Answers

Short answer

1 The radiograph shows enlargement of the central pulmonary arteries, with attenuation of the peripheral vessels, suggestive of pulmonary hypertension (fig 2).

View larger version (159K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 2 Patient’s chest radiograph showing enlargement of the central pulmonary arteries (arrowheads), with attenuation of the peripheral vessels (arrows)

 

2 Pulmonary hypertension can be associated with pulmonary arterial hypertension, either idiopathic, familial, or associated (with collagen vascular disease, left to right intracardiac shunts, portal hypertension, HIV infection, anorectic drugs, stimulants, or pulmonary venous obstruction); left heart disease; lung diseases or hypoxia; chronic thrombotic or embolic disease; and other diseases such as sarcoidosis or compression of pulmonary vessels.

3 Transthoracic echocardiography is the preferred non-invasive screening test to estimate pulmonary artery systolic pressure.

4 Non-invasive diagnostic tests include ventilation-perfusion scanning, pulmonary function tests, overnight oximetry, serology (liver function tests, HIV screening, antinuclear antibody tests), and the six minute walking test. Invasive right heart catheterisation is also needed to confirm the diagnosis.

Long answers
1 Findings on radiography
The characteristic radiographic findings of pulmonary hypertension are enlargement of the pulmonary hila and attenuation of the peripheral vessels, resulting in oligaemic lung fields. The accuracy of chest radiography in detecting pulmonary arterial hypertension is unknown. Chest radiography is abnormal at the time of diagnosis in 90% of patients with idiopathic pulmonary arterial hypertension.¹ The posteroanterior view may show a right descending pulmonary artery diameter greater than 18 mm and right atrial and ventricular enlargement (55% of cases).²

Bilateral hilar enlargement can be caused by enlarged lymph nodes or central pulmonary arterial dilatation (fig 3). The following two radiographic signs can help to distinguish between these two causes:³

• The hilum convergence sign. The hilar shadows mainly represent the pulmonary arteries, which taper gradually and have vessels arising from their periphery. The size and density of the pulmonary hila increase with the enlargement of the pulmonary arteries, but the hila retain their vascular appearance. The appearance of pulmonary vessels converging on the lateral aspect of the hilum is termed the hilum convergence sign and is indicative of vascular dilatation as the cause of hilar enlargement (fig 4).
  
• The hilar angle sign. The vessels of the upper lobe and the interlobar pulmonary artery form an angle in the right hilum, which is normally concave. Lymphadenopathies or hilar masses result in a focal alteration of the normal hilar contour, giving a convex appearance. When the pulmonary arteries are enlarged the hilar angle retains its normal concave appearance (fig 5).
  

View larger version (36K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 3 Diagram showing a normal chest radiograph (left panel), increased hilar size caused by enlarged lymph nodes (middle panel, arrows), and increased hilar size caused by central pulmonary arterial dilatation (right panel, arrowheads)

 

View larger version (125K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 4 Detail of the right hilum in an 83 year old woman with malignant diffuse large cell lymphoma (left panel). Dotted lines represent vessels converging on the hilum. Continuous lines represent a possible mass filling in the hilar shadow. The hilum convergence sign is not apparent. Detail of the right hilum of our patient (right panel). Dotted lines represent vessels converging on the hilum—the hilum convergence sign

 

View larger version (124K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 5 Detail of the right hilum in an 83 year old woman with a malignant diffuse large cell lymphoma (left panel). Dotted lines show the convex appearance. Detail of the right hilum of our patient (right panel). Dotted lines show the concave appearance

 
As well as indicating pulmonary arterial hypertension, chest radiography can provide additional information about its causes and consequences.

2 Causes
Pulmonary hypertension has many causes. The World Health Organization (WHO) has classified pulmonary hypertension into five groups according to the mechanistic basis (box).⁴ Pulmonary arterial hypertension is a category of pulmonary hypertension (group 1). The two terms are not synonymous. Pulmonary hypertension is defined by a mean pulmonary artery pressure >25 mm Hg at rest or >30 mm Hg with exercise. Patients with pulmonary arterial hypertension also have a normal (15 mm Hg) pulmonary capillary wedge pressure and a pulmonary vascular resistance greater than 3 Wood units. The diagnosis of pulmonary arterial hypertension requires the identification of one of the entities included in WHO group 1.

Revised WHO classification of pulmonary hypertension4    1. Pulmonary arterial hypertension 1.1. Idiopathic 1.2. Familial 1.3. Associated with: 1.3.1. Connective tissue disease 1.3.2. Congenital systemic to pulmonary shunts 1.3.3. Portal hypertension 1.3.4. HIV infection 1.3.5. Drugs and toxins 1.3.6. Other (thyroid disorders, glycogen storage disease, Gaucher’s disease, hereditary haemorrhagic telangiectasia, haemoglobinopathies, myeloproliferative disorders, splenectomy) 1.4. Associated with venous or capillary disease 1.4.1. Pulmonary veno-occlusive disease 1.4.2. Pulmonary capillary haemangiomatosis 1.5. Persistent pulmonary hypertension of the newborn    2. Pulmonary hypertension associated with left heart disease 2.1. Left sided atrial or ventricular heart disease 2.2. Left sided valvular heart disease    3. Pulmonary hypertension associated with lung respiratory diseases or hypoxia (or both) 3.1. Chronic obstructive pulmonary disease 3.2. Interstitial lung disease 3.3. Sleep disordered breathing 3.4. Alveolar hypoventilation disorders 3.5. Chronic exposure to high altitude 3.6. Developmental abnormalities    4. Pulmonary hypertension caused by chronic thrombotic disease or embolic disease (or both) 4.1. Thromboembolic obstruction of proximal pulmonary arteries 4.2. Thromboembolic obstruction of distal pulmonary arteries 4.3. Non-thrombotic pulmonary embolism (tumour, parasites, foreign material)    5. Miscellaneous Sarcoidosis, histiocytosis X, lymphangiomatosis, compression of pulmonary vessels (adenopathy, tumour, fibrosing mediastinitis)

3 Confirmation of the diagnosis
The diagnosis of pulmonary hypertension requires a strategy based on a series of investigations intended to⁵:

• Generate a clinical suspicion of pulmonary hypertension.
  
• Detect pulmonary hypertension.
  
• Classify pulmonary hypertension according the WHO classification (box) and evaluate functional capacity and haemodynamics.
  

Generating a clinical suspicion of pulmonary hypertension A history should be taken and physical examination, chest radiography, and electrocardiography performed in all patients with suspected pulmonary hypertension. Pulmonary hypertension should be suspected in patients with dyspnoea associated with exertion, fatigue, or weakness. Clinical suspicion may also arise because of abnormalities detected by electrocardiography or chest radiography. In our patient, the history of exertional dyspnoea, the tricuspid systolic murmur on physical examination, and the results of chest radiography (fig 1) and electrocardiography (fig 6) suggested pulmonary hypertension.

View larger version (62K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 6 The patient’s 12 lead electrocardiograph

 
Electrocardiography is not sensitive enough to be a screening tool for pulmonary hypertension. The sensitivities of right ventricular hypertrophy and right axis deviation were 55% and 73%, respectively, in 61 patients with pulmonary arterial hypertension or idiopathic pulmonary arterial hypertension; specificity was 70%.⁶ Chest radiography is even less sensitive,⁷ but it can help define related conditions by identifying signs of chronic obstructive pulmonary disease, kyphosis, or pulmonary venous congestion.

Detection of pulmonary hypertension If the history, physical examination, chest radiography, and electrocardiography point to pulmonary hypertension, transthoracic echocardiography should be performed to confirm the diagnosis.^{2 8} This test can provide an estimate of right ventricular systolic pressure using the velocity of the tricuspid regurgitation jet. Right ventricular systolic pressure is equal to systolic pulmonary artery pressure in the absence of pulmonary valve stenosis or outflow tract obstruction. One of the limitations of transthoracic echocardiography, however, is that the spectral Doppler profile of tricuspid regurgitation is too weak to be measured in 10-25% of patients.⁸

The accuracy of transthoracic echocardiography in detecting and quantifying pulmonary hypertension is unclear. The sensitivity and specificity of systolic pulmonary artery pressure estimated from transthoracic echocardiography in predicting pulmonary arterial hypertension are 79-100% and 60-98%, respectively.² Reported correlation coefficients between right ventricular systolic pressure estimated from transthoracic echocardiography or from right heart catheterisation are usually statistically significant (between r=0.57 and r=0.90²), although transthoracic echocardiography is inaccurate (difference >10 mm Hg compared with invasive measurement) in nearly half of patients.⁹

Transthoracic echocardiography can also help identify causes of pulmonary hypertension. The test can recognise left heart diseases, valvular diseases, and myocardial diseases related to pulmonary venous hypertension, as well as systemic to pulmonary shunts and congenital heart disease. In our patient, transthoracic echocardiography estimated the pulmonary artery systolic pressure to be 105 mm Hg but did not identify a cause.

Evaluating pulmonary hypertension If results from transthoracic echocardiography suggest pulmonary hypertension, the patient needs other tests to classify the disease according to the WHO system and to evaluate the type of pulmonary hypertension, and their functional capacity and haemodynamics. The sequence of testing may vary according to the patient’s characteristics. In their evidence based clinical practice guidelines for screening, early detection, and diagnosis of pulmonary arterial hypertension, the American College of Chest Physicians has graded the recommendation for various tests according to the quality of published evidence ²:

• HIV serology to detect HIV infection and testing for connective tissue disease such as scleroderma, mixed connective tissue disease, or systemic lupus erythematosus (quality of evidence: expert opinion; strength of recommendation: E). The recommendations for collecting data on the use of anorexic drugs or testing for chronic liver or renal disease and sickle cell disease are not graded.
  
• Transthoracic echocardiography to evaluate left heart disease, valvular disease, and myocardial disease (good; A). Transthoracic echocardiography to look for evidence of a systemic to pulmonary shunt or congenital heart disease (fair; B).
  
• Ventilation-perfusion lung scans to look for thromboembolic disease (low; B). Computed tomography and magnetic resonance imaging are not recommended to exclude thromboembolic disease. Chest computed tomography may, however, help evaluate the pulmonary parenchyma and discriminate between pulmonary hypertension conditions.
  
• Pulmonary function tests and arterial blood oxygenation to evaluate hypoxic lung disease, ventilatory disease, or parenchymal disease (low; B). The recommendation to perform overnight oximetry is not graded.
  
• Right heart catheterisation to confirm the presence of pulmonary hypertension, to establish the specific diagnosis, and to determine the severity of disease (good; A). Right heart catheterisation to guide treatment (low; B).
  
• Serial determination of functional class and exercise capacity using the six minute walking test to establish baseline severity of disease and to measure response to treatment and progression during follow-up (good; A).
  

4 Further investigations
According to 2009 American College of Cardiology and American Heart Association expert consensus documents,⁸ tests that are essential for a definitive diagnosis include non-invasive ones such as a ventilation-perfusion scan, pulmonary function tests, overnight oximetry, serology (liver function test, HIV screening, antinuclear antibody serology), and the six minute walking test, in addition to invasive right heart catheterisation.

Other recommended but not essential tests are transoesophageal echocardiography, computed tomography angiography, polysomnography, and vasodilator testing or left heart catheterisation.

Serology, pulmonary function tests, ventilation-perfusion scan, and chest computed tomography (fig 7) were non-diagnostic in our patient. The patient walked 200 m in six minutes.

View larger version (61K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 7 Chest computed tomography (pulmonary window). Dotted circles show the enlarged pulmonary arteries compared with the corresponding segmental bronchus in the middle lobe (left panel) and in the inferior lobes (right panel)

 
Right heart catheterisation confirmed the diagnosis and showed raised systolic right ventricular pressure (85 (normal 15) mm Hg; systolic left ventricular pressure was normal); raised pulmonary artery pressures (systolic 77 (normal 16-32)/diastolic 24 (4-12)/mean 45 (7-20); systolic aortic pressures were normal; and raised pulmonary vascular resistance (3.8 Wood units). Pulmonary artery pressure and pulmonary vascular resistance were not more than two thirds of systemic values, however. Pulmonary capillary wedge was 12.3 mm Hg. Right heart catheterisation identified an atrial septal defect (3x2 cm) at the fossa ovalis. Coronary arteriography showed an abnormal vascular fistula between the proximal left anterior descending coronary artery and the pulmonary trunk (fig 8).

View larger version (77K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 8 Coronary arteriogram, right anterior oblique view (left panel). Coronary arteriogram, left anterior oblique view (right panel). Dotted circles show the vessel fistula between the proximal left anterior descending coronary artery and the pulmonary trunk. LAD=left anterior descending, LCX=left circumflex

 
Although transthoracic echocardiography may provide a measurement of pulmonary artery systolic pressure, right heart catheterisation is the gold standard to confirm the diagnosis of pulmonary arterial hypertension.⁷ Some patients do not need right heart catheterisation, however, if an alternative diagnosis is established by non-invasive testing. Right heart catheterisation is also needed to assess the severity of the haemodynamic impairment and to test the vasoreactivity of the pulmonary circulation.⁵ This technique also excludes other causes such as cardiac shunts and left heart disease. Our patient also needed coronary arteriography to complete the diagnosis.

Transthoracic echocardiography can detect congenital heart diseases with systemic to pulmonary shunts, but in this case, the atrial septal defect was not recognised until right heart catheterisation was performed. Diagnostic tests can have false negative results, and in most cases the diagnostic protocol must be completed to reduce diagnostic uncertainty.

Patient outcome
Cardiac surgery was performed to correct the fistula and to repair the atrial septal defect, according to guidelines for the management of adults with congenital heart disease.¹⁰ Closure of an atrial septal defect should be considered in the presence of net left to right shunting, when pulmonary artery pressure and pulmonary vascular resistance are less than two thirds of systemic values, or when pulmonary artery pressure responds to either pulmonary vasodilator therapy or test occlusion of the defect. Patients with severe irreversible pulmonary arterial hypertension and those without a left to right shunt should not undergo closure because it may lead to worsening of right ventricular function and establishment of Eisenmenger physiology.

After surgery the patient’s modified New York Heart Association (NYHA) functional class improved from III to I and her polycythaemia resolved.

The presence of pulmonary arterial hypertension in association with congenital heart defects that persist until adulthood is well recognised, but coronary vessel fistulae are rare.¹¹ The identification of one cardiac defect should prompt investigation for associated cardiac abnormalities and referral to a specialised congenital heart disease programme. All patients with suspected pulmonary arterial hypertension should undergo extensive diagnostic testing, even older adults.¹²

Cite this as: BMJ 2009;339:b2920