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Managing PAH for the Cardiology Clinician
What Cardiologists Need to Know About Diagnosing and Treating PAH

Released: November 20, 2023

Vallerie V. McLaughlin
Vallerie V. McLaughlin, MD
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Key Takeaways
  • Diagnosing PAH is complex and requires thorough attention and screening practices.
  • Once a PAH diagnosis is made, it is imperative to assess patients’ risk to inform their initial treatment regimen.
  • In a phase III trial, sotatercept improved exercise tolerance in patients with PAH and could become the newest agent in the treatment armamentarium for this disease.

Pulmonary arterial hypertension (PAH) is a complex disease with a high mortality rate, and it is critical that all healthcare professionals (HCPs) are familiar with it. PAH is difficult to diagnose, as patients often present with nonspecific symptoms, such as dyspnea with exertion and fatigue. Oftentimes, HCPs will spend time looking for other, more common, causes of patients’ shortness of breath, delaying a PAH diagnosis. 

Best Practices for Screening and Diagnosing PAH
An echocardiogram will provide HCPs with the first glimpse of PAH as a potential diagnosis. Here, I want to emphasize that there is so much more to patients’ echocardiogram than their estimated right ventricular systolic pressure. Certainly, this number is important, but it is also imperative for HCPs to look at the size and function of the right and left ventricle, motion of the interventricular septum, and many other Doppler indices that indicate stress on the right ventricle.

If there is suspicion of PAH based on patients’ medical history, physical examination, and echocardiogram, one needs to have a system for a methodical evaluation to determine the cause. There are many causes of PAH, including left heart disease, left ventricular systolic or diastolic dysfunction, and valvular disease—all of which fall under group 2 pulmonary hypertension. Furthermore, anything that causes lung disease or hypoxemia, chronic obstructive pulmonary disease, interstitial lung disease, and the like can cause group 3 pulmonary hypertension. So, it is critical to complete a methodical evaluation of the left heart and lungs, pulmonary function testing, and even a CT scan to look for group 2 or 3 causes.

One diagnosis that HCPs should pay special attention to is chronic thromboembolic pulmonary hypertension (CTEPH), which is a rare and progressive form of pulmonary hypertension. Although pulmonary embolisms (PEs) are common, some patients with CTEPH do not have a history of acute PE. Therefore, it is important to search for this diagnosis in patients who present with dyspnea and evidence of pulmonary hypertension. In my opinion, the best screening test for chronic thromboembolic pulmonary hypertension is a lung ventilation‒perfusion scan, as recommended in guidelines.

Finally, diagnosing PAH requires a right heart catheterization. I cannot emphasize enough the importance of completing a good right heart catheterization (ie, ensuring you get all the relevant hemodynamic parameters). Pulmonary artery pressure is important, so HCPs must have that on the heart catheterization. In addition, HCPs should measure patients’ left heart filling pressures and right atrial pressure, which will tell you if the right ventricle is failing. Understanding patients’ cardiac output is critical for calculating pulmonary vascular resistance. Lastly, it is important to measure saturations because we do not want to miss, for example, an atrial septal defect.

Group 1 Pulmonary Hypertension Risk
Group 1 is a very specific type of pulmonary hypertension that comes with some unique therapies. The hemodynamic definition of this is a mean pulmonary artery pressure ≥20 mm Hg in the setting of a normal capillary wedge pressure (≤15 mm Hg) and elevated pulmonary vascular resistance when at rest.

The prototype of PAH is idiopathic, or what was formerly called primary pulmonary hypertension. It can be induced by drugs and toxins or associated with other conditions, such as connective tissue disease, portal hypertension, HIV infection, and congenital heart disease. PAH also can be genetic in nature or heritable, as there are now many genes that help indicate PAH in screenings.

When HCPs make a group 1 diagnosis, the first step in treatment is to determine patients’ risk. There are many parameters that, in mostly observational studies, we have learned are associated with higher or lower risk. The factors that are important to look for include functional class, hall walk, signs of right heart failure, biomarkers such as BNP or NT-proBNP, and hemodynamics, including right atrial pressure, cardiac output, and mixed venous oxygen saturation. These hemodynamics are most relevant because they are associated with right ventricular function. Finally, understanding the right ventricular function by imaging is also important.

There are many ways to calculate risk scores to come to an objective assessment of PAH. The method that is very popular in Europe is using a 3-stratum approach, where HCPs would stratify patients into a low-, intermediate-, or high-risk category. There is also a 4-stratum approach, which separates patients in the 3-stratum intermediate-risk group further into intermediate-low and intermediate-high risk. Also, the REVEAL risk calculator is commonly used by HCPs in the United States.

Managing PAH Treatment
Once you assess patients’ risk, you can then think about what the most appropriate medication is for their initial treatment. For those at the highest risk (eg, patients who have a very low cardiac index or functional class 4 symptoms), HCPs should treat them very aggressively with combination therapy that often includes a parenteral prostacyclin, as well as oral therapy (eg, an endothelin receptor antagonist [ERA] and a phosphodiesterase 5 [PDE5] inhibitor). It is necessary to aggressively treat high-risk patients because of their high mortality risk. For those patients who have functional class 3 symptoms or fall into the intermediate-risk category at the time of diagnosis, I generally start them on dual oral combination therapy that includes an ERA and a PDE5 inhibitor. The goal of PAH treatment is to drive patients down to a low-risk status, which portends a good prognosis.

An important step in the treatment algorithm is what to do with patients based on their response to their initial treatment. HCPs should reassess patients’ risk 3 or 4 months after starting therapy. If they have not improved, you want to escalate their therapy. That might mean adding a third agent or escalating from a less invasive prostacyclin pathway agent to a more invasive one.

Continued follow-up with patients is critical. HCPs need to see individuals regularly and repeat testing periodically—including biomarker, hall walk, echocardiogram, and sometimes right heart catheterization—to ensure that patients remain in the low-risk category with treatment.

Novel Therapy Coming Soon
Unfortunately, despite all the medications that have been developed, we cannot always get patients to a low-risk status. Luckily, the FDA is evaluating a new agent called sotatercept, which has a novel mechanism of action in PAH. Sotatercept works as an activin signaling inhibitor, rebalancing pulmonary vascular homeostasis, and may have some reverse remodeling effects. In clinical trials, sotatercept improved exercise tolerance as measured by the 6-minute walk test. So, we may soon have yet another agent in our treatment armamentarium.

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