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Pulmonary hypertension is defined as a resting mean pulmonary arterial pressure of ≥25 mmHg at right heart catheterization, which is a hemodynamic feature that is shared by all types of pulmonary hypertension.
A resting mean pulmonary arterial pressure of ≤20 mmHg is considered normal, while mean pulmonary arterial pressures ranging between 21-24 mmHg are considered abnormal requiring further investigation of the clinical course of the disease.
The use of the term pulmonary arterial hypertension is restricted to those with a hemodynamic profile in which high pulmonary pressure results from elevated precapillary pulmonary resistance and normal pulmonary venous pressure and is measured as a pulmonary wedge pressure of ≤15 mmHg. This corresponds to the hemodynamic profiles of groups 3, 4, and 5 ( and of course group 1) in the Dana Point classification system, which was updated during the 5th World Symposium on Pulmonary Hypertension.
Epidemiology varies with the underlying cause and risk factors. Overall, there is a female predilection.
Risk factors include 3:
drugs and toxins
aminorex (withdrawn from the market)
toxic rapeseed oil
Classical clinical presentation of pulmonary arterial hypertension is the combination of dyspnea (especially with exercise) with symptoms and signs of elevated right heart pressures, including peripheral edema and abdominal distension 2,3.
An ECG may demonstrate right ventricular strain and hypertrophy.
Pulmonary arterial hypertension is defined as a mean pulmonary arterial pressure >25 mmHg at rest 11 or >30 mmHg with exercise and pulmonary capillary wedge pressure ≤15 mmHg measured by cardiac catheterization 3,4. It can result from either increased pulmonary venous resistance (most common) or increased pulmonary arterial flow, such as with a left-to-right shunt 2.
Even in cases of increased flow, the main factor in generating severe pulmonary hypertension is an arteriopathy, which has four main components 3:
plexiform lesions: focal proliferation of endothelial channels
The earliest change is muscular hypertrophy in muscular arteries which, over time, results in changes in the more proximal arteries. Eventually, fibrosis of the wall occurs, at which point the process is irreversible 2.
In addition to cases of idiopathic pulmonary arterial hypertension, there are numerous known causes, and these can be subdivided in many ways. A simple unofficial classification is to divide the causes of secondary pulmonary arterial hypertension anatomically:
chest wall and upper airways, e.g.
pulmonary veins and left heart, e.g.
pulmonary capillaries and pulmonary parenchyma, e.g.
pulmonary arteries, e.g.
See causes of pulmonary arterial hypertension for a complete list.
Alternative classifications include:
precapillary versus postcapillary 6
WHO classification grouping of pulmonary hypertension
group 1: pulmonary arterial hypertension - due to narrowed stiff or thickened pulmonary arteries.
group 2: due to left sided heart disease
group 3: due to lung disease hypoxia
group 4: chronic thromboembolic pulmonary hypertension (CTEPH) / other forms of pulmonary arterial obstruction
group 5: multifactorial mechanisms
By the time the diagnosis of pulmonary arterial hypertension is made, 90% of patients have an abnormal chest radiograph 3, although sensitivity and specificity are low 12. Features include11:
elevated cardiac apex due to right ventricular hypertrophy
enlarged right atrium
prominent pulmonary outflow tract
enlarged pulmonary arteries
pruning of peripheral pulmonary vessels
radiographic correlates of underlying causes like kyphoscoliosis, valvular heart disease, or changes due to interstitial lung disease can also be noted in some cases
When screening patients with a clinical suspicion of pulmonary hypertension, echocardiography findings can be used to grade the probability of elevated pulmonary artery pressures being present on right heart catheterization, as well as identify possible precipitants such as an atrial septal defect, valvular regurgitation or stenosis, or left ventricular diastolic dysfunction 20,21
The first measurement is the maximum velocity of the tricuspid regurgitant jet as observed from the apical four chambers, right ventricular inflow tract, or parasternal short (at the aortic valve level) axis views. The measured velocity informs one as follows:
velocities >3.4 m/s are definitely abnormal, and the suspicion for pulmonary hypertension is high
velocities below 2.8 m/s (or unmeasurable) and between 2.8 and 3.4 m/s require further measurements
velocities <2.8 m/s (or unmeasurable) are stratified as low suspicion if there are <2 positive categories, and intermediate if there are 2 or more
velocities between 2.8 and 3.4 m/s are either intermediate suspicion (<2 positive categories)
The ventricles (category A), pulmonary artery (category B), and right atrium and inferior vena cava (category C) may reveal suggestive findings of increased pressure/volume (a category is "positive" when one or more of the following findings are present).
The relative dimensions of the ventricles may be altered by the exaggerated interventricular dependence characteristic of elevated right heart pressures and demonstrate
a right ventricle:left ventricle basal diameter ratio exceeding 1.0 (RV/LV ratio >1)
a left ventricular eccentricity index >1.1
a manifestation of flattening of the interventricular septum, assessed by dividing the short-axis diameter of the LV parallel and then perpendicular to the septum and dividing these values to yield an eccentricity index
this is often "eyeballed" as a "D sign" (a reference to the shape of the left ventricle)
The pulmonary artery diameter and pulsed/continuous wave Doppler indices are assessed in category B for the following findings
an acceleration time (AT) of the right ventricular outflow tract <105 ms and/or mid-systolic notching of the Doppler envelope
the latter suggestive of group 1 (precapillary) pulmonary arterial hypertension
an early diastolic pulmonary regurgitation velocity over 2.2 m/s
PA diameter >25 mm
Finally, the inferior vena cava and right atrium are assessed for the following features
an inferior vena cava which is over 2.1 cm at end-expiration with <50% collapse (when an inspiratory sniff is performed)
<20% variance with quiet breathing is also a positive finding
right atrial area >18 cm2 is abnormal
measured at end-systole
Other measures such as cardiac output and pulmonary vascular resistance are also assessed when more hemodynamic information is necessary. Ultimately, diagnosis cannot be made with echocardiography, and a right heart catheterization is needed when it would inform treatment.
Mosaic attenuation pattern reflects areas of relative oligemia and is particularly common in chronic thromboembolic pulmonary hypertension. If expiratory scans are conducted they will show an increase in density (cf. mosaic attenuation due to small and large airways disease).
In pulmonary veno-occlusive disease (PVOD) / pulmonary capillary haemangiomatosis (PCH), small ill-defined centrilobular nodules and interlobular septal thickening may be apparent 3. As it is difficult to distinguish idiopathic pulmonary arterial hypertension from PVOD/PCH and the initiation of vasodilatory therapy may have detrimental effects on these patients25, the communication of imaging findings hinting at PVOD/PCH can be of great importance.
Additionally, routine CT chest and CT pulmonary angiography (CTPA) can also identify changes in the pulmonary vasculature and the heart. Features include:
Extracardiac vascular signs
enlarged pulmonary trunk (measured at pulmonary artery bifurcation on an axial slice vertical to its long axis)
>29 mm diameter is often used as a general predictive cut-off 6,10,11,19 however, a recent study suggests 7:
31.6 mm may be a more statistically robust cut-off in patients without interstitial lung disease (specificity 93%)
pulmonary trunk enlargement is a poor predictor of pulmonary hypertension in patients with interstitial lung disease (specificity ~40%)
a diameter of <29 mm does not necessarily exclude pulmonary hypertension
the dilated pulmonary trunk is considered the most specific sign on CT examination
sex-specific reference values obtained from the Framingham Heart Study suggest cut-off values of 27 mm for women and 29 mm for men (on ECG-gated non-contrast CT) 14
higher ratio correlates with higher PA pressure
the ratio obtained on the axial image at the bifurcation of the right pulmonary artery 14
adult: normal ratio is less than 1.0
children: normal up to a ratio of ~1.09 15
mural calcification in central pulmonary arteries 6
most frequently seen in patients with Eisenmenger phenomenon
evidence of previous pulmonary emboli
a segmental artery-to-bronchial diameter ratio of 1:1 11-1.25 13 or more in three or four lobes in the presence of a dilated (≥29 mm) main pulmonary artery and absence of significant structural lung disease has a specificity of 100% for the presence of pulmonary hypertension 11,13
ECG-gated CTPA ideally required:
right ventricular hypertrophy: defined as the wall thickness of >4 mm
straightening or bowing (towards the left ventricle) of the interventricular septum
right ventricular dilatation (a right ventricle–to–left ventricle diameter ratio of more than 1:1 at the midventricular level on axial images)
decreased right ventricular ejection fraction
dilatation of the inferior vena cava and hepatic veins
especially common in patients with idiopathic pulmonary arterial hypertension
pathologically: represent cholesterol granulomas, which are caused by ingestion of red blood cells by pulmonary macrophages, a result of repeated episodes of pulmonary hemorrhage
neovascularity: tiny serpiginous intrapulmonary vessels that often emerge from centrilobular arterioles but do not conform to usual pulmonary arterial anatomy and can also be seen as a manifestation of severe pulmonary hypertension (eponymously known as Sheehan vessels) 24
MRI and MR angiography have an increasing role in the management of pulmonary arterial hypertension, as dynamic imaging of both the heart and pulmonary circulation can be achieved.
Traditionally pulmonary angiography has been the gold standard to identify small peripheral occlusions and to better quantify the degree of stenosis. Increasingly this has been replaced by better quality CTPA and cardiac CT.
Care also needs to be taken when performing a pulmonary angiogram in patients with severe pulmonary hypertension.
Treatment and prognosis
Medical therapy includes 4:
calcium channel antagonists
prostanoids, e.g. epoprostenol, treprostinil, iloprost
endothelin antagonists, e.g. bosentan, sitaxentran, ambrisentan
phosphodiesterase inhibitors, e.g. dipyridamole
In selected cases, combined heart and lung transplantation can be performed 5. In patients with very high right heart pressures, an atrial septostomy has also been performed but is associated with high immediate mortality and reduces oxygenation due to the right-left shunt formed.
In cases where pulmonary arterial hypertension is due to proximal pulmonary emboli, a pulmonary thromboendarterectomy is a surgical option.
Despite extensive research and recent advances in medical management, prognosis remains poor, with a mean survival of only three years in untreated patients 5. Patients typically succumb to right heart failure or sudden death.
pulmonary arterial dilatation can occur in the absence of pulmonary hypertension in some people with pulmonary fibrosis 16
for an enlarged pulmonary artery, also consider - idiopathic dilatation of the pulmonary trunk
Consider differentials for mosaic attenuation pattern if this is the sole finding.
As a broad differential on plain film, consider:
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