Improving Risk Stratification, Diagnostic Accuracy in PAH With Cardiopulmonary Exercise Testing

While cardiopulmonary exercise testing (CPET) is a safe, noninvasive method with significant diagnostic and prognostic value in pulmonary arterial hypertension (PAH), it is generally underutilized because of a lack of expertise in its administration. In addition, functional class, hemodynamic data, and the 6-minute walk test (6MWT) have been viewed as sufficient to inform PAH risk stratification and prognosis.

Compared with the limited information derived from the 6MWT, however, CPET “has the power to reveal the underlying pathophysiological consequences of the disease process and, in recent years, several CPET variables have been recognized to be consistently altered in patients with PAH,” wrote the investigators in a recent review published in European Respiratory Review.¹ 

A 2002 study, for example, showed that exercise duration, peak exercise, peak V′O2, end-tidal carbon dioxide tension (PETCO₂) at rest, minute ventilation (V′E)/carbon dioxide production (V′CO₂) slope, diastolic blood pressure at peak exercise, and heart rate (HR) at peak exercise predicted survival in 70 patients with idiopathic PAH.²

The American Thoracic Society recommends that the 6MWT be used in combination with, rather than in lieu of, CPET.³

CPET in PAH Diagnosis         

CPET is useful in adding support to a PAH diagnosis and in guiding treatment selection. Examples of findings regarding its diagnostic role are highlighted below.

• An increase in V′E/V′CO₂ slope combined with reduced PETCO₂ values showed high diagnostic accuracy, both in patients with dyspnea of unknown origin and in cases of suspected PAH based on echocardiographic findings.^4,5
• Combined analysis of PETCO₂ and V′E/V′CO₂ ratio at the anaerobic threshold (AT) can “classify the suspicion of PAH in unlikely, suspect, likely, or very likely [individuals] and is able to guide physicians to further evaluations to confirm the diagnosis,” according to the researchers of the European Respiratory Review article. PETCO₂ at AT is <30 mm Hg points to PAH as a possible diagnosis, and a value <20 mm Hg indicates an even greater likelihood.⁶
• V′E/V ′CO₂ slope and AT combined had a specificity of 95% and a sensitivity of 92.6% for the identification of PAH.⁷

Prognostic Role of CPET in PAH

CPET parameters have been found to predict survival and add information to the prognostic value of 6MWT.⁸ In a 2012 study, significant differences were observed between survivors and non-survivors in ventilatory equivalents for oxygen (42.1±2.1 vs 56.9±2.6; P <.005) and for carbon dioxide (47.5±2.2 vs 64.4±2.3; P <.005).⁹ The risk for mortality during a  24 month-period was 1.5-fold higher in patients with peak oxygen uptake ≤10.4 mL/min^-1/kg, 2.9-fold higher with an alveolar-arterial oxygen difference ≥55 mm Hg, 5.8-fold higher with a V′E/V′CO2 slope ≥60, and 7.8-fold higher with a V′E/V′CO₂ ratio at AT ≥55.

Other research has demonstrated that the combined use of peak V′O2 and pulmonary vascular resistance led to accurate risk stratification, and in another study treatment-associated changes in V′O2 and oxygen pulse predicted survival.^10,11 Additional research with larger sample sizes is needed to further elucidate the prognostic role of CPET in PAH.