The Impact of Intravenous Ferric Carboxymaltose on Reverse Electrical Remodeling Following Cardiac Resynchronization Therapy

Abstract

Background

The influence of intravenous ferric carboxymaltose (FCM) on reverse electrical remodeling (RER) in patients with heart failure with reduced ejection fraction (HFrEF) post-cardiac resynchronization therapy (CRT) is unknown. This study examines the effect of iron replacement using intravenous FCM on RER in CRT-implanted HFrEF patients with iron deficiency anemia.

Methods

We retrospectively analyzed 65 patients with successful CRT-defibrillator between March 2017 and January 2020, all with iron deficiency anemia at implantation. The cohort comprised 35 patients in the FCM group and 30 in the non-FCM group. Follow-up data were obtained from visits 6 months post-CRT implantation including baseline characteristics, echocardiographic left ventricular measurements, and electrocardiograms. Changes in intrinsic QRS duration (iQRS) and left ventricular ejection fraction (LVEF) from baseline to 6 months were assessed.

Results

The FCM group showed a greater reduction in iQRS duration compared to the non-FCM group (-10.4 ± 2.2 ms vs. -3 ± 2.9 ms, p < 0.0001). Additionally, at the 6-month follow-up, the increase in LVEF was higher in the FCM group than in the non-FCM group (+3.6 ± 1.6% vs. -0.1 ± 1.7%, p < 0.0001). Correlations were found between changes in ferritin levels and iQRS duration (r = -0.725, p < 0.0001) and LVEF (r = 0.712, p < 0.0001). Multivariate regression analysis revealed that elevated ferritin independently influenced the increase in LVEF (p = 0.006, β = 0.554) and the decrease in iQRS (p < 0.001, β = -0.685).

Conclusions

Intravenous iron treatment with FCM may reduce iQRS duration and improve LVEF and functional status in HFrEF patients with iron deficiency anemia following CRT.

Abbreviations

ACEi, Angiotensin-converting enzyme inhibitor

ARB, Angiotensin receptor blocker

ARNi, Angiotensin receptor-neprilysin inhibitor

COPD, Chronic obstructive pulmonary disease

CRT, Cardiac resynchronization therapy

CRT-D, Cardiac resynchronization therapy-defibrillator

ECG, Electrocardiogram

eGFR, Estimated glomerular filtration rate

FCM, Ferric carboxymaltose

Hb, Hemoglobin

HFrEF, Heart failure with reduced ejection fraction

IQR, Interquartile range

iQRS, Intrinsic QRS duration

LV, Left ventricular

LVEDD, Left ventricular end-diastolic diameter

LVEDV, Left ventricular end-diastolic volume

LVEF, Left ventricular ejection fraction

LVESD, Left ventricular end-systolic diameter

LVESV, Left ventricular end-systolic volume

NYHA, New York Heart Association

RER, Reverse electrical remodeling

SD, Standard deviation

ΔQRS, Delta QRS duration

INTRODUCTION

Regardless of the presence of anemia, iron deficiency is one of the most important comorbidities seen in at least half of patients with heart failure with reduced ejection fraction (HFrEF), and it is associated with poor outcomes.^1,2 Previous and current heart failure guidelines recommend iron supplementation with intravenous ferric carboxymaltose (FCM) to improve heart failure symptoms and exercise capacity, and reduce recurrent heart failure hospitalizations in patients with HFrEF.^2,3 Iron plays a crucial role in the mitochondrial function of cardiomyocytes and therefore also in cardiac metabolism and remodeling.^4-6

For improving heart failure symptoms, functional capacity, left ventricular (LV) ejection fraction, and reducing LV size, mitral regurgitation and native QRS duration, cardiac resynchronization therapy (CRT) is a well-recognized treatment option in HFrEF patients.^7,8 However, the presence of iron deficiency at the time of CRT implantation has been associated with a poor clinical response and inadequate LV reverse remodeling following CRT.^4,8 Recently, intravenous iron replacement has been demonstrated to increase LV ejection fraction, cardiac contractility and exercise capacity, and decrease LV end systolic volume in iron deficient HFrEF patients whose left ventricular ejection fraction (LVEF) is persistently reduced after CRT. These findings suggest that intravenous FCM positively affects cardiac remodeling and functional status after CRT implantation in HFrEF patients with iron deficiency.⁶ CRT has been shown to reduce the intrinsic QRS duration, which is identified as reverse electrical remodeling (RER).⁷ However, the effect of intravenous FCM on RER in HFrEF patients with CRT implantation is unknown. The purpose of the current retrospective study is to evaluate whether iron replacement with intravenous FCM can induce RER in CRT implanted patients with iron deficiency.

METHODS

Study population and design

We conducted a retrospective, observational, single-center, case-control study, which the Local Ethics Committee approved. The inclusion criteria were as follows: older than 18 years of age, having received CRT according to guideline recommendations, having stable heart failure for at least 4 weeks under optimal medical treatment as recommended by current guidelines, having at least 98% biventricular pacing evaluated by device interrogation during follow-up, and concomitant iron deficiency (defined as ferritin < 100 μg/L) at the time of CRT implantation. The exclusion criteria were as follows: serum levels of ferritin ≥ 100 μg/L and hemoglobin > 15 g/dL at the time of CRT implantation, pacemaker dependency, being under oral iron supplementation therapy, and lack or insufficient laboratory, clinical, echocardiographic, and electrocardiographic follow-up data just before and after CRT implantation.

After screened the patients with chronic heart failure who underwent successful CRT-D device implantation between March 2017 and January 2020 for the inclusion and exclusion criteria, they were divided into two groups: (1) those who underwent intravenous FCM during CRT implantation, and (2) those who did not. According to the medical records of the patients who received intravenous FCM supplementation, FCM (Ferinject®, Abdi İbrahim, Turkey) was administered intravenously for at least 15 minutes by diluting in 250 mL of 0.9% NaCl. It was administered to the patients at a maximum of 1000 mg infusion at one time, in accordance with the recommendations in the package insert. In addition, the intravenous FCM dose was administered by calculating the patient’s hemoglobin (Hb) level and body weight based on the dosing scheme in Table 1. After 1-2 weeks, the remaining dose was given to patients requiring > 1000 mg of FCM.

Table 1. Dosing scheme of intravenous ferric carboxymaltose.

Hemoglobin (g/dL)	Body weight (kg)
	< 70	≥ 70
< 10	1000 + 500 mg	1000 + 1000 mg
45579	1000 mg	1000 + 500 mg
> 14-< 15	500 mg	500 mg

Follow-up data obtained from the 6-month routine follow-up visits of the patients after CRT implantation were collected and analyzed retrospectively. Data including demographic information, laboratory results, medical history, medication details, New York Heart Association (NYHA) functional class, information on whether intravenous FCM therapy was administered during CRT device implantation as a heart failure guideline recommendation, echocardiographic left ventricular measurements, baseline electrocardiogram (ECG) recorded before CRT device implantation, and follow-up ECG were collected for analysis for each patient from medical records.

Electrocardiogram analysis

Baseline ECG, which was obtained just before CRT device implantation, and follow-up ECG (without biventricular pacing), which was acquired 6 months after post-CRT device implantation, were assessed in respective of intrinsic QRS duration. A follow-up ECG (without biventricular pacing) at 6 months after CRT device implantation was routinely recorded for each patient by temporarily reprogramming the VVI to 35/min to allow for natural rhythm. The intrinsic QRS duration was measured after ensuring a stable QRS morphology for each patient at baseline and without biventricular pacing during a follow-up visit from 12-lead surface ECG. All 12-lead surface ECGs were recorded with a paper speed of 25 mm/second and an amplification of 10 mm/mV. The QRS duration was measured with a digital caliper on the lead presenting the widest QRS complex by two independent cardiologists blinded to patient data. Delta QRS duration (ΔQRS) was calculated as the change between the intrinsic QRS duration value at the time of implantation and 6 months after implantation. We aimed to investigate the effect of intravenous FCM treatment on RER. Thus, the primary endpoint was the change in intrinsic QRS duration (without biventricular pacing) from baseline to 6-months of follow-up.

Transthoracic echocardiography analysis

Each patient underwent standard transthoracic echocardiographic examinations using a commercially available system (Vivid 7, General Electric-Vingmed Ultrasound, Horten, Norway) at rest before CRT device implantation and during the follow-up visit 6 months after implantation.

Standard apical four-chamber as well as parasternal long- and short-axis views of the LV were used to measure echocardiographic parameters. LV end-diastolic and end-systolic volumes and LVEF were calculated using the biplane Simpson’s method. The LV end-diastolic diameter (LVEDD) and LV end-systolic diameter (LVESD) were measured by an experienced echocardiographer using two-dimensional guided M-mode, and Doppler echocardiography based on the recommendations for chamber quantification.⁹

The effect of intravenous FCM treatment on reverse remodeling following CRT device implantation was the secondary purpose of this study. Therefore, changes in LVEF, LVEDD, LVESD, LV end-diastolic and end-systolic volumes were assessed as secondary endpoints of the study. In addition, an echocardiographic CRT response or LV reverse remodeling was defined as a reduction in the left ventricular end-systolic volume (LVESV) by ≥ 15% or an increase in LVEF by ≥ 5%. Clinical CRT response was defined as at least one NYHA class improvement in the functional status.¹⁰ The ratios of both echocardiographic responders and clinical responders were determined for each study group from the 6-month routine follow-up visit records according to these definitions.

Statistical analysis

Normally distributed continuous data were presented as mean ± standard deviation (SD) and continuous data with skewed distribution were presented as median and interquartile range (IQR, range from the 25th to the 75th percentile). Categorical data were expressed in percentage (%) or frequency. Normal distribution of the continuous data was assessed using the Kolmogorov-Smirnov test. The paired Student’s t-test was used for comparisons of normally distributed continuous variables. Otherwise, we used the Mann-Whitney U test for skewed continuous variables. Changes in both intrinsic QRS duration and echocardiographic parameters in response to intravenous FCM following CRT were examined with the Wilcoxon signed-rank test. The chi-squared test or Fisher’s exact test was used to compare categorical data. Spearman correlation analysis was used in the correlation analysis. Multivariate linear regression analysis was performed to identify the independent effects of changes in Hb and ferritin levels following intravenous FCM treatment on changes in intrinsic QRS duration and LVEF.

A two-sided p < 0.05 was considered statistically significant. All statistical analyses were performed with SPSS statistics software, version 28.0 (IBM, Armonk, NY).

RESULTS

Between March 2017 and January 2020, a total of 142 patients who underwent successful CRT-D device implantation were screened for the inclusion and exclusion criteria. Consequently, the data of 65 patients were found to be eligible for analysis in this retrospective study. Thirty-five of these patients who were administered intravenous FCM were included in the FCM group, and the remaining 30 who did not receive intravenous FCM were included in the non-FCM group. The baseline characteristics of the patients are shown in Table 2. The baseline characteristics of the patients and the cardiac medications they used were similar between the two study groups, except for baseline ferritin levels, which were significantly lower in the FCM group. Patients in the FCM group received a mean dose of 1500 ± 500 mg FCM, and an additional second dose was administered within 10-15 days after the first dose of intravenous FCM.

Table 2. Baseline characteristics of the study patients.

Variable	FCM group (n = 35)	Non-FCM group (n = 30)	p value
Demographics
Age, years, mean ± SD	53 ± 11	56 ± 10	0.135
Female sex, n (%)	14 (40)	13 (43)	0.786
Physical findings
Body surface area (m2)	1.72 ± 0.10	1.76 ± 0.08	0.188
Body mass index (kg/m2)	23.8 ± 2.7	23.9 ± 2.1	0.827
Systolic blood pressure, mmHg	119 ± 14	113 ± 24	0.503
Medical history, n (%)
Hypertension	11 (31)	9 (30)	0.901
Diabetes mellitus	12 (34)	9 (30)	0.713
COPD	9 (26)	8 (27)	0.931
Smoking	12 (34)	7 (23)	0.333
Atrial fibrillation	3 (9)	2 (7)	0.774
Heart failure etiology
Ischaemic, n (%)	22 (63)	19 (63)	0.968
Functional status, n (%)
NYHA class II	15 (43)	19 (63)	0.099
NYHA class III	20 (57)	11 (37)	0.099
Baseline LVEF, %	31 ± 4	31 ± 3	0.853
Baseline LVEDD, mm	65 ± 8	64 ± 8	0.747
Baseline LVESD, mm	56 ± 8	55 ± 8	0.772
Baseline LVESV, mL	165 ± 58	167 ± 58	0.885
Baseline LVEDV, mL	234 ± 67	234 ± 65	0.974
Baseline QRS duration, ms	148.4 ± 5.3	149.8 ± 5.0	0.363
Laboratory data
Hemoglobin, g/dL	9.9 ± 0.7	10.3 ± 0.7	0.055
Ferritin, μg/L	10.7 ± 5.0	13.5 ± 3.9	0.012
eGFR, mL/min/1.73 m2	65 ± 10	67 ± 11	0.623
C-reactive protein, mg/L	2.97 ± 0.60	2.82 ± 0.64	0.387
Heart failure medications, n (%)
ACEi/ARB/ARNi	26 (74)	22 (73)	0.931
ARNi	4 (11)	3 (10)	0.853
Spironolactone/eplerenone	24 (67)	22 (73)	0.674
Beta-blocker	28 (80)	24 (80)	1.000
Loop diuretics	22 (63)	21 (70)	0.544
Ivabradine	15 (43)	14 (47)	0.758

Values are given as mean ± standard deviation or n (%).

ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNi, angiotensin receptor-neprilysin inhibitor; COPD, chronic obstructive pulmonary disease; eGFR, estimated glomerular filtration rate; FCM, ferric carboxymaltose; LVEDD, left ventricular end-diastolic diameter; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic diameter; LVESV, left ventricular end-systolic volume; NYHA, New York Heart Association; SD, standard deviation.

As expected, at the 6-month follow-up visit, both mean ferritin and Hb levels increased significantly in the FCM group compared to baseline (from 10.7 ± 5.0 to 86.5 ± 7.6 μg/L, p < 0.0001; from 9.9 ± 0.7 to 12.7 ± 0.6 g/dL, p < 0.0001, respectively), while these levels were not significantly increased in the non-FCM group (from 13.5 ± 3.9 to 14.1 ± 4.2 μg/L, p = 0.962; from 10.3 ± 0.7 to 10.5 ± 0.9 g/dL, p = 0.07, respectively).

The baseline QRS durations were similar in both groups. There were significant reductions in intrinsic QRS duration at 6-months of follow-up after CRT implantation compared to baseline in both the FCM and non-FCM groups (from 148.4 ± 5.3 to 138.0 ± 5.1 ms, p < 0.0001; from 149.8 ± 5.0 to 146.8 ± 4.6 ms, p < 0.0001, respectively). However, the change in intrinsic QRS duration from baseline to 6-months of follow-up (delta QRS duration) was significantly greater in the FCM group than in the non-FCM group (-10.4 ± 2.2 ms vs. -3 ± 2.9 ms, p < 0.0001), as shown in Figure 1A.

Figure 1.

Change in primary and secondary endpoints. The changes in intrinsic QRS duration (delta QRS duration) (A), left ventricular ejection fraction (B), left ventricular end-diastolic diameter (C), left-ventricular end-systolic diameter (D), left ventricular end-diastolic volume (E), and left ventricular end-systolic volume (F) at 6-month follow-up of the CRT implantation. FCM, ferric carboxymaltose; LVDD, left ventricular end-diastolic diameter; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; LVESD, left-ventricular end-systolic diameter; LVESV, left ventricular end-systolic volume.

At the 6-month follow-up visit, the change in LVEF from baseline was significantly higher in the FCM group than in the non-FCM group (+3.6 ± 1.6% vs. -0.1 ± 1.7%, p < 0.0001), as shown in Figure 1B. Treatment with FCM resulted in a significant improvement in LVEF 6 months after CRT device implantation, however there was no significant change or improvement in the non-FCM group (from 30.9 ± 3.9% to 34.5 ± 3.8%, p < 0.0001; from 31.4 ± 2.8% to 31.3 ± 2.8%, p = 0.943, respectively). Additionally, as shown in Figure 1C-F, LVEDD, LVESD, LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV) were significantly decreased in the FCM group 6 months after CRT device implantation compared to the non-FCM group.

Functional status significantly improved in the FCM group after 6 months but remained unchanged in the non-FCM group. Thus, at the 6-month follow-up visit, there were significantly more NYHA class II patients and significantly fewer NYHA class III patients in the FCM group compared to the non-FCM group (see Table 3). This result indicated that treatment with FCM at 6 months significantly improved the functional status of the patients. The heart failure drugs of the patients in both groups did not change significantly during the follow-up period, and there was no significant difference in drug use between the two groups at 6-months of follow-up.

Table 3. Change in functional status in study groups at 6 months.

	FCM group (n = 35)			Non-FCM group (n = 30)
	Baseline	6-month follow-up	p value	Baseline	6-month follow-up	p value
NYHA Class II	43% (15/35)	91% (32/35)	< 0.0001	63% (19/30)	60% (18/30)	1.000
NYHA Class III	57% (20/35)	9% (3/35)		37% (11/30)	40% (12/30)

Results reported as % (n/N).

FCM, ferric carboxymaltose; NYHA, New York Heart Association.

As shown in Table 4, the change in ferritin level was negatively correlated with the change in intrinsic QRS duration (r = -0.725, p < 0.0001). Moreover, the change in ferritin level was negatively correlated with the changes in LVEDD, LVESD, LVEDV, and LVESV values (see Table 4), while there was a positive correlation between the change in ferritin level and the change in LVEF (r = 0.712, p < 0.0001, see Table 4).

Table 4. Correlations of change in serum ferritin levels with reverse electrical remodeling and left ventricular reverse remodeling.

Variables	Ferritin
	r	p value
ΔQRS	-0.725	< 0.0001
Change in LVEF	0.712	< 0.0001
Change in LVEDD	-0.641	< 0.0001
Change in LVESD	-0.620	< 0.0001
Change in LVEDV	-0.683	< 0.0001
Change in LVESV	-0.663	< 0.0001

ΔQRS, delta QRS duration (change between baseline value of intrinsic QRS duration and value at 6 months after CRT device implantation); LVEDD, left ventricular end-diastolic diameter; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic diameter; LVESV, left ventricular end-systolic volume; r, Spearman’s correlation coefficient.

At 6-months of follow-up, there were significantly more echocardiographic and clinical CRT responders in the FCM group than in the non-FCM group, while the rates of hospitalization for heart failure and CRT-D shock events were similar in both groups (see Table 5).

Table 5. Echocardiographic and clinical response, hospitalization for heart failure, and CRT-D shock event by groups at 6 months of CRT-D device implantation.

Variable	FCM group(n = 35)	Non-FCM group (n = 30)	p value
Echocardiographic response	25 (71%)	5 (17%)	< 0.0001
Clinical response	19 (54%)	5 (17%)	0.002
Hospitalization for heart failure	4 (11%)	6 (20%)	0.340
CRT-D shock event	2 (6%)	3 (10%)	0.518

Results reported as n (%). The p values were derived from chi-square test.

CRT-D, cardiac resynchronization therapy-defibrillator; FCM, ferric carboxymaltose.

Seventeen (89%) patients had LV reverse remodeling among the clinical CRT responders in the FCM group. Conversely, only two patients (40%) had LV reverse remodeling among the clinical CRT responders in the non-FCM group.

Multivariate linear regression analysis was used to assess the impact of elevated Hb and ferritin levels in cases of an increase in LVEF and a decrease in intrinsic QRS duration 6 months after CRT device implantation. In the multivariate model, we observed a significant independent effect of elevation in ferritin level on the increase in LVEF and decrease in intrinsic QRS duration. However, there was no significant independent effect of the elevation in Hb level on either the increase in LVEF or the decrease in intrinsic QRS duration (see Table 6).

Table 6. Multivariate linear regression analysis.

Variable	Change in LVEF			Change in intrinsic QRS
	β	t	p	β	t	p
Change in ferritin levels	0.554	2.847	0.006	-0.685	-4.026	< 0.0001
Change in Hb levels	0.220	1.133	0.262	-0.149	-0.876	0.385

Hb, hemoglobin; LVEF, left ventricular ejection fraction.

DISCUSSION

In the current retrospective study, we mainly investigated the benefit of FCM treatment on CRT-induced RER. Firstly, our findings suggest that intravenous iron replacement may result in further improvement in RER by causing a stronger decrease in intrinsic QRS duration with CRT. Secondly, we observed significant improvements in LVEF as well as LV dimensions and volumes, which may imply significant favorable LV reverse remodeling with intravenous iron replacement therapy in CRT-implanted patients. Thirdly, we also found that intravenous iron repletion improved the functional status of patients implanted with CRT. Furthermore, we observed significant correlations between the change in ferritin levels and the changes in intrinsic QRS duration, LVEF, LV dimensions and LV volumes, supporting the benefit of intravenous iron replacement treatment.

In previous studies, CRT has been shown to cause shortening of the native QRS interval, which is called RER.^11,12 Nevertheless, the mechanisms underlying the reduction in native QRS duration with CRT have yet to be elucidated. This change in intraventricular conduction may be explained by an increase in impulse conduction velocity due to the possible regeneration of conduction tissue or improvement in both hemodynamics and LV remodeling. A previous animal study showed that biophysical factors such as hemodynamics or mechanics play a crucial role in differentiation of the intraventricular conduction system during development.¹³ Boriani et al. demonstrated an association between QRS shortening and LV reverse remodeling following CRT.¹¹ Another animal study showed that CRT partly ameliorates dyssynchronous contraction-induced adverse ion channel remodeling and anomalous calcium homeostasis while reducing the territorial heterogeneity of action potential duration by shortening the action potential duration in lateral wall LV cells.¹⁴

However, the effect of iron therapy on surface QRS duration in patients with iron deficiency and HFrEF is unknown. A recent study showed that prolonged Tp-e interval and elevated Tp-e/QT and Tp-e/QTc ratios in iron-deficient heart failure patients improved 12 weeks after treatment with FCM.¹⁵ These findings suggest that iron replacement may affect electrocardiographic parameters in heart failure patients with iron deficiency. Moreover, Martens et al. recently demonstrated that intravenous FCM treatment improved LVEF and LVESV in HFrEF patients with iron deficiency whose LVEF was persistently reduced despite CRT treatment.⁶ Nonetheless, no studies have examined the effect of intravenous FCM treatment on QRS duration in CRT recipients with iron deficiency. Based on the association between shortened intrinsic QRS duration and improvements in LVEF and LV volumes as shown previously,¹¹ we designed this study considering that intravenous iron replacement may also have a beneficial effect on RER in patients with iron deficiency and HFrEF following CRT. Ultimately, the findings of our study demonstrate that intravenous iron replacement may lead to further narrowing of the native QRS duration with CRT, and that the change in native QRS duration is also inversely related to ferritin levels. However, our study cannot explain the role of iron in RER due to its retrospective observational nature.

Nevertheless, it raises the question of whether the favorable findings of intravenous iron replacement detected in our study are related to the correction of anemia. In a previous study, treatment with intravenous FCM resulted in improvements in 6-min-walk-test distance in patients with and without anemia, suggesting that the favorable results of intravenous iron treatment are not associated with the correction of anemia.¹⁶ Recently, intravenous FCM administration has been reported to lead to changes associated with myocardial iron repletion in T2* and T1 mapping cardiac magnetic resonance sequences in patients with heart failure and iron deficiency.¹⁷ Furthermore, a significant correlation has been found between T2* changes and improvements in LVEF and LVESV following FCM administration in patients with chronic HFrEF of non-ischemic etiology and iron deficiency, regardless of Hb changes.¹⁸ These findings suggest that the favorable effects that we observed on LV reverse remodeling and RER of intravenous iron treatment following CRT may be related to myocardial iron repletion. In addition, our multivariate regression analysis results showed that the increase in ferritin levels, but not the increase in Hb levels, had a significant and independent impact on improving LV function and RER. This finding also validates the previous suggestions.

Study limitations

The study’s primary limitation is the relatively small sample size, as it was a single-center retrospective study and relied on a limited amount of patient data available from the medical records. Additionally, potential uncontrolled and unrecognized confounders may have affected our findings due to the retrospective observational nature of the current study. Another limitation is that LVEF and LV volumes were measured by 2D echocardiography instead of 3D echocardiography or magnetic resonance imaging. The last limitation is that our study could not explain the role of iron in RER.

New knowledge gained

To the best of our knowledge, the current study is the first to examine the influence of intravenous FCM treatment on RER in HFrEF patients with iron-deficiency anemia following CRT implantation. Intravenous iron therapy with FCM may induce more RER in CRT recipients with iron deficiency anemia during CRT device implantation while improving LV remodeling. We observed significant correlations between an increase in ferritin levels and a decrease in intrinsic QRS duration and improvements in LVEF, LV sizes and volumes. This observation supports the potential favorable effects of intravenous iron replacement treatment on reverse electrical and LV reverse remodeling in CRT recipients with iron deficiency anemia.

CONCLUSIONS

In conclusion, the present study suggests that intravenous FCM therapy may have beneficial effects on both RER and LV remodeling while improving functional status in HFrEF patients with iron deficiency anemia following CRT implantation. Prospective studies with a larger sample size are necessary to confirm our findings and clarify the effect of intravenous iron replacement therapy on RER in CRT recipients.

DECLARATION OF CONFLICT OF INTEREST

All the authors declare no conflict of interest.