How is Pulmonary arterial hypertension (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.1 As a result, PAH is a challenging disease to identify and the diagnosis cannot be made on symptoms alone.1,2

The non-specific nature of the symptoms, coupled with the rarity of the disease, means that many patients are not diagnosed until the disease is already quite severe.1

Early diagnosis and therapeutic intervention can offer an improved outlook for patients.3 That is why it is so critical to identify patients at risk of PAH and refer them to a specialist centre at the earliest opportunity to confirm the diagnosis. 

Diagnosis of PAH

PAH should be considered in the differential diagnosis of exertional dyspnoea, syncope, angina and/or progressive limitation of exercise capacity, particularly in patients without apparent risk factors, symptoms or signs of common cardiovascular and respiratory disorders. Special awareness should be directed towards patients with associated conditions and/or risk factors for the development of PAH:2

  • Family history
  • Connective tissue disease
  • Congenital heart disease 
  • Human immunodeficiency virus (HIV) infection
  • Portal hypertension 
  • A history of drug or toxin intake known to induce PAH

When PAH is suspected, clinical history, symptoms, signs, electrocardiogram (ECG), chest radiograph, echocardiogram, PFTs, CT of the chest and a V/Q scan are all required in order to exclude diagnosis of left heart disease, lung disease or chronic thromboembolic pulmonary hypertension (CTEPH). To confirm diagnosis of PAH, referral to a PH specialist centre for RHC is required. A diagnostic-based algorithm can be found in the 2015 ESC/ERS clinical guidelines for the diagnosis and treatment of PH.2

 

Adapted from Galiè et al. 20162
CT, computed tomography; CTEPH, chronic thromboembolic pulmonary hypertension; DLCO, diffusing capacity for carbon monoxide; ECG, electrocardiogram; ERS, European Respiratory Society; ESC, European Society of Cardiology; HRCT, high-resolution computed tomography; mPAP, mean pulmonary arterial pressure; PAH, pulmonary arterial hypertension; PAWP, pulmonary artery wedge pressure; PFT, pulmonary function test; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; RHC, right heart catheterisation; RV, right ventricle; V/Q, ventilation-perfusion

Screening for PAH

The implementation of screening programmes targeting high-risk patient groups can help to identify patients earlier. The 2015 European Society of Cardiology and European Respiratory Society (ESC/ERS) guidelines recommend annual echocardiographic screening in asymptomatic systemic sclerosis (SSc) patients.2

Screening for PAH in patients with SSc has shown to result in an increase of 47% in survival after 8 years vs those detected during routine clinical practice.4

Adapted from Humbert et al. 20114
CI, confidence interval; HR, hazard ratio; PAH, pulmonary arterial hypertension; SSc, systemic sclerosis

Screening

2015 ESC/ERS guidelines

Annual screening with echocardiography, PFTs and biomarkers may be considered in patients with systemic sclerosis2.

Echocardiography should always be performed when pulmonary hypertension (PH) is suspected, and may be used to infer a diagnosis of PH in patients in whom multiple different echocardiographic measurements are consistent with this diagnosis.2 A transthoracic echocardiogram (TTE) is a non-invasive screening test for PH that may provide an estimate of the right ventricular systolic pressure, which is equivalent to the systolic pulmonary arterial pressure and the systolic right ventricular pressure.7 In the initial investigation of patients with PAH it is important to obtain adequate images of the right heart.2 Tricuspid regurgitation velocity and the presence of other echocardiographic signs should be combined to estimate the probability of PH.2

 

Adapted from Galiè et al. 20162
PH, pulmonary hypertension

Adapted from Galiè et al. 2016
PA, pulmonary artery; PH, pulmonary hypertension
*Echocardiographic signs from at least two different categories (A/B/C) from the list should be present to alter the level of echocardiographic probability of pulmonary hypertension.

 

Right heart catheterisation (RHC) is required for the definitive diagnosis of PAH.2 RHC involves directing a pulmonary artery catheter into the right side of the heart to assess the cardiopulmonary haemodynamics. The procedure is technically demanding so it is recommended that RHC is only undertaken at specialist pulmonary hypertension (PH) centres.2

Confirmation of PH2

  • mPAP ≥25 mmHg (according to current guidelines)

Confirmation of PAH2

  • mPAP ≥25 mmHg
  • Normal PAWP (≤15 mmHg)
  • PVR >3 Wood units
  • Excluding other causes of pre-capillary PH

 

Adapted from Pagnamenta et al. 20178
mPAP, mean pulmonary arterial pressure; PAP, pulmonary arterial pressure; PAWP, pulmonary artery wedge pressure; PVR, pulmonary vascular resistance; RAP, right arterial pressure; RHC, right heart catheterisation; RVP, right ventricular pressure

Upon diagnosis, patients are assessed for risk of disease progression. Guidelines recommend regular multiparameter risk assessment, both at diagnosis and follow-up (every 3–6 months) to allow the treatment strategy to be tailored to the individual patient at the earliest opportunity. The risk status of patients can be categorised as either low, intermediate or high. This corresponds to an estimated 1-year mortality of <5%, 5–10% or >10% respectively and is based on a number of determinants including WHO functional class, exercise capacity and haemodynamic parameters. There is no single variable that can provide sufficient prognostic information on its own; a multidimensional approach is required.2

 

Adapted from Galiè et al. 20162
BNP, brain natriuretic peptide; CI, cardiac index; CMR, cardiovascular magnetic resonance; NT-proBNP, N-terminal pro-B-type natriuretic peptide; PH, pulmonary hypertension; RA, right atrium; RAP, right atrial pressure; 6MWD, 6-minute walk distance; SvO2, mixed venous oxygen saturation; VE/VCO2, ventilatory equivalents for carbon dioxide; VO2, oxygen consumption; WHO, World Health Organization

 

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