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

Study Overview
=================
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.

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

Conditions
-----------------
HF - Heart Failure, Iron-deficiency

Intervention / Treatment
-----------------
* Diagnostic Test: 31Phosphor Magnetic Resonance Spectroscopy


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: 31Phosphor Magnetic Resonance Spectroscopy|Measurement of skeletal oxidative metabolism with 31phosphor magnetic resonance spectroscopy|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ΔPi/PCr from baseline to maximum exercise | Δ ratio of inorganic phosphate/Phosphocreatinin concentrations 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) | 

Secondary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
31P MRS, 31Phosphor Magnetic Resonance Spectroscopy, HFpEF, HFrEF, Oxidative Skeletal Muscle Metabolism