Chronic Pulmonary Embolism

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CHAPTER 98 Chronic Pulmonary Embolism

Pulmonary hypertension is defined as a mean arterial pressure of greater than 25 mm Hg at rest and 30 mm Hg with exercise.¹ Symptoms are often nonspecific and include dyspnea on exertion and easy fatigability. When it is severe, pulmonary hypertension can be severely debilitating and even fatal. During the past decade, advances in diagnosis and therapeutics have markedly affected the mortality of pulmonary hypertension.² What was once a lethal condition without transplantation has become a condition that may be managed with various medications.

In 2003, an international multidisciplinary conference held in Venice, Italy, revisited the classification of pulmonary hypertension with a goal of classifying pulmonary hypertension into categories based on treatment algorithms that may be beneficial.³ The result was five main categories: pulmonary arterial hypertension, pulmonary hypertension due to left-sided heart disease, pulmonary hypertension from chronic hypoxia, pulmonary hypertension due to chronic embolic disease, and pulmonary hypertension from miscellaneous causes. Of these categories, pulmonary hypertension due to chronic embolic disease is the only one that may benefit from pulmonary thromboendarterectomy and one of the only forms of pulmonary hypertension that may be cured.⁴ The goal of this chapter is to highlight the imaging findings of chronic pulmonary embolism and to help delineate those patients who may benefit from surgical intervention.

CHRONIC PULMONARY EMBOLISM

Definition

Chronic pulmonary embolism is more accurately referred to as chronic thromboembolic pulmonary hypertension (CTPH) to distinguish it from chronic emboli from foreign materials, such as talc, or parasitic ova, such as schistosomiasis.³ CTPH represents cytokine-mediated scarring of the pulmonary circulation from even one episode of acute pulmonary embolism.⁵^,⁶ The net effect of the scarring is decreased luminal volume for the pulmonary circulation. This decrease in arterial volume results in increased pulmonary pressures.

Prevalence and Epidemiology

In the age of cross-sectional imaging, CTPH may be more common than previously thought. Prior reports suggested that less than 0.1% of patients with an episode of acute pulmonary embolism will go on to develop CTPH and pulmonary hypertension.⁷ More recent studies suggest that this number is an underestimation of the true incidence and prevalence. In one prospective follow-up study of 78 patients with acute pulmonary embolism, 4 patients (5%) went on to develop definite CTPH, and in another of 223 patients with acute pulmonary embolism, 3.8% went on to develop symptomatic CTPH at 2 years.⁸^,⁹ Estimations of true incidence are hindered by the large number of patients with CTPH who may not have had any history or memory of symptomatic pulmonary embolism in the past. As many as two of three patients with CTPH may not have had a documented history of acute pulmonary embolism.⁶

Etiology and Pathophysiology

CTPH is a cytokine-mediated condition that may follow even one episode of acute pulmonary embolism. This is important to consider so that it is not confused with recurrent acute pulmonary embolism, which represents either failure of anticoagulation or a manifestation of a hypercoagulable state.⁶ CTPH also does not represent failure of an acute pulmonary embolism from resolution. Instead, CTPH represents the end of a cycle of in situ thrombus, scarring, and vascular remodeling that occurs after a vascular insult, usually acute pulmonary embolism.⁵

Manifestations of Disease

Clinical Presentation

Like other causes of pulmonary hypertension, CTPH usually is manifested with vague symptoms and nonspecific findings.¹⁰^,¹¹ Patients tend to notice decrease in exercise tolerance, easy fatigability, and dyspnea on exertion. As the condition progresses, they may find that they develop dyspnea at rest. The mean time from onset of symptoms to diagnosis is about 3 years, highlighting the insidious, nonspecific nature of this process.⁶^,¹⁰

Imaging Indications and Algorithm

Imaging of a patient with suspected pulmonary hypertension from CTPH is aimed at answering four main questions: (1) What is the degree of pulmonary hypertension? (2) What is the etiology of the pulmonary hypertension—is chronic pulmonary embolism the cause or is another entity more likely? (3) Are changes of chronic pulmonary embolism surgically accessible? (4) Are any new pulmonary emboli present? Imaging usually begins with a chest radiograph, which might suggest pulmonary hypertension, and quickly moves to an echocardiogram, which is used to estimate pulmonary pressures and to assess cardiac function.¹² Traditionally, ventilation-perfusion scintigraphy (V/Q scan) has been used to assess for CTPH in combination with CT to exclude interstitial lung disease.^6,^12,¹³ At many institutions, however, the pulmonary embolism protocol CT has replaced both studies.¹⁴ This single study, especially when it is performed on a multidetector row CT (MDCT) scanner, allows the simultaneous assessment for CTPH and interstitial lung disease.

MR may allow a noninvasive assessment of pulmonary pressures, but its routine use for exclusion of CTPH remains somewhat experimental.¹⁵ If pulmonary hypertension is confirmed on any of the modalities, patients tend to be referred for right-sided heart catheterization so that accurate measurements of pulmonary pressures and right-sided heart hemodynamics may be performed. If CTPH is uncovered, patients may go on to pulmonary angiography to assess whether pulmonary thromboendarterectomy may be beneficial. Multiplanar postprocessing of MDCT data and thin maximum intensity projections (usually 4 to 7 mm) may provide equivalent information and avoid angiography altogether.

Imaging Techniques and Findings

Radiography

Conventional radiography may show enlargement of the right side of the heart, with increased convexity of the right border of the heart on the frontal projection and filling in of the retrosternal clear space on the lateral projection (Figs. 98-1 and 98-2). The pulmonary arteries may be enlarged. Features unique to CTPH are rarely observed.

FIGURE 98-1 A 38-year-old man with progressive shortness of breath after a kayaking episode 2 years ago showing the classic features of chronic pulmonary embolism. A and B, Frontal and lateral chest radiographs show large pulmonary arteries and enlarged right cardiac chambers. The radiograph suggests pulmonary hypertension but does not allow a more specific diagnosis. C and D, Perfusion (C) and ventilation (D) images from a V/Q scan show multiple wedge-shaped perfusion abnormalities with normal ventilation. This study was interpreted as a “high probability” study for pulmonary embolism and, in this setting, favored chronic pulmonary embolism. No information is provided on surgical accessibility of the disease. E and F, Soft tissue windows from contrast-enhanced CT show the enlarged main pulmonary artery and an eccentric filling defect in the right pulmonary artery (arrows in E) in keeping with chronic pulmonary embolism. The enlarged right side of the heart with hypertrophy results from the severe pulmonary hypertension. G, Lung windows from CT show the mosaic perfusion pattern; the darker areas represent abnormal lung. H, Coronal thin maximum intensity projection CT image (6 mm) shows the beaded appearance of the lower lobe pulmonary arteries with a clear-cut web in the left lower lobe (arrow). I and J, Pulmonary angiography performed as part of preoperative planning confirms the beaded appearance of the pulmonary arteries and the web (arrow in J).

FIGURE 98-2 A 64-year-old woman with progressive dyspnea. A and B, Frontal and lateral chest radiographs show enlarged pulmonary arteries in keeping with pulmonary hypertension. C to E, Contrast-enhanced CT shows an eccentric thrombus (arrow in C) and enlarged bronchial arteries (arrow in D). The enlarged right side of the heart in C confirmed the diagnosis of pulmonary hypertension from chronic pulmonary embolism. F to H, Coronal thin maximum intensity projection images (6 mm) show the CT findings of chronic pulmonary embolism including beaded vessels, enlarged bronchial arteries (arrows in G), and vessel cutoff (arrow in H). In many ways, the CT findings are easier to appreciate on the coronal images. I and J, Pulmonary angiography confirms the extensive disease and exhibits the finding of “pouching” with a convex contrast column pointing away from the hilum (arrow in J). K, The patient was thought to be a candidate for thromboendarterectomy, and postoperative CT shows the decreased clot burden. Unfortunately, the patient had only minimal decrease in pulmonary pressures from her surgery.

Ultrasonography

Echocardiography will show increase in the size of the right atrium and the right ventricle as well as the main pulmonary artery. Echocardiography may be used to estimate pulmonary pressures.¹⁶ This estimate is based on calculating the peak velocity of the tricuspid regurgitation jet and calculating a pressure based on a modified Bernoulli equation [pressure = 4 × velocity² (velocity in meters/sec)]. This value is added to an estimate of right atrial pressure, which is based on the size of the inferior vena cava and its variation during respiration.

On occasion, echocardiography may be performed with a contrast agent or agitated saline. The left atrium and ventricle are observed to confirm the absence of any echogenic material. If any is seen, this suggests that an intracardiac right-to-left shunt is present and the intravenously injected material is shunting to the left side of the heart. The shunt could be an alternative explanation for pulmonary hypertension. Care must be taken to confirm that the shunt is not a patent foramen ovale, which can be secondary to CTPH and elevated pulmonary pressures.

Computed Tomography

CT findings can be divided into three main categories: cardiac findings, pulmonary arterial findings, and parenchymal or other findings.¹⁷^–¹⁹

Cardiac findings, as with echocardiography, center on the effect of increased pulmonary pressures on the right ventricle and right atrium. Both chambers tend to be enlarged, and the right ventricle tends to be hypertrophied (see Figs. 98-1 and 98-2). The observation of muscle hypertrophy is important because right ventricular enlargement alone may be seen in the setting of acute pulmonary embolism. In this situation, right ventricular enlargement may be a finding of right-sided heart strain and may require more aggressive intervention or closer observation. With right-sided heart enlargement and right ventricle hypertrophy, the interventricular septum tends to straighten at first and then to bow toward the left. The interatrial septum also may eventually straighten and then bow toward the left. Rarely, intravenous contrast material may be seen entering the left atrium through a septal defect, or two thin membranes may be seen in the region of the atrial septum. These CT features of a patent foramen ovale can be subtle and, as with echocardiography, may be secondary to pulmonary hypertension from CTPH. One should not expect to see a defect on a single transaxial image in a patent foramen ovale. If one is observed, a true atrial septal defect may be present.

Pulmonary artery findings on CT are similar to the vascular findings on angiography.¹⁸^,¹⁹ These include thrombus along the vessel wall, abrupt vessel caliber change, abrupt vessel cutoff or thrombosed vessel, webs within the arteries, beaded vessels, and enlarged central vessels. The eccentric nature of the thrombus is key in distinguishing CTPH from acute pulmonary embolism (see Figs. 98-1 and 98-2). CTPH tends to be present along the wall of the vessel, with a flat or concave interface with the lumen.¹⁷ Conversely, acute pulmonary embolism tends to be central with vessel expansion. When it is eccentric, along the vessel wall, acute pulmonary embolism is convex toward the lumen. CTPH rarely calcifies. In fact, if calcification is seen, one must strongly consider in situ thrombus formation as can be seen in pulmonary artery aneurysms, familial pulmonary arterial hypertension, intracardiac shunts, or even mitral disease (Fig. 98-3). Many of these features are better appreciated on coronal reconstructions.

FIGURE 98-3 A 45-year-old woman with severe pulmonary hypertension. A, Contrast-enhanced CT shows the markedly enlarged pulmonary arteries with some eccentric calcification (arrow). B, The calcifications are better seen on the coronal maximum intensity projection image. These calcifications are very unusual for chronic pulmonary embolism and should prompt one to consider an intracardiac shunt or other cause of pulmonary hypertension. C, Sagittal oblique reconstruction shows the very large ostium secundum atrial septal defect (arrow) that was responsible for these CT findings.

For optimal evaluation, CT angiography according to a pulmonary embolism protocol should be performed. Review of images must be done with a window setting that allows visualization of any intraluminal webs, which tend to be less than 1 mm in size. Lung windows should also be used to look for any absent vessels. Nothing is more difficult than to look for a missing vessel on soft tissue windows. The lung windows can be helpful as they show the bronchus with a thready or absent accompanying artery.

Parenchymal or other findings are useful in confirming that the patient has CTPH as an explanation for pulmonary hypertension. These include enlarged bronchial arteries, mosaic perfusion, and bronchiectasis.²⁰^–²² The enlarged bronchial arteries tend to be variable, with only some of the arteries being enlarged. In general, these may be seen at the level of the carina as serpentine, enhancing structures near the descending aorta. They are much better delineated on coronal reconstructions. Mosaic perfusion in CTPH is a reflection of the small-vessel disease, with the darker areas representing abnormal lung with decreased vascularity. The darker lung should not demonstrate air trapping. Bronchiectasis in CTPH is a poorly understood phenomenon that has been clearly observed in the setting of CTPH. In general, the bronchiectasis is cylindrical.

Magnetic Resonance

The role of MR in the evaluation of CTPH is very much under current investigation.¹⁵ Ideally, MR would provide a one-test answer to the severity of hypertension and the location of the emboli, if present. As with echocardiography, estimation of pulmonary pressures depends on visualization of a tricuspid regurgitation jet. The excursion of the tricuspid annulus (up to 4 cm) during the cardiac cycle can make imaging of a clear dephasing jet difficult. Using a velocity-encoded phase contrast sequence, one can then obtain images orthogonal to the jet to calculate a peak velocity, which can then be used to calculate a pressure gradient. This number can be added to an estimation of right atrial pressure based on the size of the inferior vena cava and its respiratory variation.¹⁵^,¹⁶

MR can also be used to observe cardiac function noninvasively. By using flow quantification of the pulmonary artery just above the pulmonary valve, one can calculate a right-sided heart stroke volume. Short-axis imaging through the heart can be used to calculate right ventricle volumes and ejection fraction. These values can then be used to observe a patient’s response to treatment in a noninvasive fashion. In theory, this potential for MR makes this modality eclipse the others. Unfortunately, a comprehensive MR study is longer than a CT examination, taking up to 1 hour, and typically requires repetitive breath-holding, which is often not practical in patients who may be dyspneic. Postprocessing may also be tedious and time-consuming, making this type of study impractical in a diverse, busy practice.

A third feature of MR is the analysis for a potential cause of the pulmonary hypertension. MR can allow the assessment of an intracardiac shunt and with gadolinium provides excellent depiction of the pulmonary circulation. MR findings are identical to those of CT. Mosaic intensity may also be better appreciated on postcontrast images. On occasion, MR will not show CTPH as the cause of the pulmonary hypertension but may show that the hypertension is related to an interstitial lung disease. Care must be taken to assess the lungs on all sequences.

At our institution, MR is used primarily as a method to evaluate for intracardiac shunts. We are currently using the techniques to determine whether our patients can be observed noninvasively. We do not routinely use the modality to exclude CTPH.

Nuclear Medicine/Positron Emission Tomography

Nuclear medicine for CTPH primarily relies on ventilation and perfusion (V/Q) scans. There is no role for positron emission tomography in the evaluation of CTPH. As with acute pulmonary embolism, the V/Q scan in CTPH tends to show multiple perfusion defects without ventilation abnormalities.¹³^,²³ These “mismatches” can be used to diagnose CTPH in the presence of pulmonary hypertension. A potential pitfall is that subsegmental defects may be seen in veno-occlusive disease, fibrosis, and idiopathic pulmonary hypertension (Fig. 98-4).²⁴ On occasion, these defects can be difficult to separate from those of CTPH. Another shortcoming of V/Q scintigraphy is its inability to delineate location of the scars of CTPH.²³ No information about the surgical resectability of the lesions is provided by this examination. Despite these potential pitfalls, V/Q scintigraphy offers a safe, lower radiation alternative to MDCT and is still frequently used in the evaluation of pulmonary hypertension that may be secondary to CTPH.²⁵

FIGURE 98-4 A 48-year-old man with pulmonary hypertension. V/Q scan was originally interpreted as “high probability,” an opinion that changed when the nature of the disease was discovered—vasculitis. Vasculitis can occasionally be confused with chronic pulmonary embolism on V/Q scans.

Angiography

Like MDCT and contrast-enhanced MR, angiography relies on the vascular findings of CTPH: intravascular webs, eccentric thrombus, beaded vessels, vessel cutoff, and enlarged main pulmonary artery.²⁶ Because imaging is performed at various points in time, another well-described sign, known as pouching, may be seen. In pouching, a convex, enlarged vessel is seen without initial filling of peripheral vessels. Over time, the thready peripheral vessels opacify.

An advantage of angiography is that it allows simultaneous measurements of right-sided heart and pulmonary pressures. These are still considered the gold standard measurements and are used for determination of prognosis and for follow-up of the patients.⁶

During the parenchymal phase, mosaic perfusion may be observed.

Classic Signs

Classic signs of CTPH consist mostly of enlarged pulmonary arteries centrally, with increased size of the right side of the heart, mosaic perfusion, and eccentric arterial filling defects with intravascular webs. Segmental arteries tend to be thready and may be cut off or absent.

Differential Diagnosis

From Clinical Presentation

Any cause of pulmonary hypertension may mimic CTPH clinically.⁶^,²³ These include idiopathic pulmonary hypertension, Eisenmenger syndrome, pulmonary vasculitis, left-sided heart failure, chronic hypoxia, sarcoidosis, interstitial lung disease, fibrosing mediastinitis, and central bronchogenic cancer.

From Imaging Findings

Other conditions can mimic the angiographic findings. These include fibrosing mediastinitis and pulmonary vasculitis, such as Takayasu arteritis.²³ Both of these conditions may cause thready vessels with beading and vascular cutoffs. The key in excluding these other conditions is to look for soft tissue attenuation or lymphadenopathy on CT or MR (Fig. 98-5). Enhancement of the vessel wall may also be helpful. This finding is not present with CTPH.

FIGURE 98-5 A 28-year-old woman with pulmonary hypertension. A, CT angiography shows beaded vessels with calcified soft tissue (arrows) that were in keeping with lymphadenopathy. These beaded vessels could be confused with chronic pulmonary embolism. B, Conventional angiography depicts the beaded vessels but not the extrinsic nature of the disease. C, MR angiography, similar to the angiography in B, also fails to show that the compression and beading are from lymphadenopathy. This patient was found to have fibrosing mediastinitis.

Calcification of the vessel wall should also not be used as the sole diagnostic feature of CTPH. Although this finding may rarely be seen with CTPH, calcification is much more commonly seen with pulmonary hypertension from long-standing cardiac shunts, familial pulmonary hypertension, pulmonary aneurysms, or even mitral disease.

Synopsis of Treatment Options

Medical

Treatment of CTPH very much depends on the location of the scars and webs. If it is central enough, patients may be referred for surgery, which can be curative.^2,^4,¹⁸ If it is peripheral, CTPH will be treated similarly to pulmonary arterial hypertension. Vasodilator therapy may be all that can be offered to the patient. Because isolated peripheral disease will be treated like other causes of pulmonary arterial hypertension, one should not fear that tiny webs in small arterioles that may be missed on CT will alter treatment.

Surgical/Interventional

Surgical treatment consists of removal of the scar tissue so that the pulmonary vascular volume can be returned.^2,^4,¹⁸ The surgical procedure is a pulmonary thromboendarterectomy. The boundary between what is accessible and what is not depends on the experience of the surgeon. Usually, subsegmental artery thromboendarterectomy marks the limit to where a patient may be cured. This procedure is quite different from an embolectomy, which may be used in the setting of a large acute or subacute saddle pulmonary embolism. This procedure does not require stripping of the pulmonary artery intima and is quicker.