Short‐Term Effects of Inhaled Nitric Oxide on Right Ventricular Flow Hemodynamics by 4‐Dimensional–Flow Magnetic Resonance Imaging in Children With Pulmonary Arterial Hypertension

Abstract

Background Pulmonary arterial hypertension (PAH) manifests with progressive right ventricular (RV) dysfunction, which eventually impairs the left ventricular function. We hypothesized that 4‐dimensional–flow magnetic resonance imaging can detect flow hemodynamic changes associated with efficient intracardiac flow during noninvasive inhaled nitric oxide (iNO) challenge in children with PAH. Methods and Results Children with PAH (n=10) underwent 2 same‐day separate iNO challenge tests using: (1) 4‐dimensional–flow magnetic resonance imaging and (2) standard catheterization hemodynamics. Intracardiac flow was evaluated using the particle tracking 4‐flow component analysis technique evaluating the direct flow , retained inflow , delayed ejection flow , and residual volume . Respective flow hemodynamic changes were compared with the corresponding catheterization iNO challenge results. The RV analysis revealed decreased direct flow in patients with PAH when compared with controls ( P <0.001) and increase in residual volume ( P <0.001). Similarly, the left ventricular analysis revealed decreased direct flow in patients with PAH when compared with controls ( P =0.004) and increased proportion of the residual volume ( P =0.014). There was an increase in the RV direct flow during iNO delivery ( P =0.009), with parallel decrease in the residual volume ( P =0.008). Conclusions Children with PAH have abnormal biventricular flow associated with impaired diastolic filling. The flow efficiency is significantly improved in the RV on iNO administration with no change in the left ventricle. The changes in the RV flow have occurred despite the minimal change in catheterization hemodynamics, suggesting that flow hemodynamic evaluation might provide more quantitative insights into vasoreactivity testing in PAH.

Delivery of Nitric Oxide in the Cardiovascular System: Implications for Clinical Diagnosis and Therapy

“…It is with this backdrop that Carter et al designed an MRI-compatible NO delivery device, which realized simultaneous NO inhalation and measurement of vasodilation [114]. Schafer et al further quantitatively investigated the correlation between inhaled NO and hemodynamic changes in intracardiac flow with four-dimensional-flow MRI [115]. They claimed that this method can link the quantity of delivered NO to the corresponding therapeutic effects, which may help the selection of the dose in clinical decision-making processes.…”

The Delivery of Nitric Oxide in the Cardiovascular System: Implication for Clinical Diagnosis and Therapy

“…It is with this backdrop that, Carter et al designed a MRI-compatible NO delivery device, which realized the simultaneous nitric oxide inhalation and measurement of vasodilation [85]. Schafer et al further quantitatively investigated the correlation between the inhaled NO and hemodynamic changes in the intracardiac flow with four-dimensional-flow MRI [86]. They claimed that this method can link the quantity of delivered NO to the corresponding therapeutic effects, which may help the choice of dose in clinical decision-making.…”

Editorial for “Traveling Volunteers – A Multi‐Vendor, Multi‐Center Study on Reproducibility and Comparability of 4D Flow Derived Aortic Hemodynamics in Cardiovascular Magnetic Resonance”

“…Several groups of authors reported on changes and inefficient blood flow propagation in the ventricles of patients with ischemic heart disease and dilated cardiomyopathy 3,4 . Furthermore, alternations of flow were found in both ventricles of children with pulmonary artery hypertension (PAH), whilst a significant response was recorded in the right ventricle (RV) after inhaled nitric oxide challenge 5 . Patients with PAH presented with increased RV dimensions, increased RV residual volumes, and decreased direct RV inflow and RV systolic function 5 .…”

“…3,4 Furthermore, alternations of flow were found in both ventricles of children with pulmonary artery hypertension (PAH), whilst a significant response was recorded in the right ventricle (RV) after inhaled nitric oxide challenge. 5 Patients with PAH presented with increased RV dimensions, increased RV residual volumes, and decreased direct RV inflow and RV systolic function. 5 François et al analyzed 4D MRI velocity mapping in patients with repaired tetralogy of Fallot vs. controls.…”

“…5 Patients with PAH presented with increased RV dimensions, increased RV residual volumes, and decreased direct RV inflow and RV systolic function. 5 François et al analyzed 4D MRI velocity mapping in patients with repaired tetralogy of Fallot vs. controls. 6 In this study, patients with repaired tetralogy had increased diastolic over systolic flow in both caval veins into the RV, increased diastolic vortical inflow patterns in right atrium and RV, and increased vortical and helical flow features in pulmonary arteries compared to controls.…”