Comparing Cardiopulmonary Exercise Testing in Severe COPD Patients with and without Pulmonary Hypertension

Purpose

To determine; (i) the effect of PH on exercise capacity, gas exchange and oxygen pulse; (ii) the variables that correlate with mean pulmonary artery pressure (mPAP) in severe COPD patients.

Methods

We reviewed 98 severe COPD patients who had pulmonary function, right heart catheterisation, and cardiopulmonary exercise testing (CPET) performed within six months of each other. PH was defined by a resting mPAP > 25 mmHg. COPD patients with and without PH were compared using the independent samples t-test and Mann-Whitney U test. Pearson correlation coefficients were used to assess the relationship between continuous variables.

Results

PH was present in 32% of patients and the majority of PH was mild (mPAP, 25-35 mmHg). Peak workload, oxygen uptake and oxygen pulse on CPET were significantly lower in the PH group. Mean PAP was found to inversely correlate with peak oxygen uptake, with a tendency towards lower six-minute walk distance. No difference between two groups was seen in any of the gas exchange variables.

Conclusion

In severe COPD, there is a relatively high percentage of PH which causes a decrease in exercise capacity and oxygen pulse without significantly altered ventilation as measured by CPET. Lower than expected exercise performance without a change in pulmonary function may indicate a need for evaluation for possible PH.

Introduction

Secondary pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD) with a reported prevalence between 20 to 90%, depending on the criteria used [1], [2], [3], [4], [5], [6], [7]. PH is primarily seen in patients with advanced COPD or patients with severe hypoxaemia with resting PH reported in up to 30% of COPD patients and exercise-induced PH in up to 90% of patients [3], [4], [5], [6], [7], [8]. Although many factors can lead to PH in COPD, alveolar hypoxia is believed to be the main cause of PH in COPD, through an increase in pulmonary vascular resistance via a mechanism of pulmonary vasoconstriction and hypoxia induced pulmonary vascular remodelling [9].

Typical evaluation of COPD includes medical history, physical examination, pulmonary function tests (PFT), and arterial blood gases. The addition of cardiac imaging may reveal enlargement of the right ventricle [10] or other clinical signs of right heart failure or elevated pulmonary arterial pressures. Plasma levels of brain natriuretic peptide (BNP), a cardiac hormone which is synthesised by the ventricle and secreted into circulation during elevations in end-diastolic pressure, may provide an accurate and reliable test to diagnosis PH [11]. However, these biomarkers lack sensitivity and specificity because a high level may also be present in patients with cardiac disease unrelated to PH and COPD [12]. Right heart catheterisation (RHC) is presently the gold standard to diagnose PH [13]. Nevertheless, the limitations of RHC include that it is invasive, has risks for complications, is relatively limited in availability, and has a higher cost [13], [14].

Cardiopulmonary exercise testing (CPET) is considered the gold standard to evaluate the level of exercise capacity in patients with severe COPD [15], [16] and provides useful information for the assessment of PH in patients with primary PH and interstitial lung disease (ILD) [15], [17]. Altered ventilation on CPET with impaired ventilatory efficiency, which is usually expressed as an elevation of the ratio of minute ventilation to rate of carbon dioxide production (VE/VCO₂) and a decrease in the pressure of end-tidal carbon dioxide (PetCO₂), is also useful to evaluate PH in patients with normal pulmonary function [18]. Prior studies that evaluated exercise tolerance and ventilation in COPD patients with PH had varying results [6], [7], [19]. A recent study demonstrated that PH impaired both exercise capacity and gas exchange [20] while another found no significant differences [19]. Another study showed that PH caused a higher VE/VCO₂ but no significant difference in exercise capacity [7]. Anyhow, these studies included a relatively small number of subjects and some studies relied on echocardiography instead of RHC to diagnose PH. In view of the lack of clear findings of the effects of PH on exercise variables in COPD, we aimed to use a larger number of subjects with more complete data including RHC in order to test our hypothesis that the presence of PH in patients with severe COPD would impair exercise capacity and alter gas exchange compared to matched patients without PH.

The objectives of the present study were to determine (i) the effect of PH on exercise capacity and gas exchange, (ii) and to determine the variables that correlate with mean pulmonary artery pressure (mPAP) in patients with severe COPD.