Key Investigations

If you suspect your patient has PAH, there are a number of key investigations you should perform to identify and raise the suspicion of disease. Note that right heart catheterisation (RHC) is required to confirm a diagnosis of PAH, and should be performed by a PAH expert centre.1

  • Prominent pulmonary arteries contrasting with loss of peripheral blood vessels may be evident in PAH patients
  • Right atrial and RV hypertrophy may be visible
  • Signs suggestive of lung disease or left heart disease may be visible
  • A normal radiograph does not exclude PH, but 90% of patients with iPAH have an abnormal chest radiograph at the time of diagnosis
  • Consider using a lateral image as well
 
PAH with evidence of cardiomegaly and enlarged pulmonary arteries
  • ECG abnormalities may not be detected in all patients with PAH, and a normal ECG does not exclude the presence of severe PAH. ECG abnormalities may include:
    • P pulmonale
    • Right axis deviation
    • RV hypertrophy
    • RV strain
    • Right bundle branch block
    • QTc prolongation
  • Changes are indicative of RV hypertrophy only, and are not diagnostic of PH in themselves
PAH with evidence of cardiomegaly and enlarged pulmonary arteries
  • Although diffusion capacity can be normal in PAH, most patients have decreased DLCO
  • Normal spirometry and lung volumes (or mild restriction) with reduced DLCO (40–80% predicted) is indicative of PAH
  • Decreased lung volume together with a decrease in DLCO may indicate interstitial lung disease
  • CT scans should be used to assess severity of emphysema or interstitial lung disease
  • COPD as a cause of hypoxic PH can be diagnosed on evidence of irreversible airflow obstruction, together with increased residual volumes and reduced DLCO or increased CO2 tension
Echocardiography is an essential diagnostic tool in the investigation of suspected PH, and should always be performed as part of a patient’s work-up, providing evidence that can raise the suspicion of PH and build a case for definitive diagnosis with right heart catheterisation.1 By measuring multiple echocardiographic parameters, it’s possible to determine the echocardiographic probability of PH. Parameters include:
  • Peak tricuspid regurgitations velocity >2.8 m/s
  • RV/LV basal diameter ratio >1.0
  • Flattening of the IVS
  • RV outflow Doppler acceleration time <105 m/s and/or mid-systolic notching
  • Early diastolic pulmonary regurgitation velocity >2.2 m/s
  • PA diameter >25 mm
  • IVC diameter >21 mm with decreased inspiratory collapse (sniff test)
  • End-systolic RA area >18 cm2
Echocardiography (echo) should always be performed when PH is suspected and may be used to infer a diagnosis.1
PAH with evidence of cardiomegaly and enlarged pulmonary arteries
Echocardiographic probability of PH in symptomatic patients with a suspicion of PH
*See table below. Adapted from Galie N, et al. 2016.1
In instances where peak TRV is technically difficult to measure, it may be helpful to use contrast echocardiography with i.v.-administered agitated saline to improve the Doppler signal.1
It’s important to note that despite its strong correlation with the tricuspid regurgitation pressure gradient, Doppler-derived estimates based on TRV may be inaccurate, and may be significantly underestimated, especially in cases with severe tricuspid regurgitation.1 For this reason, a low TRV alone cannot be used to exclude PH.1 Echocardiographic signs suggesting PH used to assess the probability of PH in addition to tricuspid regurgitation velocity measurement
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 PH. Adapted from Galie N, et al. 2016.1
  • RVSP is a derived parameter that is considered equal to systolic pulmonary artery pressure in most patients (in absence of pulmonary outflow obstruction). The estimation is made taking into account RAP using the simplified Bernoulli equation:1,3

RVSP=4V2 + RAP

V=velocity of tricuspid jet (TRV, metres/sec); RAP=right atrial pressure

The value for RAP used in this equation is estimated by echocardiography based on the diameter and respiratory variation in diameter of the IVC.1 An IVC diameter <2.1 cm that collapses >50% with a sniff suggests a normal RA pressure of 3 mmHg (range 0–5 mmHg), whereas an IVC diameter >2.1 cm that collapses <50% with a sniff or <20% on quiet inspiration suggests a high RA pressure of 15 mmHg (range 10–20 mmHg).1

  • RVSP >40 mmHg generally warrants further evaluation in patients with unexplained dyspnoea, in the absence of other potential aetiologies of PH, such as left heart disease or advanced lung disease3
  • In PH, a study utilising data from the National Echo Database Australia (NEDA) found that patients with eRVSP >30 mmHg have a significantly increased risk of mortality4

RHC is required to definitively diagnose PAH and CTEPH, as it is the only way to directly and accurately measure haemodynamic impairment and to undertake vasoreactivity testing.1 RHC should only be performed once other investigations have been completed with the objective of answering specific diagnostic questions, particularly pertaining to haemodynamics in the context of echocargiographic findings.1

Due to its technically demanding nature and the meticulous attention to detail required to obtain clinically useful information, RHC should only be performed in expert PAH expert centres.1 As well as helping to provide the most useful clinical information, this will help to ensure patients are not put at unnecessary risk.1

RHC should only be performed at expert centres, where the risk of morbidity and mortality are low (1.1% and 0.055%, respectively)1
If, based on your investigations, you Suspect PAH, the best practice is to refer your patient to a PAH expert centre as soon as possible.1

Remember, if you see unexplained breathlessness similar to the cases above, Suspect PH.

References
  1. Galiè N, et al. Eur Heart J 2016; 37:67–119.
  2. Galiè N, et al. Eur Resp Rev J 2009; 34:1219–63.
  3. Rudski LG, et al. J Am Soc Echocardiogr 2010; 23:685–713.
  4. Strange G, et al. J Am Coll Cardiol 2019; 73(21):2660–72.
Footnotes
COPD=chronic obstructive pulmonary disease; CT=computed tomography; CTEPH=chronic thromboembolic pulmonary hypertension; DLCO=diffusing capacity of the lung for carbon monoxide; ECG=electrocardiography; iPAH=idiopathic PAH; IVC=inferior vena cava; PA=pulmonary artery; PAH=pulmonary arterial hypertension; PH=pulmonary hypertension; RA=right atrium; RHC=right heart catheterisation; RV=right ventricle; RVSP=right ventricular systolic pressure; TRV=tricuspid regurgitation velocity.

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World Health Organization functional class (WHO-FC) for patients with PH3,5

This system grades PH severity according to the patient’s functional status, by linking symptoms with activity limitations. WHO-FC remains a powerful predictor of outcomes in patients with PAH.

WHO - FC Description
I
Patients with PH in whom there is no limitation of usual physical activity; ordinary physical activity does not cause increased dyspnoea, fatigue, chest pain, or presyncope.
II
Patients with PH who have mild limitation of physical activity. There is no discomfort at rest, but normal physical activity causes increased dyspnoea, fatigue, chest pain, or presyncope.
III
Patients with PH who have a marked limitation of physical activity. There is no discomfort at rest, but less than ordinary activity causes increased dyspnoea, fatigue, chest pain, or presyncope.
IV
Patients with PH who are unable to perform any physical activity at rest and who may have signs of right ventricular failure. Dyspnoea and/or fatigue may be present at rest, and symptoms are increased by almost any physical activity.
Adapted from McGoon M, et al. 2004.5
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