By Akshay Bhatnagar, MD, Raed Dweik, MD, and Neal F. Chaisson, MD
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Pulmonary hypertension, defined as an elevated pulmonary arterial pressure (≥ 25 mm Hg) on right heart catheterization, has a myriad of causes. The World Health Organization (WHO) classifies pulmonary hypertension into 5 separate groups based on the pathophysiologic mechanism:
- Group 1 — pulmonary arterial hypertension (PAH), due to narrowed pulmonary arteries
- Group 2 — due to left heart disease
- Group 3 — due to lung disease or hypoxia, or both
- Group 4 — due to chronic thromboembolism or other pulmonary artery obstruction
- Group 5 — due to uncertain or multifactorial causes
Group 5: miscellaneous forms of pulmonary hypertension
WHO group 5 pulmonary hypertension encompasses disorders whose pathophysiology does not fit neatly within the context of the other pulmonary hypertension subtypes. Nonetheless, appreciation of these disorders is important in determining the etiology and appropriate therapy for patients with pulmonary hypertension. The mechanism driving abnormal pulmonary arterial pressures in patients with group 5 pulmonary hypertension is not always clear and may involve intrinsic or extrinsic factors.
Diseases within group 5 include those that cause extrinsic compression of the pulmonary arteries (i.e., fibrosing mediastinitis) or intrinsic elevations in pulmonary vascular resistance (sarcoidosis, pulmonary Langerhans cell histiocytosis, sickle cell anemia, polycythemia vera and malignancy).
The most common cause of pulmonary hypertension in this category is sarcoidosis. Current theories suggest that, for most patients, invasion of granulomatous inflammation within the arterial walls induces PAH via fibrotic or inflammatory vascular occlusion. Extrinsic compression due to lymphadenopathy, right or left ventricular dysfunction due to cardiac myocite infiltration, and endothelin-induced pulmonary vasoconstriction are other possible links between the PAH and sarcoidosis.
Other posts discuss diagnostic techniques for WHO groups 1-4.
Prognostic risk stratification in patients with PAH
The final challenge in evaluating patients with suspected PAH is to estimate their risk of death. Although nonmodifiable risk factors including age, sex and associated comorbidities play a significant role in determining prognosis, several potentially modifiable risk factors should be used to estimate the one-year mortality risk. These include features on physical examination consistent with right heart failure, New York Heart Association functional class, six-minute walking distance or cardiopulmonary exercise capacity, N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and findings on echocardiography and right heart catheterization.
Cardiac magnetic resonance imaging (MRI) has gained popularity as a noninvasive and reproducible alternative to echocardiography. Image fidelity and characterization of right ventricular function and right ventricular ejection fraction are all more accurate than with echocardiography, and serial MRI has proven valuable in its ability to guide patient prognosis.
However, MRI is more expensive than echocardiography, and some patients cannot tolerate the procedure. In addition, for those who can tolerate it, MRI is not a suitable alternative to right heart catheterization, since it cannot accurately estimate pulmonary artery occlusion pressure or pulmonary arterial pressures. For these reasons, cardiac MRI use varies across pulmonary hypertension centers.
A goal of treatment is to reduce a patient’s risk. While no consensus has been achieved over which PAH-specific therapy to start with, evidence is robust that using more than one class of agent is beneficial, capitalizing on multiple therapeutic targets.
Dr. Bhatnagar is staff in the Department of Regional Anesthesiology. Dr. Dweik is Chair, Respiratory Institute. Dr. Chaisson is staff in the Departments of Critical Care Medicine and Pulmonary Medicine, Respiratory Institute.
This abridged article originally appeared in Cleveland Clinic Journal of Medicine.