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

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).

Study Overview

• Status: Enrolling by invitation
• Conditions: Iron-deficiency; HF - Heart Failure
• Intervention / Treatment: Diagnostic test: 31Phosphor Magnetic Resonance Spectroscopy

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 Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713GZ
    • UMCG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

For this study, we will include 40 non-anaemic patients with stable chronic HF, subdivided in 20 patients with HFrEF and 20 subjects with HFrEF. HFpEF and HFrEF patients will be further subdivided into 10 patients with ID and 10 patients without ID. These patients will be recruited from the outpatient clinic of the Department of Cardiology, UMCG. Patients must be stable at the time of inclusion (i.e. no medication changes <1 month prior to study).

Description

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 Plan

How is the study designed?

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)

Collaborators and Investigators

• Sponsor: University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2021
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: October 5, 2021
• First Submitted That Met QC Criteria: February 27, 2023
• First Posted (Actual): March 2, 2023

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: February 27, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: HFrEF; HFpEF; 31P MRS; 31Phosphor Magnetic Resonance Spectroscopy; Oxidative Skeletal Muscle Metabolism
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Heart Failure; Anemia, Iron-Deficiency
• Other Study ID Numbers: 201700917

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No