Approach Considerations
Findings from the history, physical examination, chest radiography, and electrocardiography (ECG) may suggest the presence of pulmonary hypertension and right ventricular 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 pulmonary hypertension is necessary, or if further information is required for surgical intervention.
Laboratory Studies
A complete blood cell (CBC) count, 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.
Even in cases in which group 3 etiology of pulmonary hypertension seems most likely, laboratory studies evaluating for other causes of pulmonary hypertension should still be obtained. 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 patients at risk.
Chest Radiography
The classic finding on a chest radiograph from a patient with pulmonary hypertension is enlargement of central pulmonary arteries, attenuation of peripheral vessels, and oligemic lung fields. 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.
Echocardiography
Two-dimensional
Echocardiography is generally used 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 right ventricular 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, right ventricular dilatation occurs, leading to right ventricular hypokinesis. Right atrial dilatation, septal flattening, tricuspid regurgitation, pulmonic insufficiency, and midsystolic closure of the pulmonic valve may develop.
Doppler
Doppler echocardiography is the most reliable noninvasive method of estimating pulmonary arterial pressure.
Tricuspid regurgitation is usually present in patients with pulmonary arterial hypertension, 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 pulmonary hypertension, 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 right ventricular Doppler flow velocity envelope provides insight into the hemodynamic basis of pulmonary arterial hypertension. [10] Midsystolic notch was associated with the most severe pulmonary vascular disease and right-sided heart dysfunction.
Ventilation-Perfusion Lung Scanning
Ventilation-perfusion scanning should be performed to exclude chronic thromboembolic pulmonary hypertension. 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 chronic thromboembolic pulmonary 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.
Right-Sided Cardiac Catheterization
Right-sided heart catheterization is the procedure of choice in the diagnosis, quantification, and characterization of pulmonary hypertension. Left-sided heart dysfunction and intracardiac shunts can be excluded, and the cardiac output can be measured.
The indications for right-sided cardiac catheterization are as follows:
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Difficulty in measuring pulmonary arterial hypertension accurately with Doppler echocardiography
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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. [11]
Other Tests
Electrocardiography
On electrocardiography, signs of right ventricular 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.
Polysomnography
In patients with symptoms of suspected obstructive sleep apnea, polysomnography should be performed. Polysomnography may offer both diagnostic and therapeutic options for sleep-disordered breathing.
Histologic Findings
The histopathologic lesions in patients with group 3 pulmonary hypertension are similar to those observed in patients with primary pulmonary arterial hypertension. These pathologic changes are the result of longstanding hypertension rather than a consequence of different causes.
The plexiform lesion is observed in patients with all types of pulmonary arterial hypertension. 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 pulmonary arterial hypertension, and a plexiform lesion reflecting the abrupt onset of pulmonary arterial hypertension is likely, rather than the lesion being a distinctive cause.
