Pathophysiological relevance of IRON deficiency and related mitochondrial dysfunction in Heart Failure with Preserved Ejection Fraction (IRON-HFpEF)

Phase 2

Recruiting

Conditions: 10019280
heart failure with preserved ejection fraction
diastolic heart failure

Registration Number: NL-OMON54927

Lead Sponsor: Vrije Universiteit Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 45

Inclusion Criteria

1. Diagnosis of heart failure with preserved ejection fraction
a. signs/and symptoms of heartfailure (NYHA II or higher)
b. Left ventricular ejection fraction >=50%
c. evidence of left ventricular diastolic dysfunction:
-pulmonary capillary wedge pressure (PCWP) at rest >= 15mmHg and/or PCWP
leg-raise >= 20mmHg and/or PCWP during exercise >= 25mmHg
or if no right heart catheterisation has been performed:
-HFpEf score >= 6;
-diastolic dysfunction grade II or higher on echocardiogram + NTproBNP of
>125 pg/mL
d. no other significant cardiac (e.g. significant valvular disease) or
extra-cardiac con-dition (e.g. severe COPD) that explains symptoms
2. Optimal medical treatment
3. Clinically stable
4. Iron deficient (ferritin <100pg/L or ferritin 100-300pg/L and transferrin
saturation or TSAT <20%).
5. Hemoglobin >9.0 g/dL (5.6 mmol/L)

Exclusion Criteria

1. No informed consent
2. Contra indication ferric carboxy maltose
a. known allergic reaction to product; b. clinical signs of an acute infection;
c. conditions with high risk for an allergic reaction: severe asthma or eczema,
systemic lu-pus erhytematosus, rheumatoid arthritis or concurrent use of
significant immunosuppres-sive therapy (With an exception of patients who
previously have received intravenous iron without allergic response. As
allergic reaction is unlikely in these patients).; severe liver disease
3. History of (previous 2 months) or planned use of intravenous/oral iron,
erythro-poietin or blood transfusion
4. Indication for iron supplementation according to Dutch guidelines.
5. Acute coronary syndrome, TIA/CVA, PCI/CABG/valve replacement or any major
surgery within 3 months prior;
6. Unable to undergo the complete study protocol (i.e. right heart
catheterisation, 6 minute walk distance)
7. Indication for iron supplementation

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Exercise PCWP measured by right heart catheterisation (gold standard<br /><br>for evaluation of left ventricular diastology)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>1. Myocardial and skeletal muscle PCr/ATP-ratio at rest measured by<br /><br>31P-MRS.<br /><br>2. PCr/ATP ratio in skeletal muscle during exercise . And PCr recovery<br /><br>after exercise<br /><br>3. Change in mitochondrial function measured in plasma<br /><br>(eg.acetylcarnitines)<br /><br>4. Correction of iron storage in plasma (ao ferritin and TSAT) and organs<br /><br>(MRI of heart / skeletal muscle)<br /><br>5. Safety endpoints (SAE's)<br /><br>6. Change in symptoms (NYHA, fatigue score, and quality of life questionairres<br /><br>(KCCQ<br /><br>and EQ-5D)<br /><br>7. Change in exercise tolerance (6 minute walk test; bicycle ergometry)<br /><br>8. Change in NTproBNP<br /><br>9. Verandering in microvasculaire functie</p><br>