Apparent Aortic Stiffness in Children With Pulmonary Arterial Hypertension: Existence of Vascular Interdependency?

Abstract

Background: Left ventricular dysfunction, mediated by ventricular interdependence, has been associated with negative outcomes in children with pulmonary arterial hypertension (PAH). Considering the dilation of the pulmonary arteries as a paramount sign of PAH, we hypothesized that the ascending aorta will present signs of apparent stiffness in children with PAH and that this effect may be because of mechanical interaction with the dilated main pulmonary artery (MPA).

Methods and results: Forty-two children with PAH and 26 age- and size-matched controls underwent comprehensive cardiac magnetic resonance evaluation. Assessment of aortic stiffness was evaluated by measuring pulse wave velocity, aortic strain, and distensibility. Children with PAH had significantly increased pulse wave velocity in the ascending aorta (3.4 versus 2.3 m/s for PAH and controls, respectively; P=0.001) and reduced aortic strain (23% versus 29%; P<0.0001) and distensibility (0.47 versus 0.64%/mm Hg; P=0.02). Indexed MPA diameter correlated with pulse wave velocity (P=0.04) and with aortic strain (P=0.02). The ratio of MPA to aortic size correlated with pulse wave velocity (P=0.0098), strain (P=0.0099), and distensibility (P=0.015). Furthermore, aortic relative area change was associated with left ventricular ejection fraction (P=0.045) and ventricular-vascular coupling ratio (P=0.042).

Conclusions: Pediatric PAH patients have increased apparent ascending aortic stiffness, which was strongly associated with the degree of MPA distension. We speculate that distension of the MPA may play a major role in limiting full aortic expansion during systole, which modulates left ventricular performance and impacts systemic hemodynamics in pediatric PAH.

Keywords: aortic stiffness; heart rate; interdependency; pediatric pulmonary hypertension; pulse wave analysis.

Figure 1

(a) MRA reconstructed aorta with superimposed PC-MRI magnitude image plane depicting the flow hemodynamic computation locations. (b) Corresponding phase image with segmented ascending and descending aortic lumens for flow hemodynamic quantification (c and d) and reconstructed flow-wave form (e).

Figure 2

The PWV computation algorithm. The PWV was calculated from the flow-area plots by using a linear regressional model to create a line fitted to the flow-area curve at early systole. The calculated model coefficients then served for computation of PWV.

Figure 3

The median values and corresponding IQRs of aortic area strain among specific WHO functional classes (FC). There was no observed inter-group variability between WHO-FC with respect to the most significantly altered measured stiffness metric – relative area change (RAC) (p = 0.171, Kruskal-Wallis).

Figure 4

The subanalysis of ascending aortic stiffness metrics between CHD-PAH, IPAH, and control groups. IPAH and CHD-PAH groups did not present any significant variability in any considered aortic stiffness metrics. However, in the case of RAC and PWV representing local aortic stiffness, both PAH groups showed significant differences from the control group. No variability existed among considered groups in distensibility and capacitance assessing rather global aortic stiffness. K-W = Kruskal-Wallis

Figure 5

The subanalysis of vessel size metrics between CHD-PAH, IPAH, and control groups. Both MPA normalized diameter and MPA to ascending aortic ratio revealed significantly higher average values for both considered PAH groups when compared to controls. However, no differences were observed between PAH groups. K-W = Kruskal-Wallis

Figure 6

Associations between MPA/Ascending aorta size ratio and LV ejection fraction (left) and LV ventricular-vascular coupling ratio (right). Both trends are suggestive of negative MPA expansion effect on the ascending aorta resulting in increased LV afterload. Both models are adjusted for age and sex.

Figure 7

Pulmonary Artery Impingement Upon Aorta. A) On this representative pediatric PAH patient one can immediately notice a severely dilated MPA impinging on the ascending aorta. Wall deformation analysis from segmented PC-MRI magnitude images shows reduced range of motion along the aortic – MPA interface highlighted by red triangles. B) Conversely, representative control subject reveals size proportional vessel and uniform aortic expansion along the central axis.

Figure 8

Proposed schematic of overall interdependency phenomenon in pediatric PAH. Paramount signs of PAH, increased mPAP and PVRI appears to mechanically affect LV functionality via both proximal pulmonary vascular and ventricular interdependency.