Behind the Biomarkers

Searching for Clues Within PH Classifications

About 25 years ago, cardiologist Jane Leopold, M.D., noticed how the structure and function of blood vessels differed in various diseases.

In particular, the differences associated with pulmonary hypertension (PH) couldn’t be explained clinically and scientifically by what happened with other blood vessels.

She also observed that people with PH differed from her typical cardiac patients with chest pain and heart attacks. Those with some forms of PH were younger, sicker and had more physical limitations. They also seemed to be hospitalized more frequently with heart failure, shortness of breath and other issues.

Since then, PH research has led to advancements in PH diagnosis and treatment. But researchers still need to better understand the disease to identify and develop the right drugs to make people feel better and live longer, says Dr. Leopold, director of the Women’s Interventional Cardiology Health Initiative at Brigham and Women’s Hospital in Boston.

“What we have is still not good enough,” she says. “We can’t predict who will develop PH, what medicines the patients will respond to or how sick they will get.”

Dr. Leopold is among the investigators of a pulmonary vascular disease (PVD) omics study funded by the National Institutes of Health, National Heart, Lung, and Blood Institute and Pulmonary Hypertension Association (PHA).

The study, “Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics (PVDOMICS),” aims to identify biomarkers to improve PH diagnosis and treatment.

The study will help Dr. Leopold and her colleagues find subgroups of patients that cluster together within the five PH groups based on underlying cause. Their findings could upend the current PH classifications.

Investigators believe they will find more alike people within the subgroups than within their “assigned” groups, based on disease severity, life expectancy and response to medication. They also want to learn whether people stay in the same subgroup or shift among them.

‘Patients never fall neatly into a single category, and those within each group are really different from each other. Let’s find out what the new groups should be, based on blood samples and clinical testing.’ — Jane Leopold, M.D. X Redefining PH classifications

Patient involvement

The study follows 1,200 people who have PH or risk developing PH, as well as a few healthy individuals. Investigators track data from clinical histories, physical exams, blood samples, right heart catheterization and other heart and lung tests.

“For the first time, can compare patients with PAH and those with CTEPH or other types of PH.”

“We need to get people to come into the study with really different backgrounds and experiences to find out what’s going on with the disease,” she says.

In late 2019, investigators enrolled the last patients in Phase I. They began Phase II in early 2020 with about 400 people.

When COVID-19 was a declared a public health emergency, investigators had to switch from inperson clinical and blood tests to phone follow-ups. Soon after, they learned that they received more funding to follow a subset of seriously ill people with Group 2 and 3 PH.

“There’s going to be a lot interesting information from this study,” Dr. Leopold says. “We’re just starting to look at the first data.”

Dr. Leopold hopes her work to better understand, identify and treat PH will improve the patient journey and decrease the times patients are misdiagnosed.

Ideally, Dr. Leopold would love to see the study expand throughout the United States.

The research wouldn’t have been possible without PHA and people with PH enrolled in the study, Dr. Leopold says. “We could not have done this without you.”

Find out more about current clinical trials in PH through PHA’s Clinical Trial Finder: PHAssociation.org/ClinicalTrials.