How New Guidelines Can Influence PH Diagnosis and Treatment

BY MELANIE PADGETT POWERS

New European guidelines for the diagnosis and treatment of pulmonary hypertension (PH) include updates on how PH is defined, diagnosed and treated.

The guidelines, published in August 2022 in the European Heart Journal and the European Respiratory Journal, were developed by a task force of the European Society of Cardiology and the European Respiratory Society.

Guidelines in health care are recommendations — not requirements — based on the most updated evidence on how to treat and manage a particular condition or disease. While these new guidelines are European, they could be used by health care providers around the world. In the U.S., organizations such as the American Heart Association and American College of Chest Physicians have not changed their guidelines or the PH definition.

“I don’t think that we can fully apply everything from these guidelines to the United States, but they certainly will influence practice in the United States,” said Anna Hemnes, M.D., PHA’s Scientific Leadership Council chair and associate professor of medicine and assistant director of the Pulmonary Vascular Center at

Vanderbilt University Medical Center in Nashville, Tennessee.

“We use the guidelines as practitioners to benchmark our care for patients, but there are reasons that we may differ from guidelines in any specific patient — because a guideline that’s meant to address the vast majority of patients can’t address every single patient and their own complexity, ultimately,” Hemnes said. The last European guidelines on PH were published in 2015, so it was time for an update, according to Marc Humbert, M.D., Ph.D., the lead author of the guidelines. Humbert is director of the French Pulmonary Hypertension Reference Center, professor of respiratory medicine at the University of Paris-Saclay in France and president of the European Respiratory Society.

“Pulmonary hypertension is a very important topic in medicine because it is fast moving, fast progressing,” Humbert said. “There have been a lot of important discoveries in the last seven years, and it is really important to regularly update the guidelines to match the current evidence.”

Changing The Definition Of Ph

The guidelines start with a change to the definition of PH. Pulmonary hypertension is high blood pressure measured by the force of blood flowing through the lungs. It is measured by right-heart catheterization. International and U.S. guidelines consider pulmonary artery pressure to be normal at 8-20 mmHg. In previous guidelines, it was considered abnormally high if the pressure was more than 25 mmHg at rest.

However, Humbert pointed out, the measurement from 21 to 24 mmHg was considered abnormal but wasn’t included in previous definitions. “There was a gray zone which did not define pulmonary hypertension, but everybody knew that these values were not normal,” he said.

“For many patients, these values reflect early pulmonary vascular disease, and these patients will need to see a specialist regularly to keep an eye on the evolution of their condition,” Humbert said. “This is particularly the case in patients with increased risk of pulmonary hypertension such as scleroderma or when there is a past history of pulmonary embolism.

“It doesn’t mean that you need a drug, but it means that you need attention,” he continued. “We want to make it clear that the upper limit of normal is 20 mmHg. Any value above 20 mmHg is abnormal. Thanks to PHA and to other government and non-government organizations, there are many specialists of pulmonary hypertension worldwide who are available to give the best counseling to the people who have elevated pulmonary artery pressure.”

New Ways To Screen And Diagnose

The guidelines include a new three-step screening algorithm for PH. This is an attempt to diagnose PH earlier. The first step acknowledges that most PH patients first visit a health care provider complaining of shortness of breath. If the clinician can’t find a common respiratory or cardiac reason for shortness of breath, the patient should be referred to a specialist, usually a pulmonologist or a cardiologist. The guidelines recommend that specialists conduct lung and heart tests, including an echocardiography, which is an ultrasound to look at the heart. If PH is suspected, the patient should be referred to a PH center for further diagnosis and evaluation.

The guidelines also present a new risk stratification for pulmonary arterial hypertension (PAH), also known as Group 1 PH. PAH is when the arteries in the lungs become narrowed, thickened or stiff. A risk stratification is a process that allows physicians to assign a level of risk to a person with a certain condition, to help determine the proper treatment.

Hemnes said it’s important for patients to know that risk stratification is commonplace in treatment, even if

Variations in PAH Severity

different clinicians use different types of risk tables.

“We’ve gotten more evidence based in our ability to use these risk stratification tools to guide therapy in the last several years, and that’s been incorporated into these guidelines,” Hemnes said. “Exactly what tool people use may be different based on their preferences and on available data or just their read of the literature, but in general, incorporation of some sort of risk stratification tool in decisions about what therapies should be used are now considered standard of care.”

The PAH risk stratification at initial diagnosis divides patients into low, intermediate and high risk categories.

“The risk stratification table is one of the most important additions in the guidelines for the community,” Humbert said. “We really want to make sure that everybody will riskstratify Group 1 PH before treatment — because when you have a high risk of mortality at one year, there is a recommendation to treat you upfront more aggressively.”

Currently, the three potential drug treatments used in the initial treatment strategy are endothelin receptor antagonists, phosphodiesterase type 5 inhibitors and prostacyclin derivatives.

“For the severe [PAH] patients who have more than 20% risk of mortality at one year, you need to start with a combination of three drugs, including a prostacyclin derivative used subcutaneously or intravenously,” Humbert explained. “But for the people who have a low or intermediate risk, we usually start with initial combination therapy of two oral drugs: one endothelin receptor antagonist and one phosphodiesterase type 5 inhibitor.”

At follow-up visits, the risk stratification expands from three to four categories: low, intermediate-low, intermediate-high and high risk.

The goal is for the treatment to move patients into the lowrisk category. The follow-up risk stratification process has been simplified to include three mostly non-invasive measures. They include the World Health Organization’s “functional class,” which describes the severity of a person’s PH symptoms. The other two are a six-minute walk test and a NT-proBNP test, which is taken from a blood sample.

When needed, other tests such as echocardiography and right-heart catheterization can be added to better estimate the situation, Humbert said.

“We have divided the intermediate risk into two subgroups: intermediatelow and intermediate-high risk because intermediate risk represents around two-thirds of the patients treated,” Humbert said. “You have some intermediate risk patients who are doing better than others. Distinguishing these two categories is important at follow-up with a different treatment approach which will be more aggressive in the intermediatehigh risk.”