Elevated Plasma sRAGE and IGFBP7 in Heart Failure Decrease After Heart Transplantation in Association with Haemodynamics

Figures

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  Figure 1. Overview of the study set‐up. Statistical significance in (A) was P < 0.008; false discovery rate <0.01. Statistical significance for correlations of change in (B)–(D) was P < 0.021; false discovery rate <0.1. IGFBP7, insulin‐like growth factor‐binding protein 7; sRAGE, soluble receptor for advanced glycation end products.

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  Figure 2. (A) Plasma levels of soluble receptor for advanced glycation end products (sRAGE) in controls, pre‐heart transplantation (HT), and post‐HT. (B–E) Correlations between changes in plasma sRAGE and changes in haemodynamics. In (A), statistical significance was P < 0.008; false discovery rate <0.01. *** P < 0.0001. Statistical significance for correlations of change was considered P < 0.021; false discovery rate <0.1. mPAP, mean pulmonary arterial pressure; PAC, pulmonary arterial compliance; PAWP, pulmonary arterial wedge pressure; PVR, pulmonary vascular resistance; WU, Wood units.

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  Figure 3. (A) Plasma levels of insulin‐like growth factor‐binding protein 7 (IGFBP7) in controls, pre‐heart transplantation (HT), and post‐HT. (B) Correlations between changes in plasma IGFBP7 and changes in mean right atrial pressure (MRAP), as well as (C) N‐terminal pro‐brain natriuretic peptide (NT‐proBNP). In (A), statistical significance was P < 0.008; false discovery rate <0.01. *** P < 0.0001. Statistical significance for correlations of change was considered P < 0.021; false discovery rate <0.1.

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  Figure 4. (A) Different mechanisms may stimulate the production of AGEs. AGE binds to its receptor RAGE, whereof diverse pathways involved in heart failure and pulmonary hypertension (PH) pathophysiology and progression are activated. Heart failure patients with or without PH were heart transplanted, and correlations of the improved haemodynamic profile along with the change (Δ) in sRAGE were present. sRAGE may be a biomarker reflecting the mechanical state of pulmonary vasculature as well as pulmonary passive congestion, typically found in PH secondary to heart failure. (B1) Elevated IGFBP7 was present during haemodynamic overload. This imbalance was restored by heart transplantation (green). The source of plasma IGFBP7 may be the failing heart or other organs. (B2) ΔIGFBP7 correlated with improved haemodynamics, suggesting it to be a biomarker in heart failure and PH. MRAP, mean right atrial pressure; NT‐proBNP, N‐terminal pro‐brain natriuretic peptide; PAC, pulmonary arterial compliance; PAWP, pulmonary arterial wedge pressure; PVR, pulmonary vascular resistance.