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Evaluating suspected pulmonary hypertension: A structured approach

Cleveland Clinic Journal of Medicine. 2018 June;85(6):468-480 | 10.3949/ccjm.85a.17065
June 1, 2018|Cleveland Clinic Journal of Medicine
Akshay Bhatnagar, MD;Jonathan Wiesen, MD;Raed Dweik, MD;Neal F. Chaisson, MD
Author and Disclosure Information

Akshay Bhatnagar, MD
Department of Internal Medicine, Cleveland Clinic

Jonathan Wiesen, MD
Community Intensivists, Cleveland, OH; Ben Gurion University, Be’er Sheva, Israel

Raed Dweik, MD
Interim Institute Chair, Respiratory Institute, Cleveland Clinic; Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Neal F. Chaisson, MD
Department of Critical Care Medicine, Respiratory Institute, Cleveland Clinic; Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Address: Neal F. Chaisson, MD, Respiratory Institute, A90, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; chaissn@ccf.org

ABSTRACT

Pulmonary arterial hypertension (PAH) is a common consideration when patients have unexplained signs of cardiopulmonary disease. Guidelines have been issued regarding diagnosis and management of this condition. Since multiple conditions can mimic components of PAH, the clinician should think about the patient’s total clinical condition before diagnosing and categorizing it. Proper evaluation and etiologic definition are crucial to providing the appropriate therapy. This review offers a case-based guide to the evaluation of patients with suspected PAH.

KEY POINTS

  • PAH has nonspecific symptoms, largely attributable to right ventricular dysfunction but seen in a host of other common cardiopulmonary ailments.
  • In a patient suspected of having pulmonary hypertension, it is important to take a methodic diagnostic approach to identify underlying contributors and minimize unnecessary testing.
  • Patients suspected of having PAH should be referred to a pulmonary hypertension center of excellence for evaluation and right heart catheterization.
  • Once testing is complete, therapy and management should be guided both by data obtained during the initial evaluation and by factors with prognostic significance. This approach has changed PAH from a disease with a grim outlook to one in which appropriate evaluation and guidance can improve patient outcomes.

EVALUATION OF LUNG DISEASE (WHO GROUP 3)

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.1

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 vasoconstrictionn (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.20

Obstructive sleep apnea. Up to 70% of patients with obstructive sleep apnea have pulmonary hypertension.21 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.22 Because typical methods of obstructive sleep apnea screening (eg, the Epworth Sleep Scale) have been historically poor at discriminating PAH patients with obstructive sleep apnea from those without, patients diagnosed with PAH should be considered for formal sleep testing.23,24

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.1

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.

A patient with combined pulmonary fibrosis and emphysema
Figure 4. 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.
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.1 However, since the diagnostic accuracy of echocardiography (Figure 4) is lower in patients with advanced lung disease,25 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 (eg, transplant, lung volume reduction) should undergo further testing and be evaluated at a pulmonary hypertension referral center.1

In our patient, CT of the chest did not show any evidence of parenchymal lung disease, and pulmonary function tests showed no evidence of obstruction or restriction. There was a moderate decrease in Dlco, which did not reach normal limits when adjusted for lung volumes. In this setting, further evaluation of her PAH was warranted.

EVALUATION OF THROMBOEMBOLIC DISEASE (WHO GROUP 4)

Once pulmonary hypertension due to underlying left heart disease or parenchymal lung disease has been excluded, testing for chronic thromboembolic pulmonary hypertension is necessary, even in the absence of prior known pulmonary embolism. Identifying these patients is paramount, as chronic thromboembolic pulmonary hypertension (WHO group 4) is the only type of pulmonary hypertension for which a definitive cure is available.26

Up to 9% of patients who survive acute pulmonary embolism exhibit features of chronic proximal thrombosis and remodeling of distal pulmonary arteries.27

It remains unknown exactly why some patients develop chronic thromboembolic pulmonary hypertension and others do not, but the pathophysiology involves inappropriate thrombus resolution after venous thromboembolic events. Monocyte recruitment (which plays an important role in thrombus resolution) is reduced, angiogenesis is impaired (preventing effective vascular collateralization), and abnormal fibroblast proliferation leads to distal pulmonary vascular wall thickening.28 There is some evidence of increased thrombophilic risk in this population, and approximately 10% to 20% of patients are positive for antiphospholipid antibodies or lupus anticoagulant.29,30

Patients with chronic thromboembolic pulmonary hypertension usually present with symptoms similar to those of WHO group 1 PAH. Up to one-quarter of patients have no recollection of prior pulmonary embolism.31 As the disease progresses, signs and symptoms related to elevated pulmonary vascular resistance and right ventricular dysfunction are common.32,33

Although thrombi usually resolve quickly, the diagnosis of chronic thromboembolic pulmonary hypertension should be made only after at least 3 months of appropriate anticoagulation to avoid treatment of transient hemodynamic changes often seen after an acute pulmonary embolism.1

Radiographic changes associated with chronic thromboembolic pulmonary hypertension are distinct from the intraluminal filling defects seen with acute thromboembolism, since chronic thrombi tend to become organized and eccentric. On imaging, one may see features of rapid luminal narrowing or eccentric filling defects rather than the conventional central filling defects of acute pulmonary embolism. These changes are often overlooked by radiologists who are not specifically looking for chronic thromboembolic pulmonary hypertension.34 For this reason, the sensitivity and specificity of identifying chronic thromboembolic disease using radionuclide ventilation-perfusion lung scanning is superior to that of CT angiography.

All patients with suspected PAH should undergo a ventilation-perfusion scan.1,35 In patients with ventilation-perfusion mismatch on radionuclide scanning, pulmonary angiography can fulfill multiple goals of measuring pulmonary arterial pressures, identifying the extent and location of chronic thromboemboli, and can determine whether surgical thromboendarterectomy is feasible.

If chronic thromboembolic pulmonary hypertension is identified, it is imperative that patients be referred to a center of excellence specializing in its management regardless of symptom severity, as surgery can be curative and may prevent development of progressive right ventricular dysfunction.36

Our patient’s ventilation-perfusion scan was normal, effectively ruling out the possibility of chronic thromboembolism as a cause of her pulmonary hypertension.

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