Abnormal pulmonary perfusion heterogeneity in patients with Fontan circulation and pulmonary arterial hypertension

Abstract

Key points: The distribution of pulmonary perfusion is affected by gravity, vascular branching structure and active regulatory mechanisms, which may be disrupted by cardiopulmonary disease, but this is not well studied, particularly in rare conditions. We evaluated pulmonary perfusion in patients who had undergone Fontan procedure, patients with pulmonary arterial hypertension (PAH) and two groups of controls using a proton magnetic resonance imaging technique, arterial spin labelling to measure perfusion. Heterogeneity was assessed by the relative dispersion (SD/mean) and gravitational gradients. Gravitational gradients were similar between all groups, but heterogeneity was significantly increased in both patient groups compared to controls and persisted after removing contributions from large blood vessels and gravitational gradients. Patients with Fontan physiology and patients with PAH have increased pulmonary perfusion heterogeneity that is not explainable by differences in mean perfusion, gravitational gradients, or large vessel anatomy. This probably reflects vascular remodelling in PAH and possibly in Fontan physiology.

Abstract: Many factors affect the distribution of pulmonary perfusion, which may be disrupted by cardiopulmonary disease, but this is not well studied, particularly in rare conditions. An example is following the Fontan procedure, where pulmonary perfusion is passive, and heterogeneity may be increased because of the underlying pathophysiology leading to Fontan palliation, remodelling, or increased gravitational gradients from low flow. Another is pulmonary arterial hypertension (PAH), where gravitational gradients may be reduced secondary to high pressures, but remodelling may increase perfusion heterogeneity. We evaluated regional pulmonary perfusion in Fontan patients (n = 5), healthy young controls (Fontan control, n = 5), patients with PAH (n = 6) and healthy older controls (PAH control) using proton magnetic resonance imaging. Regional perfusion was measured using arterial spin labelling. Heterogeneity was assessed by the relative dispersion (SD/mean) and gravitational gradients. Mean perfusion was similar (Fontan = 2.50 ± 1.02 ml min^-1 ml^-1 ; Fontan control = 3.09 ± 0.58, PAH = 3.63 ± 1.95; PAH control = 3.98 ± 0.91, P = 0.26), and the slopes of gravitational gradients were not different (Fontan = -0.23 ± 0.09 ml min^-1 ml^-1 cm^-1 ; Fontan control = -0.29 ± 0.23, PAH = -0.27 ± 0.09, PAH control = -0.25 ± 0.18, P = 0.91) between groups. Perfusion relative dispersion was greater in both Fontan and PAH than controls (Fontan = 1.46 ± 0.18; Fontan control = 0.99 ± 0.21, P = 0.005; PAH = 1.22 ± 0.27, PAH control = 0.91 ± 0.12, P = 0.02) but similar between patient groups (P = 0.13). These findings persisted after removing contributions from large blood vessels and gravitational gradients (all P < 0.05). We conclude that patients with Fontan physiology and PAH have increased pulmonary perfusion heterogeneity that is not explained by differences in mean perfusion, gravitational gradients, or large vessel anatomy. This probably reflects the effects of remodelling in PAH and possibly in Fontan physiology.

Keywords: Fontan procedure; arterial spin labeling; functional lung imaging; perfusion heterogeneity; pulmonary arterial hypertension; pulmonary circulation.

Figure 1.. Representative sagittal ASL perfusion images from one subject from each of the subject groups

Note the overall small lung size in the Fontan patient compared to control, and the increased size of the large vessels seen as the red tubular structures in the central image in the patient with PAH. Colour scale is perfusion in ml min⁻¹ ml⁻¹.

Figure 2.. Perfusion vs. height from the most gravitationally dependent lung (mean and standard deviation)

For visualization purposes, standard deviation is shown for Fontan and PAH patients only. Closed circles, Fontan patients (n = 5); open circles, Fontan controls (n = 5); closed squares, PAH (n = 6); open squares, PAH controls (n = 6).

Figure 3.. Perfusion heterogeneity in patients with Fontan circulation and PAH patients compared to controls

Top, heterogeneity of perfusion as measured by the relative dispersion of perfusion including gravitational effects and large vessels. There was a significant main effect of group (P = 0.002) and both patient groups differed from their respective controls, but the Fontan patients did not differ significantly from PAH patients. Bottom, isogravitational relative dispersion. The differences in heterogeneity between patient groups and their respective control groups persisted when the influence of gravity was eliminated (Omnibus P = 0.004), but the Fontan patients did not differ significantly from PAH. Horizontal bar and error bars are means ± SD for each group.