How is PAH diagnosed?

The early symptoms of Pulmonary arterial hypertension (PAH) -such as Dyspnoea, dizziness and fatigue - are often mild and are common to many other conditions. At rest there are often no symptoms and no apparent signs of illness. As a result, diagnosis can be delayed for months or even years meaning that Pulmonary Arterial Hypertension (PAH) is frequently not recognised until the disease is relatively advanced.¹ Pulmonary Arterial Hypertension (PAH) is often diagnosed only once other conditions have been investigated and ruled out.

The non-specific nature of symptoms associated with Pulmonary Arterial Hypertension (PAH) means that the diagnosis cannot be made on symptoms alone. A series of investigations is required to make an initial diagnosis, to refine that diagnosis in terms of clinical class of pulmonary hypertension (please click here for classification of pulmonary hypertension) and to evaluate the degree of functional and haemodynamic impairment (Figure 2).  Consequently, it can be useful to adopt a four stage approach:

   Figure 2: Click to enlarge

   Figure 3: Click to enlarge

Echocardiography - value as a screening tool
Transthoracic Doppler-echocardiography (TTE) is a non-invasive screening test for pulmonary hypertension. TTE is able to estimate pulmonary arterial systolic pressure, which is equivalent to right ventricular systolic pressure in the absence of pulmonary outflow obstruction, and can provide additional information about the cause and consequences of PH, including right and left ventricular dimensions and function, heart valve abnormalities, right ventricular ejection and left ventricular filling characteristics and presence of a pericardial effusion. In the initial investigation of patients with Pulmonary Arterial Hypertension (PAH) it is important to obtain adequate images of the right heart. Pulmonary arterial pressure can be estimated from the tricuspid regurgitant (TR) jet (Figure 4).

   Figure 4: Click to enlarge

Right heart catheterisation - the diagnostic gold standard
Right heart catheterisation is required for a definitive diagnosis of Pulmonary Arterial Hypertension (PAH) (Figure 5 and 6),^1,2  to assess the severity of haemodynamic impairment and to test the vasoreactivity of the pulmonary circulation. The following parameters should always be assessed: right atrial pressure (RAP), pulmonary arterial pressure (PAP [systolic, diastolic and mean]), pulmonary capillary wedge pressure (PCWP), cardiac output / index, pulmonary (PVR) and systemic vascular resistance, blood pressure and arterial and mixed venous oxygen saturation.
Pulmonary Arterial Hypertension (PAH) is defined as a sustained elevation of mean pulmonary arterial pressure to > 25 mmHg at rest or to > 30 mmHg while exercising, with a mean pulmonary wedge pressure or left ventricular end-diastolic pressure of < 15 mmHg and pulmonary vascular resistance of ≥3 woods units.¹ A positive vasoreactive response is defined as a reduction in mean Pulmonary artery pressure (mPAP) ≥ 10 mmHg to reach an absolute value of mPAP ≤ 40 mmHg with an increase or unchanged cardiac output. A positive response is shown in only 10-15% of patients, and sustained response is shown in even fewer (less than 7%).³

   Figure 5.

   Figure 6: Click to enlarge

6-minute walk test - evaluation of exercise capacity
In patients with Pulmonary Arterial Hypertension (PAH), the 6-MWT to evaluate exercise capacity is reflective of activities of daily living;⁴ the distance a Pulmonary Arterial Hypertension (PAH) patient can walk in 6 minutes is a critical endpoint in studies evaluating the benefit of different therapeutic options.

To allow meaningful comparisons, it is important that the 6-MWT be performed under supervision according to a standardised protocol.⁵

• A 30 m corridor should be available, marked at 3 m intervals
• The patient should rest for at least 10 minutes prior to the test and should not have performed any rigorous exercise within the previous 2 hours
• The patient should be asked to rate their baseline dyspnoea
• The patient should be instructed to walk to their maximum capacity but not to run or jog; they should be permitted to rest as necessary
• The supervisor should count each lap as the patient finishes it
• The patient should be asked to rate their dyspnoea at the end of the test
• The test should be repeated at approximately the same time of day on each occasion

References
1. Gaine SP, Rubin LJ. Primary Pulmonary Hypertension. Lancet  1998; 352: 719-25
2. Barst RJ, McGoon M, Torbicki A et al. Diagnosis and differential assessment of pulmonary arterial hypertension. J Am Coll Cardiol 2004;43 (Suppl S): 40S-47S
3. Sitbon O, Humbert M, Jaïs X et al. Long-term response to Calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation 2005; 11:3105-11
4. Solway S, Brooks D, Lacasse Y, Thomas S. A qualitative systematic overview of the measurement properties of functional walk tests used in the cardiorespiratory domain. Chest 2001; 119(1): 256-70.
5. ATS. ATS statement: guidelines for the 6-minute walk test. Am J Crit Care 2002; 166: 111-7.