Doctors diagnosing pulmonary arterial hypertension (PAH) — elevated pulmonary pressure due to an issue in the small vessels of the lung — rely on a hemodynamic threshold set in the early 1970s to determine whether patients would be candidates for pulmonary vasodilator therapy.
But the standard for identifying patients with this rare disease, a subgroup of pulmonary hypertension, is based on expert opinion and not on evidence-based research, according to a new study.
The study, with major participation from Vanderbilt University Medical Center, suggests a new evidence-based threshold for diagnosing such patients, which could capture perhaps 60% more patients with pulmonary vascular disease than are currently being diagnosed, said Evan Brittain, MD, MSCI, associate professor of Medicine, co-first author of the study.
The study, published in The Lancet Respiratory Medicine, suggests that the current threshold for diagnosis — a pulmonary vascular resistance (PVR) of 3 units — may warrant reconsideration to a value around 2.2 units.
“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. “That was our goal, in an unbiased way, to identify an evidence-based threshold that finds the population at risk.”
Investigators from Brigham and Women’s Hospital in Boston and Brown University, among other institutions, studied mortality in a cohort of more than 40,000 patients of the Veterans Affairs medical system. Because the cohort was mostly male, it was validated with a smaller, sex-balanced cohort of patients from VUMC’s electronic health record. VUMC biostatistician Shi Huang provided statistical support.
Brittain said the study suggests trials in patients with lower pulmonary vascular resistance values are warranted to determine whether a lower threshold for diagnosis and treatment 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,” he said.
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, Brittain said.
“We know that general patients with pulmonary arterial hypertension show up to the doctor very ill, very late in the disease,” he said, “and so one of our hopes is that if we can identify a population that is at risk or has evidence of early disease based on this pulmonary vascular resistance that is lower than the historic threshold, we might be able to intervene earlier and that might allow us to slow or reverse the course of the disease.”
