Magnetic resonance imaging of organ iron before and after correction of iron deficiency in patients with heart failure

Abstract

Aims: Intravenous iron therapy (IVIT) is known to improve functional status in chronic heart failure (CHF) patients. The exact mechanism is not completely understood. We correlated magnetic resonance imaging (MRI) patterns of T2* iron signal in various organs to systemic iron and exercise capacity (EC) in CHF before and after IVIT.

Methods and results: We prospectively analysed 24 patients with systolic CHF for T2* MRI pattern of the left ventricle (LV), small and large intestines, spleen, liver, skeletal muscle, and brain for iron. In 12 patients with iron deficiency (ID), we restored iron deficit by IVIT using ferric carboxymaltose. The effects after 3 months were analysed by spiroergometry and MRI. Patients with vs. without ID showed lower blood ferritin, haemoglobin (76 ± 63 vs. 196 ± 82 μg/L and 12.3 ± 1.1 vs. 14.2 ± 1.1 g/dL, all P < 0.002), and in trend a lower transferrin saturation (TSAT) (19.1 [13.1; 28.2] vs. 25.1 [21.3; 29.1] %, P = 0.05). Spleen and liver iron was lower as expressed by higher T2* value (71.8 [66.4; 93.1] vs. 36.9 [32.9; 51.7] ms, P < 0.002 and 33.5 ± 5.9 vs. 28.8 ± 3.9 ms, and P < 0.03). There was a strong trend for a lower cardiac septal iron content in ID (40.6 [33.0; 57.3] vs. 33.7 [31.3; 40.2] ms, P = 0.07). After IVIT, ferritin, TSAT, and haemoglobin increased (54 [30; 104] vs. 235 [185; 339] μg/L, 19.1 [13.1; 28.2] vs. 25.0 [21.0; 33.7] %, 12.3 ± 1.1 vs. 13.3 ± 1.3 g/L, all P < 0.04). Peak VO₂ improved (18.2 ± 4.2 vs. 20.9 ± 3.8 mL/min/kg^-1 , P = 0.05). Higher peak VO₂ at anaerobic threshold was associated with higher blood ferritin, reflecting higher metabolic exercise capacity after therapy (r = 0.9, P = 0.0009). Increase in EC was associated with haemoglobin increase (r = 0.7, P = 0.034). LV iron increased by 25.4% (48.5 [36.2; 64.8] vs. 36.2 [32.9; 41.9] ms, P < 0.04). Spleen and liver iron increased by 46.4 and 18.2%, respectively (71.8 [66.4; 93.1] vs. 38.5 [22.4; 76.9] ms, P < 0.04 and 33.5 ± 5.9 vs. 27.4 ± 8.6 ms, P < 0.007). Iron in skeletal muscle, brain, intestine, and bone marrow remained unchanged (29.6 [28.6; 31.2] vs. 30.4 [29.7; 30.7] ms, P = 0.7, 81.0 ± 6.3 vs. 82.9 ± 9.9 ms, P = 0.6, 34.3 ± 21.4 vs. 25.3 ± 14.1 ms, P = 0.2, 9.4 [7.5; 21.8] vs. 10.3 [6.7; 15.7] ms, P = 0.5 and 9.8 ± 1.5 vs. 13.7 ± 8.9 ms, P = 0.1).

Conclusions: CHF patients with ID showed lower spleen, liver, and in trend lower cardiac septal iron. After IVIT, iron signal of the left ventricle as well as spleen and liver increased. Improvement in EC was associated with increase in haemoglobin after IVIT. In ID, liver, spleen, and brain but not heart iron were associated with markers of systemic ID.

Keywords: Heart failure; Iron; MRI.

Figure 1

Iron signal of the heart, skeletal muscle, liver, spleen, bone marrow, brain, small intestine, and colon in patients with chronic heart failure with normal iron status and with iron deficiency. High organ iron signal (TE) in [ms] relates to lower organ iron content. CHF, chronic heart failure.

Figure 2

Iron signal of the heart septum in patients with chronic heart failure with normal iron status and with iron deficiency. High organ iron signal (TE) [ms] relates to lower septal heart iron content. CHF, chronic heart failure.

Figure 3

Blood ferritin in [μg/L], transferrin saturation in [%] and haemoglobin in [g/dL] in patients with chronic heart failure before and after intravenous iron therapy. CHF, chronic heart failure; Hb, haemoglobin; IVIT, intravenous iron therapy; TSAT, transferrin saturation.

Figure 4

Change in MR iron organ signal before (1) and 3 months after (2) intravenous iron therapy as assessed by MR T2* echo time (TE) in [ms]. High organ iron signal (TE) relates to lower organ iron content.

Figure 5

Change in magnetic resonance imaging iron signal of the left ventricle before (white circle) and 3 months after (black circle) intravenous iron therapy in all 12 patients with iron deficit at baseline assessed by MRI T2* echo time (TE) in [ms]. A decrease in echo time indicates an increase in left ventricle's iron content. IVIT, intravenous iron therapy.

Figure 6

Peak oxygen consumption in [mL/kg/min] in patients with chronic heart failure before and 3 months after intravenous iron therapy. CHF, chronic heart failure; IVIT, intravenous iron therapy; peak VO₂, peak oxygen consumption.

Figure 7

Association of blood ferritin in [μg/L] with peak oxygen consumption at anaerobic threshold in [mL/kg/min] in patients with chronic heart failure 3 months after intravenous iron therapy. CHF, chronic heart failure; IVIT, intravenous iron therapy; peakVO₂ AT, peak oxygen consumption at anaerobic threshold.

Figure 8

Association of change in haemoglobin in [g/dL] with change in peak oxygen consumption [mL/kg/min] measured at 3 months after intravenous iron therapy in patients with chronic heart failure. CHF, chronic heart failure; IVIT, intravenous iron therapy; peakVO₂, peak oxygen consumption.