Redefining the standard could be lifesaving for many patients.

A new evidence-based study suggests a lower Woods unit threshold may be needed to better identify patients at high risk for pulmonary hypertension (PH), particularly those who may benefit from pulmonary vasodilator therapy.

The research, published in The Lancet Respiratory Medicine, suggests there is potentially high diagnostic value to lowering the threshold from 3.0 to around 2.2 Wood units. That change could capture perhaps 60 percent more patients with elevated pulmonary vascular resistance (PVR), said Evan Brittain, M.D., an associate professor of medicine at Vanderbilt University Medical Center and co-first author of the study.

“Most studies to date had never taken a large referral population and determined what threshold of pulmonary vascular resistance is associated with hard adverse outcomes such as mortality and hospitalization,” Brittain said. “Our goal was to identify in an unbiased way an evidence-based threshold that finds the population at risk.”

“Our goal was to identify in an unbiased way an evidence-based threshold that finds the population at risk.”

Brittain and colleagues previously produced evidence for lowering the threshold for right ventricular systolic pressure on echocardiography in diagnosing patients with mild PH.

Assessing All-cause Mortality

The researchers retrospectively analyzed the relationship between PVR and adverse clinical outcomes in PH with the primary outcome of all-cause mortality. They collaborated with Brigham and Women’s Hospital and Brown University, among other institutions, to compile a cohort of more than 40,000 patients of the Veterans Affairs medical system undergoing right heart catheterization (RHC) from 2007 to 2016.

Because the VA cohort was 97 percent male, hazard ratios were validated in a smaller, sex-balanced RHC cohort (3,699 patients) from Vanderbilt’s EHR. Vanderbilt biostatistician Shi Huang, Ph.D., provided statistical support.

Widening the Risk Continuum

The researchers focused on patients at risk for PH with a mean pulmonary artery pressure (mPAP) of at least 19 mmHg. When modelled as a continuous variable, all-cause mortality hazard for PVR increased for these patients at around 2.2 Wood units. For at-risk patients who also had a pulmonary artery wedge pressure of 15 mmHg or less, the adjusted hazard ratio for mortality was 1.71 in the primary cohort and 1.81 in the validation cohort.

“These data widen the continuum of clinical risk for mortality and heart failure in patients referred for RHC,” the authors wrote.

Testing the new value in at-risk populations with fewer cardiopulmonary comorbidities is warranted, Brittain said, to determine whether the lower threshold should become common practice. “I think our data provide strong support for performing such trials and for identifying and closely following patients with a PVR of 2.2 to 3.0 in the absence of left heart disease.”

Enabling Earlier Intervention

Brittain says lowering the threshold may prove to be a life-or-death decision for patients with pulmonary vascular disease, who have a median survival of five years with the condition.

“We know that generally patients with pulmonary arterial hypertension show up to the doctor very ill, very late in the disease. If we can identify a population that is at risk or has evidence of early disease based on PVR that is lower than the historic threshold, we might be able to intervene earlier. That might allow us to slow or reverse the course of the disease,” Brittain said.

“If we can identify a population that is at risk or has evidence of early disease based on PVR that is lower than the historic threshold, we might be able to intervene earlier.”

About the Expert

Evan Brittain, M.D.

Evan Brittain, M.D., M.S.C.I., is assistant professor of medicine in the Division of Cardiovascular Medicine and director of the cardiovascular imaging fellowship program at Vanderbilt University Medical Center. His research focuses on mechanisms and epidemiology of pulmonary vascular disease.