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

Conditions
Ferric Carboxymaltose
Heart Failure With Reduced Ejection Fraction
Arrhythmias, Cardiac
Interventions
Registration Number
NCT04974021
Lead Sponsor
Aristotle University Of Thessaloniki
Brief Summary

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

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
106
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.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
ParticipantsFerric carboxymaltoseHFrEF 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.
Primary Outcome Measures
NameTimeMethod
Ferritin6 and 12 months

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%

Hemoglobin6 and 12 months

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%

Transferrin saturation6 and 12 months

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%

Secondary Outcome Measures
NameTimeMethod
Left ventricular mass index (LVMi)6 and 12 months

Compared to baseline. Measured in g/m\^2.

HF-related hospitalizations6 and 12 months

Hospitalizations due to acute-on-chronic heart failure or worsening heart failure (compared with 12 months preceding treatment)

EQ-5D-5L6 and 12 months

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%.

Ventricular triple premature complexes during 24-hour Holter monitoring6 and 12 months

Compared with baseline.

Non-sustained ventricular tachycardias recorded by cardiac implantable electronic device6 and 12 months

Compared with 12 months preceding recruitment.

Left ventricular end-diastolic volume index (LVEDVi)6 and 12 months

Compared to baseline. Measured in mL/m\^2.

Left ventricular ejection fraction (LVEF)6 and 12 months

Compared to baseline. Measured as a percentage.

Right ventricular fractional area change (RV FAC)6 and 12 months

Compared to baseline. Measured as a percentage.

N-terminal prohormone of brain natriuretic peptide (NT-proBNP)6 and 12 months

NT-proBNP levels measured in serum (compared to baseline). NT-proBNP values are reported in pg/mL.

Appropriate therapies administered by cardiac implantable electronic device6 and 12 months

Compared with 12 months preceding recruitment.

Left ventricular global longitudinal strain (LV GLS)6 and 12 months

Compared to baseline. Measured as a percentage.

6-minute walking distance (6MWD)6 and 12 months

Distance recorded during six-minute walk testing. Measured in meters. Compared to baseline.

Kansas City Cardiomyopathy Questionnaire6 and 12 months

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)

Ventricular tachycardias recorded by cardiac implantable electronic device6 and 12 months

Compared with 12 months preceding recruitment.

Ventricular premature complexes during 24-hour Holter monitoring6 and 12 months

Compared with baseline.

Peak early diastolic tissue velocity (e')6 and 12 months

Μeasured at the septal and lateral mitral annulus. Used to calculate E/e' ratio. Measured as m/s.

Minute ventilation/carbon dioxide production slope (VE/VCO2 slope)6 and 12 months

The VE/VCO2 slope recorded during cardiopulmonary exercise testing. Absolute unit. Compared to baseline.

Deceleration capacity6 and 12 months

(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).

Appropriate atrial mode switch events recorded by cardiac implantable electronic device6 and 12 months

Compared with 12 months preceding recruitment.

Non-sustained ventricular tachycardias recorded during 24-hour Holter monitoring6 and 12 months

Compared with baseline.

Ventricular runs recorded during 24-hour Holter monitoring6 and 12 months

Compared with baseline.

Ventricular dual premature complexes during 24-hour Holter monitoring6 and 12 months

Compared with baseline.

E-wave mitral inflow velocity (E)6 and 12 months

Used to calculate E/e' ratio. Measured as m/s.

Late potentials6 and 12 months

Signal Averaged ECG (SAECG) enables the detection of late potentials. Specialist software automatically performs the detection of late potentials in patients' Holter monitor recordings.

End-tidal carbon dioxide at anaerobic threshold (etCO2-AT)6 and 12 months

Recorded during cardiopulmonary exercise testing. Measured in mmHg. Compared to baseline.

Heart rate turbulence (HRT)6 and 12 months

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.

Maximal oxygen consumption (VO2 max)6 and 12 months

Maximal oxygen consumption recorded during cardiopulmonary exercise testing. Measured in mL/kg/min. Compared to baseline.

Microvolt T-wave Alternans (TWA)6 and 12 months

Specialist software quantifies microvolt TWA voltage in patients' Holter monitor recordings. microvolt TWA is measured in μV.

Trial Locations

Locations (1)

Hippokration General Hospital of Thessaloniki, Third Department of Cardiology (Aristotle University of Thessaloniki)

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Thessaloníki, Macedonia, Greece

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