by Phyllis Hanlon, Contributing Writer

Although there are 14 different Food and Drug Administration (FDA)-approved therapies for treating World Health Organization (WHO) Group 1 pulmonary hypertension (PH) (pulmonary arterial hypertension, or PAH), there remains a need for treatments that can be used across varying classifications of PH. In 2017, the Critical Care Medicine Department of the National Institutes of Health (NIH) Clinical Center and the Pulmonary Hypertension Association (PHA) organized a joint symposium to discuss challenges in treating different types of PH. The American Journal of Respiratory Care and Critical Care Medicine published discussion points from that meeting.

Discussion at the symposium focused on differences between PAH and other types of PH, and whether approved PAH-specific therapies could be effective across three types of PH: heart failure with preserved ejection fraction and PH (HFpEF-PH, a type of WHO Group 2 PH), interstitial lung disease with PH (ILD-PH, a type of WHO Group 3 PH), and pulmonary venoocclusive disease/pulmonary capillary hemangiomatosis (PVOD/PCH, a type of WHO Group 1 PH). All these conditions may present to health care providers with similar clinical features at the surface (high blood pressure in the vessels of the lungs and right ventricular dysfunction), however, when looking deeper they have very different hemodynamic and phenotypical features. Additionally, individual patients can have elements that fall into multiple categories.

To date, no large multicenter, randomized clinical trial has shown effectiveness in treating HFpEF-PH with PAH-specific therapies. The authors felt that this may not necessarily be because certain patients with HFpEF-PH would not benefit from these therapies, but perhaps that the studies have looked at patients with the wrong characteristics. For example, HFpEF-PH patients in these trials who had more advanced disease were more likely to respond to PAH-specific therapies. However, the authors also highlighted evidence that shows treating these patients with PAH-specific therapies can cause their PH to worsen, thus more research is needed.

There also is no conclusive evidence yet supporting the use of PAH-specific therapies in patients with ILD-PH, however, a survey of current practice patterns suggests that most PH referral centers prescribe PAH-specific therapy in some of these patients despite current guidelines. Since the benefit of PAH-specific therapy to these patients is largely untested, the authors recommend adhering to current guidelines by optimizing oxygen delivery, treating underlying conditions and comorbidities and referral of patients to expert centers.

PVOD/PCH, which is sometimes mistaken for idiopathic PAH (IPAH), is seen less often than PAH, ILD-PH or HFpEF-PH and has no approved drug treatment. As with the other conditions, getting the diagnosis correct is the first step in developing a treatment plan. According to the authors, this can be aided by a series of tests, such as CT scans, diffusing lung capacity of carbon monoxide (DLCO), arterial blood gas analysis and six-minute walk distance (6MWD) with pulse oximetry. They noted that genetic testing is more recently available to help guide health care providers to an accurate diagnosis. However, even with a correct PVOD diagnosis, treatment with PAH-specific therapies in this population is complicated and should be done only at an experienced expert center.

The authors concluded that deep phenotyping and further research is needed to identify patients who are more likely to respond to drugs in order to design future trials. Additional well-planned, randomized, placebo-controlled trials are needed for each of these conditions, along with studies from research programs like the National Heart, Lung and Blood Institute (NHLBI) Pulmonary Vascular Disease Phenomics Program (PVDOMICS), with additional support from the PHA.