In recent decades, there’s been a sea change in the understanding of pulmonary arterial hypertension (PAH), which in turn has affected the patient journey in this disease. The prognosis of PAH has evolved from impending death with few treatment options to a chronic condition notable for improved survival.1
Improved patient survival has been realized due to the development of effective therapies and the expansion of risk-stratification scores, which aid clinicians in clinical decision-making. Although PAH can now be better controlled — with improved quality of life and clinical course for patients — patients still face barriers to care. The treatment burden is cumbersome and hinders quality of life, and many with the condition initially present with advanced or end-stage disease.1
Changes and Challenges in Disease Diagnosis
A focus on early disease detection and new clinical outcomes findings have changed the definitions of PH and PAH.2-4 According the 2022 ESC/ERS Guidelines for Pulmonary Hypertension, patients with a mean pulmonary artery pressure of more than 20 mmHg measured by right heart catheterization are now considered to have PH. A pulmonary vascular resistance or more than 2.0 Wood units and pulmonary arterial wedge pressure of at least 15 mm Hg further implies the existence of PAH.3,4
“These lowered thresholds aim to identify patients early in the disease course, which is important because delay to diagnosis of PH is common and linked to elevated morbidity and shortened lifespan,” according to the author of a review published in the Journal of the American Heart Association.2
Although the 2022 ESC/ERS Guidelines for Pulmonary Hypertension cover the whole spectrum of PH, these updated guidelines include “an emphasis on diagnosing and treating pulmonary arterial hypertension.”4
Within the 2022 guidelines, the principal diagnostic algorithm for PH has been streamlined to a 3-step approach3 that includes:
- suspicion by first-line physicians;
- detection by echocardiography; and
- confirmation via right-heart catheterization at PH specialty centers.
In an exclusive interview, Jean Elwing, MD, FCCP, Chair of the Pulmonary Vascular and Cardiovascular Network with the American College of Chest Physicians, provided guidance on how to best recognize PH in patients, and to then identify PAH.
“Pulmonary hypertension can present with multiple nonspecific symptoms and can be very challenging to diagnose,” she said. “When patients have progressive dyspnea, exercise limitation, and exertional chest discomfort, we have to think about potential causes that are both pulmonary and cardiac. When we are thinking of cardiac causes, one of the best tools to use is an echocardiogram. The echocardiogram will give us insight into the likelihood of pulmonary hypertension.”
She advised that PH should be a differential diagnosis in anyone with unexplained dyspnea/exercise limitation or other nonspecific symptoms such as intermittent chest discomfort with exertion, dizziness, lightheadedness, fatigue, and swelling. The index of suspicion should be high in patients with a higher risk of developing the disease, and their clinical trajectory should be followed closely.
For instance, if a patient with HIV, liver disease with portal hypertension, or connective tissue disease develops shortness of breath, an echocardiogram should be performed followed by right-heart catheterization, if needed, to rule out PH.
Socioeconomic Factors Affecting PAH
Dr. Elwing also remarked on the impact of socioeconomic factors in the recognition of PH. “Social challenges and socioeconomic status can play a significant negative role in pulmonary hypertension diagnosis and lead to delays in care. This is an area where we need to be very mindful and consider all patients equally when assessing symptoms and pursuing further work-up of pulmonary hypertension,” she stated.
For instance, women and men present with PH and PAH in a similar fashion, but due to a lower prevalence of the disease in men, symptoms could be overlooked.
As for race and ethnicity, she said, “We believe that different races/ethnicities present with similar symptoms of pulmonary hypertension but the etiologies of pulmonary hypertension in these cell populations may differ. Hispanic patients are more at risk for congenital heart disease-associated pulmonary arterial hypertension and have an increased risk of viral hepatitis increasing their risk of portal hypertension and portal portopulmonary hypertension. Connective tissue disease-associated pulmonary hypertension has been shown to be more common in Black patients in available registry data.”
The Evolution of PAH Treatment
Over the past 3 decades, much has been clarified regarding pulmonary hypertension treatment; 30 years ago, the only treatment available involved high dosages of calcium-channel antagonists, which improved survival only in a handful of those with pulmonary arterial hypertension.5
Approved medical treatments for PAH (along with their routes of administration) include the following2:
- prostacyclin derivatives (inhaled iloprost, intravenous [IV] epoprostenol, IV/subcutaneous or inhaled or oral treprostinil);
- selective prostacylin (intraperitoneal injection) receptor agonist (oral selexipeg)
- endothelin receptor antagonists (oral bosentan, oral ambrisentan, oral macitentan)
- PDE5 inhibitors (oral/IV sildenafil, oral tadalafil)
- soluble guanylyl cyclase stimulator (oral riociguat)
In the aggregate, these agents help improve outcomes such as exercise tolerance and capacity, as well as mitigating clinical deterioration.2
In addition to pharmacologic therapies, there are also nonpharmacologic interventions that may improve patient well-being. These revolve around diet, sleep, and exercise, said Dr. Elwing.
“A balanced diet with monitoring of salt and fluid intake can have a major impact on right heart-failure management and other comorbidities. Exercise can improve dyspnea and tolerance of many health conditions. This is important for exercise tolerance as well as overall well-being,” she said.
“Sleep is imperative for mood and resilience. Good sleep hygiene and assessment of sleep disorders is critical for patients to feel well and have the reserve to care for themselves with this complex medical condition,” she added.
The Patient Journey in PAH
Helping patients with PAH through the rigors of diagnosis and treatment requires empathetic conversations by specialists. Unfortunately, due to time constraints, it is hard for clinicians to make patients comfortable enough to open up about their goals and to revisit these goals over time. Instead, expedient visits pinpoint clinical factors, therapy, and medication adherence/tolerability.1
Outside of clinicians, there are a few options patients and their caregivers may be encouraged pursue for further information and support, including Living with PAH, an online support and discussion community, and the American Lung Association Patient & Caregiver Network.
Dr. Elwing recommends that specialists take time to partner with patients to improve care.
“Knowledge is power, especially in complex diseases like pulmonary hypertension. Taking the time to educate patients will pay off for the patient and the provider in multiple ways,” she stressed. “Successful treatment and best outcomes can be achieved with joint efforts of the care provider as well as the patient. In order to achieve this, patients need to be educated on the disease and made aware of the importance of medication adherence, close follow-up, testing, and potential for medication changes.”
She added, “Once patients understand the disease itself and the medications/therapies, the next step really would be to help them understand risk assessment and goals of low-risk status. Calculating a risk score in PAH is not just a number. Using a risk assessment tool helps guide medical therapy and provides some insight in terms of prognosis for that individual.”
On a final note, Dr. Elwing exhorted providers to take time to consider the patient in a holistic sense.
“We need to understand their level of medical literacy, ability to communicate, social support, and the severity of the illness. We assess patients’ risk status and design a treatment approach based on that. We choose the type of medications and the delivery system based on what the patient is able to tolerate and use safely,” Dr Elwing noted.
“We should closely monitor every PAH patient and provide opportunities to use our most aggressive therapies but may have to tailor medications based on that individual patient’s needs for the patient’s safety and ability for them to use medications consistently,” she added.
- Ismail R, Hegab S, Kelly B, Franco-Palacios DJ, Grafton G, Smith ZR, Awdish RLA. Serious illness conversations in pulmonary hypertension. Pulm Circ. 2021;11(4):20458940211037529. doi:10.1177/20458940211037529
- Maron BA. Revised definition of pulmonary hypertension and approach to management: a clinical primer. J Am Heart Assoc. 2023 Apr 18;12(8):e029024. doi:10.1161/JAHA.122.029024
- Mukherjee, D. 2022 ESC/ERS Guidelines for pulmonary hypertension: key points. American College of Cardiology. Published August 30, 2022. Accessed April 24, 2023.
- Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: Developed by the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). Endorsed by the International Society for Heart and Lung Transplantation (ISHLT) and the European Reference Network on rare respiratory diseases (ERN-LUNG). Eur Heart J. 2022;43(38): 3618-3731. doi:10.1093/eurheartj/ehac237
- Otani N, Tomoe T, Kawabe A, Sugiyama T, Horie Y, Sugimura H, Yasu T, Nakamoto T. Recent Advances in the Treatment of Pulmonary Arterial Hypertension. Pharmaceuticals (Basel). 2022;15(10):1277. doi:10.3390/ph15101277