Noninvasive wave intensity analysis predicts functional worsening in children with pulmonary arterial hypertension

Abstract

The purpose of the present study was to characterize pulmonary vascular stiffness using wave intensity analysis (WIA) in children with pulmonary arterial hypertension (PAH), compare the WIA indexes with catheterization- and MRI-derived hemodynamics, and assess the prognostic ability of WIA-derived biomarkers to predict the functional worsening. WIA was performed in children with PAH ( n = 40) and healthy control subjects ( n = 15) from phase-contrast MRI-derived flow and area waveforms in the main pulmonary artery (MPA). From comprehensive WIA spectra, we collected and compared with healthy control subjects forward compression waves (FCW), backward compression waves (BCW), forward decompression waves (FDW), and wave propagation speed ( c-MPA). There was no difference in the magnitude of FCW between PAH and control groups (88 vs. 108 mm·s·ml, P = 0.239). The magnitude of BCW was increased in patients with PAH (32 vs. 5 mm·s·ml, P < 0.001). There was no difference in magnitude of indexed FDW (32 vs. 28 mm·s·ml, P = 0.856). c-MPA was increased in patients with PAH (3.2 vs. 1.6 m/s, P < 0.001). BCW and FCW correlated with mean pulmonary arterial pressure, right ventricular volumes, and ejection fraction. Elevated indexed BCW [heart rate (HR) = 2.91, confidence interval (CI): 1.18-7.55, P = 0.019], reduced indexed FDW (HR = 0.34, CI: 0.11-0.90, P = 0.030), and increased c-MPA (HR = 3.67, CI: 1.47-10.20, P = 0.004) were strongly associated with functional worsening of disease severity. Our results suggest that noninvasively derived biomarkers of pulmonary vascular resistance and stiffness may be helpful for determining prognosis and monitoring disease progression in children with PAH. NEW & NOTEWORTHY Wave intensity analysis (WIA) studies are lacking in children with pulmonary arterial hypertension (PAH) partially because WIA, which is necessary to assess vascular stiffness, requires an invasive pressure-derived waveform along with simultaneous flow measurements. We analyzed vascular stiffness using WIA in children with PAH who underwent phase-contrast MRI and observed significant differences in WIA indexes between patients with PAH and control subjects. Furthermore, WIA indexes were predictive of functional worsening and were associated with standard catheterization measures.

Genotypes and Phenotypes: Making Progress Toward a Precision Medicine Approach in Pediatric Pulmonary Hypertension

“…45 Similarly, wave intensity analysis reveals increased pulmonary vascular stiffness in children with PAH relative to controls. 46 Increased main pulmonary artery stiffness and decreased wall stress correlate with metrics of RV performance and predict clinical outcomes in a pediatric PAH cohort. 47 Much of the focus of recent pediatric studies has been on determining utility of specific MRI biomarkers to predict outcomes.…”

Assessing pulmonary circulation in severe bronchopulmonary dysplasia using functional echocardiography

“…Combination of the above indices has been used to characterize ventriculo-arterial coupling for risk stratification and long-term monitoring in children with PH (Levy et al, 2016(Levy et al, , 2018(Levy et al, , 2019. The association between elevated PVR and the RV dysfunction, and its association with sequelae in BPD infants and other clinical situations is known (Blanca et al, 2018;Levy et al, 2019;Schäfer et al, 2018; T A B L E 5 Comparison of FGR versus AGA cohorts for % change from baseline with 100% oxygen (O 2 ) versus inhaled nitric oxide (iNO) Abbreviations: AGA, appropriate for gestational age; FGR, fetal growth restriction; TAPSE, tricuspid annular plane systolic excursion; TDI, tissue Doppler imaging; TPV/RVET, time to peak velocity/right-ventricular ejection time.…”

“…A recent study on pediatric PH patients using CATH and echocardiography noted that the Doppler Echo-derived TAPSE/ (TPV: RVET) relationship inversely correlated with invasive systolic pulmonary pressure and PVR (Levy et al, 2018). It is an important prognostic indicator, as pulmonary vascular stiffness predicts mortality in pediatric PH patients (Douwes et al, 2013;Friesen et al, 2019;Schäfer et al, 2018).…”

Cardiovascular magnetic resonance imaging derived septal curvature in neonates with bronchopulmonary dysplasia associated pulmonary hypertension

“…While invasive hemodynamic assessment with cardiac catheterization remains the gold standard for diagnosis of PH, it may be challenging in critically ill neonates. Increasingly, cardiovascular magnetic resonance (CMR) is used for non-invasive assessment of PH in adult and older pediatric populations and recent advances in CMR pulse sequences and equipment have allowed for assessment of the lung parenchyma and cardiac morphology of infants with BPD and BPD-PH [12][13][14][15][16][17][18][19][20].…”