Impact of pulmonary vascular stiffness and vasodilator treatment in pediatric pulmonary hypertension: 21 patient-specific fluid-structure interaction studies

Abstract

Recent clinical studies of pulmonary arterial hypertension (PAH) have found correlations between increased pulmonary vascular stiffness (PVS) and poorer disease outcomes. However, mechanistic questions remain about the relationships amongst PVS, RV power, and vascular hemodynamics in the setting of progressive PAH that are difficult or impossible to answer using direct measurements. Clinically validated patient-specific computational modeling may allow exploration of these issues through perturbation-based predictive testing. Here we use a simple patient-specific model to answer four questions: how do hemodynamics change as PAH worsens? How does increasing PVS impact hemodynamics and RV power? For a patient with moderate PAH, what are the consequences if the pressures increase modestly yet sufficiently to engage collagen in those vessels? What impact does pressure-reducing vasodilator treatment have on hemodynamics? Twenty-one sets of model-predicted impedance and mean PA pressure (mPAP) show good agreement with clinical measurements, thereby validating the model. Worsening was modeled using data from three PAH outcomes groups; these show not only the expected increase in mPAP, but also an increase in pressure pulsatility. Interestingly, chronically increasing mPAP decreased WSS, suggesting that increased PA cross-sectional area affected WSS greater than increased PVS. For a patient with moderately high PVR (12.7 WU) with elastin-based upstream vascular remodeling, moving from elastin-dominant vessel behavior to collagen-dominant behavior caused substantial increases in mPAP, pressure and WSS pulsatility. For the same patient, reducing PVR through a simulated vasodilator to a value equivalent to mild PAH did not decrease pressure pulsatility and dramatically increased WSS pulsatility. Overall, these results suggest a close association between PVS and hemodynamics and that hemodynamics may play an important role in progressing PAH. These support the hypothesis that treatments should target decreasing or reversing upstream vascular remodeling in addition to decreasing mean pressures.

Fig. 1

The schematic of the two dimensional symmetric pulmonary artery model.

Fig. 2

Comparison of the mean main pulmonary arterial pressure between numerical (mPAP_N) and clinical (mPAP_C) results.

Fig. 3

Comparison of the input impedance modulus Z₁ in pulmonary normotensive and hypertensive states.

Fig. 4

The inlet flow rate from the clinical data before and after polynomial data fitting.

Fig. 5

Comparison of the blood outflow, stretch ratio, wall pressure and WSS as a function of time during one cardiac cycle for three outcome categories in PAH.

Fig. 6

Comparison of the input impedance modulus for three outcome categories in PAH.

Fig. 7

Comparison of the blood outflow, stretch ratio, wall pressure and WSS as a function of time during one cardiac cycle for OC 2 and collagen engagement.

Fig. 8

Comparison of the blood outflow, stretch ratio, wall pressure and WSS as a function of time during one cardiac cycle for OC1, OC2 and vasodilator treatment of OC2.