The Imaging of Pulmonary Hypertension
Section snippets
Pathophysiology
PAH represents a spectrum of idiopathic and associated diseases that result in vascular remodeling primarily of preacinar and intra-acinar muscular arteries with an external diameter of 50-400 μm.8, 9 PAH is characterized by an increase in vascular smooth muscle cells with medial proliferation and smooth muscle cell extension into intra-acinar arterioles. Functionally, there are endothelial dysfunction and vasoconstriction, mediated in part by inflammation and defects in apoptosis.10 Resistance
The Imaging of PH
The PH-induced alterations of pulmonary vasculature truly reflect the underlying mural architecture of the vessels.22, 23 The central pulmonary arteries coursing to the level of the segmental bronchi are formed of multiple parallel elastic laminae and therefore dilate in the face of elevated pulmonary vascular resistance. These vessels gradually transition to muscular arteries along the distal segmental and subsegmental airways. With a media of tightly packed smooth muscle cells, the muscular
A Spectrum of Diseases
It is important for radiologists to recognize the diagnostic framework of the Dana Point Symposium classification, which organizes this broad spectrum of diseases into 5 groups. Group 1 (identifiable conditions of PAH with high pulmonary vascular resistance), group 3 (pulmonary disease and hypoxic states), group 4 (chronic thromboembolic disease), and group 5 (multifactorial or unusual scenarios, eg, sarcoidosis, mediastinal fibrosis) are regarded as primarily precapillary disorders (with the
Idiopathic PAH and Heritable PAH
Idiopathic PAH (formerly termed primary PH) (group 1) is a severe and sporadic form of PH with no identifiable risk factor or familial association. The prevalence of IPAH is about 6 persons per million and has clear female predominance (almost 2:1) with mean age 37 years. Heritable PAH (formerly termed familial PH) (group 1) is distinguished from IPAH only by the presence of germline mutations, chiefly in the bone morphogenetic protein receptor type 2 gene with an autosomal dominant pattern of
Congenital Heart Disease
PAH complicates CHD with systemic-to-pulmonary shunts (group 1). Without correction, a ventricular septal defect (VSD), an atrial septal defect (ASD), a patent ductus arteriosus, or a truncus arteriosus may relentlessly assault the pulmonary arterial circuit with high flow volume and systemic arterial pressure. Cascades of vasoconstriction, shear stress, intimal injury, angiogenesis, thrombosis, and vascular remodeling ensue. As vascular resistance meets systemic levels, Eisenmenger syndrome
Chronic Thromboembolic PH
CTEPH (group 4) is not easily discerned clinically from other causes of PAH, including IPAH. Approximately 4% of acute pulmonary embolism cases may progress to CTEPH within 2 years. Risk factors include elevated factor VIII, antiphospholipid antibodies, malignancy, chronic inflammatory disease, previous splenectomy, and hypothyroidism. CTEPH appears to be instigated by incomplete resolution of acute pulmonary embolism followed by vascular inflammation, fibroblast migration, obstruction,
Pulmonary Interstitial Disease and Hypoxic States
In the setting of many obstructive or restrictive interstitial lung diseases, associated PH significantly diminishes patient functional status and survival. This is well recognized in COPD and IPF. Additional pulmonary diseases associated in this category include chronic bronchiectasis, cystic fibrosis, pulmonary Langerhans cell histiocytosis, idiopathic nonspecific interstitial pneumonia (NSIP), and smoking-related pulmonary fibrosis. PH related to sleep disordered breathing, chronic
Associated Systemic Disorders
This section describes a group of diseases strongly associated with PAH. Although a clear cause currently eludes researchers, the PAH is currently regarded as multifactorial and results from variable measures of autoimmunity, vasculitis, vasoconstriction, hypercoagulability, cardiac disease, and pulmonary parenchymal disease. It is again notable that the presence and severity of PAH does not uniformly correlate with severity of parenchymal disease: significant hemodynamic derangement can exist
PVOD and PCH
PVOD and PCH are rare and aggressive idiopathic subgroups of PAH that typically manifest in young to middle-aged adult patients. PVOD is defined by widespread occlusive intimal fibrosis of the small pulmonary veins and venules. PCH is characterized by multiple nodular lesions of capillary proliferation. Both diseases produce severe elevations of mPAP with rapid clinical progression over months to a few short years, and both are difficult to discern from IPAH. Lung biopsy is required for
PH Secondary to Left-Sided Cardiac Disease
PH secondary to left-sided cardiac disease (group 2) reflects retrograde transmission of elevated pressure across the postcapillary circulation and capillary bed. PH in this scenario is defined as an mPAP of 20 mm Hg with a pulmonary wedge pressure of >15 mm Hg. The distinction between PAH and pulmonary venous hypertension due to left heart disease is crucial because treatment and prognosis are different. Myocardial disease with systolic or diastolic failure, valvular disorders, pericardial
Extravascular Constriction
Any lesion that encases central pulmonary vessels can produce PH by extrinsic vasoconstriction. Central lung neoplasm, fibrosis after radiation therapy, and mediastinal fibrosis can each produce secondary PH, and its presence negatively impacts prognosis. Mediastinal fibrosis (group 5) appears to be an immune-mediated fibroinflammatory disease provoked by sarcoid-related lymphadenitis or previous mycobacterial or fungal infection, most commonly Histoplasma capsulatum in North America.
Conclusions
PH is a critical hemodynamic derangement of the pulmonary circulation driven by complex cascades of inflammation, vasoconstriction, embolic phenomena, and vascular remodeling. Extrinsic agents, systemic diseases, idiopathic disorders, congenital lesions, hypoxic states, and comorbidities comprise the spectrum of PH. Often a relentlessly progressive condition of insidious onset, PH warrants early detection and diagnostic categorization according to the recent Dana Point classification system.
References (98)
- et al.
Diagnosis and assessment of pulmonary arterial hypertension
(2009) - et al.
ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association
J Am Coll Cardiol
(2009) - et al.
Different distribution of plexiform lesions in primary and secondary pulmonary hypertension
Hum Pathol
(1995) - et al.
Inflammation in pulmonary arterial hypertension
Chest
(2012) - et al.
Primary pulmonary hypertension: A histopathologic study of 80 cases
Mayo Clin Proc
(1985) - et al.
Pulmonary vascular lesions occurring in patients with chronic major vessel thromboembolic pulmonary hypertension
Chest
(1993) - et al.
Pulmonary arterial hypertension
J Am Coll Cardiol
(2008) - et al.
Development and pathology of pulmonary hypertension
J Am Coll Cardiol
(2009) - et al.
Utility of CT scan evaluation for predicting pulmonary hypertension in patients with parenchymal lung disease
Chest
(1998) Right ventricular adaptation and maladaptation in chronic pulmonary arterial hypertension
Cardiol Clin
(2012)