Evaluating Suspected Pulmonary Hypertension, WHO Group 3

By Akshay Bhatnagar, MD, Raed Dweik, MD, and Neal F. Chaisson, MD

All patients with suspected pulmonary hypertension should also be assessed for underlying pulmonary parenchymal or physiologic disease.

WHO group 3 consists of pulmonary disorders that, over an extended time, can lead to pulmonary hypertension. The most common of these disorders include chronic obstructive pulmonary disease, interstitial lung disease and combined pulmonary fibrosis and emphysema.

Pulmonary hypertension in these patients is precapillary, and changes in pulmonary vascular resistance are influenced by multiple factors, the most significant of which is alveolar hypoxia. Hypoxia induces pulmonary artery vasoconstriction (in contrast to the reflexive hemodynamics seen in peripheral tissues, where systemic vascular tone is generally lower in states of hypoxia) as a mechanism to divert pulmonary blood flow to well-ventilated portions of the lung and maintain ventilation-perfusion matching.

Repeated chronic hypoxia also alters cellular structure and function of pulmonary vessels and leads to medial hypertrophy and increased vascular tone, thus contributing to the development of pulmonary hypertension in many of these patients.

Obstructive sleep apnea

Up to 70 percent of patients with obstructive sleep apnea have pulmonary hypertension. Chronic repetitive hypoxia throughout the night increases the levels of reactive oxygen species and alters cellular and molecular signaling, thus inducing vascular remodeling. In addition, apneic events during sleep promote catecholamine-driven elevations in systemic blood pressure. Over time, patients are at higher risk of developing left ventricular dysfunction and concomitant postcapillary group 2 pulmonary hypertension. Because typical methods of obstructive sleep apnea screening (e.g., the Epworth Sleep Scale) have been historically poor at discriminating pulmonary arterial hypertension (PAH) patients with obstructive sleep apnea from those without, patients diagnosed with PAH should be considered for formal sleep testing.

Pulmonary function tests, chest imaging

Pulmonary function tests and high-resolution computed tomography are essential to any PAH evaluation and help to exclude WHO group 3 pulmonary hypertension.

An abnormal result on CT or spirometry can help point toward parenchymal lung disease. Normal spirometry and lung volumes with an isolated reduction in the diffusing capacity of the lung for carbon monoxide (Dlco) is typical of patients with WHO group 1 PAH.

As in WHO group 2 pulmonary hypertension, patients with significant obstructive sleep apnea or underlying parenchymal lung disease who exhibit only features of mild pulmonary hypertension usually do not require further pulmonary hypertension evaluation, as management of the underlying lung disease is the preferred treatment in these patients. However, since the diagnostic accuracy of echocardiography is lower in patients with advanced lung disease, those who have inconclusive echocardiographic results, who have symptoms consistent with advanced pulmonary hypertension or right ventricular dysfunction, or who are planning to undergo a surgical procedure (e.g., transplant, lung volume reduction) should undergo further testing and be evaluated at a pulmonary hypertension referral center.

Other posts discuss diagnostic techniques for WHO groups 1-2 and 4-5.

Feature image: A patient with combined pulmonary fibrosis and emphysema. In patients with findings consistent with underlying structural lung disease, further diagnostic testing for pulmonary arterial hypertension may not be warranted.

Dr. Bhatnagar is staff in the Department of Regional Anesthesiology. Dr. Dweik is Interim Institute Chair, Respiratory Institute, Cleveland Clinic. Dr. Chaisson is staff in the Department of Critical Care Medicine, Respiratory Institute.

This abridged article originally appeared in Cleveland Clinic Journal of Medicine.