(Radiographics. 2000;20:491-524.)
© RSNA, 2000
From the Archives of the AFIP
Pulmonary Vasculature: Hypertension and Infarction1 (CME available in print version and on RSNA Link)
Aletta Ann Frazier, MD,
Jeffrey R. Galvin, MD ,
Teri J. Franks, MD and
Melissa L. Rosado-de-Christenson, Col, USAF, MC
1 From the Departments of Radiologic Pathology (A.A.F., J.R.G., M.L.R.) and Pulmonary and Mediastinal Pathology (T.J.F.), Armed Forces Institute of Pathology, 6825 16th St NW, Bldg 54, Room M-121, Washington, DC, 20306-6000; the Department of Radiology, University of Maryland Medical System, Baltimore (J.R.G.); and the Department of Radiology and Nuclear Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD (M.L.R.). Received October 26, 1999; revisions requested November 24 and received December 28; accepted December 29. Address reprint requests to A.A.F. (e-mail: frazier@afip.osd.mil).
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Abstract
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Pulmonary hypertension is the hemodynamic consequence of vascular changes within the precapillary (arterial) or postcapillary (venous) pulmonary circulation. These changes may be idiopathic, as in primary pulmonary hypertension or pulmonary veno-occlusive disease, but more commonly they represent a secondary response to alterations in pulmonary blood flow. The pulmonary and systemic bronchial circulations form broad anastomoses that largely prevent infarction except in settings of markedly elevated pulmonary venous pressure, underlying malignancy, or excessive embolic burden. Causes of precapillary pulmonary hypertension include long-standing cardiac left-to-right shunt, chronic thromboembolic disease, and widespread pulmonary embolism arising from intravascular malignant cells, parasites, or foreign materials. The classic radiologic features of precapillary pulmonary hypertension are central arterial enlargement, sharply pruned peripheral vascularity, and right-sided heart hypertrophy and chamber dilatation. Postcapillary pulmonary hypertension may develop secondary to focal venous constriction or to compromised pulmonary venous drainage due to left atrial neoplasia, mitral stenosis, or left ventricular failure. Radiologic manifestations of postcapillary pulmonary hypertension include prominent septal lines, small pleural effusions, and occasionally air-space opacities. In addition, radiologic evaluation of postcapillary pulmonary hypertension may demonstrate evidence of pulmonary arterial hypertension, secondary to the retrograde transmission of elevated pulmonary venous pressure across the capillary bed.
Index Terms: Hypertension, pulmonary, 564.78, 565.78 • Pulmonary arteries, stenosis or obstruction, 564.78 • Pulmonary veins, stenosis or obstruction, 565.78
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Introduction
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The subject of pulmonary hypertension has undergone extensive investigation and reclassification by some of the most erudite pathologists of the 20th century. The radiology literature, however, rarely delves deeply into this complex topic and thus often limits radiologists' understanding of the causes, features, and distribution of hypertensive vascular changes within the pulmonary circulation. In accordance with the established approach of pathologists, pulmonary hypertension may be categorized as either precapillary (with changes limited to the arterial side of the pulmonary circulation) or postcapillary (with primary findings located within the pulmonary venous circulation, between the capillary bed and the left atrium). This article uses this simple framework to define and illustrate the underlying histopathologic characteristics, clinical features, and distinguishing radiologic manifestations of pre- and postcapillary pulmonary circulation.
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Anatomy of the Dual Pulmonary Circulation
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Two separate but vital vascular networks, often forming rich anastomoses, support the complex anatomy and physiology of the lung parenchyma. The primary pulmonary circulation comprises the entire venous return of the body, flowing forward from the main pulmonary artery, ramifying throughout the pulmonary interstitium and airways, and reconstituting itself into pulmonary veins before entering the left atrium. A second, "bronchial" circulation draws approximately 1% of the systemic cardiac output and transmits blood at six times the pressure of the pulmonary circulation (1). The pulmonary and bronchial circulations communicate with one another by several microvascular interconnections (2).
The large (500 to >1,000 µm in diameter) elastic pulmonary arteries travel along the lobar and segmental bronchi down to the subsegmental level and match the caliber of adjacent airways (Fig 1) (3–5). Their walls comprise multiple parallel elastic lamellae, smooth muscle cells, and collagen fibrils (6). Beyond the intrapulmonary cartilaginous bronchi, these vessels transition to muscular arteries (50–1,000 µm), which accompany subsegmental airways down to the level of the terminal bronchioles (Fig 1) (3,5,6). Medial smooth muscle fibers in the muscular arteries provide active vasodilation and constriction (4). As smooth muscularization progressively thins, these arteries become arterioles (15–150 µm), which proceed along the respiratory bronchioles and alveolar ducts to finally form a capillary network in the alveolar walls (Fig 1) (3–5). The venules accept flow from these capillary beds and unite to form pulmonary veins, which course within interlobular fibrous septa, apart from the airways (Fig 1). Two veins from each hilum drain into the left atrium (3–6).
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Figure 1. Cross-sectional drawings depict normal pulmonary vascular anatomy. Arterial vessels are located adjacent to a schematic airway (A). The walls of elastic arteries (a) contain multiple parallel elastic lamellae, smooth muscle cells, and collagen fibrils. The muscular arteries (b) contain a media of smooth muscle fibers, bordered by distinct internal and external elastic laminae. Arterioles (c) are distinguished by the absence of a distinct external elastic lamina. Veins (d) are identified by their septal location (S) and a media of loosely organized smooth muscle fibers.
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The bronchial circulation arises from the thoracic aorta or intercostal arteries to supply the esophagus, trachea, visceral pleura, lymph nodes, extra- and intrapulmonary airways, bronchovascular and neural bundles, and vasa vasora of the pulmonary circulation (Fig 2) (2,4). Each lung is typically supplied by two bronchial vessels that impart several branches to the extrapulmonary mediastinal structures en route to the pulmonary hila, where they enter the peribronchial sheath of each mainstem airway. The bronchial arteries then form a dual-layered adventitial and submucosal plexus along the airways that communicates freely across airway muscular walls and nourishes the bronchial tree down to the terminal bronchioles (2,4,6). Unlike the pulmonary arteries, bronchial arteries are notably smaller than their adjacent airways and follow more tortuous paths (4).
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Figure 2. Schematic illustrates how the bronchial arteries (ba) supply the visceral pleura, airways, vasa vasora of pulmonary arteries, lymph nodes, and bronchovascular and neural bundles. Extrapulmonary bronchial veins (ev) drain to the right side of the heart, and intrapulmonary veins (iv) anastomose with pulmonary arteries and return to the left side of the heart.
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Anastomoses between the bronchial and pulmonary arteries occur not only along the bronchioles but also beyond the pulmonary lobule, where the bronchial microvasculature broadly interconnects with the pulmonary arterial circulation via alveolar capillary beds (2). Anastomoses also exist between precapillary-sized bronchial arteries (in the pleura and bronchial walls) and pulmonary veins (2). In addition, the bronchial venous drainage located in the peripheral lung forms broad venous networks that communicate extensively with the pulmonary veins and ultimately drain into the left side of the heart, creating the so-called bronchial systemic-to-pulmonary flow (2,4). The bronchial circulation responds to decreased pulmonary flow and ischemia with enlargement, hypertrophy, and focal proliferation across these meshlike anastomotic channels (Fig 3) (2,7). Bronchial blood flow has been shown to increase by 300% in the weeks following pulmonary artery embolization (8).
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Figure 3. Contrast material-enhanced chest computed tomographic (CT) scan (mediastinal window) of a patient with corrected transposition demonstrates thrombosis of the right pulmonary artery (*) secondary to slow flow. There is compensatory enlargement and tortuosity of bronchial arteries within the mediastinum and along central airways (arrows).
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Despite the protective effect of the bronchial circulation, pulmonary infarction does occur. It is less likely to develop in cases of central pulmonary arterial occlusion, in which massive bronchial collateral flow is easily accommodated by the pulmonary arterial circuit (2,9–11). The likelihood of infarction increases when a more distal medium- or small-sized (approximately 3 mm or less) artery is obstructed and the high-pressure collateral bronchial influx must be accommodated within a smaller intravascular volume (Fig 4). This reperfusion by the bronchial circulation, combined with locally increased vascular permeability due to tissue ischemia and capillary endothelial injury, causes the intraalveolar extravasation of blood cells. This creates a confined region of pulmonary hemorrhage (Fig 5a) (2,10–13). Within this area, the underlying tissue architecture is preserved and usually restored to a normal state once blood cells are resorbed (11). Nevertheless, localized pulmonary hemorrhage tends to progress to infarction in settings of underlying malignancy, high embolic burden, diminished bronchial flow (due to shock, hypotension, or impaired circulation in chronic disease), vasodilator use, or elevated pulmonary venous pressure, and interstitial edema (typically due to heart failure) (2,9–12,14). Heart failure is generally considered the single most important predisposing condition in the development of pulmonary infarction (10).
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Figure 4. Schematics show the anastomosis of a bronchial artery (b) and pulmonary arteriole (p) at an alveolar capillary loop (9). Normal (nl) antegrade flow in both vessels is shown in A. Occlusion of the pulmonary arteriole by thrombus, with recruitment of bronchial flow and consequent extravasation of blood cells into alveoli (arrows), is seen in B. Elevated postcapillary pulmonary pressure (P), combined with arterial occlusion, causes more significant intraalveolar hemorrhage (arrows), as illustrated in C. This higher degree of hemorrhage predisposes the patient to infarction.
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Figure 5a. Pulmonary hemorrhage and infarction. (a) Photograph of a gross specimen with pleural-based pulmonary hemorrhage shows thrombosis of the feeding vessel (arrow) and preservation of the underlying lung architecture. Scale is in millimeters. (b) Low-power photomicrograph (original magnification, x4; hematoxylin-eosin [H-E] stain) of a subpleural pulmonary infarct shows the triangular area of coagulation necrosis (*) surrounded by hemorrhage (arrows). (c) Photograph of a gross specimen with a wedge-shaped pulmonary infarct shows necrotic destruction of the affected parenchyma, surrounded by inflammatory infiltrates (solid arrows) and a rim of reactive hyperemia from bronchial arterial collateral flow (open arrows). (Fig 5a and 5c reprinted, with permission, from reference 13.)
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Figure 5b. Pulmonary hemorrhage and infarction. (a) Photograph of a gross specimen with pleural-based pulmonary hemorrhage shows thrombosis of the feeding vessel (arrow) and preservation of the underlying lung architecture. Scale is in millimeters. (b) Low-power photomicrograph (original magnification, x4; hematoxylin-eosin [H-E] stain) of a subpleural pulmonary infarct shows the triangular area of coagulation necrosis (*) surrounded by hemorrhage (arrows). (c) Photograph of a gross specimen with a wedge-shaped pulmonary infarct shows necrotic destruction of the affected parenchyma, surrounded by inflammatory infiltrates (solid arrows) and a rim of reactive hyperemia from bronchial arterial collateral flow (open arrows). (Fig 5a and 5c reprinted, with permission, from reference 13.)
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Figure 5c. Pulmonary hemorrhage and infarction. (a) Photograph of a gross specimen with pleural-based pulmonary hemorrhage shows thrombosis of the feeding vessel (arrow) and preservation of the underlying lung architecture. Scale is in millimeters. (b) Low-power photomicrograph (original magnification, x4; hematoxylin-eosin [H-E] stain) of a subpleural pulmonary infarct shows the triangular area of coagulation necrosis (*) surrounded by hemorrhage (arrows). (c) Photograph of a gross specimen with a wedge-shaped pulmonary infarct shows necrotic destruction of the affected parenchyma, surrounded by inflammatory infiltrates (solid arrows) and a rim of reactive hyperemia from bronchial arterial collateral flow (open arrows). (Fig 5a and 5c reprinted, with permission, from reference 13.)
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Once pulmonary hemorrhage evolves into infarction, the alveolar walls, bronchi, and vessels undergo ischemic coagulative necrosis (Fig 5b). Faint, ghostlike structures of lung tissue may remain evident at histologic examination (11,13). The outer perimeter of an infarct accumulates erythrocytes, neutrophils, and histiocytes deposited by the adjacent bronchial circulation (11,15). At gross inspection, a recent lung infarct consists of dark, necrotic material surrounded by a narrow rim of hyperemia and inflammation (Fig 5c). Septic emboli are associated with cavitation of an infarct, which may simulate or produce a lung abscess (7,11,15). Vascular fibrous tissue eventually replaces the infarction in ensuing weeks, folding into a collagenous platelike mass that produces pleural retraction (11,15).
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Pulmonary Hypertension: Definition and Causes
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Pulmonary hypertension is hemodynamically defined as a mean pulmonary artery pressure greater than 25 mm Hg at rest or greater than 30 mm Hg during exercise, with increased pulmonary vascular resistance (16). The diagnosis is made with clinical assessment of hemodynamic parameters, medical history, and histologic findings (3). Both precapillary (arterial) and postcapillary (venous) pulmonary hypertension are regarded as secondary when a cause is established (Fig 6). Causes of precapillary pulmonary hypertension include congenital cardiac left-to-right shunt; thromboembolic disease; tumor embolism; embolization of parasites, talc crystals, and other foreign materials; chronic alveolar hypoxia; and chronic interstitial lung disease (3,5,17). Primary pulmonary hypertension (PPH) is an idiopathic condition at the precapillary level that occurs in the absence of an embolic source or any other identifiable cause such as cardiac shunt, toxic insult, or interstitial lung disease (Fig 6) (16). Postcapillary lesions producing pulmonary venous hypertension include mediastinal fibrosis (which may also affect the precapillary vessels); an obstructive left atrial mass; mitral valve stenosis; left ventricular failure; and, rarely, invasive neoplasm, congenital venous stenosis, or anomalous pulmonary venous connections (3,17). The postcapillary counterpart to PPH is pulmonary veno-occlusive disease (PVOD), a rare idiopathic condition that diffusely affects the postcapillary pulmonary circulation (Fig 6) (16).
The vascular changes of precapillary (arterial) pulmonary hypertension include intimal cellular proliferation and medial smooth muscle hypertrophy, chiefly in the walls of muscular arteries (Figs 7, 8a, 8b) (3,4,16). Necrotizing arteritis and plexiform lesions are additional histologic features that are exclusively found in PPH and in pulmonary hypertension caused by a congenital cardiac shunt (Figs 7, 8c, 8d) (3,16). A plexiform lesion is the hallmark of sustained and irreversible pulmonary arterial hypertension and is defined as focal disruption of the internal elastic lamina of a muscular pulmonary artery by a "glomeruloid" plexus of endothelial channels, which proceed to ramify into alveolar septal capillaries (3,6,16). The complications of sustained pulmonary hypertension include central arterial thrombosis, premature atherosclerosis of central elastic and muscular pulmonary arteries, aneurysmal dissection of pulmonary arteries, and hypertrophy and dilatation of the right side of the heart (Fig 9) (4,5,18–20).
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Figure 7. Schematics demonstrate the vascular changes of pulmonary arterial hypertension. In cross-section A, medial hypertrophy produces marked thickening of the medial smooth muscle in between internal and external elastic laminae. In cross-section B, intimal proliferation thickens the intima in concentric layers. In cross-section C, a plexiform lesion is characterized by intimal proliferation and interruption of the media by a "glomeruloid" proliferation of small vascular channels.
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Figure 8a. Microscopic features of pulmonary arterial hypertension. (a) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a muscular artery shows medial hypertrophy of the vessel wall (arrows). (b) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a muscular artery shows intimal proliferation (arrow). (c) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a plexiform lesion in a muscular artery shows intimal proliferation with aneurysmal disruption of the wall (*) by proliferative vascular channels (arrows). (d) Medium-power photomicrograph (original magnification, x10; H-E stain) of a muscular artery shows a plexiform lesion, identified by the glomeruloid proliferation (curved arrow) and dilatation (straight arrows) of vascular channels.
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Figure 8b. Microscopic features of pulmonary arterial hypertension. (a) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a muscular artery shows medial hypertrophy of the vessel wall (arrows). (b) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a muscular artery shows intimal proliferation (arrow). (c) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a plexiform lesion in a muscular artery shows intimal proliferation with aneurysmal disruption of the wall (*) by proliferative vascular channels (arrows). (d) Medium-power photomicrograph (original magnification, x10; H-E stain) of a muscular artery shows a plexiform lesion, identified by the glomeruloid proliferation (curved arrow) and dilatation (straight arrows) of vascular channels.
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Figure 8c. Microscopic features of pulmonary arterial hypertension. (a) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a muscular artery shows medial hypertrophy of the vessel wall (arrows). (b) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a muscular artery shows intimal proliferation (arrow). (c) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a plexiform lesion in a muscular artery shows intimal proliferation with aneurysmal disruption of the wall (*) by proliferative vascular channels (arrows). (d) Medium-power photomicrograph (original magnification, x10; H-E stain) of a muscular artery shows a plexiform lesion, identified by the glomeruloid proliferation (curved arrow) and dilatation (straight arrows) of vascular channels.
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Figure 8d. Microscopic features of pulmonary arterial hypertension. (a) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a muscular artery shows medial hypertrophy of the vessel wall (arrows). (b) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a muscular artery shows intimal proliferation (arrow). (c) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a plexiform lesion in a muscular artery shows intimal proliferation with aneurysmal disruption of the wall (*) by proliferative vascular channels (arrows). (d) Medium-power photomicrograph (original magnification, x10; H-E stain) of a muscular artery shows a plexiform lesion, identified by the glomeruloid proliferation (curved arrow) and dilatation (straight arrows) of vascular channels.
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Figure 9a. Complications of pulmonary arterial hypertension. (a) Photograph of a sagittal cut section of the right pulmonary hilum shows golden atherosclerotic plaques (arrows) and thrombosis (*) within the central arteries. (b) Photograph of an opened central pulmonary artery reveals pale tan intimal atherosclerotic plaques (arrows). Scale is in centimeters. (c) Photograph of the heart (coronal cut section) shows marked right ventricular hypertrophy (arrow), in this case accompanied by left ventricular hypertrophy (*).
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Figure 9b. Complications of pulmonary arterial hypertension. (a) Photograph of a sagittal cut section of the right pulmonary hilum shows golden atherosclerotic plaques (arrows) and thrombosis (*) within the central arteries. (b) Photograph of an opened central pulmonary artery reveals pale tan intimal atherosclerotic plaques (arrows). Scale is in centimeters. (c) Photograph of the heart (coronal cut section) shows marked right ventricular hypertrophy (arrow), in this case accompanied by left ventricular hypertrophy (*).
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Figure 9c. Complications of pulmonary arterial hypertension. (a) Photograph of a sagittal cut section of the right pulmonary hilum shows golden atherosclerotic plaques (arrows) and thrombosis (*) within the central arteries. (b) Photograph of an opened central pulmonary artery reveals pale tan intimal atherosclerotic plaques (arrows). Scale is in centimeters. (c) Photograph of the heart (coronal cut section) shows marked right ventricular hypertrophy (arrow), in this case accompanied by left ventricular hypertrophy (*).
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The characteristic histologic changes of postcapillary (venous) pulmonary hypertension are venous medial hypertrophy and intimal proliferation, with marked prominence of the venous internal elastic lamina (Fig 10a). Secondary changes include capillary congestion, with adjacent vascular proliferation, and interlobular septal edema and fibrosis (Figs 10a, 10b) (3,21–23). Paraseptal venous infarcts may occur adjacent to complete venous occlusion, particularly when markedly elevated pulmonary venous pressure is present (Fig 10c) (22,24,25).
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Figure 10a. Microscopic features of pulmonary venous hypertension. (a) Low-power photomicrograph (original magnification, x4; H-E stain) shows a dilated vein (*) surrounded by a collar of fibrosis within a thickened interlobular septum (arrows). (b) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) demonstrates marked capillary congestion and proliferation (arrows). (c) Low-power photomicrograph (original magnification, x4; H-E stain) shows a venous infarct (*) within the interlobular septum, secondary to pulmonary venous obstruction.
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Figure 10b. Microscopic features of pulmonary venous hypertension. (a) Low-power photomicrograph (original magnification, x4; H-E stain) shows a dilated vein (*) surrounded by a collar of fibrosis within a thickened interlobular septum (arrows). (b) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) demonstrates marked capillary congestion and proliferation (arrows). (c) Low-power photomicrograph (original magnification, x4; H-E stain) shows a venous infarct (*) within the interlobular septum, secondary to pulmonary venous obstruction.
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Figure 10c. Microscopic features of pulmonary venous hypertension. (a) Low-power photomicrograph (original magnification, x4; H-E stain) shows a dilated vein (*) surrounded by a collar of fibrosis within a thickened interlobular septum (arrows). (b) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) demonstrates marked capillary congestion and proliferation (arrows). (c) Low-power photomicrograph (original magnification, x4; H-E stain) shows a venous infarct (*) within the interlobular septum, secondary to pulmonary venous obstruction.
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Precapillary Pulmonary Hypertension
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Primary Pulmonary Hypertension
Clinical Characteristics, Histopathologic Features, and Treatment.—The first English description of PPH appears in the medical literature of 1909, when Sanders reported the perplexing autopsy findings of a previously healthy young man with "enormous hypertrophy and dilatation of the right ventricle" accompanied by "primary pulmonary arteriosclerosis" in the "smaller and middle-sized branches" of the lung vasculature (26). PPH remains an enigmatic condition that creates a hemodynamic pattern of elevated right atrial and mean pulmonary arterial pressures, normal pulmonary-capillary wedge pressures, and decreased cardiac output (27).
Patients with PPH present with progressive dyspnea (60% of cases), fatigue, angina, syncope, cor pulmonale, and Raynaud phenomenon (27,28). Women are affected three times as often as men, and onset is typically in youth or middle age (29). Patients with portal hypertension (with or without liver disease), collagen vascular disease, human immunodeficiency virus infection, or a history of aminorex fumarate (an appetite suppressant) ingestion have an increased risk of developing PPH, although no direct causal link has been established (3,16,22,27). Pregnant or postpartum patients and those using oral contraceptives may also be at increased risk (3). The majority of patients succumb 2–5 years following diagnosis, but prolonged survivals of up to 18 years may occur (3,27,30,31). Therapeutic agents include vasodilators, calcium channel blockers, anticoagulants, and diuretics to counteract the unfavorable hemodynamics (27,32,33). Lung or combined heartlung transplantation may be performed according to organ availability and the patient's clinical status (27).
Scientific evidence supports endothelial injury and vasoconstriction of small pulmonary arteries and arterioles as the inciting mechanisms of PPH. A relentless proliferative and obliterative response ensues throughout the pulmonary vascular bed (16,34). Humoral, genetic, exogenous toxic, and autoimmune factors have all been implicated in this fatal cascade (16). The histologic features of PPH include medial hypertrophy and intimal proliferation of small precapillary pulmonary vessels, necrotizing arteritis with segmental destruction of arterial walls, and plexiform lesions (3). Although plexiform lesions are found in approximately 75% of all cases of PPH, it is interesting to note that the simple quantitation of plexiform lesions does not directly correlate with patient survival or pulmonary artery pressures (3,16).
Acute and organizing thrombi are noted in over 50% of cases of PPH, and the role of thrombosis in both primary and secondary pulmonary arterial hypertension remains controversial (3,33). Organizing thrombi often demonstrate histologic features similar to those of plexiform lesions, but thrombi are distinguished by the presence of an intact intima and elastic laminae (3,16). When in situ recanalized thrombi of the smaller, more peripheral pulmonary arteries are identified in PPH (without coexistent plexiform lesions), the term thrombotic PPH is applied by some authors (3,16). Both clinically and histologically, it may be difficult to distinguish between secondary and in situ thrombosis of peripheral vessels in PPH, and the thromboembolic forms of secondary pulmonary hypertension discussed below (3,11,19,32).
Radiologic Features.—The definitive diagnosis of PPH is often delayed because of its insidious clinical onset and minimal early radiographic findings (Fig 11a). Advanced disease produces prominent central pulmonary arteries, sharply tapering peripheral vessels, and right ventricular enlargement (Figs 11b, 12a, 12b) (28,31). Several patterns of pulmonary vascularity are recognized in both primary and secondary pulmonary arterial hypertension, although affected vessels may be beyond radiographic resolution (31). There may be oligemia and rapidly tapering vessels or overcirculation and vascular distension (31,35,36). In patients with PPH, the right descending pulmonary artery has a mean width of 25 mm at chest radiography (37).
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Figure 11a. Progression of PPH. (a) Frontal chest radiograph of a 34-year-old man who presented with mild symptoms of dyspnea and fatigue shows minimal prominence of the main pulmonary artery. (b) On a chest radiograph obtained 10 years later, when the patient returned with severe dyspnea and elevated right ventricular pressure (120 mm Hg), marked enlargement of the main pulmonary artery and hilar vessels is seen.
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Figure 11b. Progression of PPH. (a) Frontal chest radiograph of a 34-year-old man who presented with mild symptoms of dyspnea and fatigue shows minimal prominence of the main pulmonary artery. (b) On a chest radiograph obtained 10 years later, when the patient returned with severe dyspnea and elevated right ventricular pressure (120 mm Hg), marked enlargement of the main pulmonary artery and hilar vessels is seen.
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Figure 12a. PPH in a young adult woman. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show an enlarged pulmonary trunk and right ventricular dilatation. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates a widened pulmonary trunk. (d) Contrast-enhanced chest CT scan (mediastinal window) obtained at a lower level shows right ventricular dilatation and thickening of the free right ventricular wall (arrow). (e) Chest CT scan (lung window) shows large-caliber central pulmonary arteries (arrows) with abrupt tapering of the peripheral vessels (arrowheads).
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Figure 12b. PPH in a young adult woman. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show an enlarged pulmonary trunk and right ventricular dilatation. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates a widened pulmonary trunk. (d) Contrast-enhanced chest CT scan (mediastinal window) obtained at a lower level shows right ventricular dilatation and thickening of the free right ventricular wall (arrow). (e) Chest CT scan (lung window) shows large-caliber central pulmonary arteries (arrows) with abrupt tapering of the peripheral vessels (arrowheads).
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Figure 12c. PPH in a young adult woman. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show an enlarged pulmonary trunk and right ventricular dilatation. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates a widened pulmonary trunk. (d) Contrast-enhanced chest CT scan (mediastinal window) obtained at a lower level shows right ventricular dilatation and thickening of the free right ventricular wall (arrow). (e) Chest CT scan (lung window) shows large-caliber central pulmonary arteries (arrows) with abrupt tapering of the peripheral vessels (arrowheads).
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Figure 12d. PPH in a young adult woman. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show an enlarged pulmonary trunk and right ventricular dilatation. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates a widened pulmonary trunk. (d) Contrast-enhanced chest CT scan (mediastinal window) obtained at a lower level shows right ventricular dilatation and thickening of the free right ventricular wall (arrow). (e) Chest CT scan (lung window) shows large-caliber central pulmonary arteries (arrows) with abrupt tapering of the peripheral vessels (arrowheads).
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Figure 12e. PPH in a young adult woman. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show an enlarged pulmonary trunk and right ventricular dilatation. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates a widened pulmonary trunk. (d) Contrast-enhanced chest CT scan (mediastinal window) obtained at a lower level shows right ventricular dilatation and thickening of the free right ventricular wall (arrow). (e) Chest CT scan (lung window) shows large-caliber central pulmonary arteries (arrows) with abrupt tapering of the peripheral vessels (arrowheads).
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CT demonstrates the vascular and cardiac changes of both primary and secondary pulmonary hypertension, including right ventricular hypertrophy, enlargement of central pulmonary arteries, and abruptly diminished caliber of peripheral pulmonary vessels (Figs 12c–12e). The CT-determined diameter of the main pulmonary artery is measured in the scan plane of the bifurcation, at a right angle to its long axis and just lateral to the ascending aorta (38). A CT-determined mean pulmonary artery diameter of greater than or equal to 29 mm demonstrates 87% sensitivity and 89% specificity for predicting pulmonary hypertension. Specificity climbs to 100% when a mean pulmonary artery diameter of greater than or equal to 29 mm is accompanied by findings of a segmental artery-to-bronchus ratio greater than 1:1 in three of four pulmonary lobes (39). When the ratio of CT-determined pulmonary artery diameter to aortic diameter is greater than one (rPA > 1), a strong correlation with elevated mean pulmonary artery pressure has been shown, particularly in patients less than 50 years of age (40). On high-resolution CT scans, both primary and secondary forms of pulmonary hypertension may produce a mosaic pattern of lung attenuation, a finding suggestive of regional variations in parenchymal perfusion (41,42). A vascular cause for the mosaic pattern is suggested when areas of high attenuation contain larger caliber vessels and areas of low attenuation contain vessels of diminished size (42–45).
Radionuclide ventilation-perfusion scans in PPH are typically read as normal or low probability for pulmonary embolism (Fig 13) (43,46–48). Many secondary causes of pulmonary arterial hypertension may produce similar scintigraphic findings. One notable exception is acute or chronic thromboembolic disease, which typically produces a high-probability lung (46). Arteriography in PPH demonstrates symmetrically enlarged central arteries, a diffuse pattern of abruptly tapering and pruned subsegmental vessels, filamentous or "corkscrew" peripheral arteries, and occasionally subpleural collateral vessels (Figs 14, 15) (31,49,50).
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Figure 13. PPH in a young adult man. Lung perfusion scans (anterior view, left; posterior view, right) demonstrate multiple, bilateral subsegmental perfusion defects. Such a nonspecific pattern is also seen with many secondary causes of precapillary pulmonary hypertension.
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In general, magnetic resonance (MR) imaging of patients with pulmonary hypertension shows the characteristic anatomic changes of right ventricular hypertrophy, reversal of septal curvature, and dilatation of pulmonary arteries (51). A direct relationship between MR imaging–determined pulmonary artery diameter and the hemodynamic measure of pulmonary artery pressure has not been established. However, there is a direct linear correlation between mean pulmonary arterial pressure (PAP) and the ratio of mean pulmonary artery (MPA) caliber to descending aorta (AO) caliber (ie, MPA/AO) when measured on electrocardiographically gated spin-echo MR images (37,39,52,53). Further observations include abnormal intravascular signal corresponding to slow pulmonary arterial blood flow on gated spin-echo MR images in 92% of all cases of pulmonary arterial hypertension, notably with a direct relationship to elevated pulmonary vascular resistance (51).
Congenital Heart Disease
Clinical Characteristics, Histopathologic Features, and Treatment.—Precapillary pulmonary hypertension may develop from a sustained congenital left-to-right cardiac shunt (4). Patients with transposition of the great vessels are also predisposed to early onset of pulmonary arterial hypertension (4,5). Although some authors have contended that the severity of pulmonary hypertension varies according to patient age and location of the intracardiac defect, a recent large study based on data gathered at the National Institutes of Health has shown that pulmonary vascular changes secondary to congenital heart disease correspond only to the level of pulmonary arterial pressure (4,6). The pulmonary circulation in adult patients with congenital heart disease and secondary pulmonary hypertension has shown adaptive anastomotic pathways that connect pulmonary arterial vessels (containing plexiform lesions) to the bronchial arteries located within terminal bronchioles and the vasa vasora of pulmonary arteries (54).
In the current era of medical care, congenital cardiac lesions that may eventually cause pulmonary hypertension are now often detected and repaired at an early age, before marked vascular changes ensue (Burke AP, written communication, December 1999). In unusual cases in which severe pulmonary hypertension is suspected on the basis of clinical and hemodynamic findings, lung biopsy may be performed to determine operability and prognosis by assessing the potential reversibility of pulmonary hypertension after corrective surgery (3,15). The pathologic findings are graded on a spectrum of severity according to the Heath and Edwards system (22). Grades I and II represent mild, potentially reversible disease and are characterized by medial hypertrophy, intimal proliferation, and the abnormal muscularization of the pulmonary arterioles (5,22). The presence of intimal laminar fibrosis and progressive vessel obliteration represents grade III disease, which is considered borderline for reversibility. The more severe grades IV, V, and VI are largely irreversible and are characterized by plexiform lesions, aneurysmal muscular arteries ("dilatation lesions"), and sites of necrotizing arteritis (3,5,22).
Radiologic Features.—The radiographic features of pulmonary hypertension caused by a chronic shunt physiology include the familiar complex of a prominent pulmonary trunk and central pulmonary arteries in concert with sharply diminished peripheral pulmonary vascularity (Fig 16a, 16b) (6,55). Although the right ventricle and atrium typically enlarge in proportion to the volume overload, a normal-sized cardiac silhouette may actually reflect diminished intracardiac shunting due to a markedly elevated pulmonary vascular resistance (55). Linear calcification and thrombus may be evident in the central pulmonary arteries at CT (Fig 16c–16e) (6,55). In cases of a patent ductus arteriosus, mural calcification or aneurysmal dilatation of the ductus may be identified (6). In some cases, significant cardiac volume overload may eventually produce superimposed findings of secondary pulmonary venous hypertension (55). MR imaging may reveal enlargement of the main pulmonary artery, cardiac chamber dilatation, septal defects, right ventricular hypertrophy, and abnormal intravascular signal in the central pulmonary arteries (Fig 17) (51).
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Figure 16a. Pulmonary arterial hypertension in a 39-year-old woman with atrial septal defect. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show enlargement of the pulmonary trunk and hilar vessels and a prominent right ventricle. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates marked enlargement of the central pulmonary arteries, which contain extensive thrombus and calcified atherosclerotic plaques. (d) Radiograph of the right lung specimen reveals linear calcific deposits compatible with advanced atherosclerosis of the central pulmonary arteries. (e) Low-power photomicrograph (original magnification, x4; Movat pentachrome elastic stain) of a large elastic pulmonary artery shows organizing intraluminal thrombus (*).
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Figure 16b. Pulmonary arterial hypertension in a 39-year-old woman with atrial septal defect. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show enlargement of the pulmonary trunk and hilar vessels and a prominent right ventricle. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates marked enlargement of the central pulmonary arteries, which contain extensive thrombus and calcified atherosclerotic plaques. (d) Radiograph of the right lung specimen reveals linear calcific deposits compatible with advanced atherosclerosis of the central pulmonary arteries. (e) Low-power photomicrograph (original magnification, x4; Movat pentachrome elastic stain) of a large elastic pulmonary artery shows organizing intraluminal thrombus (*).
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Figure 16c. Pulmonary arterial hypertension in a 39-year-old woman with atrial septal defect. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show enlargement of the pulmonary trunk and hilar vessels and a prominent right ventricle. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates marked enlargement of the central pulmonary arteries, which contain extensive thrombus and calcified atherosclerotic plaques. (d) Radiograph of the right lung specimen reveals linear calcific deposits compatible with advanced atherosclerosis of the central pulmonary arteries. (e) Low-power photomicrograph (original magnification, x4; Movat pentachrome elastic stain) of a large elastic pulmonary artery shows organizing intraluminal thrombus (*).
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Figure 16d. Pulmonary arterial hypertension in a 39-year-old woman with atrial septal defect. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show enlargement of the pulmonary trunk and hilar vessels and a prominent right ventricle. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates marked enlargement of the central pulmonary arteries, which contain extensive thrombus and calcified atherosclerotic plaques. (d) Radiograph of the right lung specimen reveals linear calcific deposits compatible with advanced atherosclerosis of the central pulmonary arteries. (e) Low-power photomicrograph (original magnification, x4; Movat pentachrome elastic stain) of a large elastic pulmonary artery shows organizing intraluminal thrombus (*).
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Figure 16e. Pulmonary arterial hypertension in a 39-year-old woman with atrial septal defect. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show enlargement of the pulmonary trunk and hilar vessels and a prominent right ventricle. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates marked enlargement of the central pulmonary arteries, which contain extensive thrombus and calcified atherosclerotic plaques. (d) Radiograph of the right lung specimen reveals linear calcific deposits compatible with advanced atherosclerosis of the central pulmonary arteries. (e) Low-power photomicrograph (original magnification, x4; Movat pentachrome elastic stain) of a large elastic pulmonary artery shows organizing intraluminal thrombus (*).
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Figure 17a. Pulmonary arterial hypertension secondary to long-standing ventricular septal defect (VSD). (a) Axial spin-echo T1-weighted MR image (cardiac gated) demonstrates a large VSD (*) and biventricular hypertrophy (arrows). (b) Axial spin-echo T1-weighted MR image (cardiac gated) shows dilatation of the main pulmonary artery (*) and mixed signal intensity within the bifurcation compatible with flow-related artifact (arrow).
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Figure 17b. Pulmonary arterial hypertension secondary to long-standing ventricular septal defect (VSD). (a) Axial spin-echo T1-weighted MR image (cardiac gated) demonstrates a large VSD (*) and biventricular hypertrophy (arrows). (b) Axial spin-echo T1-weighted MR image (cardiac gated) shows dilatation of the main pulmonary artery (*) and mixed signal intensity within the bifurcation compatible with flow-related artifact (arrow).
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Pulmonary Embolism
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Clinical Characteristics, Histopathologic Features, and Treatment.—Pulmonary embolism may be a complication of deep venous or pelvic vein thrombosis, right atrial neoplasia or thrombus, thrombogenic intravenous catheters, or endocarditis of the tricuspid or pulmonic valves (4,5,11,56–59). Pulmonary emboli are often multiple, bilateral, and more numerous in the right lung (11). Although acute pulmonary embolism may produce a temporary mild elevation of pulmonary arterial pressure (in 70%–80% of cases), verifiably sustained thromboembolic pulmonary hypertension is attributed to chronic, recurrent major vessel pulmonary thromboembolism (4,60). An estimated 1%–5% of patients with acute pulmonary thromboembolism go on to develop chronic thromboembolic pulmonary hypertension (CTEPH), and pulmonary infarction is a well-documented complication (61,62). CTEPH may mimic PPH clinically, making precise diagnosis difficult (35,63,64).
Patients with CTEPH may be asymptomatic for several years (the "honeymoon period") before they present with recurrent acute or progressive exertional dyspnea, chronic nonproductive cough, atypical chest pain, tachycardia, syncope, and even cor pulmonale (3–5,60–62,65). In these patients, pulmonary arterial pressure is elevated (range, 36–78 mm Hg in one series), right atrial pressures are high, cardiac output is reduced, and pulmonary capillary wedge pressures are normal (60,65). Women are affected more frequently than men, and patients with underlying malignant, cardiovascular, or pulmonary disease are at increased risk of developing this condition (3–5,60). In 11%–24% of patients, a lupus anticoagulant is present (66). One series has shown that a mean pulmonary artery pressure of 30 mm Hg corresponds to 5-year survival in only 30% of patients with CTEPH (60).
The treatment of choice is surgical thromboendarterectomy (operative mortality, 7%–40%) (3, 60,61). Surgical accessibility must be established preoperatively to ensure that the organized thrombi are not located beyond the margin of a safe dissection plane for endarterectomy, namely distal to the lobar arteries or to the origin of the segmental vessels (66). Radiologic imaging, most often conventional pulmonary angiography ("the gold standard"), is used to assess the presence and extent of disease (66,67). Contrast-enhanced helical CT is an excellent, noninvasive modality with which to demonstrate emboli in the central pulmonary vessels and segmental arterial branches (see discussion below) (67). Nevertheless, in cases in which imaging is limited, direct inspection of vessels may be achieved with a fiberoptic angioscope to visualize the intimal surface configuration of pulmonary arteries (66,67). Operative risk assessment for pulmonary thromboendarterectomy also weighs comorbid conditions (such as coronary artery disease and parenchymal lung disease) and the patient's status of cardiac, hemodynamic, and ventilatory compromise (66). Supplemental warfarin anticoagulation therapy is also indicated, in some cases combined with vasodilators, to treat the more peripheral thrombotic occlusions that are beyond the segmental arteries and not amenable to surgical resection (60,61).
At gross inspection, the main pulmonary arteries and their branches contain fibrous webs and bands corresponding to organized thromboemboli, often with overlying recent thrombosis (4,5). Marked right ventricular hypertrophy is typical (4). At histologic examination, various stages of organized and recanalized thromboemboli in both the elastic and muscular arteries are confirmed (Fig 18) (3–5). "Organization" of a thrombus implies its transition to a vascularized lesion of connective tissue that adheres to the vessel wall (11). The "recanalization" of an organized clot implies the presence of a vascular channel network that may reduce the "organized" portion to septations of collagen and elastic fibers, often lined by endothelium (4,11). In response to elevations in pulmonary pressure produced by CTEPH, the patent pulmonary arterial vessels develop medial hypertrophy, intimal thickening, and atherosclerotic plaques compatible with hypertensive changes (4,60). In accordance with our understanding of the bronchial circulation, the bronchial arteries in CTEPH may dilate and form extensive collateral pathways to minimize areas of lung infarction (4,62).
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Figure 18. Microscopic features of CTEPH. High-power photomicrograph (original magnification, x40; Movat pentachrome elastic stain) of a muscular artery shows eccentric intimal thickening (*) and organized thrombus (T) containing recanalized vascular channels (arrows).
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Radiologic Features.—In early CTEPH, the chest radiographic findings may be normal despite significant cardiopulmonary symptoms (65). Eventually, prominence of the right side of the heart and asymmetric enlargement of the central pulmonary arteries develop (66). Oligemic vascularity in a patchy distribution may be evident (65). When it occurs, pulmonary infarction may produce radiographic findings of a triangular or rounded opacity with adjacent pleural thickening (Figs 19a, 20a) (65). After pulmonary thromboendarterectomy, a form of noncardiogenic pulmonary edema described as "reperfusion edema" may manifest as patchy, bilateral perihilar alveolar opacities (68).
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Figure 19a. Pulmonary embolism in a 60-year-old woman with atrial fibrillation. (a) Frontal chest radiograph reveals a rounded homogeneous opacity in the right lower lung. (b) Collimated chest CT scan (lung window) demonstrates a pulmonary infarct as a wedge-shaped, pleural-based area of high attenuation.
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Figure 19b. Pulmonary embolism in a 60-year-old woman with atrial fibrillation. (a) Frontal chest radiograph reveals a rounded homogeneous opacity in the right lower lung. (b) Collimated chest CT scan (lung window) demonstrates a pulmonary infarct as a wedge-shaped, pleural-based area of high attenuation.
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Figure 20a. Pulmonary embolism in a 22-year-old man with right atrial myxoma. (a) Frontal chest radiograph shows ill-defined bibasilar opacities (arrows). (b) Contrast-enhanced chest CT scan demonstrates a filling defect in the right atrium (arrow) and a wedge-shaped consolidation in the right lower lobe, confirmed as being a pulmonary infarction at biopsy.
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Figure 20b. Pulmonary embolism in a 22-year-old man with right atrial myxoma. (a) Frontal chest radiograph shows ill-defined bibasilar opacities (arrows). (b) Contrast-enhanced chest CT scan demonstrates a filling defect in the right atrium (arrow) and a wedge-shaped consolidation in the right lower lobe, confirmed as being a pulmonary infarction at biopsy.
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CT findings of CTEPH include mosaic attenuation of lung parenchyma (Fig 21); hypertrophy and enlargement of the right atrium and right ventricle; variable central arterial dilatation with atherosclerotic calcifications; intraluminal clot; eccentric or longitudinal filling defects; and marked caliber reduction of the affected main, lobar, segmental, and subsegmental pulmonary arteries (43,44,64,69–71). Pulmonary infarcts typically manifest as subpleural linear or wedge-shaped areas of consolidation in areas of decreased lung attenuation (Figs 19b, 20b) (43,44,69,72). Helical CT provides an excellent delineation of central and segmental vessel thromboembolism and has been shown to have greater sensitivity and accuracy for depicting central disease than either pulmonary angiography or MR imaging (67). High-resolution CT findings of CTEPH include the combination of mosaic lung attenuation and a marked regional variation in segmental vessels that can help distinguish CTEPH from the more diffuse pattern of findings in PPH and other causes of pulmonary arterial hypertension (43). High-resolution CT has also revealed cylindrical bronchial airway dilatation adjacent to the stenotic or obstructed pulmonary arterial segments in two-thirds of patients with CTEPH (44).
Lung scintigraphic findings in CTEPH are characteristically read as high probability (unlike those of PPH), with asymmetric segmental or larger mismatched perfusion defects, which often leads to underestimation of the extent of central thromboembolism (46–48,65,73). Chronic thromboembolism may also manifest with predominantly unilateral hypoperfusion or occlusion on radionuclide scans (74).
Pulmonary angiography maintains greater specificity in the demonstration of central thromboembolic disease than either helical CT or MR imaging and outlines webs, bands, stenotic or absent arterial segments, pouchlike filling defects, and abrupt cutoffs that are often confined to one or two lung segments (50,60,65,69,75,76). As with lung scintigraphy, pulmonary angiography may also demonstrate unilateral occlusion or hypoperfusion with diminished segmental arteries and results in underestimation of the proximal extent of thromboembolism because of underlying vessel recanalization and smoothly adherent mural thrombi (50,60,64,76–79).
On T1-weighted static systolic spin-echo MR images, chronic thrombi within the major pulmonary vessels are visualized as discrete, fixed areas of abnormal low-to-medium signal intensity that do not change in configuration throughout the cardiac cycle (51,76,80). However, spin-echo MR images that demonstrate slow flow in central vessels due to pulmonary hypertension may actually obscure the fixed signal caused by central emboli (67). In addition, the limited spatial resolution of MR imaging may not allow detection of more subtle, smoothly contoured chronic thrombi (67). Two-dimensional spoiled gradient-recalled echo MR angiograms may reveal thromboembolic material within central and segmental pulmonary arteries, but this technique is somewhat limited by the ability of dyspneic patients to cooperate with breath-hold commands (67). In general, current MR imaging techniques have the lowest sensitivity, specificity, and accuracy for the detection of central, segmental, and lobar vessel chronic thromboemboli compared with both conventional angiography and helical CT (67). MR angiography has been shown to have an accuracy identical to that of radionuclide imaging in distinguishing patients with CTEPH (characterized by absent vessels and a discrepancy in vessel size between segments) from those with PPH (manifested by large proximal vessel caliber and diffuse, marked peripheral vessel tapering) (73).
Bronchial artery dilatation and tortuosity were observed at high-resolution CT in 77% of patients with CTEPH in one series, and, notably, these findings were statistically significant predictors of patient survival immediately following thromboendarterectomy (8). Contrast-enhanced helical CT may clearly demonstrate prominent bronchial collateral circulation within the mediastinum of patients with chronic thromboembolism (67). Selective bronchial arteriography has demonstrated the presence of remarkable bronchial arterial dilatation and bronchopulmonary collateral circulation in CTEPH, with bronchial flow drawing almost 30% of the systemic blood flow to fill pulmonary arteries "downstream" from sites occluded by chronic thromboemboli (50).
Tumor Embolism
Clinical Characteristics, Histopathologic Features, and Treatment.—Approximately 2%–26% of patients with a known solid malignancy develop microscopic tumor emboli to the pulmonary circulation. The diagnosis of tumor embolism is frequently missed until postmortem examination (81,82). Patients may present with progressive dyspnea, hypoxemia (PaO2 levels typically well below 50 mm Hg), cough, hemoptysis, pleuritic chest pain, syncope, or subacute cor pulmonale (81–86). Several reports suggest that the development of cor pulmonale in these patients is an ominous sign and often heralds death within 4–12 weeks (82–85).
Tumor cells form emboli in the vena cava and subsequently occlude small muscular pulmonary arteries and peripheral arterioles (81,83). Gastric carcinoma is the most common clinically occult neoplasm to embolize and produce pulmonary hypertension (84,87). Other neoplasms with this tendency include breast, prostate, lung, hepatocellular, renal, and ovarian carcinomas, as well as osteosarcoma, lymphoma, choriocarcinoma, and right atrial myxoma (3,15,22,56,81,83,88–90). Unlike most malignancies, right atrial myxoma and renal cell carcinoma tend to embolize to the large central and segmental pulmonary arteries (15).
In these cases, histologic examination of medium-sized peripheral pulmonary arteries and smaller arterioles reveals intravascular malignant cells, acute and organizing platelet-fibrin thrombi, small artery intimal fibrosis, and adjacent intralymphatic tumor (Fig 22) (3,81,82,84). Tumor emboli, particularly from gastric adenocarcinoma or malignant melanoma, may produce focal myxoid intimal hyperplasia (so-called carcinomatous endarteritis), which further promotes vascular obliteration (15,87). The heart often demonstrates moderate right ventricular hypertrophy, with or without dilatation (15,81,83,87,91). Tumor emboli may produce multiple small, subpleural pulmonary infarcts, in accordance with our knowledge of malignancy as a predisposing condition (56,83,87,91). Tumor emboli may coexist with lymphangitic carcinomatosis and often occur in the absence of interstitial pulmonary metastases (22,81,83,84,87,91).
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Figure 22a. Microscopic features of tumor embolism. (a) Low-power photomicrograph (original magnification, x4; H-E stain) shows a muscular pulmonary artery distended by thrombus that contains tumor cells (arrow). (b) Low-power photomicrograph (original magnification, x4; H-E stain) reveals tumor cells (*) filling subpleural lymphatic vessels, with secondary edema of the adjacent interlobular septum (arrow).
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Figure 22b. Microscopic features of tumor embolism. (a) Low-power photomicrograph (original magnification, x4; H-E stain) shows a muscular pulmonary artery distended by thrombus that contains tumor cells (arrow). (b) Low-power photomicrograph (original magnification, x4; H-E stain) reveals tumor cells (*) filling subpleural lymphatic vessels, with secondary edema of the adjacent interlobular septum (arrow).
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Radiologic Features.—Chest radiographic findings may be normal, or enlarged central pulmonary arteries and cardiomegaly compatible with pulmonary arterial hypertension may be seen. Ill-defined nodular and confluent peripheral parenchymal opacities are present when multiple pulmonary infarcts have occurred (58,82,84,86,87,90).
CT reveals subpleural linear and wedge-shaped opacities at sites of pulmonary infarction (Fig 23a) (81,90). CT also may demonstrate companion radiologic manifestations of malignancy, including lymphadenopathy, pulmonary venous hypertension, or lymphangitic carcinomatosis (Fig 24) (81,87,91). Contrast-enhanced CT may demonstrate filling defects in the main pulmonary arterial branches or multifocal beading and dilatation of the peripheral subsegmental pulmonary arteries (90,92).
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Figure 23a. Tumor embolism in a middle-aged woman with severe dyspnea and adenocarcinoma of unknown origin. Frontal chest radiograph was normal. (a) Chest CT scan (lung window) demonstrates bibasilar subpleural wedge-shaped areas of consolidation compatible with areas of pulmonary infarction. (b) Lung perfusion scans show multiple subsegmental perfusion defects.
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Figure 23b. Tumor embolism in a middle-aged woman with severe dyspnea and adenocarcinoma of unknown origin. Frontal chest radiograph was normal. (a) Chest CT scan (lung window) demonstrates bibasilar subpleural wedge-shaped areas of consolidation compatible with areas of pulmonary infarction. (b) Lung perfusion scans show multiple subsegmental perfusion defects.
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Figure 24a. Tumor embolism in a 42-year-old man with dyspnea, hemoptysis, and hematuria secondary to transitional cell carcinoma of the bladder. (a) Chest CT scan (lung window) reveals nodular thickening of the minor fissure (white arrow), thickening of the bronchovascular bundles and interlobular septa (black arrow), and a masslike consolidation in the right lower lobe. (b) Photograph of a cut section of the lung demonstrates subpleural and peribronchovascular tan masses (arrows) consistent with capillary and lymphangitic spread of tumor.
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Figure 24b. Tumor embolism in a 42-year-old man with dyspnea, hemoptysis, and hematuria secondary to transitional cell carcinoma of the bladder. (a) Chest CT scan (lung window) reveals nodular thickening of the minor fissure (white arrow), thickening of the bronchovascular bundles and interlobular septa (black arrow), and a masslike consolidation in the right lower lobe. (b) Photograph of a cut section of the lung demonstrates subpleural and peribronchovascular tan masses (arrows) consistent with capillary and lymphangitic spread of tumor.
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Lung scintigraphy produces nonspecific findings of multiple small, subsegmental unmatched perfusion defects (Fig 23b) (82,85,86,92). Pulmonary angiography demonstrates a delayed arterial phase, filling defects and occlusions of subsegmental arterial branches, arterial wall irregularities, and associated peripheral pruning of the smaller arteries (86,87,90–92).
Parasitic Embolism
Clinical Characteristics, Histopathologic Features, and Treatment.—Cardiopulmonary schistosomiasis is usually attributed to Schistosoma mansoni infection, which is endemic in the Middle East, Africa, the Atlantic coast of South America, and the Caribbean (93,94). S japonicum and S haematobium are less commonly implicated (94). The disease may be seen in travelers and immigrants entering the United States from endemic areas (94,95). A prolonged period of at least 5 years of continuous ova secretion is usually required for the development of cardiopulmonary disease (94,96). The resultant pulmonary arterial hypertension and cor pulmonale usually occur in adults aged 25–35 years (range, 1–93 years), who present with gradually worsening hepatosplenomegaly, dyspnea, cough, chest pain, severe hypoxemia, cyanosis, and digital clubbing (87,93,97,98). The prevalence of cor pulmonale ranges from 2% to 33%, and portal hypertension with periportal hepatic fibrosis appears to be a prerequisite condition (94,96–98).
In humans, S mansoni eggs may travel as emboli in the portal-systemic collateral pathways to lodge ultimately in pulmonary muscular arteries and arterioles (50–150 µm in diameter) (15,93,96). The trapped eggs are antigenic and produce an obliterative endarteritis due to delayed host hypersensitivity (94,96,98). This inflammatory process eventually leads to pulmonary arterial hypertension by inciting intravascular and perivascular granulomas, intimal hyperplasia, medial hypertrophy, and eventual concentric collagen deposition and fibrosis of the vessel wall (Fig 25) (15,94,96,97). A localized alveolitis with eosinophilic infiltration is also often present (96,98). Pulmonary infarction has not been reported in pulmonary schistosomiasis (15). The reversibility of pulmonary hypertensive vascular changes following drug therapy (with praziquantel and oxamniquine) is currently unknown (94,98).
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Figure 25. Microscopic features of schistosomal embolism. High-power photomicrograph (original magnification, x40; H-E stain) shows a cluster of S mansoni eggs that has obliterated the pulmonary artery lumen (arrows) and is surrounded by interstitial fibrosis and inflammation.
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Radiologic Features.—In approximately 70% of patients with the clinical manifestations of pulmonary hypertension, chest radiography demonstrates cardiomegaly and central pulmonary arterial enlargement (Fig 26) (94,98). In some cases, tiny scattered parenchymal nodular opacities representing the granulomas are evident radiographically (94,95,98). High-resolution CT of pulmonary schistosomiasis may show nodules, interstitial thickening, and patchy ground-glass attenuation in addition to dilatation of the central pulmonary arteries and the right atrium and right ventricle (98,99).
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Figure 26. Schistosomiasis with pulmonary arterial hypertension in a 25-year-old Asian woman. Frontal chest radiograph shows mild cardiomegaly and prominence of the main pulmonary artery and hilar vessels.
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Pulmonary Talcosis
Clinical Characteristics, Histopathologic Features, and Treatment.—Pulmonary talcosis chiefly affects intravenous drug abusers and progresses with the chronic injection of suspensions prepared from crushed tablet compounds (100). Talc is a common insoluble pharmaceutical binding agent that forms microemboli in the pulmonary circulation (Fig 27a) (22). Pulmonary arterial hypertension ensues when widespread talc emboli incite a pronounced foreign body granulomatous response in the lungs (3,22). Additional complications of talc embolization include mycotic pulmonary artery aneurysm; right-sided endocarditis with septic emboli; chronic respiratory failure; emphysema; and systemic talc breakthrough to the liver, spleen, kidneys, and retina (22,100–103).
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Figure 27a. Microscopic features of pulmonary talcosis. (a) Electron microscopic image shows irregular crystalline plates of talc (arrow) embedded in the lung parenchyma. (b) Low-power photomicrograph (original magnification, x4; H-E stain) under polarized light reveals a central deposition of birefringent talc particles and obliteration of the surrounding pulmonary architecture by dense fibrosis. (c) Photograph of the cut lung surface shows a large fibrotic mass (*) emanating from the hilum (arrow) that exerts traction on the upper lobe.
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Figure 27b. Microscopic features of pulmonary talcosis. (a) Electron microscopic image shows irregular crystalline plates of talc (arrow) embedded in the lung parenchyma. (b) Low-power photomicrograph (original magnification, x4; H-E stain) under polarized light reveals a central deposition of birefringent talc particles and obliteration of the surrounding pulmonary architecture by dense fibrosis. (c) Photograph of the cut lung surface shows a large fibrotic mass (*) emanating from the hilum (arrow) that exerts traction on the upper lobe.
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Figure 27c. Microscopic features of pulmonary talcosis. (a) Electron microscopic image shows irregular crystalline plates of talc (arrow) embedded in the lung parenchyma. (b) Low-power photomicrograph (original magnification, x4; H-E stain) under polarized light reveals a central deposition of birefringent talc particles and obliteration of the surrounding pulmonary architecture by dense fibrosis. (c) Photograph of the cut lung surface shows a large fibrotic mass (*) emanating from the hilum (arrow) that exerts traction on the upper lobe.
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Histologic examination of the lung reveals widespread granulomas that are packed with doubly refractile talc particles, which expand the walls of muscular pulmonary arteries and arterioles, the perivascular connective tissue, and the alveolar septa (Fig 27b) (3,22). The muscular arteries demonstrate characteristic findings of pulmonary hypertension, including medial hypertrophy with areas of thrombosis and recanalization (3,22). At gross inspection, the lung contains multiple, scattered whitish nodules (0.3–3 mm in diameter) that converge into gritty fibrotic masses measuring several centimeters in the central and upper lungs (Fig 27c). These lesions are similar to those observed in silicosis, coal-worker's pneumoconiosis, and advanced sarcoidosis (100–102,104).
Radiologic Features.—Early pulmonary talcosis manifests radiographically as diffuse, tiny (2–3-mm) well-defined opacities (100,103). As the disease advances, conglomerate masses may form in the upper lungs to produce hilar elevation and hyperlucency at the lung bases (Fig 28a) (100,102,105). In subtle contrast to the progressive massive fibrotic lesions of the pneumoconioses, these masses tend to arise slightly closer to the pulmonary hila and have less distinct peripheral margins (102). With steroid therapy, these masses may stabilize or regress (102).
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Figure 28a. Pulmonary talcosis in a 37-year-old woman with a history of chronic intravenous injection of crushed pentazocine lactate (Talwin) and methylphenidate hydrochloride (Ritalin) tablets. (a) Frontal chest radiograph reveals micronodular opacities in the upper lungs and irregular perihilar masses, with upward hilar retraction and marked hyperlucency at the lung bases. (b) High-resolution CT scan (lung window) reveals fine, scattered, bilateral interstitial nodules. (c) Chest CT scan (mediastinal window) of the left lung shows an irregular, high-attenuation perihilar mass.
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Figure 28b. Pulmonary talcosis in a 37-year-old woman with a history of chronic intravenous injection of crushed pentazocine lactate (Talwin) and methylphenidate hydrochloride (Ritalin) tablets. (a) Frontal chest radiograph reveals micronodular opacities in the upper lungs and irregular perihilar masses, with upward hilar retraction and marked hyperlucency at the lung bases. (b) High-resolution CT scan (lung window) reveals fine, scattered, bilateral interstitial nodules. (c) Chest CT scan (mediastinal window) of the left lung shows an irregular, high-attenuation perihilar mass.
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Figure 28c. Pulmonary talcosis in a 37-year-old woman with a history of chronic intravenous injection of crushed pentazocine lactate (Talwin) and methylphenidate hydrochloride (Ritalin) tablets. (a) Frontal chest radiograph reveals micronodular opacities in the upper lungs and irregular perihilar masses, with upward hilar retraction and marked hyperlucency at the lung bases. (b) High-resolution CT scan (lung window) reveals fine, scattered, bilateral interstitial nodules. (c) Chest CT scan (mediastinal window) of the left lung shows an irregular, high-attenuation perihilar mass.
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At CT, pulmonary talcosis manifests with widespread ground-glass attenuation and scattered fine micronodules. In advanced cases, CT demonstrates lung distortion and confluent perihilar masses that contain high-attenuation areas of accumulated talc (Fig 28b, 28c) (100).
Foreign Body Embolism
Clinical Characteristics, Histopathologic Features, and Treatment.—Extensive metallic mercury embolization, acquired by either accidental or intentional intravenous injection, at first produces mild pulmonary inflammation (31). The intravascular mercury eventually becomes encased in thrombus or migrates into the pulmonary interstitium or alveolar spaces (31). The consequent significant granulomatous response in the lung causes narrowing or obstruction of the pulmonary vessels, and pulmonary hypertension may be the end result (3).
Radiologic Features.—Mercury embolism manifests radiographically as high-density, fine-caliber branching structures in a symmetric distribution that correspond to intraarterial mercury (Fig 29) (31). Mercury may also collect within the heart, particularly in the apex of the right ventricle (31).
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Figure 29. Frontal chest radiograph of a young man, following a suicide attempt with intravenous injection of mercury, shows bibasilar high-density branching structures that represent extensive intravascular accumulation of the liquid metal.
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Postcapillary Pulmonary Hypertension
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Pulmonary Veno-occlusive Disease
Clinical Characteristics, Histopathologic Features, and Treatment.—PVOD is a rare idiopathic condition and the postcapillary counterpart to PPH. In addition to certain hemodynamic derangements of pulmonary arterial hypertension (elevated pulmonary artery and right atrial pressures, decreased cardiac output), PVOD produces distinctive findings of normal or variably elevated capillary wedge pressures (3,5,27,106). Normal left atrial and left ventricular pressures are also characteristic of PVOD and help exclude cardiac disease as the cause of venous hypertension (107). Patients present with progressive dyspnea, hemoptysis, and antecedent flulike symptoms (22,106,108). One-third of PVOD cases occur in children with equal sex distribution, and there is a slight male predominance in adult patients (3,22,109). PVOD may be associated with pregnancy, bone marrow transplantation, or drug toxicity (carmustine, bleomycin, mitomycin) (3,22,110–113). The diagnosis is often missed initially because both the clinical presentation and radiographic findings are suggestive of interstitial lung disease (16). It is essential for clinicians to distinguish PVOD from precapillary pulmonary hypertension, because potentially fatal pulmonary edema may be induced by the administration of vasodilator therapy for presumed pulmonary arterial hypertension (114). Although treatment with anticoagulants has had limited success in PVOD, this disease is usually fatal within 3 years of diagnosis (5,109).
The proposed initial insult in PVOD is venous thrombosis, possibly initiated by infection, toxic exposure, or immune complex deposition (22, 109,115). The unique histologic hallmarks of PVOD are webs, recanalized thrombosis, and intimal fibrosis within the pulmonary veins (Fig 30) (3,5,16). These findings are specific to PVOD and suggest that thrombosis is an essential pathogenetic factor (3,109). Microscopy may also reveal sheets and nodular collections of thin-walled capillaries invading pulmonary arteries, veins, bronchioles, and the pleura (3). Although this proliferation of capillaries, called "capillary hemangiomatosis," is recognized by some authors as a separate clinical entity, it most likely represents one subset or morphologic expression of PVOD (3,16,22). The distribution of venous damage from PVOD is characteristically localized and patchy, which explains the intrinsic variability of pulmonary capillary wedge pressures found in these patients (22,27). The nonspecific changes of venous hypertension are also present in PVOD, including venous medial hypertrophy, septal edema and fibrosis, paraseptal venous infarction, interstitial and pleural lymphatic dilatation, intraalveolar hemosiderin-laden macrophages, and features of secondary pulmonary arterial hypertension (3,5,16,22,24,108,116).
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Figure 30. Hallmark microscopic features of PVOD. High-power photomicrograph (original magnification, x40; elastic stain) shows an intralobular vein obstructed by connective tissue (*) that contains multiple recanalization channels (arrows).
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Radiologic Features.—The specific diagnosis of PVOD is suggested radiographically when features of pulmonary arterial hypertension are accompanied by evidence of diffuse pulmonary interstitial edema and a normal-sized left atrium (Fig 31a, 31b) (31,111,112,117,118). Mediastinal lymphadenopathy may also be present (119).
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Figure 31a. PVOD in a 20-year-old man with progressive dyspnea. (a) Frontal chest radiograph shows central pulmonary arterial enlargement and diffuse reticular opacities. (b) Collimated view of the right lower lobe shows prominent septal lines. (c) High-resolution CT scan (lung window) demonstrates enlarged central arteries, peribronchovascular thickening, and prominent interlobular septa.
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Figure 31b. PVOD in a 20-year-old man with progressive dyspnea. (a) Frontal chest radiograph shows central pulmonary arterial enlargement and diffuse reticular opacities. (b) Collimated view of the right lower lobe shows prominent septal lines. (c) High-resolution CT scan (lung window) demonstrates enlarged central arteries, peribronchovascular thickening, and prominent interlobular septa.
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Figure 31c. PVOD in a 20-year-old man with progressive dyspnea. (a) Frontal chest radiograph shows central pulmonary arterial enlargement and diffuse reticular opacities. (b) Collimated view of the right lower lobe shows prominent septal lines. (c) High-resolution CT scan (lung window) demonstrates enlarged central arteries, peribronchovascular thickening, and prominent interlobular septa.
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CT of PVOD may demonstrate features of secondary pulmonary arterial hypertension in addition to distinctive findings of markedly small central pulmonary veins, central and gravity-dependent ground-glass lung attenuation, smoothly thickened interlobular septa, pleural effusions, a normal-sized left atrium, and centrilobular nodules (Fig 31c) (112,114,119).
Limited reports of the scintigraphic findings of PVOD describe a patchy distribution of technetium-99m–labeled microaggregated albumin on perfusion scans, a pattern attributed to "upstream" pulmonary arterial hypertension secondary to pronounced postcapillary hypertension (48,117,118). Pulmonary angiography in PVOD shows enlarged central pulmonary arteries and right ventricle, prolonged parenchymal phase enhancement, delayed filling of normal pulmonary veins, and the outline of a normal to small left atrium (120,121).
Mediastinal Fibrosis
Clinical Characteristics, Histopathologic Features, and Treatment.—Mediastinal fibrosis is a progressive proliferation of fibrous tissue and collagen in the mediastinum attributed to various causes, most importantly prior granulomatous (especially Histoplasma capsulatum and tuberculosis) infection (24). It may constrict or completely occlude vital mediastinal structures, including the superior vena cava, central airways, esophagus, pericardium, central pulmonary arteries, and draining pulmonary veins (24,122–125). Pulmonary vascular occlusion is produced by fibrous encasement of the pulmonary arteries or veins in a nonuniform pattern. The clinical presentation of dyspnea, hemoptysis, and signs of pulmonary arterial involvement by mediastinal fibrosis is often mistaken for chronic large vessel thromboembolic disease (25,122,123,126). Use of cardiac catheterization in cases of venous involvement typically reveals a low left atrial pressure with widely differential elevations of pulmonary capillary wedge pressures (122,123,127). Surgical resection of the fibrotic tissue has been effective in treating focal pulmonary venous obstruction; steroid therapy has met with limited success (25,123,126).
Microscopy reveals the nonspecific venous changes of postcapillary hypertension (refer to Fig 10a), as well as focal fibrous bands that segmentally encase, infiltrate, and occlude central pulmonary veins and venules (24). Edematous and fibrotic alveolar septa, multifocal paraseptal venous infarcts, hemosiderosis, and vascular changes of secondary arterial hypertension are associated findings localized to affected areas of the lung (16,24,25,124). Partially occlusive thrombi may develop at the atrial orifice of involved pulmonary veins (127).
Radiologic Features.—Radiographic features that suggest the diagnosis of mediastinal fibrosis with constriction of individual pulmonary veins include asymmetric mediastinal widening with calcifications accompanied by a hilar mass and ipsilateral Kerley B lines (23,24,123,124,127,128). Main pulmonary artery and right-sided heart enlargement may also be present when elevated venous pressures have produced secondary pulmonary arterial hypertension (123,127). Atelectasis and central airway narrowing may occur when the fibrosis has affected central airways (122).
Although it may be difficult to distinguish unilateral chronic thromboembolism from mediastinal fibrosis, both clinically and radiologically, CT of mediastinal fibrosis typically demonstrates mediastinal and hilar nodal masses of soft-tissue attenuation that contain coarse calcifications (Fig 32). An area of venous infarction may be visualized as a peripheral wedge-shaped consolidation on CT scans (Fig 32) (24,123,124,126).
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Figure 32a. Mediastinal fibrosis and focal pulmonary venous constriction in a 45-year-old woman with dyspnea and hemoptysis. (a) CT scan (mediastinal window) reveals a perihilar soft-tissue mass containing coarse calcifications. (b) CT scan (lung window) shows a pleural-based area of high attenuation corresponding to macroscopic venous infarction.
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Figure 32b. Mediastinal fibrosis and focal pulmonary venous constriction in a 45-year-old woman with dyspnea and hemoptysis. (a) CT scan (mediastinal window) reveals a perihilar soft-tissue mass containing coarse calcifications. (b) CT scan (lung window) shows a pleural-based area of high attenuation corresponding to macroscopic venous infarction.
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Ventilation-perfusion scintigraphy may show unilateral hypoperfusion or a more localized distribution of large segmental and smaller subsegmental unmatched perfusion defects (46,123). Pulmonary angiography reveals unilateral or asymmetric narrowing of central pulmonary arteries and distal arterial cutoffs when mediastinal fibrosis affects the arterial side of the pulmonary circulation; with involvement of pulmonary veins, the venous-phase angiograms show nonuniform pulmonary vein obstruction, stenosis, or focal dilatation near the left atrium (25,107,123,129).
Cardiac Disease
Clinical Characteristics, Histopathologic Features, and Treatment.—Pulmonary venous hypertension is most commonly caused by left-sided heart disease, such as left ventricular failure, left atrial thrombus, neoplasia (myxoma, sarcoma, metastasis), mitral stenosis, and congenital cardiac anomalies (3,130,131). Patients with left atrial myxoma commonly present with dyspnea, tachyarrhythmias, and pulmonary venous hypertension caused by interference with pulmonary venous drainage or mitral valve function (132–134). Secondary pulmonary arterial hypertension may eventually develop, and one series has shown a positive correlation between the weight of excised atrial myxoma and preoperative mean pulmonary artery pressure (134–136). In rare cases, direct pulmonary venous invasion by either an atrial (or even bronchogenic) neoplasm can produce marked pulmonary edema and paraseptal venous infarction (137–139).
Both obstructive left atrial myxoma and severe mitral stenosis have been shown to produce an abnormal systolic reversal of the pulmonary venous flow (measured with transesophageal and transthoracic Doppler echocardiography, and phase-shift MR imaging) that is caused by retrograde transmission of an elevated left atrial pressure throughout the cardiac cycle (140–147). These alterations in pulmonary venous flow may be generalized to other situations in which left atrial pressure is elevated, left atrial compliance is decreased, or the pulmonary veins are constricted (144,145). These findings illustrate the underlying hemodynamics that may lead to the development of pulmonary venous hypertension and its consequences in left-sided cardiac lesions.
As expected, the histologic features of chronic pulmonary venous hypertension due to functional or mechanical obstruction distal to the pulmonary veins include venous medial hypertrophy, interlobular septal and pleural edema, lymphatic dilatation, capillary bed congestion, alveolar hemosiderosis, and secondary changes of pulmonary arterial hypertension (Fig 33) (5). Venous infarction with thickening of the interlobular septum may be found in significant pulmonary venous occlusion (137).
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Figure 33. Venous changes of postcapillary pulmonary hypertension, secondary to obstructive left atrial neoplasm. Low-power photomicrograph (original magnification, x4; H-E stain) shows a thick-walled, dilated vein (*) within a fibrotic interlobular septum (arrow).
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Radiologic Features.—Left-sided cardiac disease such as myocardial dysfunction, occlusive left atrial myxoma, or mitral valve disease may mimic PVOD radiographically with features of pulmonary interstitial edema, Kerley B lines, pleural effusions, and secondary central pulmonary arterial prominence (Fig 34a). However, the presence of left atrial enlargement can help one distinguish left-sided cardiac lesions, such as mitral stenosis, from PVOD (Fig 35) (117,148). Hemosiderosis caused by long-standing pulmonary venous hypertension produces fine reticular opacities on chest radiographs, and tiny (1–3-mm) calcified ossific nodules are the hallmark of mitral stenosis (31). In rare cases, a left atrial myxoma manifests as a heavily calcified mass (133,148).
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Figure 34a. Severe pulmonary venous hypertension secondary to a left atrial mass in an 82-year-old woman. (a) Frontal chest radiograph shows cardiomegaly and diffuse bilateral air-space opacities representing pulmonary edema. (b) Echocardiogram demonstrates a left atrial mass (*) that is adherent to the mitral valve. (c) CT scan (mediastinal window) reveals a large soft-tissue mass filling the left atrial chamber (*). (d) Photograph of a cut section shows a large bosselated fibrosarcoma resected from the left atrium. Scale is in centimeters.
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Figure 34b. Severe pulmonary venous hypertension secondary to a left atrial mass in an 82-year-old woman. (a) Frontal chest radiograph shows cardiomegaly and diffuse bilateral air-space opacities representing pulmonary edema. (b) Echocardiogram demonstrates a left atrial mass (*) that is adherent to the mitral valve. (c) CT scan (mediastinal window) reveals a large soft-tissue mass filling the left atrial chamber (*). (d) Photograph of a cut section shows a large bosselated fibrosarcoma resected from the left atrium. Scale is in centimeters.
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Figure 34c. Severe pulmonary venous hypertension secondary to a left atrial mass in an 82-year-old woman. (a) Frontal chest radiograph shows cardiomegaly and diffuse bilateral air-space opacities representing pulmonary edema. (b) Echocardiogram demonstrates a left atrial mass (*) that is adherent to the mitral valve. (c) CT scan (mediastinal window) reveals a large soft-tissue mass filling the left atrial chamber (*). (d) Photograph of a cut section shows a large bosselated fibrosarcoma resected from the left atrium. Scale is in centimeters.
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Figure 34d. Severe pulmonary venous hypertension secondary to a left atrial mass in an 82-year-old woman. (a) Frontal chest radiograph shows cardiomegaly and diffuse bilateral air-space opacities representing pulmonary edema. (b) Echocardiogram demonstrates a left atrial mass (*) that is adherent to the mitral valve. (c) CT scan (mediastinal window) reveals a large soft-tissue mass filling the left atrial chamber (*). (d) Photograph of a cut section shows a large bosselated fibrosarcoma resected from the left atrium. Scale is in centimeters.
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Figure 35a. Severe mitral stenosis with secondary pulmonary venous hypertension in a middle-aged woman. Posteroanterior (a) and lateral (b) radiographs of the chest show marked left atrial dilatation, prominent upper lobe vessels, and an enlarged pulmonary trunk.
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Figure 35b. Severe mitral stenosis with secondary pulmonary venous hypertension in a middle-aged woman. Posteroanterior (a) and lateral (b) radiographs of the chest show marked left atrial dilatation, prominent upper lobe vessels, and an enlarged pulmonary trunk.
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Echocardiography has replaced angiography in the evaluation of intracardiac lesions to delineate their size, configuration, mobility, attachment site, and relationship to the atrioventricular valve (Fig 34b) (148,149). CT often complements echocardiography by demonstrating an intracardiac soft-tissue mass with additional evidence of extracardiac extension when present, interstitial edema, vascular congestion, pleural effusions, and enlargement of central vessels due to secondary pulmonary arterial hypertension (Fig 34c, 34d) (134,138).
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Summary
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Precapillary pulmonary hypertension affects the arterial side of the pulmonary circulation, chiefly at the level of the muscular arteries. The marked hemodynamic changes of elevated pulmonary arterial pressure and high vascular resistance are associated with histologic findings of medial hypertrophy; intimal cellular proliferation; thrombosis; and in certain severe conditions, proliferative plexiform lesions. Pulmonary infarction may occur when peripheral pulmonary arteries are occluded, particularly in the setting of elevated pulmonary venous pressure or underlying malignancy. Diseases implicated in the development of pulmonary arterial hypertension include idiopathic PPH; sustained cardiac left-to-right shunt; chronic thromboembolic disease; and pulmonary emboli arising from tumor cells, parasitic organisms, talc particles, or liquid mercury.
The radiologic manifestations of pulmonary arterial hypertension reflect central pulmonary arterial enlargement with sharply diminished peripheral vascularity, mosaic perfusion, and right-sided hypertrophy and chamber dilatation of the heart. Findings are characteristically diffuse in distribution with the exception of chronic thromboembolic disease, which may be limited to a few segmental or subsegmental vessels. Dilatation of bronchial arteries, subpleural pulmonary infarcts, calcified plaques lining the larger pulmonary arteries, and dissection or massive thrombosis of the central pulmonary arteries are complications that may be evident radiologically. Certain radiologic findings are helpful in distinguishing the causes of pulmonary arterial hypertension and pulmonary infarction. Coexistent lymphangitic carcinomatosis suggests tumor embolism as the underlying mechanism. Hepatosplenomegaly is associated with cardiopulmonary schistosomiasis. Pulmonary talcosis manifests with distinctive micronodular opacities and diffuse ground-glass attenuation, which may eventually converge into perihilar fibrotic masses containing high-density material.
Postcapillary pulmonary hypertension affects the venous side of the pulmonary circulation and produces either a uniform or widely variable elevation of pulmonary capillary wedge pressures. Attributed to the communication of high venous pressure across the capillary bed, the hemodynamic derangements of pulmonary arterial hypertension also may be present. The histologic changes are venous medial hypertrophy and intimal proliferation, thickening of the venous internal elastic lamina, capillary congestion and proliferation, interlobular septal thickening, lymphatic dilatation, and in some cases, venous infarction. The causes of postcapillary pulmonary hypertension include intrinsic PVOD (diagnosed on the basis of microscopic findings of recanalized thrombosis within the pulmonary veins), extrinsic lesions compressing pulmonary veins such as mediastinal fibrosis, and left-sided cardiac lesions that compromise normal pulmonary venous drainage.
The radiologic appearance of pulmonary venous hypertension typically demonstrates features of pulmonary interstitial edema superimposed on pulmonary arterial hypertension. Prominent central pulmonary arteries, Kerley B lines, thickened pleural fissures, and small effusions are characteristic findings that may be accompanied by a wedge-shaped consolidation when macroscopic venous infarction is present. The CT features that suggest PVOD are marked narrowing of the central pulmonary veins and a normal-sized left atrium. Mediastinal fibrosis is distinguished by a soft-tissue mediastinal or hilar mass containing coarse calcifications, accompanied by a regional distribution of Kerley B lines. A left atrial mass obstructing pulmonary venous outflow is often revealed by echocardiography or contrast-enhanced chest CT. Remarkable left atrial enlargement in pulmonary venous hypertension suggests severe underlying mitral stenosis.
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Acknowledgments
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The authors thank Allen P. Burke, MD, in the Department of Cardiovascular Pathology at the AFIP for sharing his tremendous expertise in this complex topic. We also extend our warmest thanks to Diane C. Strollo, MD, at the University of Pittsburgh Medical Center, Pennsylvania; Charles S. White, MD, at the University of Maryland Medical System in Baltimore; and Milton Gallant, MD, at the General Hospital of Passaic, New Jersey, for contributing such fine illustrative cases. Finally, we express our deep appreciation to Teresa A. Choi, BA, in the Department of Radiologic Pathology at the AFIP, and Paula R. Arantes, MD, at the Clinical Hospital of the University of Sao Paolo, Brazil, for their dedication and great skill in the preparation of illustrations for this manuscript.
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Footnotes
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Abbreviations: CTEPH = chronic thromboembolic pulmonary hypertension
H-E = hematoxylin-eosin
PPH = primary pulmonary hypertension
PVOD = pulmonary veno-occlusive disease
LEARNING OBJECTIVES After reading this article and taking the test, the reader will be able to:
• Outline the underlying histopathologic features and complications of precapillary (arterial) and postcapillary (venous) pulmonary hypertension.
• Define the clinical and prognostic characteristics of idiopathic and secondary conditions that produce pulmonary hypertension.
• Describe the classic radiologic manifestations of pre- and postcapillary pulmonary hypertension and recognize distinguishing features that may assist in its differential diagnosis.
The opinions and assertions contained herein are the private views of the authors and are not to be construed as official nor as representing the views of the Departments of the Air Force or Defense.
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References
|
|---|
-
Heath D. Pulmonary vascular disease. In: Hasleton PS, eds. Spencer's pathology of the lung. 5th ed. New York, NY: McGraw-Hill, 1996; 1283.
-
Deffebach ME, Charan NB, Lakshminarayan S, Butler J. The bronchial circulation: small, but a vital attribute of the lung. Am Rev Respir Dis 1987; 135:463-481.[Medline]
-
Burke A, Virmani R. Mini-symposium: pulmonary pathology—evaluation of pulmonary hypertension in biopsies of the lung. Curr Diagn Pathol 1996; 3:14-26.
-
Wagenvoort CA, Wagenvoort N. Pathology of pulmonary hypertension 1st ed. New York, NY: Wiley, 1977.
-
Edwards WD. Pathology of pulmonary hypertension. In: Brest AN, eds. Cardiovascular clinics. Philadelphia, Pa: Davis, 1988; 321-359.
-
Virmani R, Roberts WC. Pulmonary arteries in congenital heart disease: a structure-function analysis. In: Roberts WC, eds. Adult congenital heart disease. 1st ed. Philadelphia, Pa: Davis, 1987; 77-130.
-
Mathes ME, Holman E, Reichert FL. A study of the bronchial, pulmonary, and lymphatic circulations of the lung under various pathologic conditions experimentally produced. J Thorac Surg 1932; 1:339-362.
-
Kauczor HU, Schwickert HC, Mayer E, Schweden F, Schild HH, Thelen M. Spiral CT of bronchial arteries in chronic thromboembolism. J Comput Assist Tomogr 1994; 18(6):855-861.[Medline]
-
Dalen JE, Haffajee CI, Alpert JSIII, Howe JP, Ockene IS, Paraskos JA. Pulmonary embolism, pulmonary hemorrhage, and pulmonary infarction. N Engl J Med 1977; 296:1431-1435.[Abstract]
-
Tsao MS, Schraufnagel D, Wang NS. Pathogenesis of pulmonary infarction. Am J Med 1982; 72:599-606.[Medline]
-
Wagenvoort CA. Pathology of pulmonary thromboembolism. Chest 1995; 107(suppl 1):10S-17S.[Abstract/Free Full Text]
-
Schraufnagel DE, Tsao MS, Yao YT, Wang NS. Factors associated with pulmonary infarction: a discriminant analysis study. Am J Clin Pathol 1985; 84:15-18.[Medline]
-
Lammers RJ, Bloor CM. Edema, emboli, and vascular anomalies. In: Dail DH, Hammar SP, eds. Pulmonary pathology. 1st ed. New York, NY: Springer-Verlag, 1988; 1200.
-
Alderson PO, Martin EC. Pulmonary embolism: diagnosis with multiple imaging modalities. Radiology 1987; 164:297-312.[Free Full Text]
-
Mark EJ. Lung biopsy interpretation 1st ed. Baltimore, Md: Williams & Wilkins, 1984.
-
Burke AP, Farb A, Virmani R. The pathology of primary pulmonary hypertension. Mod Pathol 1991; 4:269-282.[Medline]
-
Rubin LJ. Primary pulmonary hypertension (see comments). Chest 1993; 104:236-250.[Free Full Text]
-
Masuda S, Ishii T, Asuwa N, Ishikawa Y, Kiguchi H, Uchiyama T. Concurrent pulmonary arterial dissection and saccular aneurysm associated with primary pulmonary hypertension. Arch Pathol Lab Med 1996; 120:309-312.[Medline]
-
Moser KM, Fedullo PF, Finkbeiner WE, Golden J. Do patients with primary pulmonary hypertension develop extensive central thrombi?. Circulation 1995; 91:741-745.[Abstract/Free Full Text]
-
Moore GW, Smith RR, Hutchins GM. Pulmonary artery atherosclerosis: correlation with systemic atherosclerosis and hypertensive pulmonary vascular disease. Arch Pathol Lab Med 1982; 106:378-380.[Medline]
-
Contis G, Fung RH, Vawter GF, Nadas AS. Stenosis and obstruction of the pulmonary veins associated with pulmonary artery hypertension. Am J Cardiol 1967; 20:718-724.[Medline]
-
Katzenstein AL. Katzenstein and Askin's surgical pathology of non-neoplastic lung disease 3rd ed. Philadelphia, Pa: Saunders, 1997.
-
Belcourt CL, Roy DL, Nanton MA, Finley JP, Gillis DA, Krause VW. Stenosis of individual pulmonary veins: radiologic findings. Radiology 1986; 161:109-112.[Abstract/Free Full Text]
-
Katzenstein AL, Mazur MT. Pulmonary infarct: an unusual manifestation of fibrosing mediastinitis. Chest 1980; 77:521-524.[Abstract/Free Full Text]
-
Dye TE, Saab SB, Almond CH, Watson L. Sclerosing mediastinitis with occlusion of pulmonary veins: manifestations and management. J Thorac Cardiovasc Surg 1977; 74:137-141.[Abstract]
-
Sanders WE. Primary pulmonary arteriosclerosis with hypertrophy of the right ventricle. Arch Intern Med 1909; 3:257-262.
-
Rubin LJ. Primary pulmonary hypertension. N Engl J Med 1997; 336:111-117.[Free Full Text]
-
Dresdale DT, Schultz M, Michtom RJ. Primary pulmonary hypertension. Am J Med 1951; 11:686-705.[Medline]
-
Rubin LJ. Approach to the diagnosis and treatment of pulmonary hypertension (clinical conference) (see comments). Chest 1989; 96:659-664.[Free Full Text]
-
Galie N, Manes A, Uguccioni L, et al. Primary pulmonary hypertension: insights into pathogenesis from epidemiology. Chest 1998; 114(suppl 3):184S-194S.[Abstract/Free Full Text]
-
Fraser RS, Pare PD, Müller NL, Colman N, eds. Pulmonary hypertension 4th ed. Philadelphia, Pa: Saunders, 1999.
-
Rich S. Primary pulmonary hypertension. Prog Cardiovasc Dis 1988; 31:205-238.[Medline]
-
Rich S. The role of thrombosis in pulmonary hypertension (editorial). Chest 1993; 103:660-661.[Free Full Text]
-
Fishman AP. Etiology and pathogenesis of primary pulmonary hypertension: a perspective. Chest 1998; 114(suppl 3):242S-247S.[Abstract/Free Full Text]
-
Kereiakes DJ, Herfkens RJ, Brundage BH, Gamsu G, Lipton MJ. Computerized tomography in chronic thromboembolic pulmonary hypertension. Am Heart J 1983; 106:1432-1436.[Medline]
-
Ravin CE, Greenspan RH, McLoud TC, Lange RC, Langou RA, Putman CE. Redistribution of pulmonary blood flow secondary to pulmonary arterial hypertension. Invest Radiol 1980; 15:29-33.[Medline]
-
Kanemoto N, Furuya H, Etoh T, Sasamoto H, Matsuyama S. Chest roentgenograms in primary pulmonary hypertension. Chest 1979; 76:45-49.[Abstract/Free Full Text]
-
Naidich DP, Webb WR, Müller NL, Krinsky GA, Zerhouni EA, Siegelman SS. Computed tomography and magnetic resonance of the thorax Philadelphia, Pa: Lippincott-Raven, 1999.
-
Tan RT, Kuzo R, Goodman LR, Siegel R, Haasler GB, Presberg KW, Medical College of Wisconsin Lung Transplant Group. Utility of CT scan evaluation for predicting pulmonary hypertension in patients with parenchymal lung disease. Chest 1998; 113:1250-1256.[Abstract/Free Full Text]
-
Ng CS, Wells AU, Padley SPG. A CT sign of chronic pulmonary arterial hypertension: the ratio of main pulmonary artery to aortic diameter. J Thorac Imaging 1999; 14:270-278.[Medline]
-
Sherrick AD, Swensen SJ, Hartman TE. Mosaic pattern of lung attenuation on CT scans: frequency among patients with pulmonary artery hypertension of different causes. AJR Am J Roentgenol 1997; 169:79-82.[Abstract/Free Full Text]
-
Worthy SA, Müller NL, Hartman TE, Swensen SJ, Padley SPG, Hansell DM. Mosaic attenuation pattern on thin-section CT scans of the lung: differentiation among infiltrative lung, airway, and vascular diseases as a cause. Radiology 1997; 205:465-470.[Abstract/Free Full Text]
-
Bergin CJ, Rios G, King MA, Belezzuoli E, Luna J, Auger WR. Accuracy of high-resolution CT in identifying chronic pulmonary thromboembolic disease. AJR Am J Roentgenol 1996; 166:1371-1377.[Abstract/Free Full Text]
-
Remy-Jardin M, Remy J, Louvegny S, Artaud D, Deschildre F, Duhamel A. Airway changes in chronic pulmonary embolism: CT findings in 33 patients. Radiology 1997; 203:355-360.[Abstract/Free Full Text]
-
Primack SL, Müller NL, Mayo JR, Remy-Jardin M, Remy J. Pulmonary parenchymal abnormalities of vascular origin: high-resolution CT findings. RadioGraphics 1994; 14:739-746.[Abstract]
-
Powe JE, Palevsky HI, McCarthy KE, Alavi A. Pulmonary arterial hypertension: value of perfusion scintigraphy. Radiology 1987; 164:727-730.[Abstract/Free Full Text]
-
D'Alonzo GE, Bower JS, Dantzker DR. Differentiation of patients with primary and thromboembolic pulmonary hypertension. Chest 1984; 85:457-461.[Abstract/Free Full Text]
-
Rich S, Pietra GG, Kieras K, Hart K, Brundage BH. Primary pulmonary hypertension: radiographic and scintigraphic patterns of histologic subtypes. Ann Intern Med 1986; 105:499-502.
-
Randall PA, Heitzman ER, Bull MJ, et al. Pulmonary arterial hypertension: a contemporary review. RadioGraphics 1989; 9:905-927.[Abstract]
-
Endrys J, Hayat N, Cherian G. Comparison of bronchopulmonary collaterals and collateral blood flow in patients with chronic thromboembolic and primary pulmonary hypertension. Heart 1997; 78:171-176.[Abstract/Free Full Text]
-
White RD, Higgins CB. Magnetic resonance imaging of thoracic vascular disease. J Thorac Imaging 1989; 4:34-50.[Medline]
-
Moore NR, Scott JP, Flower CD, Higenbottam TW. The relationship between pulmonary artery pressure and pulmonary artery diameter in pulmonary hypertension. Clin Radiol 1988; 39:486-489.[Medline]
-
Murray TI, Boxt LM, Katz J, Reagan K, Barst RJ. Estimation of pulmonary artery pressure in patients with primary pulmonary hypertension by quantitative analysis of magnetic resonance images. J Thorac Imaging 1994; 9:198-204.[Medline]
-
Yaginuma G, Mohri H, Takahashi T. Distribution of arterial lesions and collateral pathways in the pulmonary hypertension of congenital heart disease: a computer aided reconstruction study. Thorax 1990; 45:586-590.[Abstract/Free Full Text]
-
Higgins CB. Essentials of cardiac radiology and imaging 1st ed. Philadelphia, Pa: Lippincott, 1992.
-
Virmani R, Clark MA, Posey DM, McAllister HA, Jr. Right atrial myxoma causing pulmonary emboli and pulmonary hypertension. Am J Forensic Med Pathol 1982; 3:249-252.[Medline]
-
Heck HA, Jr, Gross CM, Houghton JL. Long-term severe pulmonary hypertension associated with right atrial myxoma. Chest 1992; 102:301-303.[Abstract/Free Full Text]
-
Jardine DL, Lamont DL. Right atrial myxoma mistaken for recurrent pulmonary thromboembolism. Heart 1997; 78:512-514.[Abstract/Free Full Text]
-
Tai AR, Gross H, Siegelman SS. Right atrial myxoma and pulmonary hypertension. N Y State J Med 1970; 70:2996-3000.[Medline]
-
Rich S, Levitsky S, Brundage BH. Pulmonary hypertension from chronic pulmonary thromboembolism. Ann Intern Med 1988; 108:425-434.
-
Dunning J, McNeil K. Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension. Thorax 1999; 54:755-756.[Free Full Text]
-
Widimsky J. Acute pulmonary embolism and chronic thromboembolic pulmonary hypertension: is there a relationship?. (editorial). Eur Respir J 1991; 4:137-140.
-
Moser KM, Bloor CM. Pulmonary vascular lesions occurring in patients with chronic major vessel thromboembolic pulmonary hypertension (see comments). Chest 1993; 103:685-692.[Abstract/Free Full Text]
-
Kereiakes DJ, Lipton MJ. Diagnosis of thromboembolic pulmonary hypertension (letter). Ann Intern Med 1983; 99:880.
-
Moser KM, Auger WR, Fedullo PF, Jamieson SW. Chronic thromboembolic pulmonary hypertension: clinical picture and surgical treatment. Eur Respir J 1992; 5:334-342.[Abstract]
-
Auger WR, Channick RN, Kerr KM, Fedullo PF. Evaluation of patients with suspected chronic thromboembolic pulmonary hypertension. Semin Thorac Cardiovasc Surg 1999; 11:179-190.[Medline]
-
Bergin CJ, Sirlin CB, Hauschildt JP, et al. Chronic thromboembolism: diagnosis with helical CT and MR imaging with angiographic and surgical correlation. Radiology 1997; 204:695-702.[Abstract/Free Full Text]
-
Miller WT, Jr, Osiason AW, Langlotz CP, Palevsky HI. Reperfusion edema after thromboendarterectomy: radiographic patterns of disease. J Thorac Imaging 1998; 13:178-183.[Medline]
-
King MA, Ysrael M, Bergin CJ. Chronic thromboembolic pulmonary hypertension: CT findings. AJR Am J Roentgenol 1998; 170:955-960.[Free Full Text]
-
Remy-Jardin M, Remy J, Artaud D, Deschildre F, Duhamel A. Peripheral pulmonary arteries: optimization of the spiral CT acquisition protocol (see comments). Radiology 1997; 204:157-163.[Abstract/Free Full Text]
-
Remy-Jardin M, Remy J, Artaud D, Deschildre F, Fribourg M, Beregi JP. Spiral CT of pulmonary embolism: technical considerations and interpretive pitfalls. J Thorac Imaging 1997; 12:103-117.[Medline]
-
Sinner WN. Computed tomographic patterns of pulmonary thromboembolism and infarction. J Comput Assist Tomogr 1978; 2(4):395-399.[Medline]
-
Bergin CJ, Hauschildt J, Rios G, Belezzuoli EV, Huynh T, Channick RN. Accuracy of MR angiography compared with radionuclide scanning in identifying the cause of pulmonary arterial hypertension. AJR Am J Roentgenol 1997; 168:1549-1555.[Abstract/Free Full Text]
-
Bergin CJ, Hauschildt JP, Brown MA, Channick RN, Fedullo PF. Identifying the cause of unilateral hypoperfusion in patients suspected to have chronic pulmonary thromboembolism: diagnostic accuracy of helical CT and conventional angiography. Radiology 1999; 213:743-749.[Abstract/Free Full Text]
-
Nicod P, Peterson K, Levine M, et al. Pulmonary angiography in severe chronic pulmonary hypertension. Ann Intern Med 1987; 107:565-568.
-
Brown KT, Bach AM. Paucity of angiographic findings despite extensive organized thrombus in chronic thromboembolic pulmonary hypertension. J Vasc Interv Radiol 1992; 3:99-102.[Medline]
-
Garg K, Welsh CH, Feyerabend AJ, et al. Pulmonary embolism: diagnosis with spiral CT and ventilation-perfusion scanning—correlation with pulmonary angiographic results or clinical outcome (see comments). Radiology 1998; 208:201-208.[Abstract/Free Full Text]
-
Remy-Jardin M, Remy J, Wattinne L, Giraud F. Central pulmonary thromboembolism: diagnosis with spiral volumetric CT with the single-breath-hold technique—comparison with pulmonary angiography. Radiology 1992; 185:381-387.[Abstract/Free Full Text]
-
Godwin JD, Webb WR, Gamsu G, Ovenfors CO. Computed tomography of pulmonary embolism. AJR Am J Roentgenol 1980; 135:691-695.[Abstract]
-
Fisher MR, Higgins CB. Central thrombi in pulmonary arterial hypertension detected by MR imaging. Radiology 1986; 158:223-226.[Abstract/Free Full Text]
-
Kane RD, Hawkins HK, Miller JA, Noce PS. Microscopic pulmonary tumor emboli associated with dyspnea. Cancer 1975; 36:1473-1482.[Medline]
-
Schriner RW, Ryu JH, Edwards WD. Microscopic pulmonary tumor embolism causing subacute cor pulmonale: a difficult antemortem diagnosis (published erratum appears in Mayo Clin Proc 1991; 66:439) (see comments). Mayo Clin Proc 1991; 66:143-148.[Medline]
-
Gonzalez-Vitale JC, Garcia-Bunuel R. Pulmonary tumor emboli and cor pulmonale in primary carcinoma of the lung. Cancer 1976; 38:2105-2110.[Medline]
-
Hirata K, Miyagi S, Tome M, Asato H, Uechi N, Kunishima N. Cor pulmonale due to tumor cell microemboli: report of a case with occult gastric carcinoma. Arch Intern Med 1988; 148:2287-2289.[Abstract/Free Full Text]
-
Kupari M, Laitinen L, Hekali P, Luomanmaki K. Cor pulmonale due to tumor cell embolization: report of a case and a brief review of the literature. Acta Med Scand 1981; 210:507-510.[Medline]
-
Chan CK, Hutcheon MA, Hyland RH, Smith GJ, Patterson BJ, Matthay RA. Pulmonary tumor embolism: a critical review of clinical, imaging, and hemodynamic features. J Thorac Imaging 1987; 2:4-14.[Medline]
-
Scully RE, Galdabini JJ, McNeely BU. Case records of the Massachusetts General Hospital: weekly clinicopathological exercises—case 43-1980. N Engl J Med 1980; 303:1049-1056.[Medline]
-
Seemann MD, Brenner P. Demonstration of spiral CT scans and reconstructions of a right atrial myxoma with bilateral pulmonary tumor emboli and a coincidental benign mediastinal thymoma. Eur J Med Res 1996; 1:515-519.[Medline]
-
Graham JP, Rotman HH, Weg JG. Tumor emboli presenting as pulmonary hypertension: a diagnostic dilemma. Chest 1976; 69:229-230.[Abstract]
-
Shepard JA, Moore EH, Templeton PA, McLoud TC. Pulmonary intravascular tumor emboli: dilated and beaded peripheral pulmonary arteries at CT (see comments). Radiology 1993; 187:797-801.[Abstract/Free Full Text]
-
Roglan A, Artigas A, Sole J. Severe pulmonary artery hypertension (clinical conference). Intensive Care Med 1988; 14:510-518.[Medline]
-
Miyauchi Y, Endo T, Kuroki S, Hayakawa H. Right atrial myxoma presenting with recurrent episodes of pulmonary embolism. Cardiology 1992; 81:178-181.[Medline]
-
Goncalves EC, Fonseca AP, Pittella JE. Frequency of schistosomiasis mansoni, of its clinicopathological forms, and of the ectopic locations of the parasite in autopsies in Belo Horizonte, Brazil. J Trop Med Hyg 1995; 98:289-295.[Medline]
-
Morris W, Knauer CM. Cardiopulmonary manifestations of schistosomiasis. Semin Respir Infect 1997; 12:159-170.[Medline]
-
Pagan Saez H. Schistosoma mansoni: its radiographic manifestations. Presented at the International Congress of Radiology, Brussels 1981. Bol Asoc Med P R 1985; 77:195-201.
-
Chaves E. The pathology of the arterial pulmonary vasculature in Manson's schistosomiasis. Dis Chest 1966; 50:72-77.
-
Sadigursky M, Andrade ZA. Pulmonary changes in schistosomal cor pulmonale. Am J Trop Med Hyg 1982; 31:779-784.
-
Bethlem EP, Schettino GdP, Carvalho CR. Pulmonary schistosomiasis. Curr Opin Pulm Med 1997; 3:361-365.[Medline]
-
Boueri FMV, Barbas Filho JV, Saldiva PHH, et al. Pulmonary involvement in Manson's schistosomiasis. Chest 1993; 104(suppl 2):66S.
-
Padley SP, Adler BD, Staples CA, Miller RR, Müller NL. Pulmonary talcosis: CT findings in three cases. Radiology 1993; 186:125-127.[Abstract/Free Full Text]
-
Zientara M, Moore S. Fatal talc embolism in a drug addict. Hum Pathol 1970; 1:324-327.[Medline]
-
Sieniewicz DJ, Nidecker AC. Conglomerate pulmonary disease: a form of talcosis in intravenous methadone abusers. AJR Am J Roentgenol 1980; 135:697-702.[Abstract]
-
Pare JP, Cote G, Fraser RS. Long-term follow-up of drug abusers with intravenous talcosis. Am Rev Respir Dis 1989; 139:233-241.[Medline]
-
Crouch E, Churg A. Progressive massive fibrosis of the lung secondary to intravenous injection of talc: a pathologic and mineralogic analysis. Am J Clin Pathol 1983; 80:520-526.[Medline]
-
Pare JA, Fraser RG, Hogg JC, Howlett JG, Murphy SB. Pulmonary 'mainline' granulomatosis: talcosis of intravenous methadone abuse. Medicine (Baltimore) 1979; 58:229-239.[Medline]
-
Carrington CB, Liebow AA. Pulmonary veno-occlusive disease. Hum Pathol 1970; 1:322-324.[Medline]
-
Williamson WA, Tronic BS, Levitan N, Webb-Johnson DC, Shahian DM, Ellis FH, Jr. Pulmonary venous infarction. Chest 1992; 102:937-940.[Abstract/Free Full Text]
-
Wagenvoort CA. Vasoconstrictive primary pulmonary hypertension and pulmonary veno-occlusive disease. In: Brest AN, eds. Cardiovascular clinics. Philadelphia, Pa: Davis, 1972; 98-113.
-
Wagenvoort CA, Wagenvoort N, Takahashi T. Pulmonary veno-occlusive disease: involvement of pulmonary arteries and review of the literature. Hum Pathol 1985; 16:1033-1041.[Medline]
-
Joselson R, Warnock M. Pulmonary veno-occlusive disease after chemotherapy. Hum Pathol 1983; 14:88-91.[Medline]
-
Tsou E, Waldhorn RE, Kerwin DM, Katz S, Patterson JA. Pulmonary venoocclusive disease in pregnancy. Obstet Gynecol 1984; 64:281-284.[Medline]
-
Maltby JD, Gouverne ML. CT findings in pulmonary venoocclusive disease. J Comput Assist Tomogr 1984; 8(4):758-761.[Medline]
-
Lombard CM, Churg A, Winokur S. Pulmonary veno-occlusive disease following therapy for malignant neoplasms. Chest 1987; 92:871-876.[Abstract/Free Full Text]
-
Dufour B, Maitre S, Humbert M, Capron F, Simonneau G, Musset D. High-resolution CT of the chest in four patients with pulmonary capillary hemangiomatosis or pulmonary venoocclusive disease. AJR Am J Roentgenol 1998; 171:1321-1324.[Abstract/Free Full Text]
-
Katz DS, Scalzetti EM, Katzenstein AL, Kohman LJ. Pulmonary veno-occlusive disease presenting with thrombosis of pulmonary arteries. Thorax 1995; 50:699-700.[Abstract/Free Full Text]
-
Hasleton PS, Ironside JW, Whittaker JS, Kelly W, Ward C, Thompson GS. Pulmonary veno-occlusive disease: a report of four cases. Histopathology 1986; 10:933-944.[Medline]
-
Scheibel RL, Dedeker KL, Gleason DF, Pliego M, Kieffer SA. Radiographic and angiographic characteristics of pulmonary veno-occlusive disease. Radiology 1972; 103:47-51.[Medline]
-
Chawla SK, Kittle CF, Faber LP, Jensik RJ. Pulmonary venoocclusive disease. Ann Thorac Surg 1976; 22:249-253.[Abstract]
-
Sondheimer HM, Lum Lung MC, Brugman SM, Ikle DN, Fan LL, White CW. Pulmonary vascular disorders masquerading as interstitial lung disease. Pediatr Pulmonol 1995; 20:284-288.[Medline]
-
Shackelford GD, Sacks EJ, Mullins JD, McAlister WH. Pulmonary venoocclusive disease: case report and review of the literature. AJR Am J Roentgenol 1977; 128:643-648.[Abstract]
-
Matsumoto JS, Hoffman AD. Pediatric case of the day: pulmonary venoocclusive disease. AJR Am J Roentgenol 1993; 160:1331-1332.[Free Full Text]
-
Botticelli JT, Schlueter DP, Lange RL. Pulmonary venous and arterial hypertension due to chronic fibrous mediastinitis: hemodynamics and pulmonary function. Circulation 1966; 33:862-871.[Abstract/Free Full Text]
-
Berry DF, Buccigrossi D, Peabody J, Peterson KL, Moser KM. Pulmonary vascular occlusion and fibrosing mediastinitis. Chest 1986; 89:296-301.[Abstract/Free Full Text]
-
Mendelson EB, Mintzer RA, Hidvegi DF. Venoocclusive pulmonary infarct: an unusual complication of fibrosing mediastinitis. AJR Am J Roentgenol 1983; 141:175-176.[Free Full Text]
-
Arnett EN, Bacos JM, Macher AM, et al. Fibrosing mediastinitis causing pulmonary arterial hypertension without pulmonary venous hypertension: clinical and necropsy observations. Am J Med 1977; 63:634-643.[Medline]
-
Espinosa RE, Edwards WD, Rosenow EC. Idiopathic pulmonary hilar fibrosis: an unusual cause of pulmonary hypertension. Mayo Clin Proc 1993; 68:778-782.[Medline]
-
Nasser WK, Feigenbaum H, Fisch C. Clinical and hemodynamic diagnosis of pulmonary venous obstruction due to sclerosing mediastinitis. Am J Cardiol 1967; 20:725-729.[Medline]
-
Adey CK, Soto B, Shin MS. Congenital pulmonary vein stenosis: a radiographic study. Radiology 1986; 161:113-117.[Abstract/Free Full Text]
-
Williamson WA, Tronic BS, Levitan N, Webb-Johnson DC, Shahian DM, Ellis FH, Jr. Pulmonary venous infarction secondary to squamous cell carcinoma. Chest 1992; 102:950-952.[Abstract/Free Full Text]
-
DeLuca A, Daniels S, Pathak N. Pulmonary edema due to extreme left atrial compression. N J Med 1991; 88:37-38.[Medline]
-
Kawanishi K, Sato K, Ofuji T, Ogawa K. A case of left atrial myxoma accompanied by pancytopenia and pathological findings suggestive of pulmonary hypertension. Acta Med Okayama 1974; 28:433-440.
-
Larsson S, Lepore V, Kennergren C. Atrial myxomas: results of 25 years' experience and review of the literature. Surgery 1989; 105:695-698.[Medline]
-
Molina JE, Edwards JE, Ward HB. Primary cardiac tumors: experience at the University of Minnesota. Thorac Cardiovasc Surg 1990; 38(suppl 2):183-195.
-
Nakano T, Mayumi H, Morita S, Shiraishi K, Kanegae Y, Yasui H. Left atrial myxoma associated with severe congestive heart failure, pulmonary hypertension, and multiple organ insufficiency. Jpn Heart J 1995; 36:829-834.[Medline]
-
Nakano T, Mayumi H, Hisahara M, Yasui H, Tokunaga K. The relationship between functional class, pulmonary artery pressure, and size in left atrial myxoma. Cardiovasc Surg 1996; 4:320-323.[Medline]
-
Mittal SR, Jain S, Mathur DK, Gokhroo RK. Pulmonary regurgitation due to pulmonary artery hypertension secondary to left atrial tumor (letter). Indian Heart J 1997; 49:555-556.[Medline]
-
Stevens LH, Hormuth DA, Schmidt PE, Atkins S, Fehrenbacher JW. Left atrial myxoma: pulmonary infarction caused by pulmonary venous occlusion. Ann Thorac Surg 1987; 43:215-217.[Abstract]
-
Dawson WB, Mayo JR, Müller NL. Computed tomography of cardiac and pericardial tumors. Can Assoc Radiol J 1990; 41:270-275.[Medline]
-
Mehan VK, Deshpande J, Dalvi BV, Kale PA. Direct extension of bronchogenic carcinoma through pulmonary veins into the left atrium mimicking left atrial myxoma. Chest 1992; 101:1722-1723.[Abstract/Free Full Text]
-
Lee MM, Park SW, Kim CH, et al. Relation of pulmonary venous flow to mean left atrial pressure in mitral stenosis with sinus rhythm. Am Heart J 1993; 126:1401-1407.[Medline]
-
Palileo RA, Santos RJ. Transesophageal echo-cardiographic Doppler study of the pulmonary venous flow pattern in severe mitral stenosis with variable degrees of mitral regurgitation. J Am Soc Echocardiogr 1997; 10:540-544.[Medline]
-
Biasucci LM, De Benedittis G, Alecce G, Lombardo A, Loperfido F. Doppler analysis of pulmonary venous flow in left atrial myxoma. Chest 1994; 105:315-317.[Abstract/Free Full Text]
-
Klein AL, Bailey AS, Cohen GI, et al. Effects of mitral stenosis on pulmonary venous flow as measured by Doppler transesophageal echocardiography. Am J Cardiol 1993; 72:66-72.[Medline]
-
Tice FD, Heinle SK, Harrison JK, et al. Transesophageal echocardiographic assessment of reversal of systolic pulmonary venous flow in mitral stenosis. Am J Cardiol 1995; 75:58-60.[Medline]
-
Mohiaddin RH, Amanuma M, Kilner PJ, Pennell DJ, Manzara C, Longmore DB. MR phase-shift velocity mapping of mitral and pulmonary venous flow. J Comput Assist Tomogr 1991; 15(2):237-243.[Medline]
-
Kisanuki A, Shibata K, Otsuji Y, et al. Pulmonary venous flow patterns assessed by transesophageal pulsed Doppler echocardiography in left atrial myxoma. Am J Cardiol 1993; 72:1089-1093.[Medline]
-
Panidis IP, Mintz GS, McAllister M. Hemodynamic consequences of left atrial myxomas as assessed by Doppler ultrasound. Am Heart J 1986; 111:927-931.[Medline]
-
St John Sutton MG, Mercier LA, Giuliani ER, Lie JT. Atrial myxomas: a review of clinical experience in 40 patients. Mayo Clin Proc 1980; 55:371-376.[Medline]
-
Semb BKH, Wexels JC, Vatne K, Bjornstad PG. Angiographic and echocardiographic observations in surgical patients with atrial myxoma. Cardiovasc Interv Radiol 1985; 8:119-126.[Medline]
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Abstract
Introduction
