Pulmonary Arterial Hypertension (PAH)

Oxygen Supplementation for PAH

Pulmonary arterial hypertension (PAH) treatment guidelines recommend supplemental oxygen therapy only for patients with the disease to maintain an arterial oxygen saturation >91%.¹

However, a recent review analyzed studies of both adult and pediatric pulmonary arterial hypertension (PAH) patients, suggesting that oxygen therapy is beneficial for all PAH patients and not just those who develop severe hypoxemia. The review analyzed 9 studies of PAH patients (including those without hypoxemia) who were acutely exposed to 100% oxygen for 15-30 minutes. All studies except one showed that brief oxygen supplementation significantly reduced pulmonary vascular resistance (PVR) by about 20%-30% and mean pulmonary arterial pressure (mPAP) by around 10% in PAH patients. In addition, the review analyzed 5 studies of long-term oxygen treatment in PAH patients (including normoxemic patients), of which 4 studies showed beneficial effects of long-term oxygen therapy.^2,3 Another recent study showed that oxygen therapy can reduce PVR and mPAP, even in patients who were not hypoxemic.⁴

Preventive Care in PAH

Preventive care in patients with PAH includes maintaining optimal weight, regular physical activity, avoidance of pregnancy, and vaccination for seasonal flu and pneumonia infection.

In approximately 7% of patients with PAH, pneumonia is the cause of mortality.¹ Thus, PAH patients are recommended to receive vaccinations against influenza and pneumococcal pneumonia to decrease the risk of developing pneumonia.¹

Pregnancy in women with PAH is associated with a mortality rate between 30% and 56%.⁵ In addition, the medications used to treat PAH pose a high risk to the fetus. Thus, all female patients of childbearing age should be counseled to practice birth control and strongly advised against pregnancy.⁶

Pharmacologic Therapy for PAH

Pharmacologic therapy includes diuretics for fluid overload and right ventricular failure; digoxin for short-term improvement in right ventricular contractility and cardiac output; oral anticoagulant (warfarin) for thrombotic lesions in pulmonary vessels; and specific drug therapies that target the nitric oxide, endothelin, and prostacyclin pathways. Specific drug therapies include phosphodiesterase-5 inhibitors or PDE5i (sildenafil and tadalafil), soluble guanylate cyclase stimulators (riociguat), endothelin receptor antagonists (ambrisentan, bosentan, and macitentan), prostacyclin analogs (epoprostenol, iloprost and treprostinil), and prostacyclin receptor agonists (selexipag).

Learn more about PAH therapies.

Balloon Atrial Septostomy

Balloon atrial septostomy (BAS), first reported in 1983 as a palliative measure in patients with severe PAH, involves the surgical creation of a right-to-left shunt that links the atriums using percutaneous balloon dilations across the interatrial septum. This procedure reduces right ventricular pressure and volume and increases cardiac output despite an initial decrease in systemic oxygen saturation, which is compensated by increased systemic blood transport.

BAS has shown hemodynamic and symptomatic benefits (increased cardiac index, decreased right atrial pressure, and improved functional capacity) in selected patients with severe World Health Organization (WHO) functional class (FC) IV symptoms due to right heart ventricular failure despite maximal medical therapy.⁷ However, the impact of atrial septostomy on long-term survival has not been established, and current guidelines recommend atrial septostomy only as a palliative measure (prior to transplantation) when medical therapy fails in experienced centers.⁸

PAH and Lung Transplantation

Lung transplantation is important for patients with severe PAH who are refractory to medical therapy. A patient is indicated for lung transplantation if the patient’s predicted 2-3 year survival is estimated to be less than 50%.⁸ Criteria for the referral consist of WHO-FC III or IV symptoms despite maximal medical therapy, markedly low (less than 350 m) or declining 6-minutes walking distance test, cardiac index of less than 2L/min/m2, and central venous pressure ≥ 15 mmHg.⁸

Most PAH patients (about 91%) receive bilateral lung transplants with good results.⁸ Patients with end-stage PAH and severe cardiac dysfunction have the option of receiving heart-lung transplantation.⁸

Consultations in PAH

Once patients are confirmed with a diagnosis of Group 1 PAH, they should be referred to a PH specialty care center (SCC) to guide treatment and coordinate management between specialists such as cardiologists, pulmonologists, and internists. A recent study found that early referral of patients to SCCs improves clinical outcomes, which may be attributed to frequent vasodilator therapy and disease monitoring.⁹ In 2014, the Pulmonary Hypertension Association initiated a program called the PH Care Centers (PHCC) program that aimed to raise the overall quality of care and improve outcomes in patients with PAH. Patients who have severe PAH and refractory to maximal medical therapy need to be referred to a lung transplantation center.⁹

Pulmonary Arterial Hypertension Diet

There are no specific dietary guidelines for patients with PAH. Although treatment of systemic arterial hypertension involves diet modifications such as alcohol restriction, low-sodium intake (in order to minimize excessive fluid retention), and increased intake of fruits, vegetables, whole grains, fish, nuts, and olive oil, these interventions have not been incorporated into PAH treatment guidelines.¹

Deficiency of iron and vitamin D has been found to be more prevalent in PAH patients and some studies suggest they may aggravate disease progression. Some studies have linked scurvy caused by vitamin C deficiency with PAH. In animal studies, flavonoids, isoflavonoids, and other dietary polyphenols have been found to slow the progression of PAH.¹⁰

PAH and Activity

Regular physical activity has been shown to improve symptoms, exercise capacity, and the quality of life in patients with PAH.¹¹ Thus, treatment guidelines recommend that PAH patients undertake safe physical activities (such as light resistance exercises, walking, and swimming) but avoid excessive activity that leads to distressing symptoms such as chest pain, dizziness, or severe dyspnea. Patients who are physically deconditioned are advised to undertake supervised exercise training.¹²

Prevention of PAH

The majority of cases of PAH cannot be prevented. Patients with drug- or toxin-induced PAH should avoid using drugs or toxins such as appetite suppressant agents (such as aminorex fumarate, fenfluramine, dexfenfluramine), illicit drugs (such as methamphetamine), industrial chemicals (such as toxic rapeseed oil), and FDA-approved therapeutic drugs (such as dasatinib and interferon). Smoking should be avoided since it was shown to be associated with worse clinical outcomes in newly diagnosed PAH patients in a recent study.¹³

Long-Term Monitoring of PAH

PAH patients should be evaluated at regular intervals by a PAH specialist. Complete medical assessment of multiple variables — including 6-minute walk distance (6MWD) testing, cardiopulmonary exercise testing, echocardiography, and cardiac magnetic resonance imaging (MRI) — should be performed at optimal intervals to assess for a decline in functional status. Right heart catheterization is performed for patients who show a change in clinical status.¹⁴

References

1. Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint 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: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37(1):67-119. doi:10.1093/eurheartj/ehv317
2. Green S, Stuart D. Oxygen and pulmonary arterial hypertension: effects, mechanisms, and therapeutic benefits. Eur J Prev Cardiol. 2021;28(1):127-136. doi:10.1093/eurjpc/zwaa001
3. Green S, Stuart D. Oxygen therapy for pulmonary arterial hypertension: we need to rethink and investigate. Respirology. 2020;25(5):470-471. doi:10.1111/resp.13797
4. Green S, Stuart D. Effects of oxygen therapy in a pediatric normoxemic patient with pulmonary arterial hypertension and congenital heart disease. Pulm Circ. 2019;9(2):11772045894019846000. doi:10.1177/2045894019845610
5. Weiss BM, Zemp L, Seifert B, Hess OM. Outcome of pulmonary vascular disease in pregnancy: a systematic overview from 1978 through 1996. J Am Coll Cardiol. 1998;31(7):1650-1657. doi:10.1016/s0735-1097(98)00162-4
6. Hill W, Holy R, Traiger G. Intimacy, contraception, and pregnancy prevention in patients with pulmonary arterial hypertension: are we counseling our patients? Pulm Circ. 2018;10(4):2045894018785259. doi:10.1177/2045894018785259
7. Khan MS, Memon MM, Amin E, et al. Use of balloon atrial septostomy in patients with advanced pulmonary arterial hypertension: a systematic review and meta analysis. Chest. 2019;156(1):53-63. doi:10.1016/j.chest.2019.03.003
8. Mayeux JD, Pan IZ, Dechand J, et al. Management of pulmonary arterial hypertension. Curr Cardiovasc Risk Rep. 2021;15(1):2. doi:10.1007/s12170-020-00663-3
9. Pi H, Kosanovich CM, Handen A, et al. Outcomes of pulmonary arterial hypertension are improved in a specialty care center. Chest. 2020;158(1):330-340. doi:10.1016/j.chest.2020.01.046
10. Callejo M, Barberá JA, Duarte J, Perez-Vizcaino F. Impact of nutrition on pulmonary arterial hypertension. Nutrients. 2020;12(1):169. doi:10.3390/nu12010169
11. Waller L, Krüger K, Conrad K, Weiss A, Alack K. Effects of different types of exercise training on pulmonary arterial hypertension: a systematic review. J Clin Med. 2020;9(6):1689. doi:10.3390/jcm9061689
12. Vinke P, Jansen SM, Witkamp RF, van Norren K. Increasing quality of life in pulmonary arterial hypertension: is there a role for nutrition? Heart Fail Rev. 2018;23(5):711-722. doi:10.1007/s10741-018-9717-9
13. Frost A, Zhao C, Farber H, Benza R, Selej M, Elliott G. Smoking history and pulmonary arterial hypertension (PAH) onset and clinical outcomes (REVEAL). European Respiratory Journal. 2020;56:3552. doi:10.1183/13993003.congress-2020.3552
14. Yaghi S, Novikov A, Trandafirescu T. Clinical update on pulmonary hypertension. J Investig Med. 2020;68(4):821-827. doi:10.1136/jim-2020-001291

Reviewed by Michael Sapko, MD, on 7/1/2021.

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Erum Naqvi, PhD

Erum Naqvi obtained her Ph.D. in Molecular Medicine from Hannover Medical School (Germany) after completing her Masters in Biomedical Science and Bachelors in Microbiology from University of Delhi (India). She has several years of experience as a science writer.