Cardiopulmonary exercise (CPX) testing is an established assessment procedure in the heart failure population as well as those with unexplained exertional dyspnea (2). More recently, an impressive amount of literature has mounted in support of the use of CPX to reflect disease severity in patients with resting pulmonary arterial hypertension (PAH) (1). The value of CPX for this purpose centers on the measures of ventilatory efficiency, specifically the minute ventilation/carbon dioxide production (V˙E/V˙CO2) ratio and the partial pressure of end-tidal carbon dioxide production (PETCO2) during exercise. As pulmonary pressure progressively rises, ventilation-perfusion matching progressively worsens, which seems to be accurately reflected by an abnormally high and low V˙E/V˙CO2 and PETCO2, respectively.
There is initial evidence to indicate that individuals with normal pulmonary pressure at rest who have an abnormal rise during exertion are accurately identified through V˙E/V˙CO2 and PETCO2 abnormalities. Raeside et al. (4) reported a significant correlation between V˙E/V˙CO2 and pulmonary artery pressure during exercise in 10 patients with suspected PAH. The authors posited that the abnormal ventilatory response was caused by an increase in physiologic dead space secondary to exercise-induced PAH.
The eloquent work presented by Fowler et al. (3) adds invaluable information to this area of research and further supports the role of CPX in evaluating patients at risk for PAH. A clear strength of the current investigation is the simultaneous assessment of ventilatory expired gas analysis and pulmonary hemodynamics via catheterization. Subjects with resting PAH had a highly abnormal V˙E/V˙CO2 (mean = 51) and PETCO2 (mean = 28 mm Hg) at the anaerobic threshold. Comparatively, the abnormalities in the V˙E/V˙CO2 (mean = 41) and PETCO2 (mean = 33 mm Hg) at the anaerobic threshold were less severe in subjects with exercise-induced PAH, although these are still significantly different compared with controls and subjects with exercise-induced left ventricular dysfunction. Although the current analysis by Fowler et al. (3) is compelling and consistent with the finding of other investigations, additional studies are needed given the relatively small sample size, particularly when subjects were divided into subgroups according to their hemodynamic response. A key area for future investigation is to therefore further confirm that CPX can act as an independent, noninvasive first-line assessment that accurately diagnoses PAH. In addition, the current investigation performed exercise testing in the semirecumbent position while current clinical exercise assessments are typically performed in the upright position. There is initial evidence to indicate V˙E/V˙CO2 and PETCO2 abnormalities in subjects with PAH are more profound during treadmill testing compared with upright lower extremity ergometry (5). It does not seem that an investigation comparing the V˙E/V˙CO2 and PETCO2 exercise response during upright and recumbent testing has been conducted at this time. This type of investigation is needed to identify the testing procedure with the greatest diagnostic accuracy and establish optimal threshold values for key CPX variables.
In conclusion, Fowler et al. should be commended for their work in an important area of research. Hopefully, these types of investigations will continue, better elucidating the role of CPX in diagnosing PAH in clinical practice.
Ross Arena,PhD, PT, FACSM
Departments of Internal Medicine
Physiology and Biophysics, and Physical Therapy
Virginia Commonwealth University
1. Arena R, Lavie CJ, Milani RV, Myers J, Guazzi M. Cardiopulmonary exercise testing in patients with pulmonary arterial hypertension: an evidence-based review. J Heart Lung Transplant
2. Balady GJ, Arena R, Sietsema K, et al. Clinician's guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart Association. Circulation
3. Fowler RM, Maiorana AJ, Jenkins SC, Gain KR, O'driscoll G, Gabbay E. Implications of exercise-induced pulmonary arterial hypertension. Med Sci Sports Exerc
4. Raeside DA, Smith A, Brown A, et al. Pulmonary artery pressure measurement during exercise testing in patients with suspected pulmonary hypertension. Eur Respir J
5. Valli G, Vizza CD, Onorati P, et al. Pathophysiological adaptations to walking and cycling in primary pulmonary hypertension. Eur J Appl Physiol