Nonidiopathic Pulmonary Hypertension Workup

Updated: Dec 20, 2017
  • Author: Nader Kamangar, MD, FACP, FCCP, FCCM; Chief Editor: Ryland P Byrd, Jr, MD  more...
  • Print

Approach Considerations

Findings from the history, physical examination, chest radiography, and electrocardiography (ECG) may suggest the presence of pulmonary arterial hypertension (PAH) and right ventricular (RV) dysfunction. Two-dimensional transthoracic echocardiography with Doppler analysis can be used to estimate the pulmonary artery pressure and assess ventricular function.

In patients without cardiac disease, pulmonary function tests should be performed, including blood gas determinations and assessment for possible nocturnal desaturation. Any abnormality should be evaluated further with computed tomography (CT) and possibly a lung biopsy. Patients with normal pulmonary function test results should undergo perfusion lung scanning, and if defects are present, pulmonary angiography or spiral CT should be performed.

Right-sided cardiac catheterization is recommended if noninvasive testing does not provide definitive results, if confirmation of PAH is necessary, if assessment of the reversibility of PAH with a vasodilator is required, or if further information is required for surgical intervention.

Diagnostic confirmation of chronic thromboembolic pulmonary hypertension (CTEPH) requires right-sided cardiac catheterization for pulmonary angiography. The angiographic features in these patients are quite different from the features observed in patients with acute embolism. Marked narrowing of central pulmonary arteries is observed, as compared with the intraluminal filling defects observed in patients with acute embolism.


Laboratory Studies

A complete blood count (CBC), biochemistry panel, prothrombin time (PT), and activated partial thromboplastin time (aPTT) should be obtained at baseline. Arterial blood gas determinations should be performed to assess for hypoxemia.

Collagen-vascular disease screening should be performed. This includes measuring the erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) levels, antinuclear antibody (ANA) levels, antineutrophil cytoplasmic antibody (ANCA), and SCL70.

Synthetic liver function test results (ie, albumin levels, PT, and bilirubin levels) may indicate liver disease associated with portal hypertension.

Brain natriuretic peptide (BNP of NT-proBNP) should be performed on appropriate patients.

HIV testing and hepatitis serology tests should be performed on patient at risk.

A study by Soon et al concluded that iron deficiency is prevalent in patients with pulmonary artery hypertension (PAH) and is significantly more common in patients with idiopathic PAH (IPAH) than in those with chronic thromboembolic pulmonary hypertension (CTEPH). [13]


Chest Radiography

The classic finding on a chest radiograph from a patient with pulmonary arterial hypertension is enlargement of central pulmonary arteries, attenuation of peripheral vessels, and oligemic lung fields (see the first and second images below). Findings of right ventricular (diminished retrosternal airspace) and right atrial dilatation (prominent right heart border) are possible. Abnormalities may be followed up with spiral CT (see the third image below).

Chest radiograph of patient with nonidiopathic pul Chest radiograph of patient with nonidiopathic pulmonary hypertension shows enlarged pulmonary arteries. This patient had atrial septal defect.
54-year-old woman with history of scleroderma (CRE 54-year-old woman with history of scleroderma (CREST variety—ie, calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia) developed dyspnea that worsened upon exertion. The patient was found to have severe pulmonary arterial hypertension.
54-year-old woman with history of scleroderma (CRE 54-year-old woman with history of scleroderma (CREST variety—ie, calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia) developed dyspnea that worsened on exertion. Spiral CT showed enlarged pulmonary arteries but no evidence of thromboembolism.



Echocardiogram is generally employed to screen patients for pulmonary hypertension. It is also used to rule out left ventricular and valvular dysfunction.

On two-dimensional echocardiography, signs of chronic RV pressure overload are present, including increased thickness of the right ventricle and paradoxical bulging of the septum into the left ventricle during systole. In later stages, RV dilatation occurs, leading to RV hypokinesis. Right atrial dilatation, septal flattening, tricuspid regurgitation, pulmonic insufficiency, and mid-systolic closure of the pulmonic valve may develop.


Doppler echocardiography is the most reliable noninvasive method of estimating pulmonary arterial pressure.

Tricuspid regurgitation is usually present in patients with PAH, which facilitates measurement of pulmonary arterial pressure with the modified Bernoulli equation. The efficacy of Doppler echocardiography depends on the ability to locate the tricuspid regurgitant jet. Furthermore, acoustic windows may be limited in patients who have other diseases (eg, chronic obstructive pulmonary disease [COPD]) or in those who are obese.

Tricuspid regurgitation is generally detected in more than 90% of patients with severe PH, and a correlation of greater than 95% is observed when the pressure is measured by means of catheterization. Doppler echocardiography is a useful noninvasive test for long-term follow-up.

Visual inspection of the shape of the RV Doppler flow velocity envelope provides insight into the hemodynamic basis of PAH. [14] Midsystolic notch was associated with the most severe pulmonary vascular disease and right-heart dysfunction.


Ventilation-Perfusion Lung Scanning

Ventilation-perfusion scanning should be performed to exclude CTEPH. A high- or low-probability scan result is most useful, whereas intermediate-probability results should lead to the performance of pulmonary angiography.

Diffuse mottled perfusion can be observed in patients with pulmonary arterial hypertension, as opposed to the segmental or subsegmental mismatched defects observed in patients with CTEPH (see the image below).

Ventilation-perfusion scan of bilateral mismatched Ventilation-perfusion scan of bilateral mismatched segmental and subsegmental defects, suggesting chronic thromboembolic hypertension.

Pulmonary Function Testing

Pulmonary function tests (ie, spirometry and diffusing capacity for carbon monoxide) should be performed in patients with pulmonary hypertension to exclude an underlying pulmonary disorder. Diffusing capacity is universally reduced in patients with pulmonary hypertension.

These tests may show an obstructive pattern suggestive of COPD or a restrictive pattern suggestive of an interstitial lung disease. Furthermore, the severity of the lung disorder may be established by pulmonary function test findings because these tests provide both qualitative and quantitative data.



In patients with symptoms of suspected obstructive sleep apnea (OSA), polysomnography should be performed. Polysomnography may offer both diagnostic and therapeutic options for sleep-disordered breathing.


Right-Sided Cardiac Catheterization

Right-sided heart catheterization is the procedure of choice in the diagnosis, quantification, and characterization of PH. Left-sided heart dysfunction and intracardiac shunts can be excluded, and the cardiac output can be measured.

See the images below.

Left pulmonary arterial angiogram shows large cent Left pulmonary arterial angiogram shows large central pulmonary arteries and attenuation of peripheral vessels, but thrombosis cannot be identified, because it has organized along vessel walls.
Bilateral angiography should be performed in patie Bilateral angiography should be performed in patients suspected of having chronic thromboembolic pulmonary arterial hypertension. This right pulmonary arterial angiogram shows no evidence of filling defect, therefore excluding acute thrombosis. Angioscopy is potentially useful in this setting.

The indications for right-sided cardiac catheterization are as follows:

  • Difficulty in measuring PAH accurately with Doppler echocardiography
  • Need for a precise measurement of pulmonary vascular resistance to conduct a vasodilator trial for assessment of the acute response to vasodilators

Acute vasoreactivity is determined by administering a short-acting vasodilator such as prostacyclin, inhaled nitric oxide, or adenosine. An acute response often predicts a beneficial effect from oral agents, such as calcium channel blockers. [15]


Other Studies


On ECG, signs of RV hypertrophy or strain may be observed. These include right axis deviation, an R-to-S wave ratio greater than 1 in lead V1, increased P-wave amplitude, and an incomplete or complete right bundle-branch block pattern.

Pulmonary angioscopy

Pulmonary angioscopy findings have proven valuable for confirming the presence of chronic thromboembolic obstruction and determining whether it is amenable to surgical intervention. The pulmonary angioscope is a fiberoptic device that allows visualization of the pulmonary arteries to the segmental level.


Histologic Findings

The histopathologic lesions in patients with nonidiopathic pulmonary hypertension are similar to those observed in patients with primary PAH. These pathologic changes are the result of long-standing hypertension rather than a consequence of different causes.

The plexiform lesion is observed in patients with all types of PAH. These lesions consist of medial hypertrophy, eccentric or concentric laminar intimal proliferation and fibrosis, fibrinoid degeneration, and thrombotic lesions. Fresh or organized and recanalized thrombi may also be present. Diverse types of intimal and muscular lesions of the small muscular arteries may cause the clinical syndrome of PAH, and a plexiform lesion reflecting the abrupt onset of PAH is likely, rather than the lesion being a distinctive cause.