Impact of chronic obstructive pulmonary disease on exercise ventilatory efficiency in heart failure

Abstract

Background

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) coexistence increases morbidity and mortality. The intercept of ventilation ($\dot{\mathrm{V}}$Eint) on the $\dot{\mathrm{V}}$E vs. carbon dioxide production ($\dot{\mathrm{V}}$CO₂) relationship during exercise has been found to vary in proportion with dead space (VD) in HF. Considering that increased VD is the key pathophysiological abnormality in COPD but a secondary finding in HF we hypothesized that a high $\dot{\mathrm{V}}$Eint would be useful in suggesting COPD as HF co-morbidity. Our aim was to assess whether an elevated $\dot{\mathrm{V}}$Eint suggests the presence of COPD in HF.

Methods

In a multicenter retrospective study, the $\dot{\mathrm{V}}$E–$\dot{\mathrm{V}}$CO₂ relationship was analyzed both as slope and intercept in HF (n = 108), HF–COPD (n = 106) and COPD (n = 95). Patients with pulmonary arterial hypertension (PAH) (n = 85) and healthy subjects (HF) (n = 56) served as positive and negative controls relative to $\dot{\mathrm{V}}$E–$\dot{\mathrm{V}}$CO₂ abnormalities, respectively.

Results

Slope and $\dot{\mathrm{V}}$Eint varied in opposite directions in all groups (p < 0.05) being $\dot{\mathrm{V}}$E–$\dot{\mathrm{V}}$CO₂ slope highest and lowest in PAH and healthy subjects, respectively. No slope differences were observed among HF, HF–COPD and COPD (32 ± 7, 31 ± 7, and 31 ± 6, respectively). $\dot{\mathrm{V}}$Eint was higher in HF–COPD and COPD compared to HF, PAH and controls (4.8 ± 2.4 L/min, 5.9 ± 3.0 L/min, 3.0 ± 2.6 L/min, 2.3 ± 3.3 L/min and 3.9 ± 2.5 L/min, respectively; p < 0.01). A $\dot{\mathrm{V}}$Eint ≥ 4.07 L/min identified patients with high probability of having COPD or HF–COPD (sensitivity of 71.6% and specificity of 72.0%).

Conclusion

These data provide novel evidence that a high $\dot{\mathrm{V}}$Eint (≥ 4.07 L/min) should be valued to suggest coexistent COPD in HF patients.

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 ($\dot{\mathrm{V}}$E) is needed to meet the peripheral metabolic demands (as expressed, for example, by changes in carbon dioxide output ($\dot{\mathrm{V}}$CO₂)). Interestingly, while in HF this mainly reflects the functional adaptation of $\dot{\mathrm{V}}$E to a chronically-increased sympathetic tonus [7], [8], the $\dot{\mathrm{V}}$E–$\dot{\mathrm{V}}$CO₂ relationship in COPD is strongly modulated by the extent at which $\dot{\mathrm{V}}$E is “wasted” in the dead space (VD) [9]. From a practical perspective, this excessive exercise $\dot{\mathrm{V}}$E has been traditionally quantified by the slope of the linear $\dot{\mathrm{V}}$E–$\dot{\mathrm{V}}$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 $\dot{\mathrm{V}}$E–$\dot{\mathrm{V}}$CO₂ parameter that may carry important information relative to the magnitude of VD increase whereas not being constrained by lung mechanical abnormalities — the $\dot{\mathrm{V}}$E intercept ($\dot{\mathrm{V}}$Eint) [16], [17]. $\dot{\mathrm{V}}$Eint represents the ventilatory requirements when pulmonary gas exchange is nil ($\dot{\mathrm{V}}$CO₂ = 0), i.e., the very definition of VD. In fact, as normal lungs have a small VD, $\dot{\mathrm{V}}$Eint has a positive value in more than 95% of healthy subjects [11], [18], [19]. Of note, we showed that $\dot{\mathrm{V}}$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 $\dot{\mathrm{V}}$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 $\dot{\mathrm{V}}$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 $\dot{\mathrm{V}}$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 $\dot{\mathrm{V}}$E–$\dot{\mathrm{V}}$CO₂ relationship ($\dot{\mathrm{V}}$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 $\dot{\mathrm{V}}$E–$\dot{\mathrm{V}}$CO₂ abnormalities [11], [22], [23]. We specifically hypothesized that increases in $\dot{\mathrm{V}}$Eint – but not changes in $\dot{\mathrm{V}}$E–$\dot{\mathrm{V}}$CO₂ slope – would be useful in indicating the presence of COPD in patients with HF.