Impact of chronic obstructive pulmonary disease on exercise ventilatory efficiency in heart failure☆
Introduction
Heart failure (HF) with reduced left ventricular ejection fraction and chronic obstructive pulmonary disease (COPD) are chronic-degenerative diseases frequently found in the general population. Both provide a poor prognosis, both have a negative influence on patients' quality of life, and both are the causes of relevant costs for the health care system [1]. Unfortunately, HF and COPD often coexist, leading to further increases in patients' disability and mortality [2], [3]. Identification of COPD in patients with established HF, however, might be troublesome in individual patients as the diseases share the same symptoms of dyspnea and fatigability on exertion and resting lung function abnormalities may occur in HF on isolation [4], [5], [6]. This state of affairs explains the clinical relevance of identifying novel functional indexes able to indicate the presence of COPD as co-morbidity of HF [1], [2]. It is noteworthy that during exercise in both HF and COPD more ventilation (E) is needed to meet the peripheral metabolic demands (as expressed, for example, by changes in carbon dioxide output (CO2)). Interestingly, while in HF this mainly reflects the functional adaptation of E to a chronically-increased sympathetic tonus [7], [8], the E–CO2 relationship in COPD is strongly modulated by the extent at which E is “wasted” in the dead space (VD) [9]. From a practical perspective, this excessive exercise E has been traditionally quantified by the slope of the linear E–CO2 relationship [10], [11]. Notably, however, whereas milder ventilatory abnormalities do not preclude HF patients in meeting the increased ventilatory demands (i.e., the slope does increase as disease progresses) [12], [13], mechanical constraints preclude or restrict COPD patients to attend those requirements (i.e., the slope diminishes as disease worsens) [14], [15]. The opposite effects of HF and COPD on the slope, therefore, make it unlikely that this parameter would be of value in separating patients with HF from those with HF–COPD overlap.
There is, however, another E–CO2 parameter that may carry important information relative to the magnitude of VD increase whereas not being constrained by lung mechanical abnormalities — the E intercept (Eint) [16], [17]. Eint represents the ventilatory requirements when pulmonary gas exchange is nil (CO2 = 0), i.e., the very definition of VD. In fact, as normal lungs have a small VD, Eint has a positive value in more than 95% of healthy subjects [11], [18], [19]. Of note, we showed that Eint increased in tandem with VD when the latter was artificially increased during exercise in both HF and healthy subjects [20]. Teopompi and colleagues [21] described significantly higher Eint in patients with COPD compared to their counterparts with HF despite similar maximal exercise capacity. Moreover, Neder and colleagues recently showed that increases in Eint better reflected the progression of functional impairment from mild to end-stage COPD [9]. Altogether, this preliminary evidence led us to hypothesize whether increased Eint would be particularly helpful in suggesting COPD as co-morbidity of HF.
This large scale, multicenter study was therefore undertaken to contrast the parameters of the E–CO2 relationship (Eint and slope) in patients with HF, COPD and HF–COPD overlap. Normal subjects and patients with pulmonary artery hypertension (PAH) served as negative and positive controls relative to E–CO2 abnormalities [11], [22], [23]. We specifically hypothesized that increases in Eint – but not changes in E–CO2 slope – would be useful in indicating the presence of COPD in patients with HF.
Section snippets
Study design and population
This is a multicenter retrospective study involving 450 patients followed in 6 Centers where CPETs are performed by experts — specifically, Centro Cardiologico Monzino, IRCCS, Milan, Italy; Cardiologia Riabilitativa, Fondazione S Maugeri, IRCCS, Milan, Italy; Department of Public Health and Infectious Diseases, Division of Pulmonary Research, “La Sapienza” University, Rome, Italy; Université de Paris 06, Equipe de Recherche ER 10 UPMC, Laboratoire de Physio-Pathologie Respiratoire, Faculté de
Resting variables
Descriptive statistics are reported in Table 1. HF, COPD and HF–COPD had similar age while PAH patients and healthy controls were younger. PAH patients were more frequently female. Left ventricular ejection fraction was 34 ± 7% and 32 ± 8% in HF–COPD and HF, respectively. As expected, COPD and HF–COPD patients showed evidence of an obstructive ventilatory defect, which, based on both FEV1 and FEV1/FVC, was more severe in COPD patients. Indeed, while the frequency of patients on stage 3 according to
Discussion
This is the first multicenter study systematically contrasting the parameters of the linear E–CO2 relationship during incremental cycle ergometry (Eint and slope) in a large number of patients with HF, COPD and HF–COPD overlap. Our main results confirm the study hypothesis of greater Eint in patients with COPD and COPD–HF than in patients with isolated HF. In contrast, there were no between-group differences in slope, making this parameter poorly discriminative. Therefore, if a Eint ≥
Conflict of interest
None declared.
Acknowledgments
The research was supported by Centro Cardiologico Monzino, IRCCS, Milano (Italy).
References (35)
The relationship of the sympathetic nervous system and the renin–angiotensin system in congestive heart failure
Am. Heart J.
(1989)- et al.
Cardiopulmonary exercise testing (CPET) in pulmonary emphysema
Respir. Physiol. Neurobiol.
(2011) - et al.
Updated clinical classification of pulmonary hypertension
J. Am. Coll. Cardiol.
(2013) - et al.
Excess ventilation and ventilatory constraints during exercise in patients with chronic obstructive pulmonary disease
Respir. Physiol. Neurobiol.
(2014) - et al.
Reproducibility of cardiopulmonary exercise measurements in patients with pulmonary arterial hypertension
Chest
(2004) - et al.
Pulmonary function changes associated with cardiomegaly in chronic heart failure
J. Card. Fail.
(2007) - et al.
Diagnostic and therapeutic challenges in patients with coexistent chronic obstructive pulmonary disease and chronic heart failure
J. Am. Coll. Cardiol.
(2007) - et al.
The prognostic influence of chronic obstructive pulmonary disease in patients hospitalised for chronic heart failure
Eur. J. Heart Fail.
(2007) - et al.
Heart failure and chronic obstructive pulmonary disease: an ignored combination?
Eur. J. Heart Fail.
(2006) - et al.
Baseline characteristics and outcomes of patients with heart failure receiving bronchodilators in the CHARM programme
Eur. J. Heart Fail.
(2010)
Lung function and exercise gas exchange in chronic heart failure
Circulation
The lungs in chronic heart failure
Eur. Heart J.
Cardiomegaly as a possible cause of lung dysfunction in patients with heart failure
Am. Heart J.
Enhanced ventilatory response to exercise in patients with chronic heart failure and preserved exercise tolerance: marker of abnormal cardiorespiratory reflex control and predictor of poor prognosis
Circulation
Exercise ventilatory inefficiency in mild to end-stage COPD
Eur. Respir. J.
Development of a ventilatory classification system in patients with heart failure
Circulation
Ventilatory efficiency during exercise in healthy subjects
Am. J. Respir. Crit. Care Med.
Cited by (60)
Beta-blockers in pulmonary arterial hypertension: Time for a second thought?
2022, Vascular PharmacologyAssociation of preoperative spirometry with cardiopulmonary fitness and postoperative outcomes in surgical patients: A multicentre prospective cohort study
2020, EClinicalMedicineCitation Excerpt :In the pragmatic design of the METS study, anaerobic threshold was determined by trained investigators at each study site; therefore, these results need to be replicated following central determination of anaerobic thresholds, and by extension, ventilatory efficiency. Notably, limitations in ventilatory efficiency have been observed in patients with symptomatic chronic obstructive pulmonary disease who have ‘out-of-proportion breathlessness’ despite preserved FEV1, suggesting that unlike FEV1, ventilatory efficiency is influenced by cardiocirculatory factors such as heart failure and pulmonary hypertension.31–33 Our observation that spirometry measures were not predictive of postoperative respiratory complications after accounting for cardiopulmonary fitness is a notable addition to the literature, where previously reported associations of spirometry measures with outcomes following extra-thoracic surgery have been inconsistent.10–13
How to perform and report a cardiopulmonary exercise test in patients with chronic heart failure
2019, International Journal of CardiologyCitation Excerpt :The analysis of the VE vs. VCO2 relationship must also consider the Y-axis intercept, i.e. the extrapolation of VE at VCO2 = 0. In HF patients, an elevated y-intercept suggests the co-existence of COPD while a negative value may indicate the presence of pulmonary hypertension [61]. Another important pattern of pathophysiological interest is the VO2 vs. Work relationship observed during the entire exercise.
Dysregulation of ventilation at day and night time in heart failure
2023, European Journal of Preventive Cardiology
- ☆
All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.