Pulmonary Arterial Hypertension (PAH)

Pulmonary arterial hypertension (PAH) prognosis has improved over the past 20 years. Prior to the introduction of the PAH-specific therapies, the 3-year survival rate was 30%-40%; that has now improved to higher than 90%. Despite significant treatment advances and a more than 2-fold increase in survival during the last 2 decades, PAH patients have a poor prognosis if they are not diagnosed in time and treated optimally.¹

Prognosis Evaluation

Prognostic evaluation of patients with PAH requires an extensive assessment and investigation of multiple variables at regular intervals in specialized pulmonary hypertension centers, since a single variable or parameter cannot provide sufficient prognostic information. The 2015 European Society of Cardiology/European Respiratory Society guidelines recommend assessing several variables in order to define patients’ status and accordingly stratify them into low-, intermediate-, and high-risk categories. Risk stratification of patients is subsequently used to guide PAH management.²

The recommended variables that should be assessed for prognosis include clinical function, World Health Organization (WHO) functional class (FC; PAH patients are categorized into 4 WHO-FC, I to IV, based on the impairment in physical ability and dyspnea), exercise capacity, and right ventricular (RV) function. These variables are assessed using procedures such as imaging (echocardiography and cardiac magnetic resonance imaging); right-heart catheterization for hemodynamic variables such as mean pulmonary arterial pressure, pulmonary vascular resistance, mean right atrial (RA) pressure, cardiac index, mixed venous oxygen saturation, and systolic blood pressure; exercise capacity testing such as the 6-minute walking distance test (6MWD) and cardiopulmonary exercise testing; and biochemical marker testing (markers of vascular dysfunction, myocardial stress, low cardiac output, and secondary organ damage).³

Other factors that should be considered in prognostic evaluation include age, sex, presence of comorbidities, background therapy, PAH subtype, rate of disease progression, and symptomatic features of heart failure. However, the importance of these factors in determining prognosis depends on individual cases.⁴

The most important variables that should be considered in the assessment process include WHO-FC and exercise capacity. WHO-FC is one of the most important predictors of survival during diagnosis as well as follow-up. The most widely used exercise test in pulmonary hypertension centers is the 6MWD. RV function is a vital determinant of exercise capacity and outcome in patients with PAH. Complete echocardiographic assessment includes a description of chamber sizes, particularly the RA area, the magnitude of tricuspid regurgitation, and RV contractility, among others.

Risk Stratification

It is difficult to reliably predict prognosis for individual cases, but patients categorized as low-risk have an estimated 1-year mortality of less than 5%. These patients belong to the WHO-FC I or II with nonprogressive disease, absence of syncope, a 6MWD of more than 440 m, and no signs of RV dysfunction. Low-risk profile suggests that the disease is well-controlled. 

Patients included in the intermediate-risk group have an estimated 1-year mortality of 5% to 10%. These patients are generally in the WHO-FC III, with moderately impaired capacity to exercise, occasional syncope with heavy exercise, and signs of RV dysfunction but not RV failure. 

Patients in the high-risk group have an estimated 1-year mortality of more than 10%. These patients are in the WHO-FC III or IV with rapidly progressive disease, repeated syncope at rest, and a 6MWD of less than 165 m, together with signs of severe RV dysfunction or RV failure and secondary organ dysfunction.¹

Echocardiography in high-risk patients reveals the presence of pericardial effusion or RA area in end-systole of more than 26 cm². One of the markers of myocardial stress in PAH patients is elevated plasma levels of the N-terminal pro-brain natriuretic peptide, which may reach levels of more than 1400 ng/L in high-risk patients.⁵

Prognosis Linked to Etiology

The prognosis of PAH varies with the underlying condition. Patients with PAH associated with connective tissue disease have a worse prognosis as compared to those with idiopathic PAH. On the other hand, patients with congenital heart disease have better survival rates. Due to the lack of effective therapies, patients with pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis have the poorest prognosis. Thus, these patients should be listed for transplantation at diagnosis.²

Read more about PAH etiology.

References

1. 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
2. Galiè N, Humbert M, Vachiery J-L, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2016;37(1):67-119. doi:10.1093/eurheartj/ehv317
3. Kondo T, Okumura N, Adachi S, Murohara T. Pulmonary hypertension: diagnosis, management, and treatment. Nagoya J Med Sci. 2019;81(1):19-30. doi:10.18999/nagjms.81.1.19
4. Lan NSH, Massam BD, Kulkarni SS, Lang CC. Pulmonary arterial hypertension: pathophysiology and treatment. Diseases. 2018;6(2):38. Published 2018 May 16. doi:10.3390/diseases6020038
5. 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

Reviewed by Kyle Habet, 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.