Measure estimates vascular loss, forecasts outcomes in pediatric PAH
Study: Higher PVC tied to worse transplant-free survival
Researchers used computer-based modeling to develop a measure, called pulmonary vascular compromise (PVC), which estimates the reduced function of the pulmonary blood vessels in children with pulmonary arterial hypertension (PAH), according to a study.
Supported by clinical data, a higher PVC, meaning a loss of the pulmonary vasculature, was tied to worse heart transplant-free survival and other clinical outcomes in pediatric PAH.
“Given this data, the model’s simple interface, and iterations taking seconds to calculate PVC, any clinician with patient [blood flow] data can employ this adjunctive diagnostic tool for PAH,” researchers wrote in the study, “Pulmonary Vascular Compromise Is Associated With Survival in Pediatric Pulmonary Hypertension: A New Computational Model,” which was published in Pulmonary Circulation.
Risk of death in PAH patients remains high despite advances
PAH is characterized by the narrowing of the blood vessels that supply the lungs, known as the pulmonary arteries. This narrowing decreases the vascular area, increases the resistance to blood flow, referred to as pulmonary vascular resistance (PVR), and drives up pulmonary arterial pressure (PAP). Due to the increased workload on the heart from the high blood pressure, PAH can eventually lead to right heart failure.
Despite advances in disease monitoring and the development of new treatments that can ease symptoms and extend survival, the risk of death in PAH patients remains high. This may be due to vascular loss early in the disease course, which occurs without symptoms or a significant rise in PAP or PVR. As the disease progresses, however, PAP and PVR may begin to rise, leading to disease symptoms.
A previous study conducted by a researcher in Canada developed a computer-based model to simulate PAH. Results suggested that up to 70% of the pulmonary vascular area is lost before PAH symptoms arise.
The current study, conducted by scientists at the University of Pennsylvania and Children’s Hospital of Philadelphia, compared clinical data from children with PAH with the computer-generated estimate of PVC.
“We hypothesized that subjects with PAH would demonstrate elevation in PVC early in the disease course… and would be associated with mortality and other measures of outcome in PAH,” the team wrote.
‘PVC greater than 70% indicated severe PAH’
The researchers collected data on blood flow, clinical outcomes, and survival from 58 children with PAH. Among them, 45 survived without a lung transplant, while the remaining 13 either died or underwent a transplant. There was no difference in age at diagnosis between survivors and non-survivors.
Non-survivors, however, were older at the time of their first right heart catheterization, a procedure in which a thin tube is inserted into a vein, allowing doctors to measure a patient’s blood flow and heart function. These patients also had more severe disease, as indicated by several assessments, including higher PVR and mean PAP (mPAP).
Based on clinical data, there were no significant changes in patients’ mPAP or PVR until the PVC, or the loss of the pulmonary vascular area, exceeded 70%. At this point, mPAP and PVR rose rapidly with increasing PVC. These findings followed the same PVC trends seen in the computer model.
“Consistent with an estimate in a theoretical PAH model, … PVC greater than 70% indicated severe PAH,” the team wrote.
In transplant-free survivors, PVC at the last catheterization test was significantly lower, or better, than at the first catheterization (66% vs. 77%), while there were no differences in PVC between tests in non-survivors. PVC levels in survivors were lower than those in non-survivors at both the initial and final catheterizations.
Patients with PVC less than 80% at the first catheterization consistently had lower PVC throughout the study period when compared with patients with PVC of more than 80% at the first catheterization.
Lower PVC was associated with better clinical outcomes
Starting from the most recent catheterization, the 10-year survival rate nearly doubled when PVC was less than 80% compared with those with a PVC of more than 80% (100% vs. 54%). Death was also linked to an older age at catheterization and several abnormal measures of blood flow, including PVC, PVR, mPAP, and the distance walked in six minutes.
In an adjusted statistical analysis, death at one year was associated with PVR, right atrial pressure (pressure in the heart’s top right chamber), six-minute walking results, and the log Qpi, a measure of pulmonary blood flow. When PVR was replaced with PVC in the calculations, PVC, right atrial pressure, and log Qpi were significantly linked with one-year mortality.
In comparison, lower PVC was associated with better clinical outcomes, including a longer distance walked in six minutes, a lower one-year death rate, and reduced levels of markers of heart disease.
“The computational model presented in this study used [blood flow] data and lung dimensions from pediatric patients with PAH to generate values of PVC that conformed to theoretically modeled PAH,” the researchers wrote. “Future studies are needed to confirm these observations in other patient populations and to evaluate whether PVC decreases with PH-directed therapy.”
About the Author
