fnrernarionai Journal of Curdzotogy, 30 (1991) 321-327 a 1991 Elsevier Science Publishers B.V. 0167-5273/91/$03.50 ADONIS 0167527391OtX?813

CARD10

321

01208

Ventilatory threshold during exercise in patients with mild to moderate chronic heart failure: deter~nation, relation with lactate t~esho~d and reproducibility Alain Cohen-Solal, Joelle Benessiano, Dominique Himbert, Catherine Paillole and Rent? Gourgon Service de Cardiologie, H6pital Bichat, Paris, France (Received

1 June 1990; revision

accepted

24 October

1990)

Cohen-Solal A, Benessiano J, Himbert D, Paillole C. Gourgon R. Ventilatory threshold during exercise in patients with mild to moderate chronic heart failure: deter~nation, relation with lactate threshold and reproducibility. Int J Cardiol 1991;30:321-32’7. Detection of the ventilatory threshold during exercise has been proposed in order to assess exercise tolerance in patients with chronic heart failure. The relation between the different methods of detecting the ventilatory threshold and the lactate threshold, however, and their reproducibility, have not really been assessed. Forty-three patients with chronic heart failure underwent an exercise test with respiratory gas analysis. A lactate threshold could be determined in 36 patients and a ventilatory threshold in 27 to 38 patients, depending on the method of determination of the ventilatory threshold. The greatest number of determinations (38) and the best correlation coefficient with the lactate threshold (r = 0.87 and 0.88, respectively) were obtained with the method of the ventilatory equivalent for oxygen and by averaging the different methods of ~te~ination. Repr~~ibili~ of the ventilatory threshold was only moderately good (T = 0.83) and less satisfacto~ than that of the peak oxygen uptake (r = 0.97). We conclude that unless the way of detecting the ventilatory threshold is improved in patients with chronic heart failure, the peak oxygen uptake will remain more reproducible. Key words:

Exercise

testing;

Ventilatory

threshold;

Introduction Exercise testing with analysis of respiratory gases has been proposed as a useful method of assessing the functional capacity in patients with chronic heart failure [l-3]. The lactate threshold

Correspondence to: AIain Cardiologie, HBpital Bichat. Paris. France.

Cohen-Solal, M.D., Service de 46, rue Henri Huchard, 75018

Chronic

heart failure

has been related to the point where oxygen delivery is not sufficient to meet oxygen consumption and anaerobic mechanisms are needed to supplement aerobic energy production during exercise [4,5], Recent studies, however, have emphasized important conceptual and methodolo~cal problems associated with the determination of a lactate threshold and a ventilatory threshold in normal subjects [6-121, raising doubts about the validity of these parameters in patients with chronic heart failure. No previous study has ex-

322

amined each of the methods of determining ventilatory threshold separately in patients with chronic heart failure. This study was undertaken, first, to correlate the different criteria of determination of ventilatory threshold and lactate threshold and, second, to evaluate the reproducibility of ventilatory threshold in patients with chronic heart failure.

Methods Forty-three patients, with stable chronic heart failure, mean age 56 it 10 years, were studied: 32 with idiopathic cardiomyopathy, four with ischemic cardiomyopathy, four with mitral regurgitation, two with mitral stenosis and one with aortic regurgitation All patients with cardiomyopathy had an ejection fraction less than 40% or an enlarged left ventricle (echographic end-diastolic left ventricle diameter > 3 cm/m2). Twenty were in class II of the classification of the New York Heart Association, 19 in class III and four in class IV. Six of the seven patients with valvular disease underwent surgery within three months after the tests. Exercise tests were carried out on a bicycle ergometer. All patients performed at least one preliminary exercise test before the study for familiarization with the technique and exclusion of patients stopping exercise for reasons other than fatigue and/or dyspnea (ischemic electrocardiographic changes, angina, rhythm disturbances, etc...). None had respiratory disease and treatments were not modified before exercise. Respiratory gas analysis was performed with a Sensormedics Horizon II system, using rapid analyzers for oxygen and carbon dioxide. In this system, expired gas volume was measured with a jewel-mounted turbine with the temperature continuously monitored. The oxygen analyzer is a poly~ap~c sensor, the carbon dioxide analyzer an infrared optical system. Uptake of oxygen (CO,) and production of carbon dioxide (I&JO,) were calculated from standard formulae. Data were processed on-line by a microprocessor programmed to correct for delays between signals for

volume and gas concentration, to perform standard calculations, and to print average values every 15 seconds in a real time report. Calibration was performed before each test. Accuracy of the results provided by this system has been reported [13,14]. After a 2 min equilibration period, workload was increased by 10 watts per minute, 20 watts per 2 minutes or 30 watts per 3 minutes (according to the clinical status) after an initial workload of 10, 20 or 30 watts, in an air conditioned room. The patients breathed through a low resistance threeway valve (Hans Rudolph, dead-space 100 ml). Oxygen consumption ( PO2 ), CO, production (I?O,), expired ventilatory volume (PE), respiratory exchange ratio (R), respiratory equivalent for 0, and CO, (PEO,, DECO,) (respectively, ratio of the expired ventilatory volume to FO, and ratio of the expired ventilatory volume to FCO,) were obtained every 15 seconds. Patients were regularly encouraged to perform maximal exercise. Maximal oxygen uptake obtained was defined as peak oxygen uptake (peak PO,). Ventilatory threshold was defined as the level of oxygen uptake where: _ a non-linear increase in carbon dioxide relative to time occurred (FCO, criterion), _ a non-linear increase in the expired ventilatory volume relative to time occurred (FE criterion), _ a non-linear increase in the respiratory exchange ratio relative to time occurred (R criterion), _ the respiratory equivalent for oxygen was minimal relative to time, followed by a progressive increase, without simultaneous increase in the respiratory equivalent for carbon dioxide (fiE0, criterion). Ventilatory threshold was identified by visual inspection without knowledge of lactate threshold. Average ventilatory threshold was defined, when values obtained following these criteria were different, by the mean of the various values; however, when only one value differed markedly from the three others, it was not considered for the calculation of the average ventilatory threshold. An example of identification of the ventilatory threshold is shown in Fig. 1.

323

Determination

of lactate threshold

termined. Maximal and reproducibility

Every minute, 5 ml of venous blood were rapidly ( < 15 set) sampled from an antebrachial vein in all patients. Blood was collected on sodium fluoride and immediately put into ice and assayed with a Boehringer lactate kit (enzymatic technique) [15]. Lactate threshold was visually de-

iO2

Reproducibility oxygen uptake

normal value was 1.7 mmol/l k 5% in the laboratory.

of ventilatory

threshold

and peak

Eighteen patients underwent two tests within an eight days interval with the same protocol (10 watts per minute: 9 patients; 20 watts per 2 minutes: 2 patients; 30 watts per 3 minutes: 7 patients), at the same time of day after having eaten, without a change in medication. Neither the patient, nor the technician were aware of the previous test result. Statistical methods Values are mean t_ standard deviation. Correlation between variables was carried out using a linear regression analysis. For studying reproducibility, results of the two tests were compared using a paired Student t-test for comparison of the mean of the two series of tests. To determine the statistical significance of the deviation of the regression line from the line of identity, a paired t-test was used for comparing the means and a Fisher F-test for comparing the variances. A P value of less than 0.05 was considered significant. Results Peak oxygen uptake ranged from 8 to 32.6 ml/min/kg (mean: 20.8 + 6.2 ml/min/kg). No patient reached a true plateau of PO, max. Determination

of the lactate threshold

Plasma lactate never exceeded the value of 6 mmol/l at peak exercise. A lactate threshold was not identified in 7 patients because of a regular increase throughout exercise, of scattered values, or of a low maxima1 value ( < 2 mmol/l) suggesting that a lactate threshold was not attained. Fig. 1. Determination of the ventilatory threshold. Upper panel: oxygen uptake (li0,) and carbon dioxide production ( vCOz): middle panel: ventilatory equivalent for oxygen (PEO,) and for carbon dioxide (DECO,); lower panel: respiratory exchange ratio (R) and expired ventilatory volume (riE). ri0, is expressed in I/min. Arrow: ventilatory threshold.

Relation between lactate and ventilatory thresholds Ventilatory threshold was determined in 38 patients by the PEO, and the average ventilatory

324 TABLE Matrix

1 of the coefficients

of correlation

Ventilatoty

between

of ventilatory

threshold

and the lactate

threshold.

threshold

tico, Lactate threshold n=24 I-= 0.87 y = 0.71x + 0.3 P= O.oool GO, = oxygen uptake; oxygen: R = respiratory

the criteria

t’E

pE02

R

AVT

28 0.86 0.71x + 0.3 0.0001

28 0.87 0.72.x + 0.3 0.0001

18 0.87 0.62x + 0.4 0.0001

29 0.88 0.71x + 0.3 0.0001

gCOz = carbon dioxide production; tiE = expired ventilatory exchange ratio; AVT = average respiratory threshold.

threshold criteria, in 37 patients with the PE criterion, in 36 patients with the QCO, criterion and only in 27 patients with the respiratory exchange ratio criterion. The relation between ventilatory and lactate thresholds was studied in the 36 patients with a determined lactate threshold. Relations between the lactate threshold and the different criteria of determination of the ventilatory threshold are shown in Table 1 and Fig. 2. The respiratory exchange ratio criterion yielded fewer determinations than the other criteria.

Reproducibility oxygen uptake

volume;

GEO,

= ventilatory

of ventilatory

equivalent

threshold

for

and peak

Results of the two tests are reported in Table 2 and Fig. 3. All criteria of determination of the ventilatory threshold appear equivalent concerning reproducibility. However, a trend toward an increase in ventilator-y threshold appears during the second test, reaching significance for the average ventilatory threshold (Table 2). Reproducibility of ventilatory threshold appears inferior to that of peak oxygen uptake (Fig. 4). Discussion

y a72

The principal results of this study are, first, that a definite lactate threshold can be identified in

r i: 0.87

x + 0.3

.

p = O.ooDl il.22

/

TABLE

2

Repr~ucibil~ty of the criteria peak oxygen uptake.

-0

2

1 VENYILATORY

THRESHOLD

(CO2, llmn)

Fig. 2. Relation between the ventilatory threshold determined the ventilatory equivalent for oxygen (CEO*) method and the lactate threshold (both expressed by the corresponding liO,, in l/mm). Continuous line represents the line of identity.

Criterion

n

Mean test 1

of ventilatory

Mean test 2

threshold

F

and the

t

3c0,

11

1.05

1.14

1.51

1.22

tiE

15

1.12

1.23

1.08

1.95

ri EO, R AVT

14 7 13

1.09 0.92 1.09

1.18 1.00 1.21

1.26 1.24 1.09

1.31 1.37 2.25 *

Peak PO2

18

1.64

1.65

1.40

0.26

Mean of test 1 and test 2 are expressed in l/mm of PO,. Means were compared by a Student t-test and variances by a Fischer F-test. (* P i 0.05). Abbreviations as in Table 1.

325

1 VENTILATORY

0

(i02,

2 THRESHOLD

3 1

llmnj

Fig. 3. Reproducibility of the ventilatory threshold (identified by the PEO, method, expressed by the corresponding VO,, in I/min). Continuous line represents the line of identity. Note the trend towards an increase in the ventilatory threshold between the first and the second test.

most patients; second that a good relation is observed between lactate and ventilatory thresholds but third, that reproducibility of ventilatory threshold is only moderately good and inferior to that of peak oxygen uptake. Relation between lactate and ventilatory

threshold

In this study, the PEO, criterion permitted the greatest number of determinations of the ventilatory threshold; this corresponds to other studies in normal subjects [16,17] or patients with chronic heart failure [lg] showing that the FEO, criterion, 3r = 0.97

y=i.l4x-0.22 p

q

O.OOOl

Reproducibility

n=l0

2-

0

because of the triphasic aspect of the curve. was the most suitable to determine the ventilatory threshold. Nevertheless, the percentage of determination with the other methods was not significantly lower. except for the respiratory exchange ratio method. In 17% of the patients, a ventilatory threshold was not determined by any of the methods; marked abnormalities in the ventilatory pattern or profound deconditioning (resulting in a regular increase in lactate and in ventilation parameters without a clearcut threshold) may account for this observation. This is. in our opinion, an important limitation for the widespread use of this criterion in exercise tests during therapeutic trials. The good relation observed between lactate threshold and ventilatory threshold justifies the non-invasive determination of the ventilatory threshold. This relation between the lactate threshold and the ventilatory threshold does not mean, however. that the ventilatory threshold is the direct consequence of the lactate threshold. Furthermore, the presence of a lactate threshold does not mean the existence of an “anaerobic” threshold [19]. Heterogeneity of fiber composition and marked abnormalities in the muscular cell metabolism in patients with chronic heart failure [20] may account for the increase of lactate in plasma from the beginning of exercise. The mechanisms responsible for the increase of lactate in plasma during exercise, in normal subjects and moreover in patients with chronic heart failure. are probably far more complex than a simple transition between aerobic and anaerobic mechanisms [6,21].

1

3

2

PEAK 902 1 (Vmt’t) Fig. 4. Reproducibility of peak oxygen uptake. represents the fine of identity.

Continuous

line

The problems of determination of the ventilatory threshold in patients with chronic heart failure account for a large part, in our opinion, for the better reproducibility of peak oxygen uptake than that of ventilatory threshold in this study. Important interindividual variability of the ventilatory threshold was observed between the two tests. A trend towards an increase in the ventilatory threshold between the first and the second test was observed. We think that this could be ex-

326

plained by a familiarization of the patient with the technique, emphasizing the importance of performing one or more preliminary tests before starting a therapeutic trial [22]. Comparison

with previous studies

Various studies have assessed the comparison of the various methods of determination of the ventilatory threshold in relation with lactate threshold in normal subjects but no previous study in chronic heart failure has examined each of the methods of determining ventilatory threshold separately. The problem of the reproducibility of ventilatory threshold in normal subjects has also been extensively debated [12,16]. In patients with chronic heart failure, Weber et al. [l] did not specifically compare the relations between the different methods of determination of the ventilatory threshold and the lactate threshold. They reported a good reproducibility for the ventilatory threshold (r = 0.92) that was, however, less satisfactory than that of maximal oxygen uptake, defined as a plateauing of oxygen uptake at the end of exercise (r = 0.98). In the study of Matsumura et al. [23], methodologic assessment in determining anaerobic threshold was carried out in a group of normal and cardiac subjects; anaerobic threshold values determined by the lactate and the respiratory measurements correlated well (r = 0.962) but PE and 30, were the only ventilatory variables measured. Reproducibility was assessed by a coefficient of variation of 3.6 f 10.5%. Lipkin et al. [3] reported a retest reliability coefficient of 96% for anaerobic threshold but determination was realized with the respiratory exchange ratio criterion. Wilson et al. [24] reported the 95% interval confidence of their measurements; coefficient of regression between lactate threshold (arbitrarily defined as an increase of lactate of more than 5 mg/dl from resting value) and ventilatory threshold was 0.81, but sampling interval was larger than in other studies. Simonton et al. [18] recently reported a higher reproducibility for ventilatory threshold than for peak oxygen uptake in a group of normal and cardiac patients; however, a precise lactate level could not be predicted from the ventilatory threshold for individual patients.

Limitations

of the study

Despite cardiac or ventricular dysfunction having motivated a hospitalisation for cardiac failure or requiring a valvular surgery in all our patients, the mean peak oxygen uptake was only moderately reduced in our group of treated patients compared to the normal predicted values. This could account for the relative ease of determination of the lactate and the ventilatory thresholds in our patients and could explain the differences observed between our study and those of Wilson et al. [24] or Simonton et al. [18]. The interval of measurement for lactate and for ventilation parameters was not identical; recent studies have emphasized the value of continuously monitoring lactate concentration, allowing an easier detection of a lactate threshold in normal subjects [25]. Determination of lactate and ventilatory thresholds was subjective. Computerized models of determination of lactate and ventilatory thresholds [26-281 are not, in our opinion, suitable for patients with chronic heart failure because of the small number of values and the marked artefacts in the ventilation curve. Recently, Dickstein et al. in a group of men exercising after myocardial infarction also reported an excellent reproducibility for the ventilatory threshold [29] with an improved computerized method [30], based on the analysis of the tiO,/I?O, relationship [26]; however, the same experience and expertise required for visual detection are necessary to ensure the accuracy of the automatic calculation. Conclusion A ventilatory threshold exists in most of patients with chronic heart failure even if its determination is often difficult and its reproducibility inferior to that of peak oxygen uptake. If the good relation between ventilatory threshold and lactate threshold justifies the determination of the former, improvement in the way of detecting it is needed. Peak oxygen uptake appears, in our experience, to be the most reproducible criterion of exercise tolerance in patients with chronic heart failure [31].

327

Acknowledgements This study was supported in part by grants from SociCtC FranGaise de Cardiologie, Federation Franqaise de Cardiologie, Institut National de la Sante et de la Recherche Mtdicale (no. 87-3-2605-E & no. 48-80-02). We are grateful to Patricia Villate, R.N. and Claude Guichet, PhD, for their help in performing the study and to Dominique Guyot for her help in the statistical analysis.

References 1 Weber

2 3

4

5

6

7

8

9

10

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Ventilatory threshold during exercise in patients with mild to moderate chronic heart failure: determination, relation with lactate threshold and reproducibility.

Detection of the ventilatory threshold during exercise has been proposed in order to assess exercise tolerance in patients with chronic heart failure...
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