Definition

Pulmonary hypertension (PH) is defined as a resting mean pulmonary arterial pressure more than 25 mm Hg at rest or more than 30 mm Hg with exercise. Among the various subclassifications of PH, the subgroup referred to as pulmonary arterial hypertension adds the criterion that the pulmonary capillary wedge pressure should be 15 mm Hg or less.²

Etiology and Pathophysiology

Pathogenesis

Several mechanisms may produce a decrease in the total number of small pulmonary arteries and arterioles, thereby increasing pulmonary vascular resistance and producing elevated pulmonary arterial pressure. Such mechanisms include intraluminal arterial occlusion, muscular contraction of small pulmonary arteries, vascular remodeling with wall thickening, or conditions that produce pulmonary venous hypertension. Several of these mechanisms may be operative simultaneously in patients with PH.

The pulmonary vascular endothelium actively responds to changes in oxygen tension, transmural pressure, and pulmonary blood flow, and actively participates in the regulation of pulmonary arterial pressure through the elaboration of a number of vasoactive substances, including prostacyclin, nitrous oxide, and endothelin.³ These agents have direct effects on pulmonary vascular smooth muscle tone, promoting relaxation or vasodilation, and also may directly affect platelet function.

Various pathologic derangements may be seen in patients with PH, varying somewhat depending on the cause of PH. In general, regardless of the cause of PH, the pulmonary arteries become dilated,¹ occasionally to the point of being considered aneurysmal. Pulmonary arterial atherosclerosis, typically absent in the pulmonary arteries of normal adults, may be extensive and frequently involves smaller vessels in patients with PH. PH-related pulmonary arterial atherosclerosis histopathologically appears similar to atherosclerosis occurring in systemic arteries, although complicating features, such as necrosis, ulceration, and calcification, are relatively uncommon.

Plexogenic pulmonary arteriopathy is the term applied to a constellation of vascular changes often encountered in patients with primary PH, but may also be seen in patients with PH of other causes, including hepatic disease, connective tissue disorders, congenital cardiovascular disease, and some anorexigenic medications.²

Classification

There have been a number of proposed classification schemes to categorize the causes of PH. In 1998, during the Second World Symposium on Pulmonary Hypertension held in Evian, France, a clinical classification for PH was proposed (Box 99-1).^3–5 The aim of the Evian classification was to provide categories for causes of PH that shared similar pathophysiologic mechanisms, clinical presentations, and therapeutic considerations. Similar to oncologic staging considerations, such a classification was designed to allow standardization of diagnosis and treatment for patients with PH, conduction of trials with similar patient cohorts, and investigation of pathobiologic abnormalities in patient populations that are highly characterized. In 2003, the Third World Symposium on Pulmonary Arterial Hypertension, held in Venice, evaluated the usefulness of the Evian classification system and recommended some minor modifications. The Venice classification was adopted by the World Health Organization (WHO) and has been referred to as the Revised World Health Organization Classification of Pulmonary Hypertension (Box 99-2). More recently, the revised WHO-Venice classification underwent revision at the Fourth World Symposium on Pulmonary Hypertension held in Dana Point, California. The new classification system is referred to as the 2008 Dana Point Pulmonary Hypertension classification system.⁶ Traditionally, pulmonary hypertension has been classified into primary versus secondary causes or precapillary and postcapillary causes; this classification scheme is still in common use, particularly among interpreting physicians, and is included here as well. The pre- and postcapillary PH classification scheme is commonly reviewed in radiology texts (Box 99-3),¹ but the 2008 Dana Point classification system is in more widespread use among clinicians and investigators dealing with PH. The 2008 Dana Point classification system will be used for this chapter.

BOX 99-3 Classification of Pulmonary Hypertension: Precapillary Versus Postcapillary Etiologies

PRECAPILLARY PULMONARY HYPERTENSION

Pulmonary arterial hypertension

Congenital cardiovascular left to right shunts

Pulmonary thromboembolism

Nonthrombotic embolization (including tumor, particulate, and parasitic thromboemboli)

Chronic alveolar hypoxia.

POSTCAPILLARY PULMONARY HYPERTENSION

Left-sided cardiac obstruction—left ventricular failure, systemic hypertension, mitral valvular disease, atrial myxoma, cor triatriatum, other congenital cardiac anomalies

Pulmonary venous obstruction—fibrosing mediastinitis

Pulmonary veno-occlusive disease

In the 2008 Dana Point classification schemes, the category of pulmonary arterial hypertension (PAH) includes a subgroup of patients with PH without any identifiable cause, or idiopathic PAH,⁶ previously referred to as primary pulmonary hypertension (PPH). Other subgroups in the category of PAH include disorders that share localization of the lesions to small, muscular pulmonary arterioles, including heritable causes of PH (e.g., patients with mutations in bone morphogenetic protein receptor 2 and activin receptor-like kinase 1), drug and toxin exposures, and associations with certain conditions, such as collagen vascular diseases, HIV-related PH, portopulmonary hypertension, congenital systemic to pulmonary artery shunts, schistosomiasis, and chronic hemolytic anemias. The morphologic and clinical characteristics of these disorders are similar, and they also share a clinical response to treatment with continuous infusion of epoprostenol.⁵ Most patients previously diagnosed with primary pulmonary hypertension would now be classified as patients with idiopathic pulmonary arterial hypertension (IPAH) or, less commonly, heritable PH or anorexigen-induced PH (Box 99-4).⁷ Persistent PH of the newborn was also recognized as a cause of PAH in the 2008 Dana Point PH classification system. The Venice-revised WHO classification system also includes another subcategory in the pulmonary arterial hypertension group, referred to as “pulmonary arterial hypertension associated with significant venous or capillary involvement.” This subcategory includes pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis. In the 2008 Dana Point system, this subcategory remains a group 1 (PAH) condition, but is now referred to as “pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis” in recognition of the similarities between these two disorders (see Box 99-4). Both entities were classified differently in the Evian system.

The category referred to as pulmonary venous hypertension in the Evian system and as PH with left heart disease in the Venice-revised WHO system is now called pulmonary hypertension secondary to left heart disease (see Box 99-4). It includes systolic and diastolic dysfunction as well as left-sided valvular and myocardial conditions that require therapies directed at improving cardiac function or repairing or reducing valvular mechanical dysfunction, as opposed to treatment with vasodilator therapy.^5,6 In fact, epoprostenol infusion in these patients can be harmful. Pulmonary veno-occlusive disease and lesions producing extrinsic compression on pulmonary veins are included in this category in the Evian system, but were reclassified in the Venice-revised WHO system in 2003 and again in the 2008 Dana Point system.

PH secondary to hypoxia and/or lung disease (see Box 99-4) results from inadequate arterial blood oxygenation caused by chronic obstructive pulmonary disease, interstitial lung diseases, sleep-disordered breathing, alveolar hypoventilation, and residence at high altitude. Usually, the elevated pulmonary arterial pressures in these patients are fairly modest (<35 mm Hg).

Group 4 in the 2008 Dana Point PH classification system is chronic thromboembolic pulmonary hypertension (see Box 99-4).⁶ In many patients with chronic thromboembolic PH, the central pulmonary arteries show emboli and/or thrombi, and such patients may benefit from pulmonary endarterectomy.¹ In other patients, emboli or thrombi are relatively distally located and are not amenable to surgical treatment. These patients may respond to chronic pulmonary vasodilator therapy, similar to patients with IPAH. Both subgroups of patients are treated with lifelong anticoagulation.

PH caused by disorders of the pulmonary vasculature in the Evian system was simply referred to as the miscellaneous category in the Venice-revised WHO system, and is now called pulmonary hypertension with unclear multifactorial mechanisms in the 2008 Dana Point classification. Included in this group are a variety of disorders such as myeloproliferative diseases, splenectomy, cystic lung diseases, sarcoidosis, and metabolic disorders. External vascular compression, particularly fibrosing mediastinitis, previously considered a subcategory of pulmonary arterial hypertension in the Evian system, was moved to the miscellaneous category in the Venice-revised WHO system and is now classified as a group 5 lesion in the 2008 Dana Point system.⁶

Manifestations

Imaging Techniques and Findings

The characteristic finding of pulmonary arterial hypertension on chest radiography, CT, or MRI is dilation of the central pulmonary arteries, with rapid tapering of the pulmonary vessels as they course peripherally.¹ This pattern is present regardless of the cause of the PH.

Radiography

Chest radiography may show enlargement of the main pulmonary artery segment and dilation of the right and left interlobar pulmonary arteries in patients with PH, regardless of cause (Fig. 99-1).

FIGURE 99-1 Frontal and lateral chest radiographs show imaging findings typical of pulmonary hypertension—enlarged main pulmonary artery (arrow) and enlarged right (arrowheads) and left pulmonary arteries that rapidly taper in the lung periphery.

Ultrasound

Echocardiography is the most commonly performed examination for the noninvasive assessment of possible PH. Echocardiography, using continuous wave or pulsed Doppler, provides noninvasive measurement of pulmonary arterial pressures and also allows detailed morphologic evaluation of the right ventricle. Furthermore, stress echocardiography assesses the hemodynamic response of the pulmonary arterial circulation in response to a variety of challenges, such as exercise or pharmacologic agents in patients with PH.

Computed Tomography

The main pulmonary arterial segment cannot be directly measured on chest radiography, but is easily measured on CT or MRI. When the main pulmonary artery segment exceeds 3 cm (Fig. 99-2), PH is often present. However, PH may be present in patients with a normal-sized main pulmonary arterial segment. The main pulmonary artery–to–ascending aortic ratio is also a useful internal indicator that can suggest enlargement of the main pulmonary artery. When the ratio of the main pulmonary artery to the aorta exceeds 1, elevated pulmonary pressures are usually present.¹

FIGURE 99-2 Axial CT scan shows transverse measurement of main pulmonary artery (white line). When this measurement exceeds approximately 3 cm, PH is likely. Note that the transverse dimension of the main pulmonary artery exceeds the transverse dimension of the ascending aorta at the same level. Pulmonary arterial atherosclerosis (arrows) is present.

When PH is prolonged and severe, calcification of the pulmonary arteries, usually affecting the main, right, and/or left pulmonary arteries and, less commonly, the lobar pulmonary arteries, may be present (see Fig. 99-2). This finding is usually, but not invariably, associated with irreversible pulmonary vascular disease.

Patients with elevated pulmonary arterial pressures may also show right ventricular enlargement and right ventricular hypertrophy (Fig. 99-3) on cross-sectional imaging studies.¹ The right atrium and inferior vena cava may also be enlarged, and contrast reflux into the infradiaphragmatic inferior vena cava is also commonly seen.

FIGURE 99-3 Axial CT scan shows enlargement of the right ventricle, with leftward bowing of the interventricular septum (arrowheads). Either finding may indicate elevated pulmonary arterial pressures. Note right ventricular muscular hypertrophy, indicating long-standing pulmonary arterial pressure elevation.

Magnetic Resonance Imaging

MRI will show all the vascular abnormalities that thoracic CT detects in patients with PH, such as main pulmonary artery enlargement and right ventricular enlargement and hypertrophy.¹ Additionally, MRI can provide functional information equivalent to echocardiography, such as direction and velocity of blood flow, in addition to specific anatomic information. MRI techniques are well suited to the evaluation of patients with PH because they allow a detailed anatomic and extensive functional examination of the entire cardiovascular system.

Definition

The term primary pulmonary hypertension was first used in 1951 to describe hypertensive vasculopathy in the pulmonary arteries without an identifiable cause.⁵ More recently, it has been recognized that patients with heritable forms of PAH and those with various conditions associated with PH, including connective tissue diseases, the use of appetite suppressant medications, portopulmonary hypertension, and HIV infection, among others, may share pathologic and clinical features similar to PPH, and were previously collectively referred to as secondary PH. The disorders encompassed by the term secondary PH are a fairly heterogeneous group of conditions that also include conditions affecting the pulmonary venous circulation or pulmonary parenchyma as well. The use of secondary PH has been largely abandoned because it does not provide a useful framework for the diagnosis or treatment of patients with PH. Therefore, the Venice group recommended changing the term primary PH to idiopathic pulmonary arterial hypertension; this nomenclature was adopted in the Venice-revised WHO classification system and is maintained in the 2008 Dana Point classification system.

Etiology and Pathophysiology

The cause of IPAH is unknown. The prevalence of PAH is estimated at about 15/million.⁷ The disease affects females more commonly than males. The Venice-revised WHO classification system previously recognized two forms of IPAH, familial and idiopathic (sporadic). The 2008 Dana Point classification system now refers to familial PAH as heritable PAH, and considers IPAH as a separate subcategory of PAH (see Box 99-4).⁶ Heritable forms of PAH account for approximately 10% of PAH cases, show autosomal dominant inheritance with incomplete penetrance, and have been localized to chromosome 2 at the locus of the bone morphogenic protein receptor type II gene.⁵ Heritable PAH associated with mutations in activin receptor-like kinase type 1 may be associated with hereditary hemorrhagic telangiectasia.

The cause of IPAH remains unknown, but is generally attributable to an imbalance between vasodilating agents and vasoconstricting agents, with a relative paucity of prostacyclin and nitric oxide synthase expression and an increase in expression of endothelin-1.

Manifestations of Disease

Imaging Techniques and Findings

Radiography

Chest radiography in patients with IPAH typically shows enlargement of the main, right, and left pulmonary arteries (see Fig. 99-1), often with enlargement of the right ventricle (see Fig. 99-3) and right atrium.¹ CT and black blood MRI techniques will show these same findings to advantage. Occasionally, black blood MRI will show increased signal within the pulmonary arteries resulting from slow flow.

Computed Tomography

High-resolution CT (HRCT) in patients with IPAH may show inhomogeneous lung opacity resulting from differential pulmonary parenchymal perfusion (Fig. 99-4).¹ The regions of decreased pulmonary parenchymal attenuation represent areas of mosaic perfusion, and the vessels in these regions of lung may be visibly smaller than their counterparts in the regions of relatively increased lung attenuation. Although airway diseases may result in a similar pattern of mosaic perfusion, vascular and airway causes of mosaic perfusion may be distinguished using postexpiratory imaging. When caused by an obstructive airway process, regional differences in lung attenuation become accentuated with postexpiratory imaging, whereas a proportional increase in attenuation in areas of both increased and decreased attenuation will be seen in patients with pulmonary vascular disease.

FIGURE 99-4 Axial CT scan shows bilateral inhomogeneous lung opacity, consisting of areas of abnormally decreased opacity (arrowheads), representing mosaic perfusion, and areas of normal or increased attenuation. Note that pulmonary vessels are abnormally small in areas of decreased lung opacity.

Occasionally, HRCT will show centrilobular ground-glass opacities in patients with IPAH (Fig. 99-5), representing foci of hemorrhage, plexiform lesions, or cholesterol granulomas.⁸

FIGURE 99-5 Axial CT scan shows areas of vaguely nodular ground-glass opacity (arrowheads). In some areas, these are centrilobular in distribution. Such findings may represent areas of hemorrhage, plexiform lesions, or cholesterol granulomas.

Nuclear Medicine and Positron Emission Tomography

Ventilation-perfusion (V/Q) scintigraphy is commonly abnormal in patients with IPAH, but the findings are usually nonspecific and are often interpreted as representing a low probability for pulmonary thromboembolic disease.¹

Angiography

Catheter pulmonary angiography in patients with IPAH shows tapering peripheral vessels with a “corkscrew” appearance, occasionally with visualization of subpleural collateral vessels.¹

Definition

Pulmonary arterial hypertension related to associated conditions (APAH) includes PH in patients with connective tissue diseases, HIV infection, portal hypertension, congenital cardiovascular systemic to pulmonary shunts, schistosomiasis, and chronic hemolytic anemias.⁶ The term risk factors in the category of PAH indicates any condition suspected to play a role in predisposing or facilitating the development of PAH, whereas the term associated conditions is used when it is impossible to determine whether a predisposing factor was present prior to the development of PAH.⁵ The Evian conference in 1998 explored a number of potential risk factors and classified them according to the strength of association with PAH and the likelihood of a causal role in the development of PAH as definite, very likely, possible, or unlikely, according to the strength of available evidence in the literature (Box 99-5).

Etiology and Pathophysiology

PAH associated with connective tissue disease usually occurs in patients with systemic sclerosis, particularly those with limited forms of this disorder, such as CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia).^7,9 Although most patients with systemic sclerosis do not develop clinical evidence of PAH, histopathologic changes of PAH are common in patients with systemic sclerosis. Echocardiographic studies have suggested that mild or moderate PAH is not uncommon in patients with systemic sclerosis.

HIV has not been shown to infect pulmonary circulation endothelial cells directly, so the mechanism of action of HIV-associated PAH remains unknown. The proposed mechanism in portopulmonary arterial hypertension is thought to be the incomplete hepatic degradation of humoral factors that exert vasoconstricting and inflammatory effects on the pulmonary circulation.

Intracardiac and extracardiac systemic to pulmonary (left to right) vascular shunts, including ventricular-septal defects, atrial-septal defects, partial anomalous pulmonary venous return, transposition of the great vessels, and patent ductus arteriosus, produce increased flow through the pulmonary arterial bed. The clinical severity is not related to the mechanism of shunting but rather correlates with the degree of pulmonary artery pressure elevation.

The increased pulmonary arterial flow that results from long-standing systemic to pulmonary vascular shunting produces persistently increased vasomotor tone within the pulmonary arteries, eventually leading to the development of pulmonary plexogenic arteriopathy and irreversible pulmonary vasculopathy. Eventually, the systemic to pulmonary vascular shunting may reverse, producing a pulmonary to systemic shunt, referred to as Eisenmenger syndrome.

Most patients with congenital systemic to pulmonary vascular shunts are corrected during infancy or early childhood, before the onset of severe PAH. For the infrequent patient who escapes surgical repair of the causative lesion during childhood, lung biopsy may be performed to assess the potential success for reversing the vasculopathy following surgical intervention.¹ This histopathologic grading system is called the Heath-Edwards grading system, and was originally described using a six-point scale. More recently, a three-point system has been proposed. The Heath-Edwards grading system allows prediction of disease reversibility. Grades I and II (medial hypertrophy, intimal proliferation, and neomuscularization) represent mild reversible disease. Grade III is considered borderline and is characterized by intimal fibrosis and luminal obliteration. Higher grades, corresponding with plexiform lesions, aneurysm, and necrotizing arteritis, are considered irreversible changes, and surgical correction of the abnormality is not warranted.

In prior PH classification systems, PH with schistosomiasis was previously thought to be the result of embolic obstruction of the pulmonary arteries by the organism’s eggs. However, recent data suggest that PH related to schistosomiasis shares a clinical presentation and histopathologic findings similar to those of IPAH.⁶

PAH is increasingly recognized as a complication of chronic hemolytic anemias, particularly sickle cell disease; estimates of the prevalence of PAH in patients with sickle cell disease range from 10% to 30%.⁷ The pathophysiology of the development of PAH in patients with sickle cell disease is likely multifactorial, including a number of disparate mechanisms, such as asplenia, chronic thromboembolic disease, pulmonary parenchymal disease from repeated episodes of inflammation and scarring, vasculopathy associated with sickle cell disease, and a relative paucity of vasodilating substances, such as nitrous oxide with an abundance of vasconstricting agents, such as endothelin-1.

Pulmonary arterial hypertension with associated conditions shows histopathologic lesions identical to those of IPAH—arterial medial hypertrophy, intimal proliferation and fibrosis, necrotizing arteritis, and plexiform lesions. Superimposed organized thrombi may be seen, making the distinction between chronic thromboembolic pulmonary hypertension and other causes of IPAH occasionally difficult. It is the clinical scenario that defines these syndromes as distinct from IPAH and one another.

Manifestations of Disease

Imaging Techniques and Findings

Radiography

The various conditions associated with PAH show similar features on chest radiography- enlarged main and central pulmonary arteries, with rapid tapering of more peripheral vessels.¹ Right atrial and ventricular enlargement may be present. Patients with connective tissue disease–associated PAH may show evidence of fibrotic and/or inflammatory lung disease, although the latter is not invariably present.

Computed Tomography

Cross-sectional imaging studies show findings similar to those of patients with IPAH, including pulmonary arterial enlargement, right atrial and ventricular enlargement, and inhomogeneous lung opacity.¹ However, in patients with collagen vascular disease–associated PAH, fibrotic lung disease may be more readily visible on CT than chest radiography. Similarly, whereas chest radiography provides few clues to the hepatic cause in patients with portopulmonary PAH, cross-sectional imaging studies readily show features of cirrhosis in these patients. Imaging findings of PAH related to HIV are almost identical to those of IPAH and other causes of PAH.

Unlike many of the other conditions seen in patients with PAH, imaging studies in patients with PAH related to congenital systemic to pulmonary vascular shunts may show features that allow a specific diagnosis to be made. Furthermore, cross-sectional imaging studies may also provide methods that allow quantification of the degree of vascular shunting and thereby provide direction for treatment. The chronic increase in pulmonary flow causes the characteristic radiographic changes associated with pulmonary hypertension—increased size of the pulmonary trunk and central pulmonary arteries, diminished peripheral vessel caliber, and right ventricular chamber dilation. Often, the pulmonary arterial enlargement is striking, greater than that seen in other causes of PH (Fig. 99-6). It is important to note, however, that normal chamber size may represent increasing pulmonary pressures with progression toward Eisenmenger syndrome.

FIGURE 99-6 Frontal chest radiograph in a patient with a left to right intracardiac shunt shows massive enlargement of the central pulmonary arteries (arrows). Note the presence of pulmonary arterial calcification (arrowhead).

Thoracic CT may show calcification¹ and thrombus in the main pulmonary arteries resulting from high pressures and turbulent flow in the affected vessels. CT, particularly multislice CT pulmonary angiography, may also show abnormal vascular connections directly, such as atrial septal defects and patent ductus arteriosus. In the case of a patent ductus arteriosus, CT or MR imaging (Fig. 99-7) may reveal dilation of the patent ductus, possibly with aneurysm formation or mural calcification.

FIGURE 99-7 PH caused by congenital systemic to pulmonary shunt. This coronal three-dimensional MR angiography image shows patent ductus arteriosus (arrowheads).

Magnetic Resonance Imaging

MRI, in addition to revealing dilated pulmonary arteries and enlargement of the right ventricle, may also directly show abnormal atrial or ventricular connections, and abnormal intravascular or cardiac chamber signals, such as flow jets between vascular chambers of different pressure. Recently, time-resolved MRI techniques, in which a bolus of intravenous contrast is sequentially tracked through the vascular system, have been used to document successfully the anatomic derangements present in patients with systemic to pulmonary vascular shunts.

Definition

Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) were placed in separate groups in the Evian system (see Box 99-1), distinct from PAH. In the Venice-revised WHO system (see Box 99-2), PVOD and PCH were classified together as a subcategory of PAH in recognition of similarities in the clinical presentation, histopathologic features, and risk factors for disease of these two disorders. Such risk factors include use of anorexic medications, HIV infection, and scleroderma.⁶ PVOD and PCH also share similarities with PAH, including reports of a familial association, but there are important differences between PAH and PVOD-PCH, especially in regard to imaging findings and treatment. Therefore, PVOD and PCH are included as group 1 lesions in the Dana Point classification of PH, but in a subcategory separate from other causes of PAH (1′; see Box 99-4).

Etiology and Pathophysiology

Pulmonary veno-occlusive disease is an idiopathic condition but has been associated with factors such as pregnancy, medications (e.g., chemotherapeutic agents [bleomycin and carmustine] and oral contraceptives), toxic ingestion, systemic lupus erythematosus, some collagen vascular diseases, and bone marrow transplantation.¹¹ Mutations in the bone morphogenic protein receptor-2 have also been detected in patients with PVOD. Immunologic mechanisms and viral infections have also been implicated as potential causes.

The characteristic hemodynamic feature of PVOD is normal to low pulmonary capillary wedge pressures, with normal left atrial and ventricular function and pressures.¹¹ PVOD affects the venous bed in a patchy distribution, accounting for the variability in the wedge pressure.

Histopathologic specimens in patients with PVOD show fibrous obliteration of small pulmonary veins and venules.^11,12 Plexiform lesions are absent, but capillary proliferation may be seen, which suggests the presence of angiogenesis. Prior episodes of infarction and hemosiderosis may be encountered. Acute or recanalized thrombi may be present.

Manifestations of Disease

Imaging Techniques and Findings

Radiography

Chest radiography in patients with PVOD shows typical features of PH, but evidence of pulmonary edema is also often present (Fig. 99-8A), which is a distinguishing feature for PVOD compared with many other causes of PH.¹¹ Left atrial enlargement and redistribution of blood flow into the upper lobes are typically absent, allowing distinction from various causes of left-sided cardiac disease, particularly mitral stenosis.

FIGURE 99-8 Pulmonary arterial hypertension with significant venous or capillary involvement—pulmonary veno-occlusive disease. A, Frontal chest radiograph shows bilateral interstitial opacity and interlobular septal thickening suggestive of hydrostatic pulmonary edema. Note enlargement of the main pulmonary artery, suggesting elevated pulmonary pressures. B, Axial CT scan shows poorly defined areas of ground-glass opacity, some of which are vaguely centrilobular (arrows) in morphology. A few thickened interlobular septa were seen on other images. Unless interlobular septal thickening is pronounced, differentiation from other causes of pulmonary hypertension, especially pulmonary capillary hemangiomatosis (see Fig. 99-9), is difficult.

Computed Tomography

Thoracic CT and HRCT will show normal or small central pulmonary veins, patchy dependent ground-glass opacity, smoothly thickened interlobular septa (see Fig. 99-8B), and pleural effusions.^11,13 Ground-glass opacity centrilobular nodules may be seen.¹⁴ Mild lymphadenopathy may be present. Right-sided cardiac chambers are often enlarged, but the left atrium should not be enlarged. Multifocal air space opacities caused by pulmonary hemorrhage, air space edema, or venous infarction are uncommon. Inhomogeneous lung opacity consistent with mosaic perfusion may be present.

Nuclear Medicine and Angiography

V/Q scintigraphy in patients with PVOD will show patchy perfusion, most likely secondary to superimposed pulmonary arterial hypertension. Pulmonary angiography shows features of PH, including enlarged pulmonary arteries with peripheral pruning, but with delayed filling of the central pulmonary veins and a prolonged parenchymal enhancement phase.¹¹ These latter findings are secondary to the patchy obstruction of the venous system.

Definition

Pulmonary capillary hemangiomatosis (PCH) is an idiopathic disorder first recognized in 1978 and characterized by capillary proliferation within the alveolar walls. The widespread vascular obstruction, centered on the pulmonary alveolar capillaries, results in PH.

Etiology and Pathophysiology

Various causes have been suggested for PCH, including congenital factors, vascular neoplasia, and autoimmune disease, and as a response to PVOD. Similar to PVOD, PCH has been noted to occur in association with various other conditions, including systemic lupus erythematosus, Takayasu arteritis, scleroderma, Kartagener syndrome, and hypertrophic cardiomyopathy. Lung biopsies in patients with PCH typically show proliferation of circumscribed capillary channels within the walls of alveoli. Intervening lung tissue is often normal.¹¹ The capillary proliferation results in the appearance of densely cellular alveolar walls. The proliferating capillaries compress the walls of pulmonary veins and venules, producing intimal fibrosis and secondary venous occlusion. Progressive scarring with in situ thrombosis develops, with pulmonary infarcts occurring as a result of vascular obliteration. Compensatory muscular hypertrophy of pulmonary arteries results from the foregoing processes. Like PVOD, histopathologic specimens in patients with PCH show hemosiderosis, interstitial edema, dilation of the lymphatic system, and vascular intimal fibrosis, with arterial medial hypertrophy.

Manifestations of Disease

Imaging Techniques and Findings

Radiography

Chest radiographs in patients with PCH shows the usual findings of PH associated with bilateral, basilar reticular, and nodular opacities.¹¹ Unlike PVOD, interlobular septal thickening and pleural effusions are unusual and, when present, are usually less pronounced in patients with PCH compared with patients with PVOD. Enlargement of mediastinal lymph nodes has been reported in patients with PCH.

Computed Tomography

Thoracic CT shows enlargement of the main and central pulmonary arteries and right ventricle. Poorly defined centrilobular or lobular ground-glass opacities are also often present in patients with PCH (Fig. 99-9).¹¹ The presence of centrilobular ground-glass opacities tends to favor PCH, whereas smooth interlobular septal thickening and pleural effusions tend to favor the diagnosis of PVOD. Reports of interlobular septal thickening, pleural effusions, and lymphadenopathy in patients with PCH are noted, however, and ground-glass opacity centrilobular nodules may occur in patients with PVOD.¹⁴ Areas of mosaic perfusion reflecting oligemia may be present. Overall differentiation of PCH from PVOD by imaging is difficult.

FIGURE 99-9 Pulmonary arterial hypertension with significant venous or capillary involvement—pulmonary capillary hemangiomatosis. This axial CT scan shows numerous poorly defined centrilobular nodules (arrowheads). A few thickened interlobular septa are present, which makes differentiation from pulmonary veno-occlusive disease challenging.

Nuclear Medicine and Angiography

V/Q typically does not show findings that specifically suggest the diagnosis of PCH. V/Q scans are often abnormal in patients with PCH,¹¹ but may even be interpreted as normal. Pulmonary angiography in patients with PCH is often normal or only nonspecifically abnormal.

Definition

The most frequently encountered causes of PH with left heart disease, previously referred to as pulmonary venous hypertension in the Evian system and now referred to as pulmonary hypertension caused by left heart disease in the 2008 Dana Point classification of PH, include left ventricular systolic and diastolic dysfunction and valvular heart disease, such as aortic stenosis, aortic regurgitation, and mitral stenosis. An obstructing intra-atrial tumor or thrombus is an uncommon cause of elevated pulmonary arterial pressure.¹ In the case of patients with left-sided tumor or thrombus, the size of the obstructing lesion correlates with the degree of PH. Overall, left-sided cardiac disease, sometimes also referred to as nonpulmonary arterial pulmonary hypertension,⁷ is probably the most common cause of pulmonary hypertension.

Etiology and Pathophysiology

Secondary PH arises when increased venous pressure requires elevated arterial pressure to allow forward flow of blood. The histopathologic changes in the arterial system are therefore secondarily caused by the increased venous pressure. Histopathologic specimens from the venous system of patients with PH related to left heart disease show vascular medial hypertrophy, interstitial thickening and edema, hemosiderosis and, occasionally, venous infarction.¹ Typically, no significant gradient is seen between the elevated pulmonary arterial pressure and pulmonary capillary wedge pressure, and pulmonary vascular resistance is normal or near normal. Occasionally, in some patients, pulmonary arterial pressure rises disproportionately to left atrial pressure in patients with pulmonary hypertension caused by left heart disease, probably as a result of vascular remodeling and/or increased pulmonary vasomotor tone.

Manifestations of Disease

Imaging Techniques and Findings

Radiography

Chest radiographs and CT scans show the characteristic findings of pulmonary venous hypertension, including interlobular septal thickening (Kerley A and B lines), pleural effusion, and air space opacity representing alveolar edema (Fig. 99-10).

FIGURE 99-10 Pulmonary arterial hypertension with left heart disease—pulmonary edema. This frontal chest radiograph shows interstitial thickening and interlobular septal thickening.

Ultrasound

Echocardiography is the most common imaging method used for the evaluation of left-sided cardiac disease or suspected cardiac tumors. Echocardiography provides useful functional cardiac information, such as estimates of chamber volume and pressure and stroke volume. Echocardiography also has the ability to determine the degree of functional impairment caused by the size of a cardiac mass lesion, the degree of valvular dysfunction caused by the lesion, and the lesion’s mobility.

Computed Tomography

If pulmonary arterial hypertension has developed, the central pulmonary arteries will also be enlarged. In addition to the foregoing findings, mitral stenosis may result in ossified nodules within the pulmonary parenchyma. Atrial myxomas, if calcified, may be occasionally seen within the left atrium on chest radiographs. On contrast-enhanced thoracic CT (Fig. 99-11) or MRI scans, myxomas appear as filling defects within a cardiac chamber, most commonly the left atrium and often attached to the interatrial septum or anterior leaflet of the mitral valve.

FIGURE 99-11 Pulmonary arterial hypertension with left heart disease—left atrial myxoma. This axial CT scan shows a low attenuation filling defect (arrows) within the left atrium. The lesion attaches to the interatrial septum and prolapses through the mitral valve.

Magnetic Resonance Imaging

MRI also shows the location and morphology of cardiac masses, such as atrial myxomas, to advantage. MRI also provides valuable functional data analogous to that obtained with echocardiography. MRI is not limited by acoustic windows, unlike echocardiography, and provides a comprehensive anatomic and physiologic assessment of the heart and central cardiovascular system. Delayed enhancement techniques provide additional insight into the cause and prognosis of a number of left-sided lesions that could produce PH, in particular valvular disease, cardiomyopathy, and cor triatriatum.

Synopsis of Treatment Options

Definition

COPD includes several conditions—emphysema, chronic bronchitis, asthma, and bronchiectasis—that share the basic characteristic of poorly reversible air flow obstruction on forced expiration. Among causes of COPD, smoking-related conditions are most common. Ventilation-perfusion mismatching is the primary mechanism of hypoxemia in COPD, and regional alveolar hypoxia produces hypoxic vasoconstriction and increased resistance in the pulmonary arterial vasculature.

Interstitial lung diseases are a heterogeneous group of pulmonary disorders characterized by inflammatory and fibrotic destruction of the pulmonary parenchyma.

Prevalence and Epidemiology

The prevalence of pulmonary hypertension in patients with COPD is uncertain, but is related to disease severity.⁷ In most patients with COPD, pulmonary hypertension is mild (mean pulmonary arterial pressure [mPAP] < 35 mm Hg) and treatment is directed at the COPD itself rather than pulmonary hypertension. The onset of PH in the COPD patient is associated with a poor prognosis, with a 5-year survival of only 10% in patients with pulmonary artery pressures higher than 45 mm Hg.

PH is fairly common among patients with interstitial lung diseases, including those with idiopathic pulmonary fibrosis. The exact prevalence of PH in patients with idiopathic pulmonary fibrosis is uncertain, but has been estimated to be as high as 40% using echocardiographic assessment.⁷

Etiology and Pathophysiology

The PH that results from the aforementioned mechanisms that produce hypoxia is exacerbated by the alveolar capillary destruction that is also present in patients with COPD. Various biologic mechanisms influence the development of pulmonary hypertension in patients with COPD, and some researchers think that severe pulmonary hypertension may be a disorder that occasionally manifests in patients with COPD as much as it is a condition resulting from COPD.⁷

PH associated with interstitial lung diseases in part results from chronic hypoxemia. Fibrotic restriction of pulmonary vessels, limiting their distensibility, and reduction of the vascular surface area may also potentially play a role. In the case of connective tissue diseases, the development of PH may be related to immunologic mechanisms. Hypoxia-mediated pulmonary arteriolar vasoconstriction is present and is often associated with vascular inflammation. Eventually, pulmonary vascular remodeling occurs, and thrombotic angiopathy and perivascular fibrosis may be present in patients with PH and interstitial lung disease. In patients with idiopathic pulmonary fibrosis undergoing lung transplantation, explanted lungs often show thickening of the walls of pulmonary arteries and veins, with areas of vascular narrowing resulting from dense fibrosis. However, obliteration of small veins and venules may also be seen outside areas of dense fibrosis.

As with COPD, the degree of PH in patients with idiopathic pulmonary fibrosis is typically modest although, again like COPD, a small subset of patients with idiopathic pulmonary fibrosis may have more marked pulmonary arterial pressure elevations.⁷ The correlation between measurements of lung variables and severity of pulmonary hypertension is poor in patients with idiopathic pulmonary fibrosis, suggesting that there may be more to the development of PH than the mere degree of pulmonary fibrotic disease would predict.

The ability of thoracic CT to predict PH (mPAP > 25 mm Hg) in patients with idiopathic pulmonary fibrosis has been questioned. Considering a main pulmonary artery measurement of 29 mm or higher as abnormal, the sensitivity of this measurement for the detection of elevated pulmonary arterial pressure on right heart catheterization may exceed 85%,¹⁶ but at the expense of insufficient specificity and negative predictive value.^17,18

Sleep-disordered breathing is a term that includes a number of sleep-related breathing disorders, such as central sleep apnea, obstructive sleep apnea, and nocturnal desaturation (>10% of total time spent sleeping with arterial oxygenation <90%). The prevalence of sleep-disordered breathing may be as high as 4% in middle-aged men. Sleep-disordered breathing and other alveolar hypoventilation syndromes result in chronically depressed Po₂ and elevated Pco₂. The chronic hypoxemia produces pulmonary arterial vasoconstriction, vascular remodeling,³ and increased pulmonary arterial resistance, resulting in PH.

Manifestations of Disease

Definition

In the 2003 Venice PH classification (see Box 99-2), chronic thromboembolic pulmonary hypertension (CTEPH) included a heterogeneous group of disorders producing pulmonary arterial obstruction, such as chronic thromboemboli, foreign bodies, and tumors.⁶ However, it is now recognized that there are significant differences in the clinical presentation, imaging findings, and management of patients with chronic thromboembolic disease compared with patients with nonthrombotic pulmonary arterial embolic disease. Additionally, the Venice classification system (see Box 99-2) recognized two subgroups of CTEPH: (1) proximal disease, accessible to pulmonary thromboendarterectomy; and (2) distal disease, which is not accessible to surgical therapy. However, the distinction between proximal and distal chronic thromboembolic disease is not always clear and general agreement regarding what constitutes proximal and distal disease is lacking. Therefore, in the 2008 Dana Point PH classification, CTEPH is regarded as resulting from thromboemboli and has been maintained as a group 4 lesion, but nonthrombotic emboli are now considered group 5 lesions (PH with Unclear Multifactorial Etiologies; see Box 99-4). Additionally, the distinction of proximal and distal disease in the Venice PH classification (see Box 99-2) has been abandoned. From a radiologist’s viewpoint, however, it nevertheless remains useful to consider nonthrombotic emboli at the same sitting as CTEPH, because often nonthrombotic emboli will be encountered as pulmonary arterial filling defects during pulmonary CTA studies. Therefore, recognizing that nonthrombotic emboli are classified as group 5 lesions in the Dana Point PH classification system, particulate, tumor, and parasitic emboli will be discussed here.

Etiology and Pathophysiology

Thromboemboli have numerous sources, including the deep veins of the pelvis and thigh, the right atrium, indwelling catheters, or septic thromboemboli in patients with endocarditis involving the tricuspid or pulmonic valves.¹ Acute thromboembolic disease can produce transient pulmonary arterial pressure elevations, but sustained elevations are more likely a consequence of chronic thromboembolic disease, which may occur in up to 4% of patients with acute emboli.^6,7

Thromboemboli induce pulmonary arterial hypertension by occluding the pulmonary vascular bed. This process may occur through numerous repeated small thromboembolic episodes, a few large embolic episodes that fail to resolve completely, or the development of in situ thrombosis in small vessels and proximal migration of pulmonary arterial thrombosis, with secondary endothelial changes and cellular hyperplasia, vascular webs, and incomplete remodeling of thromboemboli.¹⁹ There are data to suggest that the latter mechanism plays some role in the development of CTEPH. The common event leading to the development of elevated pulmonary arterial pressures is cytokine-mediated pulmonary arterial scarring resulting from lysis of pulmonary thromboemboli.

Histopathologically, chronic emboli may organize, resulting in vascular channels interspersed with connective tissue. Fibrous bands and webs, representing organizing thrombi, are present,¹ often in association with fresh thromboemboli. The elevated pulmonary pressures also produce the characteristic histopathologic changes of medial hypertrophy and intimal proliferation and luminal obliteration, often in association with atherosclerosis. Plexogenic lesions are occasionally present in patients with chronic thromboembolic PH.⁷

Manifestations of Disease

Synopsis of Treatment Options

Surgical or Interventional Therapy

Surgical pulmonary thromboendarterectomy is an effective treatment for properly selected patients with CTEPH, and often provides significant immediate improvement in symptoms and pulmonary hemodynamics. However, surgical pulmonary thromboendarterectomy can be associated with significant morbidity and mortality, and another 10% to 15% of patients who undergo the procedure may fail to have substantial reductions in pulmonary vascular resistance.²³ In the hands of experienced surgeons, the mortality related to surgical pulmonary thromboendarterectomy is approximately 4% to 7%.²⁴ The best outcomes following surgical pulmonary thromboendarterectomy are seen with patients treated at centers with recognized experience in the surgical management of CTEPH, concordance between preoperative pulmonary vascular resistance and anatomic extent of disease, preoperative pulmonary vascular resistance less than 1000 to 1200, absence of a number of comorbid conditions (e.g., splenectomy) and a significant decrease in pulmonary vascular resistance following surgery. It has been suggested that a postoperative residual pulmonary vascular resistance of more than 500 dyn · s · cm⁻⁵ is associated with a mortality of just over 30% in patients undergoing surgical pulmonary thromboendarterectomy, whereas the mortality for these patients is less than 1% when the postoperative pulmonary vascular resistance falls below 500 dyn · s · cm⁻⁵ following surgery. Preoperative imaging assessment is essential for segregating those patients who stand a might benefit from surgical pulmonary thromboendarterectomy from those who will not. When visible central thromboemboli are present on multislice computed tomography pulmonary angiography (msCTPA) or catheter pulmonary angiography, it is more likely that patients will have improvements in pulmonary vascular resistance after pulmonary thromboendarterectomy. However, the amount of central thromboembolic material does not necessarily correlate with mPAP; some patients with central disease will not respond well to surgical pulmonary thromboendarterectomy, whereas others without central disease may have favorable results with surgery. The cause of this discrepancy is uncertain but suggests that factors other then mere vascular obstruction are involved in the development of chronic thromboembolic pulmonary hypertension.

Etiology and Pathophysiology

Nonthrombotic emboli may result from tumor emboli, parasitic embolization, or embolization of foreign material (e.g., mercury, talc) into the pulmonary arterial circulation, producing pulmonary hypertension.

Manifestations of Disease

Imaging Techniques and Findings

Radiography

Tumor Embolization

Chest radiographs in patients with intravascular tumor embolization are often normal. When abnormal, findings resembling those of pulmonary lymphangitic carcinomatosis are commonly seen.¹

Parasitic Embolization

Chest radiography in patients with parasitic embolization shows findings consistent with pulmonary arterial hypertension.¹ Small nodules, representing parasitic granulomas, may be seen. Pulmonary infarction is rarely seen as a result of parasitic embolization. Contrast-enhanced thoracic CT may show embolized organisms directly in the pulmonary arteries or right-sided cardiac chambers (Fig. 99-12). Thoracic CT or MRI can also show the presence, location, and morphology of cardiac or pericardial parasitic infection directly, as may occur with echinococcosis.

FIGURE 99-12 Pulmonary hypertension caused by chronic thromboembolic or embolic disease—parasitic emboli. This axial CT scan in a patient with echinococcosis shows low attenuation masses expanding the right lower lobe pulmonary artery (single arrow) and right atrium (double arrows).

Particulate Embolization

The chest radiographic findings of mercury embolization include fine, branching, symmetric nodules that result from intra-arterial mercury deposits. Metal deposits may also collect within the heart, particularly at the apex of the right ventricle.¹

Chest radiographs in patients with talc embolization show diffuse bilateral small nodular (2 to 3 mm) opacities throughout the lung parenchyma.¹ Perihilar conglomerate masses associated with fibrosis, producing retraction of lung parenchyma and relative hyperlucency in the lower lung, may be seen in some patients; these findings may resemble progressive massive fibrosis.

Computed Tomography

Tumor Embolization

In addition to the characteristic cross-sectional imaging findings of PH and thromboembolism noted, thoracic CT scans in patients with tumor emboli may reveal lymphadenopathy, findings consistent with lymphangitic carcinomatosis, and peripheral wedge-shaped opacities representing pulmonary infarction.¹ When emboli affect larger vessels, such as subsegmental pulmonary arteries, thoracic CT may reveal a beaded appearance of these vessels (Fig. 99-13). When smaller vessels are affected, such as at the centrilobular level, beading and nodularity may be observed, and the affected vessels may assume a branching configuration, resembling “tree in bud” opacity.

FIGURE 99-13 Pulmonary hypertension caused by chronic thromboembolic or embolic disease—tumor emboli. This axial CT scan in a patient with osteosarcoma shows expanded, bead-like right lower lobe pulmonary arteries (arrows), consistent with pulmonary arterial tumor embolization.

Parasitic Embolization

HRCT in patients with parasitic embolization may show nodules, interstitial prominence and thickening, and ground-glass opacity in combination with the classic findings of PH.¹

Particulate Embolization

Thoracic CT scans in patients with pulmonary talcosis often show numerous micronodules, with or without patchy ground-glass opacity. Upper lobe fibrotic opacities, resembling progressive massive fibrosis, may be present.¹ These fibrotic opacities may show high attenuation caused by the presence of talc.

Nuclear Medicine and Angiography

Tumor Embolization

V/Q scintigraphy may reveal subsegmental unmatched perfusion defects, indistinguishable from thromboembolic disease.¹ Pulmonary angiography may show a delayed arterial phase, intravascular filling defects, and peripheral pruning.

Definition

In the 2003 Venice-revised WHO classification of PH (see Box 99-2), a number of inflammatory and idiopathic causes that may be associated with PH were classified under the category “miscellaneous.” Included in this category are various conditions such as sarcoidosis, lymphangiomatosis, and extrinsic pulmonary venous compression. The latter may be caused by malignancy, such as mediastinal and hilar lymphadenopathy or tumor, but inflammatory causes, in particular fibrosing mediastinitis, may also elevate pulmonary pressures through pulmonary arterial and/or venous compression or obliteration. These conditions have been categorized as group 5 lesions in the 2008 Dana Point PH classification system (see Box 99-4). Other conditions that may be associated with PH, including hematologic abnormalities and metabolic abnormalities previously classified as group I lesions in the 2003 Venice system, as well as a number of systemic disorders, have been included in this group as well.⁶

The first subcategory of the group 5 2008 Dana Point classification of PH (see Box 99-4) includes hematologic conditions, such as myeloproliferative diseases, essential thrombocytosis, polycythemia vera, chronic myeloid leukemia, and splenectomy.⁶ Various mechanisms may result in PH in patients with these conditions, including congestive heart failure, high cardiac output, asplenia, or mechanical pulmonary arterial obstruction caused by circulating megakaryocytes. Several other systemic conditions in group 5 include sarcoidosis, Langerhans cell histiocytosis, lymphangioleiomyomatosis, pulmonary vasculitis, and neurofibromatosis. The mechanisms postulated to produce PH in patients with sarcoidosis include capillary bed destruction resulting from fibrosis, pulmonary artery and venous compression secondary to lymphadenopathy, and granulomatous inflammation directly involving the pulmonary vessels, especially the veins. PH in patients with end-stage Langerhans cell histiocytosis is common and may be related to a combination of pulmonary parenchymal destruction, hypoxemia, and vasculopathy. PH is relatively uncommon in patients with lymphangioleiomyomatosis but, when present, may be the result of hypoxemia caused by capillary destruction produced by the cystic lesions characteristic of this condition.

Also in group 5 of the 2008 Dana Point classification of PH (see Box 99-4) are a number of metabolic disorders, such as Gaucher disease, glycogen storage disease, and thyroid conditions such as hyper- and hypothyroidism.⁶ Various mechanisms for the development of PH in these conditions include hypoxemia, pulmonary parenchymal disease, portocaval shunts (in the case of type Ia glycogen storage disease), and capillary blockade by Gaucher cells. Precisely how thyroid disorders produce PH are unclear, but an association between autoimmune thyroid disease and PAH raises the possibility of a linked genetic pathogenesis.

The last subcategory of group 5 in the 2008 Dana Point classification (see Box 99-4) includes a number of disorders that produce mechanical obstruction of the pulmonary arteries and/or veins, including central obstructing tumors, metastatic microvascular obstruction, and fibrosing mediastinitis.⁶ Also included in this category is PH associated with end-stage renal disease in those on long-term hemodialysis. Tumor microvascular obstruction has been reviewed previously, and centrally obstructing tumors are usually readily apparent as a cause of symptoms suggesting PH. Fibrosing mediastinitis may present with suggestive thoracic imaging findings and will be discussed in detail in the next sections.

Fibrosing Mediastinitis

Manifestations of Disease

Clinical Presentation

Common symptoms in patients with FM depend on the structures most severely involved. Patients often present with nonspecific symptoms of pulmonary venous hypertension, including dyspnea and hemoptysis.¹ The treatment for FM is limited. If localized pulmonary venous involvement predominates, surgical treatment may be effective. Steroids have shown minor efficacy.

Imaging Techniques and Findings

Radiography

Chest radiography often shows widening of the mediastinum, with hilar prominence and calcified lymph nodes. Findings of pulmonary venous hypertension, including interlobular septal thickening and air space consolidation representing alveolar edema, may be present. FM may result in airway stenoses that present with lobar volume loss.¹

Computed Tomography

Thoracic CT will reveal extensive infiltration of the mediastinum with abnormal soft tissue. FM caused by Histoplasmosis capsulatum usually produces extensive lymph node calcification, readily identifiable by CT. Often, the abnormal mediastinal and hilar soft tissue resembles lymph nodes, and the diagnosis of FM may be mistaken for lymphadenopathy. Similarly, FM and chronic thromboembolic disease may superficially resemble one another. Contrast-enhanced CT in patients with FM may show extensive collateral vein formation resulting from fibrotic involvement of systemic thoracic veins, such as the superior vena cava or azygos vein. Pulmonary artery compression may also be directly visualized. Pulmonary venous infarcts, appearing as subpleural wedge-shaped consolidations may be seen in patients with pulmonary venous involvement.¹

Magnetic Resonance Imaging

On MRI scans, FM often manifests as homogeneous soft tissue with intermediate signal intensity on T1-weighted imaging, with variable signal on T2-weighted imaging. Both increased and decreased signal may be encountered simultaneously on T2-weighted imaging, with the decreased T2 signal probably related to calcification or fibrotic tissue, whereas the increased T1 signal is thought to be related to areas of active inflammation. Enhancement of the infiltrating mediastinal soft tissue, often rather heterogeneous, following gadolinium administration is typical.

Nuclear Medicine and Positron Emission Tomography

V/Q scintigraphy may show focal unmatched perfusion defects. Unilateral lack of perfusion of one lung has been reported in patients with FM.

Angiography

Catheter pulmonary angiography findings depend on the location of obstruction. If the arterial circulation is primarily affected, asymmetric narrowing of the pulmonary arteries will be present. When pulmonary veins are primarily affected, venous phase angiography will show stenoses, dilation, or obstruction in combination, often near the junction of the affected vein and the left atrium.¹

KEY POINTS

Pulmonary hypertension is classified according to the 2008 Dana Point classification system, which recognizes five major categories—pulmonary arterial hypertension, pulmonary hypertension secondary to left heart disease, pulmonary hypertension secondary to hypoxia and/or lung disease, chronic thromboembolic pulmonary hypertension, and pulmonary hypertension with unclear multifactorial mechanisms.

Pulmonary hypertension, regardless of cause, typically manifests on imaging as enlarged central pulmonary arteries with rapid tapering.

Imaging features specific to a particular diagnosis may be evident in selected cases.