Iron Intravenous Therapy in Reducing the Burden of Severe Arrhythmias in Heart Failure With Reduced Ejection Fraction

Study Overview
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Brief Summary
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An open label,single-center, non-interventional prospective study with the aim on investigating the effect of intravenous ferric carboxymaltose in restoring iron status and reducing the risk of severe arrhythmic events in participants with iron deficiency and a reduced ejection fraction (HFrEF).

Detailed Description
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Patients with HFrEF already scheduled to receive IV FCM to treat iron deficiency will be included in this registry trial. These patients undergo clinical examination, echocardiography, blood testing, 6-minute walking testing, cardiopulmonary exercise testing, cardiac implantable device interrogation, 24-hour Holter monitoring and quality of life quantification as part of standard clinical practice. This database will be extracted from clinical databases and stored on a separate, registry database. The study will examine the effect of IV FCM on patients' iron stores, arrhythmic burden, hospitalizations and clinical, echocardiographic, exercise-testing-derived and biological markers of disease severity such as 6-minute walking distance, peak VO2 consumption, LVEF and LV global longitudinal strain and NT-proBNP.

Official Title
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An Open Label,Single-center, Non-interventional Prospective Study to Determine the Efficacy of Iron Therapy Using Intravenous Ferric Carboxymaltose and Its Effect in Reducing Arrhythmic Events in Participants With Iron Deficiency and HFrEF

Conditions
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Ferric Carboxymaltose, Heart Failure With Reduced Ejection Fraction, Arrhythmias, Cardiac

Intervention / Treatment
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* Drug: Ferric carboxymaltose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of HFrEF (LVEF≤40%) Implanted cardiac implantable electronic device with at least 3 months of recorded arrhythmic history Patient is scheduled to receive IV ferric carboxymaltose to treat diagnosed iron deficiency Exclusion Criteria: Myocardial infarction, acute heart failure or life-threatening arrhythmias in the preceding 15 days Autoimmune disorders, cancer or other diseases other than heart failure that significantly affect patients' life expectancy, appetite and emotional status Known allergic reaction to ferric carboxymaltose.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants<br>HFrEF patients undergoing iron therapy with intravenous carboxymaltose (FCM). FCM administered dosage as per clinical routine. FCM administration is repeated no sooner than 3 months than last therapy, based on repeat ferritin and transferrin saturation levels. | Drug: Ferric carboxymaltose<br>* Intravenous ferric carboxymaltose for the treatment of iron deficiency in HFrEF as per 2016 European Society of Cardiology Heart Failure guidelines.<br>* Other names: Ferinject;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin | Measured in g/dL, will be aggregated to form a composite primary endpoint of hemoglobin ≥ 12g/dL, plasma ferritin ≥ 50 ng/mL and transferrin saturation > 20% | 6 and 12 months | 
| Ferritin | Measured in ng/mL, will be aggregated to form a composite primary endpoint of hemoglobin ≥ 12g/dL, plasma ferritin ≥ 50 ng/mL and transferrin saturation > 20% | 6 and 12 months | 
| Transferrin saturation | Measured as a percentage, will be aggregated to form a composite primary endpoint of hemoglobin ≥ 12g/dL, plasma ferritin ≥ 50 ng/mL and transferrin saturation > 20% | 6 and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HF-related hospitalizations | Hospitalizations due to acute-on-chronic heart failure or worsening heart failure (compared with 12 months preceding treatment) | 6 and 12 months | 
| N-terminal prohormone of brain natriuretic peptide (NT-proBNP) | NT-proBNP levels measured in serum (compared to baseline). NT-proBNP values are reported in pg/mL. | 6 and 12 months | 
| Kansas City Cardiomyopathy Questionnaire | HF-specific QoL quantified with the Kansas City Cardiomyopathy Questionnaire (compared to baseline). The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item self-administered questionnaire developed to independently measure the patient's perception of their health status. The questionnaire ranges from 0% (worst possible QoL) to 100% (best possible QoL) | 6 and 12 months | 
| EQ-5D-5L | General QoL is quantified with the EQ-5D-5L questionnaire (compared to baseline). EQ-5D-5L is a standardised measure of health-related quality of life. It contains a short descriptive system questionnaire and a visual analogue scale (EQ VAS). VAS ranges 0% to 100%. | 6 and 12 months | 
| Ventricular tachycardias recorded by cardiac implantable electronic device | Compared with 12 months preceding recruitment. | 6 and 12 months | 
| Non-sustained ventricular tachycardias recorded by cardiac implantable electronic device | Compared with 12 months preceding recruitment. | 6 and 12 months | 
| Appropriate therapies administered by cardiac implantable electronic device | Compared with 12 months preceding recruitment. | 6 and 12 months | 
| Appropriate atrial mode switch events recorded by cardiac implantable electronic device | Compared with 12 months preceding recruitment. | 6 and 12 months | 
| Non-sustained ventricular tachycardias recorded during 24-hour Holter monitoring | Compared with baseline. | 6 and 12 months | 
| Ventricular runs recorded during 24-hour Holter monitoring | Compared with baseline. | 6 and 12 months | 
| Ventricular triple premature complexes during 24-hour Holter monitoring | Compared with baseline. | 6 and 12 months | 
| Ventricular dual premature complexes during 24-hour Holter monitoring | Compared with baseline. | 6 and 12 months | 
| Ventricular premature complexes during 24-hour Holter monitoring | Compared with baseline. | 6 and 12 months | 
| Left ventricular end-diastolic volume index (LVEDVi) | Compared to baseline. Measured in mL/m^2. | 6 and 12 months | 
| Left ventricular ejection fraction (LVEF) | Compared to baseline. Measured as a percentage. | 6 and 12 months | 
| Left ventricular mass index (LVMi) | Compared to baseline. Measured in g/m^2. | 6 and 12 months | 
| Left ventricular global longitudinal strain (LV GLS) | Compared to baseline. Measured as a percentage. | 6 and 12 months | 
| Peak early diastolic tissue velocity (e') | Μeasured at the septal and lateral mitral annulus. Used to calculate E/e' ratio. Measured as m/s. | 6 and 12 months | 
| E-wave mitral inflow velocity (E) | Used to calculate E/e' ratio. Measured as m/s. | 6 and 12 months | 
| Right ventricular fractional area change (RV FAC) | Compared to baseline. Measured as a percentage. | 6 and 12 months | 
| 6-minute walking distance (6MWD) | Distance recorded during six-minute walk testing. Measured in meters. Compared to baseline. | 6 and 12 months | 
| Maximal oxygen consumption (VO2 max) | Maximal oxygen consumption recorded during cardiopulmonary exercise testing. Measured in mL/kg/min. Compared to baseline. | 6 and 12 months | 
| Minute ventilation/carbon dioxide production slope (VE/VCO2 slope) | The VE/VCO2 slope recorded during cardiopulmonary exercise testing. Absolute unit. Compared to baseline. | 6 and 12 months | 
| End-tidal carbon dioxide at anaerobic threshold (etCO2-AT) | Recorded during cardiopulmonary exercise testing. Measured in mmHg. Compared to baseline. | 6 and 12 months | 
| Late potentials | Signal Averaged ECG (SAECG) enables the detection of late potentials. Specialist software automatically performs the detection of late potentials in patients' Holter monitor recordings. | 6 and 12 months | 
| Microvolt T-wave Alternans (TWA) | Specialist software quantifies microvolt TWA voltage in patients' Holter monitor recordings. microvolt TWA is measured in μV. | 6 and 12 months | 
| Heart rate turbulence (HRT) | Heart rate turbulence (HRT) is the baroreflex-mediated short-term oscillation of cardiac cycle lengths after spontaneous ventricular premature complexes. Specialist software detects abnormal HRT in patients' Holter monitor recordings. The existence of abnormal heart rate turbulence is a nominal variable. | 6 and 12 months | 
| Deceleration capacity | (Heart rate) deceleration capacity is a measurement of autonomic nerve regulation in heart failure. Specialist software quantifies deceleration capacity, which is measured in milliseconds (ms). | 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ferric carboxymaltose, heart failure, arrhythmias