THE IMPORTANCE OF EARLY DIAGNOSIS
The early symptoms of 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, PAH is a challenging disease to identify and the diagnosis cannot be made on symptoms alone.1
Without treatment, the median survival of patients with idiopathic PAH (IPAH) is 2.8 years.2 Early diagnosis and therapeutic intervention may offer an improved outlook for patients. Symptoms and prognosis have both been shown to be better for patients with less severe disease (i.e. World Health Organization Functional Class [WHO FC] I/II) compared with those who do not begin targeted therapy until their PAH has reached a more severe stage (i.e. WHO FC III/IV).3,4 Disease progression may be delayed by recognising and treating patients as early as possible.5 Click here for more information on treatment and prognosis.
The non-specific nature of symptoms coupled with the rarity of the disease mean that many patients are not diagnosed until their disease is already quite severe.3
A recent survey of patients with PH in the UK found that almost half (48%) wait over a year after first experiencing symptoms before receiving a diagnosis.6
The rate at which progression occurs will vary depending on a number of factors, such as the underlying aetiology of the patient’s disease.3 However, even patients with mild disease (WHO FC II) show significant deterioration over 6 months without treatment.4 Regular screening can improve early detection in those patients with conditions known to be associated with PAH (e.g. systemic sclerosis [SSc], or congenital heart disease [CHD]).4
Figure 1. Results of the 2016 Living with PH Survey6
The 2016 Living with PH Survey was conducted by Pulmonary Hypertension Association UK (PHA UK) to understand the impact of PH on patients and their families and to promote better awareness and diagnosis of the condition. Click here to see the full results.
HOW IS PAH DIAGNOSED?
Right heart catheterisation is the only way of accurately measuring the pulmonary artery pressure and is required for the definitive diagnosis of PAH.1
Once a suspicion of PH has been raised, there are several investigations that can be used to assess the likeliness of the diagnosis. Interpretation of the results of the tests described below is complex and requires substantial experience in the management and follow-up of PAH patients. For this reason, it is recommended that patients are referred to the specialist PH centre where cases can be discussed at multidisciplinary team meetings.1 Click here for the location and details of specialist PH centres in the UK.
THE DIAGNOSTIC ALGORITHM
An algorithm to guide clinicians towards a diagnosis can be found in the European Society of Cardiology and European Respiratory Society (ESC/ERS) joint clinical guidelines for the diagnosis and treatment of PH.
Figure 2. Condensed ESC/ERS 2015 diagnostic algorithm.1 Adapted from Galiè, Eur Heart J 2016
Clinical history, symptoms, signs, electrocardiogram (ECG), chest radiograph, echocardiogram, pulmonary function tests (PFTs) and computed tomography (CT) of the chest are required in order to exclude the presence of left heart disease or lung disease:1
ECGs may provide suggestive or supportive evidence of PH by demonstrating right ventricular (RV) hypertrophy, RV strain, right axis deviation, P pulmonale and QTc prolongation.
Echo provides several variables that correlate with right heart haemodynamics, and it should always be performed in the case of suspected PH.
Chest X-rays may show evidence of right atrium (RA) and RV enlargement and pulmonary arterial (PA) dilatation. Chest X-rays may also show signs of the underlying cause (e.g. lung disease).
Figure 3. Chest X-ray in PAH (NB: A normal chest X-ray does not exclude PAH)
PFTs and arterial blood gas samples will identify the contribution of underlying airway or parenchymal lung disease.
CT imaging is a widely available tool that can provide information such as PA diameter and clues as to the form of PAH (e.g. cardiac defects, oesophageal dilation in SSc). High resolution CT (HRCT) provides detailed views of the lung parenchyma and facilitates the diagnosis of interstitial lung disease and emphysema.
Ventilation/perfusion (V/Q) scan
A V/Q lung scan is used to exclude chronic thromboembolic pulmonary hypertension (CTEPH); where there is evidence of multiple segmental perfusion defects, a diagnosis of CTEPH should be suspected. The final diagnosis of CTEPH requires CT pulmonary angiography, right heart catheterisation and selective pulmonary angiography.
THE IMPORTANCE OF ECHO
Echocardiography (echo) should always be performed when PH is suspected, and may be used to infer a diagnosis.1
Transthoracic echo (TTE) is a non-invasive screening test for PH.7 In the absence of pulmonary outflow obstruction, TTE provides an estimate of the right ventricular (RV) systolic pressure, which is equivalent to the systolic pulmonary arterial pressure. The systolic RV pressure, and thus the pulmonary arterial pressure (PAP), can be estimated from the tricuspid regurgitant jet velocity (TRV) (Figure 4). Unfortunately, the pressure estimation may not be accurate in all patients. TTE alone is therefore not suitable for screening for mild, asymptomatic PH.1
Figure 4. Estimation of systolic PAP, as described by the simplified Bernoulli equation1
TTE can also provide information about the cause and consequences of PH, including RV and left ventricular (LV) dimensions and function, heart valve abnormalities, RV ejection and LV filling characteristics, and presence of a pericardial effusion.7 In the initial investigation of patients with PAH it is important to obtain adequate images of the right heart. TRV and the presence of other echocardiographic signs should be combined to estimate the probability of PH (Figures 5 & 6).
An echo protocol developed by a group of physicians and supported by the British Society of Echocardiography provides detailed information about the echocardiographic assessment of PH and guidance on the interpretation of results. Click here to read a summary by the Project Directors and access the interactive e-book.
Figure 5. Echocardiographic probability of PH.1 Adapted from Galiè, Eur Heart J 2016
Figure 6. Echocardiographic signs suggesting PH.1 Adapted from Galiè, Eur Heart J 2016
RIGHT HEART CATHETERISATION
Right heart catheterisation (RHC) is required for the definitive diagnosis of PAH.1
It is used to assess the severity of haemodynamic impairment, and to test the vasoreactivity of the pulmonary circulation.1
RHC involves directing a pulmonary artery catheter into the right side of the heart to assess the pressure.8 The procedure is technically demanding and may be associated with serious complications. It is therefore recommended that it is only undertaken at the specialist PH centres.1 When performed in these centres, these procedures have low morbidity (1.1%) and mortality (0.055%) rates.9
Figure 7. Right heart catheterisation1,8
Vasoreactivity testing is also performed during RHC, to help identify the specific haemodynamic profile of the patient and to identify those patients who might respond to treatment with high-dose calcium channel blockers.1 A positive vasoreactive response is defined as a reduction in mean PAP ≥10 mmHg to reach an absolute value of mean PAP ≤40 mmHg, with an increased or unchanged cardiac output. A positive response is shown in only 10% of patients.1
- Galiè N, et al. Eur Heart J 2016;37:67–119
- D'Alonzo G, et al. Ann Intern Med 1991;115:343–9
- Humbert M, et al. Am J Respir Crit Care Med 2006;173:1023–30
- Humbert M, et al. Eur Resp Rev 2012;21:306–12
- Galiè N, et al. Lancet 2008;371:2093–100
- Pulmonary Hypertension Association UK (2017). What it means to live with PH today. PHA UK. Available from: www.phauk.org . Accessed January 2018
- Habib G and Torbicki A. Eur Respir Rev 2010;19(118):1–12
- Bangalore S and Bhatt D. Circulation 2011;124:e428-33
- Hoeper M, et al. J Am Coll Cardiol 2006;48:2546–52