Skip Navigation

European Journal of Heart Failure 2000 2(1):47-51; doi:10.1016/S1388-9842(99)00060-4
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (8)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Clark, A. L.
Right arrow Articles by Coats, A. J.S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Clark, A. L.
Right arrow Articles by Coats, A. J.S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2000 European Society of Cardiology

Ventilatory capacity and exercise tolerance in patients with chronic stable heart failure

Andrew L. Clarka,*, L. Ceri Daviesb, Darrel P. Francisb and Andrew J.S. Coatsb

a Department of Cardiology, Castle Hill Hospital Castle Road, Cottingham, HU16, 5JQ Hull, UK
b National Heart & Lung Institute, Imperial College of Science Technology and Medicine London, UK

* Corresponding author. Tel.: +44-1482-624087; fax: +44-1482-624085. E-mail address: c.m.porter{at}medschool.hull.ac.uk


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Background: Patients with chronic heart failure complain of breathlessness. This is associated with an increase in the ventilatory response to carbon dioxide production (VE/VCO2 slope), yet a reduction in the maximal ventilation achieved at peak exercise. We analysed ventilatory capacity in heart failure in relation to exercise capacity.

Methods: We analysed data from 74 patients with chronic stable heart failure [age (S.D.) 50.6 (8.8) years; left ventricular ejection fraction 30 (15)%] and 36 controls [48.9 (11.5) years]. Subjects undertook maximal incremental exercise testing with metabolic gas exchange measurements to derive peak oxygen consumption (VO2), the VE/VCO2 slope and ventilation. Spirometry was used to measure FEV1 and FVC. Maximal voluntary ventilation (MVV) was calculated as FEV1x35.

Results: Peak VO2 was lower in patients [20.9 (7.5) ml min–1 kg–1 vs. 34.5 (10.1); P<0.001] and VE/VCO2 greater [33.4 (10.7) vs. 26.0 (4.7); P<0.001]. Ventilation at peak exercise was lower in patients [63.5 (20.4) l/min vs. 86.9 (29.5); P<0.001], as was MVV [110.1 (37.9) l/min vs. 136.2 (53.1); P<0.001], but ventilation at peak as a proportion of MVV was the same in patients [60.0 (19.0)%] as controls [65.7 (12.4)%)]. There was an inverse relation between peak VO2 and VE/VCO2 slope (r=–0.62; P<0.001). Percentage predicted FEV1 correlated with ventilation at peak (r=0.62; P<0.001) and inversely with VE/VCO2 slope (r=–0.32; P<0.001). There was no relation between percentage of MVV achieved and peak VO2, or VE/VCO2 slope.

Conclusions: Although ventilation at peak exercise is lower in patients with heart failure than normal subjects, ventilation is the same proportion of maximal voluntary ventilation. These findings suggest that ventilatory capacity does not limit exercise capacity in heart failure.

Key Words: Ventilation • Chronic heart failure • Maximum voluntary ventilation • Exercise

Received August 17, 1999; Revised October 4, 1999; Accepted October 21, 1999


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
Chronic heart failure is a syndrome characterised by exercise intolerance. With formal exercise testing, patients have a reduction in peak oxygen consumption (VO2) and an increase in the ventilatory response to exercise [1,2], characterised as an increase in the slope relating ventilation (VE) to carbon dioxide production (VCO2). The VE/VCO2 slope correlates inversely with peak VO2 [3,4].

Although ventilation is increased relative to carbon dioxide production, and relative to exercise load, ventilation at peak exercise is lower in heart failure patients than in normal subjects [5]. This suggests that the ventilatory capacity is not limiting exercise, but it may be that the potential maximal ventilation is reduced in heart failure, and that the lower peak ventilation represents a greater proportion of maximal possible ventilation.

Maximal possible ventilation is very difficult to measure. Maximum voluntary ventilation (MVV) can be determined from forced hyperventilation over a short period, but this is an uncomfortable manoeuvre even for normal subjects. For practical purposes, therefore, MVV may be derived from the forced expiratory volume in one second (FEV1) [6,7]. Ventilation at peak exercise in normal subjects is at around 60% of MVV.

The purpose of the present study was to assess ventilatory capacity in patients with heart failure and relate this to exercise capacity.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
We retrospectively analysed data from the Royal Brompton Heart Failure Registry. The diagnosis of heart failure was based on exercise intolerance due to breathlessness or fatigue in the presence of evidence of left ventricular systolic impairment on either echocardiography or radionuclide ventriculography. Patients were included if they had completed a maximal symptom limited exercise test with metabolic gas exchange, and had had spirometry performed on the same day. All patients were clinically stable for at least 3 months at the time of testing, and had no peripheral oedema.

Patients with a history of pulmonary disease were excluded. A group of age-matched normal controls was recruited from subjects attending for routine medical examinations, or for the assessment stage of a fitness-training programme.

Exercise testing was conducted in an air conditioned room. Patients exercised using the modified Bruce protocol. Exhaled air was analysed to determine metabolic gas exchange with a respiratory mass spectrometer (Amis 2000, Odennse, Denmark) [8,9]. Subjects were encouraged to exercise to exhaustion. Spirometry was performed immediately prior to the exercise test using the respiratory mass spectrometer. The average of three maximal efforts was taken after at least two initial familiarisation tests.

Metabolic gas exchange was determined on-line every 10 s. Peak VO2 was used as an index of exercise capacity, and the VE/VCO2 slope as an index of the ventilatory response to exercise. Ventilation at peak exercise was recorded. Respiratory exchange ratio (VCO2/VO2) was used as an index of effort made. Spirometric variables were expressed as percentages of predicted values for height and age. MVV was calculated as (35xFEV1) [6].

Comparisons between patients and controls were made with unpaired t-tests. Relationships between measured variables were explored with least squares linear regression. Results are expressed as means (S.D.). A P value of <0.05 was taken to be significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
A total of 110 subjects were analysed, 74 patients and 36 controls. Demographic details are shown in Table 1. The results of exercise testing are shown in Table 2. Patients had a lower peak VO2 and higher VE/VCO2 slope than controls, and a lower ventilation at peak exercise. The respiratory exchange ratio at peak exercise was the same in both groups, suggesting equivalent levels of exertion.


View this table:
[in this window]
[in a new window]

  		Table 1 Demographic detailsa

 


View this table:
[in this window]
[in a new window]

  		Table 2 Results of spirometry and exercise testinga

 
Spirometric variables were reduced in the heart failure group. MVV was thus lower in the heart failure group. Despite the reduced absolute peak VE in the patients, a similar proportion of maximum voluntary ventilation was achieved.

There were correlations between peak VO2 and spirometric variables (see Figs. 1 and 2). There were negative correlations between spirometric variables and the VE/VCO2 slope (FEV1 r=–0.32; %FEV1 r=–0.34; FVC r=–0.34; %FVC r=–0.34). These were all statistically significant (P<0.001 for all). There was a closer relation between maximum ventilation at peak exercise and spirometric variables (Fig. 3). There was an inverse relation between peak VO2 and VE/VCO2 slope (r=–0.62; P<0.001) (Fig. 4). There was, however, no relation between percentage of MVV achieved and exercise capacity, or ventilatory response to exercise (Fig. 5).


Figure 1
View larger version (15K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 The relation between peak expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) and peak oxygen consumption (VO2).

 


Figure 2
View larger version (14K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2 The relation between peak expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), expressed as percentage of predicted value, and peak oxygen consumption (VO2).

 


Figure 3
View larger version (15K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3 The relation between peak expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) and ventilation at peak exercise.

 


Figure 4
View larger version (12K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 4 The relation between peak oxygen consumption and the slope relating ventilation to carbon dioxide production (VE/VCO2 slope).

 


Figure 5
View larger version (15K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 5 The relation between the proportion of maximal voluntary ventilation achieved at peak exercise (%MVV), and exercise capacity (peak VO2) and ventilatory response to exercise (VE/VCO2 slope).

 
It may be that those patients with severely abnormal spirometry have limiting pulmonary pathology, and so we defined those patients achieving at least 80% predicted for both FEV1 and FVC as having normal spirometry (n=45). Peak VO2 was lower in these patients than controls [23.1 (7.2) ml/min per kg vs. 34.5 (10.1); P<0.001]. There remained a relation between %FEV1 and %FVC, and peak VO2 (r=0.55; P<0.001 and r=0.59; P<0.001, respectively). For this smaller group of patients, MVV was the same as for controls [132 (32) l/min vs. 136 (53)]. Peak achieved ventilation was lower than controls [68.8 (20.2) l/min vs. 86.9 (29.5); P<0.001], and thus percentage MVV at peak exercise was lower [53.4 (14.3) vs. 65.8 (12.4); P<0.001].


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
Heart failure causes a reduction in exercise tolerance, usually expressed as breathlessness or fatigue [10]. The pathophysiology underlying exercise intolerance is still unclear [11]. It seems unlikely that central haemodynamic function is responsible [12,13], and there has been interest in pulmonary and ventilatory abnormalities as possible limiting factors [14,15]. Previous studies have shown a relation between spirometric variables and exercise capacity [16].

Although ventilation at any given workload is higher in patients than controls, ventilation at peak exercise is lower in patients. It may be that patients are less able to push themselves to maximal exertion, although the RER at peak exercise was similar in the two groups. A second possibility is that patients are terminating exercise due to inability to increase ventilation due to respiratory muscle fatigue, or because the signal to ventilation has become exhausted. Alternatively, if exercise is terminated due to non-pulmonary factors, the reduction in peak ventilation may be because workload at peak exercise is lower [5]. Peak ventilation correlates closely with peak oxygen consumption since both variables increase more-or-less linearly with increasing workload (r=0.79 in the present study; figure not shown).

Spirometric variables are variously reported to be abnormal in heart failure [17,18], although large numbers of patients have normal spirometry [5]. Where there is impairment of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), the two decrease in parallel [19] suggesting that obstructive lung pathology is unlikely to be a dominant problem. It may be that respiratory muscle weakness [20] or diffusion limitation [21] may be involved. A further contribution may come from increased heart size and an increase in central blood volume, resulting in a reduction in lung volumes.

We have confirmed a close relation between spirometric variables and exercise capacity in this present study. We had thought it likely at the outset that heart failure patients would achieve a lower proportion of their maximal ventilation, but have shown that for an unselected group of heart failure patients, there was no difference from controls. Only when we excluded patients with abnormal spirometry in a post hoc analysis was there a reduction in percent predicted MVV in patients.

Normal subjects stop exercising in all but rare instances well before achieving MVV, usually with ventilation at approximately 60% of MVV. The implication drawn is that ventilation does not limit exercise in normal subjects. We report similar findings in patients with heart failure. It has been suggested that exercise in heart failure may be limited by excessive pulmonary dead space secondary to ventilation–perfusion mismatching [14,15]. The observations in the present study suggest that ventilatory capacity and hence ventilation–perfusion matching, is not the limiting factor in incremental exercise testing. However, an alternative to this interpretation is that mismatching is responsible for increased ventilation at a given work load, and that this is interpreted subjectively by the patient as breathlessness. It might then be the breathlessness that stops exercise, rather than reaching the limit of ventilatory capacity. Against this is the observation that patients with breathlessness as their dominant symptom have much the same pathophysiological responses to exercise as those with fatigue [10].

Limitations: This was a retrospective review of patients. We have assessed maximum voluntary ventilation indirectly in our patients. MVV is difficult to measure directly even in normal subjects, and the manoeuvre required is poorly tolerated by patients with heart failure.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

  1. Rubin S.A., Brown H.V. Ventilation and gas exchange during exercise in severe chronic heart failure. Am Rev Respir Dis (1984) 129:S63–64.[Web of Science][Medline]
  2. Weber K.T., Kinasewitz G.T., Janicki J.S., Fishman A.P. Oxygen utilisation and ventilation during exercise in patients with chronic cardiac failure. Circulation (1982) 65:1213–1223.[Abstract/Free Full Text]
  3. Buller N.P., Poole-Wilson P.A. Mechanism of the increased ventilatory response to exercise in patients with chronic heart failure. Br Heart J (1990) 63:281–283.[Abstract/Free Full Text]
  4. Davies S.W., Emery T.M., Watling M.I.L., Wannamethee G., Lipkin D.P. A critical threshold of exercise capacity in the ventilatory response to exercise in heart failure. Br Heart J (1991) 65:179–183.[Abstract/Free Full Text]
  5. Clark A.L., Volterrani M., Swan J.W., Coats A.J.S. Increased ventilatory response to exercise in chronic heart failure: relation to pulmonary pathology. Heart (1997) 77:138–146.[Abstract/Free Full Text]
  6. Jones R.S., Buston M.H., Wharton M.J. The effect of exercise on ventilatory function in the child with asthma. Br J Dis Chest (1962) 56:78–86.[CrossRef][Web of Science][Medline]
  7. Miller W.F., Scacci R., Gast L.R. Laboratory evaluation of pulmonary function (1987) Philadelphia: JB Lipincott. 300.
  8. Lipkin D.P., Perrins J., Poole-Wilson P.A. Respiratory gas exchange in the assessment of patients with impaired ventricular function. Br Heart J (1985) 54:321–328.[Abstract/Free Full Text]
  9. Davies N., Denison D.M. Measurement of metabolic gas exchange and minute volume by mass spectrometry alone. Respir Physiol (1979) 36:261–267.[CrossRef][Web of Science][Medline]
  10. Clark A.L., Sparrow J.L., Coats A.J.S. Muscle fatigue and dyspnoea in chronic heart failure: two sides of the same coin? Eur Heart J (1995) 16:49–52.[Free Full Text]
  11. Clark A.L., Poole-Wilson P.A., Coats A.J.S. Exercise limitation in chronic heart failure: The central role of the periphery. J Am Coll Cardiol (1996) 28:1092–1102.[Abstract]
  12. Weber K.T., Wilson J.R., Janicki J., Likoff M.J. Exercise testing in the evaluation of the patient with chronic cardiac failure. Am Rev Respir Dis (1984) 129:S60–S62.[Web of Science][Medline]
  13. Franciosa J.A., Park M., Levine T.B. Lack of correlation between exercise capacity and indexes of resting left ventricular performance in heart failure. Am J Cardiol (1981) 47:33–39.[CrossRef][Web of Science][Medline]
  14. Sullivan M.J., Higginbotham M.B., Cobb F.R. Increased exercise ventilation in patients with chronic heart failure: intact ventilatory control despite haemodynamic and pulmonary abnormalities. Circulation (1988) 77:552–622.[Abstract/Free Full Text]
  15. Metra M., Dei Cas L., Panina G., Visioli O. Exercise hyperventilation chronic congestive heart failure and its relation to functional capacity and hemodynamics. Am J Cardiol (1992) 70:622–628.[CrossRef][Web of Science][Medline]
  16. Kraemer M.D., Kubo S.H., Rector T.S., Brunsvold N., Bank A.J. Pulmonary and peripheral vascular factors are important determinants of peak exercise oxygen uptake in patients with heart failure. J Am Coll Cardiol (1993) 21:641–648.[Abstract]
  17. Moore D.P., Weston A.R., Hughes J.M.B., Oakley C.M., Cleland J.G.F. Effects of increased inspired oxygen concentrations on exercise performance in chronic heart failure. Lancet (1992) 339:850–853.[CrossRef][Web of Science][Medline]
  18. Wright R.S., Levine M.S., Bellamy P.E., et al. Ventilatory and diffusion abnormalities in potential heart transplant recipients. Chest (1990) 98:816–820.[Abstract/Free Full Text]
  19. Wasserman K., Zhang Y-Y, Gitt A., et al. Lung function and exercise gas exchange in chronic heart failure. Circulation (1997) 96:2221–2227.[Abstract/Free Full Text]
  20. Chua T.P., Anker S.D., Harrington D., Coats A.J.S. Inspiratory muscle strength is a determinant of maximum oxygen consumption in chronic heart failure. Heart (1995) 74:381–385.[Abstract/Free Full Text]
  21. Puri S., Baker B.L., Dutka D.P., Oakley C.M., Hughes J.M.B., Cleland J.G.F. Reduced alveolar-capillary membrane diffusing capacity in chronic heart failure. Circulation (1995) 91:2769–2774.[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J Gerontol A Biol Sci Med SciHome page
C. O. Weiss, H. H. Hoenig, R. Varadhan, E. M. Simonsick, and L. P. Fried
Relationships of Cardiac, Pulmonary, and Muscle Reserves and Frailty to Exercise Capacity in Older Women
J Gerontol A Biol Sci Med Sci, October 12, 2009; (2009) glp147v1.
[Abstract] [Full Text] [PDF]

Home page
 HeartHome page
I Raymond, B A Groenning, P R Hildebrandt, J C Nilsson, M Baumann, J Trawinski, and F Pedersen
The influence of age, sex and other variables on the plasma level of N-terminal pro brain natriuretic peptide in a large sample of the general population
Heart, July 1, 2003; 89(7): 745 - 751.
[Abstract] [Full Text] [PDF]

Home page
 HeartHome page
K K A Witte, S D R Thackray, N P Nikitin, J G F Cleland, and A L Clark
Pattern of ventilation during exercise in chronic heart failure
Heart, June 1, 2003; 89(6): 610 - 614.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (8)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Clark, A. L.
Right arrow Articles by Coats, A. J.S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Clark, A. L.
Right arrow Articles by Coats, A. J.S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?