Original ArticleComparing Cardiopulmonary Exercise Testing in Severe COPD Patients with and without Pulmonary Hypertension
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.
Section snippets
Study Cohort
The Institutional Review Board of Columbia University Medical Center approved this study (IRB No. AAAJ9301). We performed a retrospective chart review of all patients with COPD referred for CPET at the Center for Chest Disease at the Columbia University Medical Center between January 1998 and June 2010. Patients were referred for CPET as part of their standard clinical evaluation for potential lung transplant, lung volume reduction surgery, or pulmonary rehabilitation programs. Inclusion
Patient characteristics
A total of 131 patients met the inclusion criteria for the study. However, because PH may result from a post-capillary component, 27 patients with pulmonary capillary wedge pressure (PCWP) > 15 mmHg and six patients with left ventricular ejection fraction (LVEF) < 30% were excluded from our analysis. Therefore, 98 patients remained for analysis. According to haemodynamic criteria as defined by a resting mPAP > 25 mmHg, 31 of 98 patients (32%) were classified as having PH. Comparison of COPD
Discussion
The main findings of this study are the following: (i) mPAP is inversely associated with exercise capacity, specifically peak VO2% predicted, (ii) PH does not appear to significantly alter gas exchange in patients with severe COPD, and (iii) PH does significantly lower oxygen pulse in patients with severe COPD.
Our study demonstrates that PH diminishes oxygen uptake and oxygen pulse at peak exercise and impairs exercise capacity in patients with COPD in addition to the usual ventilatory and
Declaration of Interest
This work had no conflict of interest and was supported by VIDDA foundation.
Acknowledgments
Author contributions:
Dr. Thirapatarapong: contributed to original and final manuscript, study concept and design, analysis and interpretation of data, and critical revision of the manuscript for important intellectual content.
Dr. Bartels: contributed to final manuscript, study concept and design, analysis and interpretation of data, and critical revision of the manuscript for important intellectual content.
Ms. Armstrong: contributed to statistical analysis and critical revision of the
References (37)
- et al.
Pulmonary Hemodynamics in Advanced COPD Candidates for Lung Volume Reduction Surgery or Lung Transplantation
Chest
(2005) - et al.
Impact of Pulmonary Artery Pressure on Exercise Function in Severe COPD
Chest
(2009) - et al.
Aerobic Exercise Capacity in COPD Patients with and Without Pulmonary Hypertension
Resp Med
(2010) - et al.
Sustained Improvement With Iloprost in a COPD Patient With Severe Pulmonary Hypertension
Chest
(2009) - et al.
Ventilatory and Cardiocirculatory Exercise Profiles in COPD: the Role of Pulmonary Hypertension
Chest
(2012) - et al.
ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension: A Report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association Developed in Collaboration With the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association
J Am Coll Cardiol
(2009) - et al.
Contrasting Cardiovascular and Respiratory Responses to Exercise in Mitral Valve and Chronic Obstructive Pulmonary Diseases
Chest
(1983) - et al.
Metabolic Acidosis During Exercise in Patients with Chronic Obstructive Pulmonary Disease. Use of the V-slope Method for Anaerobic Threshold Determination
Chest
(1988) - et al.
Hemodynamic Responses to Exercise in Patients with COPD
Eur Respir J
(2013) - et al.
Pulmonary Hypertension in COPD
Eur Respir J
(2008)
Hemodynamic Characterization of Patients with Severe Emphysema
Am J Respir Crit Care Med
Abnormal Pulmonary Arterial Pressure Limits Exercise Capacity in Patients with COPD
Wiener Klinische Wochenschrift
Pulmonary Circulation
Hypoxia on the Pulmonary Circulation. How and where it acts
Circulation
Pulmonary Hypertension and Chronic cor Pulmonale in COPD
Int J Chron Obstruct Pulmon Dis
Brain Natriuretic Peptide Is a Prognostic Parameter in Chronic Lung Disease
Am J Respir Crit Care Med
Diagnosis, Assessment, and Treatment of Non-Pulmonary Arterial Hypertension Pulmonary Hypertension
J Am Coll Cardiol
Cardiac Disease in Chronic Obstructive Pulmonary Disease
Proceedings of the American Thoracic Society
Cited by (20)
Effects of Pulmonary Hypertension on Exercise Capacity in Patients With Chronic Obstructive Pulmonary Disease
2020, Archivos de BronconeumologiaCitation Excerpt :In our study, the maximum workload achieved at the CPET was significantly lower in the COPD-PH group than in the non-PH group. This is in line with Thirapatarapong et al., who found significant difference in severe COPD patients (21(15)% predicted for COPD vs. 15(9)% predicted COPD-PH) and Skjorten et al., who studied 98 patients with a broad range of airway obstruction (72(31) watts for COPD vs 40(21) watts for COPD-PH).11,35 However, Holverda et al., Vonbank et al., Pynnaert et al., and Adir et al. did not find any difference.12–15
Management of chronic obstructive pulmonary disease beyond the lungs
2016, The Lancet Respiratory MedicineCitation Excerpt :However, there is no conclusive evidence yet to advocate this strategy. Finally, although most cardiovascular risk discussed here concerns coronary or left ventricular disease, pulmonary hypertension and right ventricular dysfunction are also common in patients with advanced COPD and have important effects on clinical outcomes.38 However, treatment of pulmonary hypertension and right ventricular dysfunction in patients with COPD has not led to clinically relevant improvements.39
Emerging phenotypes of pulmonary hypertension associated with COPD: A field guide
2022, Current Opinion in Pulmonary Medicine