Abstract Aims Iron deficiency is common in heart failure with reduced ejection fraction (HFrEF). In patients with cardiac resynchronization therapy (CRT), it is associated with a diminished reverse remodelling response and poor functional improvement. The latter is partially related to a loss in contractile force at higher heart rates (negative force–frequency relationship). Methods and results The effect of intravenous ferric carboxymaltose on reverse remodelling following cardiac resynchronization therapy (IRON‐CRT) trial is a multicentre, prospective, randomized, double‐blind controlled trial in HFrEF patients who experienced incomplete reverse remodelling (defined as a left ventricular ejection fraction below <45%) at least 6 months after CRT. Additionally, patients need to have iron deficiency defined as a ferritin below 100 μg/L irrespective of transferrin saturation or a ferritin between 100 and 300 μg/L with a transferrin saturation <20%. Patients will be randomized to either intravenous ferric carboxymaltose (dose based according to Summary of Product Characteristics) or intravenous placebo. The primary objective is to evaluate the effect of ferric carboxymaltose on metrics of cardiac reverse remodelling and contractility, measured by the primary endpoint, change in left ventricular ejection fraction assessed by three‐dimensional (3D) echo from baseline to 3 month follow‐up and the secondary endpoints change in left ventricular end‐systolic and end‐diastolic volume. The secondary objective is to determine if ferric carboxymaltose is capable of improving cardiac contractility in vivo , by assessing the force–frequency relationship through incremental biventricular pacing. A total of 100 patients will be randomized in a 1:1 fashion. Conclusions The IRON‐CRT trial will determine the effect of ferric carboxymaltose on cardiac reverse remodelling and rate‐dependent cardiac contractility in HFrEF patients.
Background: Treatment with ferric carboxymaltose (FCM) is limited to 1 g during one administration, which is insufficient in patients with a higher body weight or low haemoglobin (Hb). As a consequence, under-dosing might be common in clinical practice, yet the consequences remain unstudied.Methods: We retrospectively assessed all HFrEF-patients with iron-deficiency (ferritin <100 µg/l or between 100 and 300 µg/l if TSAT < 20%) receiving treatment with FCM between 2015 and 2017. This time-frame was chosen as during this we used a 1-g FCM-regimen for all patients (unless Hb = 14–15 mg/dl, than 500 mg). We compared the actual given dose versus the calculated target dose (according to the SmPC, with the difference between both being the dose deficit). We assessed the impact of dose deficits on clinical and biochemical status after 12 weeks.Results: A total of 211 HFrEF patients were analysed. The actual given dose FCM was 918 ± 188 mg, while the calculated target dose was 1308 ± 470 mg. In 121(61%) patients, a standard dose of 1-g FCM resulted in a dose deficit, of whom 93 had a dose deficit of 500 mg and 35 had a dose deficit of 1000 mg. Follow-up was available in 81% of patients (median = 12 weeks). A dose deficit of 500 mg was associated with a 4.93 higher odds, while a dose deficit of 1000 mg was associated with a 7.78 higher odds of residual iron deficiency. After adjusting for baseline NYHA-class, a dose deficit was associated with less symptomatic improvement. During 442 ± 292 days of follow-up, 68 patients were readmitted with heart failure and 15 patients died. In an univariate model (but not in a multivariate model), a dose deficit was associated with adverse clinical outcome.Conclusion: A majority of HFrEF patients with iron deficiency require doses exceeding 1 g of FCM, and thus require follow-up appointments to correct a residual dose deficit. A residual dose deficit is associated with less functional and biochemical improvement.
Cardiac resynchronization therapy (CRT) is one of the most effective therapies for heart failure with reduced ejection fraction and leads to improved quality of life, reductions in heart failure hospitalization rates and all-cause mortality. Nevertheless, up to two-thirds of eligible patients are not referred for CRT. Furthermore, post-implantation follow-up is often fragmented and suboptimal, hampering the potential maximal treatment effect. This joint position statement from three European Society of Cardiology Associations, Heart Failure Association (HFA), European Heart Rhythm Association (EHRA) and European Association of Cardiovascular Imaging (EACVI), focuses on optimized implementation of CRT. We offer theoretical and practical strategies to achieve more comprehensive CRT referral and post-procedural care by focusing on four actionable domains: (i) overcoming CRT under-utilization, (ii) better understanding of pre-implant characteristics, (iii) abandoning the term 'non-response' and replacing this by the concept of disease modification, and (iv) implementing a dedicated post-implant CRT care pathway.
