle Metabolism in Chronic Heart Failure Patients With and Without Iron Deficiency

• Conditions: Iron-deficiency; HF - Heart Failure

• Registration Number: NCT05750940
• Lead Sponsor: University Medical Center Groningen

Brief Summary

Observational study using in vivo noninvasive 31 phosphor magnetic resonance spectroscopy (31P MRS) to quantify the effect of iron deficiency (ID) on skeletal oxidative metabolism in patients with chronic heart failure (HF).

Detailed Description

Iron Deficiency (ID) is a comorbidity in heart failure (HF) patients with high prevalence and severe clinical consequences. Multiple studies have shown that ID in HF patients impairs exercise capacity, quality of life and outcome. It is currently unknown whether these detrimental consequences of ID are due to cardiovascular or hematologic effects, or deteriorated peripheral muscle metabolism and function. This study was designed to quantify the effect of ID on skeletal oxidative metabolism in patients with chronic HF.

Study Timeline

• Study Start: 2021-10-05
• Study First Submitted: 2021-10-05
• Status Verified: 2023-02
• Study First Submitted QC: 2023-02-27
• Last Update Submitted: 2023-02-27
• Study First Posted: 2023-03-02
• Last Update Posted: 2023-03-02
• Primary Completion: 2023-04-01
• Study Completion: 2023-05-01

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

For HFrEF patients:

• Diagnosis of chronic HF of either ischemic or non-ischemic etiology;
• Stable, evidence-based medical therapy for HF;
• LVEF <40% measured <5 year prior to inclusion;
• NYHA class II - III (symptomatic HF) at moment of inclusion;

For HFpEF patients:

• Diagnosis of chronic HF of either ischemic or non-ischemic etiology;
• LVEF >40% and one of the following parameters, measured <5 year prior to inclusion;
• Left atrial volume index (LAVI) >34 mL/m2 or
• left ventricular mass index ≥115 g/m2 (for males) or ≥95 g/m2 (for females) or
• E/e' ≥13 or
• mean e' (septal and lateral) <9 cm/s
• NYHA class II - III (symptomatic HF) at moment of inclusion;
• Serum NT-proBNP ≥125 pg/mL when in sinus rhythm; >300 pg/mL when in atrial fibrillation.

Additional inclusion criterion for subjects with ID:

• Iron deficiency, defined as TSAT <20%.

Exclusion Criteria

• Age <18 years;
• Unable or unwilling to undergo exercise MRI (e.g. pregnancy, physical disabilities, claustrophobia);
• The presence of ferromagnetic material in/on the body which cannot be removed (e.g. non-MRI-compatible cardiac devices, tattoos containing ferrous ink);
• History of erythropoietin stimulating agent, intravenous iron therapy and/or blood transfusion <3 months prior to study enrolment;
• Moderate anaemia, defined as Hb <7 mmol/L for both men and women;
• Oral iron therapy >100 mg/day <4 weeks prior to study enrolment;
• Unable to understand study procedures;
• Unable or unwilling to provide informed consent.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
ΔPi/PCr from baseline to maximum exercise	During study visit, from resting baseline to maximum exercise (from start exercise upto exhaustion for a maximum timeframe of 10 minutes)	Δ ratio of inorganic phosphate/Phosphocreatinin concentrations from baseline to maximum exercise

Secondary Outcome Measures

Name	Time	Method
PCr recovery rate during recovery	During study visit, from maximum exercise to end of recovery (upto at least 5 minutes after end of exercise)	Post-exercise phosphocreatinin recovery rate
Maximal exercise performance	During study visit, during exercise (from start exercise upto exhaustion for a maximum timeframe of 10 minutes)	Maximal exercise performance
Intramuscular pH	During study visit, during exercise (from start exercise upto exhaustion for a maximum timeframe of 10 minutes)	Rates and magnitude of change in intramuscular pH during exercise

Trial Locations

Locations (1)

UMCG; 🇳🇱 Groningen, Netherlands