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Anaerobic threshold detection in patients with congestive heart failure
Anaerobic Threshold Detection in Patients with Congestive Heart Failure Stuart D. Katz, MD, Robert Berkowitz, MD, and Thierry H. LeJemtel, MD
Anaerobic threshotd measurements determined either invadveiy by analysis of arterial lactate concentration (lactate threshold) or noninvasively by respfratory gas exchange analysis (ventilator-y threshoid) were compared in patients with chronic congestive heart failure. Sixteen patients performed symptom-limited maximal exercise on a bicycle ergometer ushrg a conthumus ramp protocol with measurement of arterial lactate concentration at 1 minute intervals, and continuous breathby-breath analysis of respiratory gas exchange. A specific tactate threshold point was detected in only 7 patients. These 7 patients had significantly greater peak oxygen uptake than did the 9 in whom no specific lactate threshold point was detected (15.9 f 1.0 VI 10.5 f 0.5 ml/icg/min; p
aximal oxygen uptake (VOz) is difficult to determine in many patients with severecongestive heart failure (CHF) who do not reliably reach a plateau in VO;! during symptom-limited maximal exercise.’ Anaerobic threshold has been proposed as an alternative objective measureof submaximal exercise capacity in this group of patients2 Anaerobic threshold can be determined either invasively by analysis of arterial lactate concentration (lactate threshold) or noninvasively by respiratory gas exchange analysis (ventilatory threshold).3y4The clinical use of anaerobic threshold determination in CHF has beenlimited by the absenceof a consensuson the best methodology for lactate and ventilatory threshold detection.5-9 Furthermore, reported methodsare subject to substantial intraand interobservervariability, becauseanaerobic threshold determination is based on subjective interpretation of lactate or gas exchangedata.lOJ* Recent refinements in exerciseprotocols and gas exchangeanalysis systems, and more objective techniques of anaerobic threshold detection have increasedthe precision and reproducibility for both lactate and ventilatory thresholds in normal human subjects.12J3 Accordingly, the present study was performed to evaluate these new methods in patients with CHF.
M
METHODS Path&u Fourteen men and 2 women (mean age 60 years, range 48 to 69) with stable CHF in New York Heart Association classII or III were studied. The etiology of CHF was coronary artery diseasein 4 patients, idiopathic dilated cardiomyopathy in 10, and hypertensive heart diseasein 2. Left ventricular ejection fraction (as determined by radionuclide angiography within 6 months of the study) averaged 25% (range 15 to 33). All patients were treated with stable dosesof digoxin, diuretics and an angiotensin-converting enzyme inhibitor. Cardiac medications were withheld on the morning of the study. By the criteria proposedby Weber et a1,14 4 patients were class B (peak VO2 16.7 to 19.4 ml/ kg/min), 8 were classC (10.3 to 14.4 ml/kg/min), and 4 were class D (9 to 9.9 ml/kg/mm). Patients with exercise-inducedmyocardial ischemia,peripheral vascular disease(ankle/arm blood pressureratio
1565
performed a symptom-limited maximal exercisetest on an electronically braked cycle ergometer (Mijnhardt Model REM III) using a continuous ramp protocol. After resting for 2 minutes on the bicycle, patients pedaled at approximately 60 rpm as the work load increased from 0 W at a rate of 5 to 10 W/mm, adjusted to patient’s previous exercise performance to maintain the duration of the test between 8 and 12 minutes. Arterial lactate sampleswere collected at rest, at l-minute intervals during exercise,and at 1 and 3 minutes after exercise. Blood samples were immediately deproteinized with iced perchloric acid for later analysis. Expired gases were collected through a low-resistance3-way valve (Hans Rudolph) for 1 to 2 minutes at rest, and continuously during exercise. VO2, carbon dioxide production (VCO3 and minute ventilation were continuously monitored on a breath-by-breath basis (Medical Graphics 2001). Becauseno plateau in VOz at end-exercisewas observedin patients, peak VOZ was defined as the aver-
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1566
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THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 69
agevalue of VOz in the last 30 secondsof exercisewhen the respiratory exchangeratio was >1.05. Detemhation of anaembic thresholdz Anaerobic threshold was determined by both arterial blood lactate concentrations (lactate threshold) and analysis of expired gases(ventilatory threshold). LACTATE THRESHOLD: Arterial blood lactate concentration was determined by a spectrophotometricmethod in mmol/liter (Sigma Kit). Lactate threshold was determined by the following 2 methods: (1) visual inspection of the plot of arterial lactate concentrationsversusVO2, and (2) log-log transformation of the lactate and VO2 data, as describedby Beaver et all2 A sharp inflection point, if present, was chosen by visual inspection, and lactate threshold was determined by a 2-segmentlinear regressionmodel. VENTILATORY THRESHOLD: Ventilatory threshold was determined by both subjective interpretation of respiratory gas exchange data (VT standard) and by a computerized method (VT-V slope). VT standard was determined independently by 2 investigators familiar with the criteria for anaerobic threshold detection, as describedby Wasserman.15VO2, VCO2, minute ventilation, respiratory exchange ratio (R), ventilatory equivalents of VOZ and VCO2 (VE/ VO2 and VE/VC02, respectively), and end-tidal partial pressuresof oxygen and carbon dioxide (Pet02 and Pet COz, respectively) were plotted versustime, using an 8breath moving averagefilter. Ventilatory threshold was considered present when: (1) the VE/V02 curve reached a minimum and began to rise, while the VE/ VCO2 curve remained flat, (2) the Pet02 curve began to rise, while the PetCO2 curve remained flat, and (3) the slopeof the R curve beganto rise more sharply during exercise.Ventilatory threshold was chosenfrom the plot that most clearly satisfied Wasserman’scriteria. Values for ventilatory threshold determined independently by each observer were highly correlated (r = 0.92, p
JUNE 15, 1992
Scheffe test for post hoc determination of statistical significance. Single linear regressionanalysis was also performed using the least-squaresmethod. Statistical significance was acceptedat the 95% confidence limit (2tailed p value <0.05). RESULTS L8&te threrhdd: Arterial lactate concentration increasedcurvilinearly as a function of VOz in 7 patients in whom a clear threshold point was detected by a loglog transformation of the data (Figure 1). Arterial lactate increasedlinearly as a function of VO2 in 9 patients in whom no clear lactate threshold could be detected even with a log-log transformation of the data (Figure 2).
Peak VO2 was significantly lower in patients without detectable lactate threshold than in those in whom lactate threshold was present (Table I). A specific lactate threshold point was not detectedin any patient with severe CHF (peak VO2 <12 ml/kg/min), but was present in all with mild to moderate CHF (>14 ml/kg/ min). For patients with peak VO2 between 12 and 14 ml/kg/min, lactate threshold was detectedin 2 and not detectedin 1. Arterial lactate concentrationsat rest and after 2 minutes of exercise (corresponding to a work load of 10 to 20 W), and percentageof peak VOX after 2 minutes of exercise were significantly greater in patients without detectable lactate threshold. (T&e II): Ventilatory threshv-old was detected from examination of standard plots in 12 patients and by the computerized V-slope method in 14. Ventilatory threshold was detectedby both methods in the 7 patients in whom lactate threshold was present. In 9 patients without detectablelactate threshold, ventilatory threshold was determined by standard plots in 5 and by the V-slope method in 7. In the remaining patients, no clear threshold point was evident on plots of respiratory gas exchange. Compvkon of m Lactate threshold (when detected) significantly correlated with both VT standard (r = 0.79, p <0.05) and VT-V slope (r = 0.78, p <0.05; Figure 3). Lactate threshold occurred at a significantly lower VO2 and arterial lactate concentration than did ventilatory anaerobic threshold determined by standard plots or the V-slope method (p <0.05; Table II and Figure 4). VT-V slope tended to occur earlier in exercise than did VT standard and was closer to the lactate threshold.
rapid early increasein lactate concentration in 15 of 48 patients studied when exercise capacity was <6 minutes, correspondingto a peak work load of <60 W on a cycle ergometer.Simonton et aL7Matsumura et al8 and TABLE I Clinical Characteristics of Patients With and Without Detectable Lactate Threshold
Age (yr) Left ventricular ejection fraction (%) Exercise duration (set) Peak VOz (ml/kg/min) Peak work rate(W) Resting lactate (mmol) Lactate at 2 minutes of exercise (mmol) % peak VOz at 2 minutes of exercise
Lactate Threshold Present
Lactate Threshold Absent
p Value
58 + 6 23 2 7
62 t 8 25 -t 8
NS NS
663 15.9 95 0.8 1.0
+ + f f 2
126 2.7 18 0.2 0.3
541 10.5 54 1.0 1.5
53 k 6
156 1.4 16 0.3 0.4
NS
77 f 9
<0.05
NS = not significant; VOa = oxygen uptake.
4
5
6
7
OXYGEN
6
9
UPTAKE
10
11
12
(mbkglmin.)
B
0.7
n +: n
0.5
n
I n
0.3
DISCUSSION In patients with severe CHF (peak VO2 <12 ml/ kg/m@, lactate threshold could not be detected with the methods used in this study. In patients with mild to moderate CHF (peak VOz >14 ml/kg/min), ventilatory threshold determined by analysis of gas exchange data was closely related to the lactate threshold. Our findings in patients with severe CHF are in agreement with previous reports. Weber and Janicki5 described a rapid linear increase in blood lactate concentration in patients with severe aerobic impairment (peak VOz
+ + f f k
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1567
LOG OXYGEN UPTAKE
ANAEROBIC
THRESHOLD
IN HEART
TABLE II Comparison of Methods for Detection of Anaerobic Threshold Lactate Threshold Pt.
Peak VO2
Peak Lactate
vo2
VT-V Slope
Lactate
vo2
VT Standard Lactate
vo2
Lactate
Lactate Threshold Present (n = 7)
1 2 3 4 5 6 7
3.3 5.2 4.7 6.1 2.8 4.0 6.0 4.6 t 1.3
12.0
13.5 14.4 19.4 17.0 18.1 16.7
Mean 2 SD
15.9 + 2.7*
8 9 10 11 12 13 14 15 16 Mean 2 SD
9.5 10.3 12.6 9.0 10.5 13.2 10.3 9.9 9.5
5.9 9.0 10.8 11.9 11.0 12.0 9.1 10.0 ‘- 2.2’1
1.1 1.6 1.5 1.3 0.9 1.1 1.9 1.3 + 0.47
8.5 9.2 10.3 14.2 11.0 13.8 12.2 1 1.3 + 2.2
1.8 1.7 1.6 3.0 0.9 1.5 2.6 1.9 r 0.7
9.3 9.9 11.4 14.0 10.6 13.7 12.5 11.6 i 1.8
2.3 2.4 2.1 2.6 1.1 1.6 3.4 2.2 i- 0.7
Lactate Threshold Absent (n = 9)
5.2 3.7 6.2 4.4 4.9 3.0 3.3 4.6 2.6 4.2 k 1.2
10.5 z 1.4
-
-
l p ~0.05 vs patients without lactate threshold; tp < 0.05 vs VT-V slope and VT standard. VO? = oxygen uptake; VT Standard = subjective analysis of gas exchange; VT-V slope = computerized
6
6
10
12
Oxygen
uptake
at lactate (ml/kg/min.)
threshold
Oxygen
uptake
mt lactate (ml/kglmln.)
threshold
15 1
1568
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THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 69
10.0 10.0 10.9 9.4 10.3 8.1 8.1 9.5 2 1.1 analysis of respimtoly
4.3 1.7 4.6 3.6 4.0 2.4 1.7 3.2 k 1.2
9.4 7.3 8.9 10.9 9.1 9.2 f 1.3
1.7 2.5 3.5 1.6 2.6 2.4 Z!I0.8
gas exchange date.
Rajfer et al9 also identified subsetsof patients with severe aerobic impairment in whom anaerobic threshold could not be detected. The inability to detect lactate threshold in severeCHF is related to the extremely limited work load capacity in these patients. Despite extremely low work loads, patients with severeCHF demonstrated anaerobic metabolism from the onset of exercise. In patients with mild to moderate CHF in whom lactate threshold was detected,the relation betweenlactate and ventilatory threshold was similar to that of previous reports. The correlation coefficients of 0.78 and 0.79 for the V-slope and standard methods of determination of ventilatory threshold, respectively, compare favorably with the r value of 0.81 reported by Wilson et a1,6but are below the r value of 0.96 reported by Matsumura et a1.8As reported in normal subjects,r2the ventilatory threshold determined by the V-slope method is closer to the lactate threshold than is ventilatory threshold determined by standard plots. Whereasarterial lactate concentration increasedlinearly from the onset of exercise, ventilatory threshold could still be detectedin approximately 50% of patients with severe CHF. The point of respiratory compensation, rather than anaerobic threshold, may have been detectedin thesepatients. This explanation is consistent with high relative VOz at ventilatory threshold determined in this group. Factors other than blood lactate concentration may have also affected the ventilatory response during exercise. Patients with McArdle’s syndrome (a congenital metabolic myopathy in which skeletal muscle lacks the ability to produce lactate) may still manifest criteria for detecting ventilatory threshold determination during graded exercise.l6 Similarly, gly-
JUNE 15, 1992
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cogen depletion in normal subjectsdecreasesblood lactate concentration, but increasesminute ventilation during exercise.” Our findings demonstratethat in patients with severeCHF, criteria for ventilatory threshold were present even in the absence of a detectable lactate threshold. Clinkal implkatiam An objective measureof functional impairment is needed in patients with severe CHF, because they are most likely to be involved in therapeutic drug trials. A power-assistedbicycle ergometer that provides extremely low work loads may allow detection of anaerobic threshold in severely impaired patients. Submaximal steady-stateexerciseprotocols to assessVOz or lactate kinetics may provide an alternative means of assessingfunctional capacity in patients with severeCHF.18 In patients with mild to moderate CHF (peak VOZ >14 ml/kg/mm), the computerized V-slope method is preferable to standard plots, becausethe values for ventilatory threshold are determined objectively and are closer to the lactate threshold point than are those determined by subjective interpretation of gas exchange data.
REFERENCES
1. LeJemtel TH, Mancini D, Gumbardo D, Chadwick B. Pitfalls and limitations of maximal oxygen uptake as an index of cardiovascular functional capacity in patients with chronic heart failure. Heart Failure 1985;1:112-124. 2. WassermanK, McIlroy MB. Detecting the thresholdof anaerobicmetabolism in cardiac patient. Am J Cardiol 1964;14:844-852. 3. Davis JA. Anaerobic threshold: review of the conceptand direction for future
VT-VSLOPE
VT-STAND
2
research.Med Sci Sports Exert 1985;17:6-18. 4. Caiozxo VJ, Davis JA, Ellis JF, Azus JL, Vandagriff R, Prietto CA, McMaster WC. A comparisonof gasexchangeindicesusedto detectthe anaerobicthreshold. J Appl fhysiol 1982;53:1184-1189. 5. Weber KT, Janicki JS. Lactate production during maximal and submaximal exercisein patientswith chronicheart failure. JAm Co11Cardioll985;6:7 17-724. 6. Wilson JR, Fink LI, Ferraro N, Dunkman WB, JonesRA. Use of maximal bicycle exercisetesting with respiratory gas exchangeanalysisto assessexercise performancein patientswith congestiveheart failure secondaryto coronary artery diseaseor to idiopathic dilated cardiomyopathy.Am J Cardiol 1986;58:601-606. 7. SimontonCA, Higginbotham MB, Cobb FR. The ventilatory threshold:Quantitative analysisof reproducibility and relation to arterial lactate concentrationin normal subjectsand in patients with chronic congestive heart failure. Am J Cardiol 1988;62:100-107. 6. Matsumura N, Nishijima H, Kojima S, Hashimoto F, Minami M, Yasuda H. Determinationof anaerobicthresholdfor assessment of functional statein patients with chronic heart failure. Circulation 1983;68:360-367. 9. Rajfer SI, Nemanich JW, Shurman AJ, RossenJD. Metabolic responsesto exercisein patientswith heart failure. Circularion 1987;76(supplVl):VI46-V153. 10. Yeh MP, Gardner RM, Adams TD, Yanowits FG, Craps RO. “Anaerobic threshold”: problemsof determination and validation. J App/ Physiol 1983;55: 1178-1186. 11. Gladden LB, Yates JW, Stremel RW, Stamford BA. Gas exchangeand lactate anaerobicthresholds:inter- and intraevaluator agreement.J Appl Physiol 1985;58:2082-2089. 12. BeaverWL, WassermanK, Whipp BJ. Improveddetectionof lactate threshold during exercise using a log-log transformation. J App/ Physic4 1985;59: 1936- 1940. 13. Beaver WL, WassermanK, Whipp BJ. A new method for detectinganaerobic threshold by gas exchange.J Appl Physiol 1986;60:2020-2027.
14. Weber KT, Kinasewitz GT, Janicki JS, FishmanAP. Oxygen utilization and ventilation during exercise in patients with chronic cardiac failure. Circularion 1982;65:1213-1223. IS. WassermanK. Determinantsanddetectionof anaerobicthresholdandconsequencesof exercise above it. Circulation 1987;76(supplVl):VI29-VI39. 16. Hagberg J, Coyle EM, Carroll JE, Miller JM, Martin WH, Brooke MH. Exercise hyperventilation in patients with McArdle’s disease.J Appl Pfiysiol 1982;52:991-994. 17. Segal SS, Brooks GA. Effect of glycogendepletion and workload on post exercise02 consumptionand bleed lactate. J Appl Physiol 1979;47:512-514. 16. WassermanK. New conceptsin assessingcardiovascularfunction. Circulorim 1988;78:1060-1071.
ANAEROBIC THRESHOLD IN HEART FAILURE 1569
Anaerobic threshotd measurements determined either invadveiy by analysis of arterial lactate concentration (lactate threshold) or noninvasively by respfratory gas exchange analysis (ventilator-y threshoid) were compared in patients with chronic congestive heart failure. Sixteen patients performed symptom-limited maximal exercise on a bicycle ergometer ushrg a conthumus ramp protocol with measurement of arterial lactate concentration at 1 minute intervals, and continuous breathby-breath analysis of respiratory gas exchange. A specific tactate threshold point was detected in only 7 patients. These 7 patients had significantly greater peak oxygen uptake than did the 9 in whom no specific lactate threshold point was detected (15.9 f 1.0 VI 10.5 f 0.5 ml/icg/min; p
aximal oxygen uptake (VOz) is difficult to determine in many patients with severecongestive heart failure (CHF) who do not reliably reach a plateau in VO;! during symptom-limited maximal exercise.’ Anaerobic threshold has been proposed as an alternative objective measureof submaximal exercise capacity in this group of patients2 Anaerobic threshold can be determined either invasively by analysis of arterial lactate concentration (lactate threshold) or noninvasively by respiratory gas exchange analysis (ventilatory threshold).3y4The clinical use of anaerobic threshold determination in CHF has beenlimited by the absenceof a consensuson the best methodology for lactate and ventilatory threshold detection.5-9 Furthermore, reported methodsare subject to substantial intraand interobservervariability, becauseanaerobic threshold determination is based on subjective interpretation of lactate or gas exchangedata.lOJ* Recent refinements in exerciseprotocols and gas exchangeanalysis systems, and more objective techniques of anaerobic threshold detection have increasedthe precision and reproducibility for both lactate and ventilatory thresholds in normal human subjects.12J3 Accordingly, the present study was performed to evaluate these new methods in patients with CHF.
M
METHODS Path&u Fourteen men and 2 women (mean age 60 years, range 48 to 69) with stable CHF in New York Heart Association classII or III were studied. The etiology of CHF was coronary artery diseasein 4 patients, idiopathic dilated cardiomyopathy in 10, and hypertensive heart diseasein 2. Left ventricular ejection fraction (as determined by radionuclide angiography within 6 months of the study) averaged 25% (range 15 to 33). All patients were treated with stable dosesof digoxin, diuretics and an angiotensin-converting enzyme inhibitor. Cardiac medications were withheld on the morning of the study. By the criteria proposedby Weber et a1,14 4 patients were class B (peak VO2 16.7 to 19.4 ml/ kg/min), 8 were classC (10.3 to 14.4 ml/kg/min), and 4 were class D (9 to 9.9 ml/kg/mm). Patients with exercise-inducedmyocardial ischemia,peripheral vascular disease(ankle/arm blood pressureratio
1565
performed a symptom-limited maximal exercisetest on an electronically braked cycle ergometer (Mijnhardt Model REM III) using a continuous ramp protocol. After resting for 2 minutes on the bicycle, patients pedaled at approximately 60 rpm as the work load increased from 0 W at a rate of 5 to 10 W/mm, adjusted to patient’s previous exercise performance to maintain the duration of the test between 8 and 12 minutes. Arterial lactate sampleswere collected at rest, at l-minute intervals during exercise,and at 1 and 3 minutes after exercise. Blood samples were immediately deproteinized with iced perchloric acid for later analysis. Expired gases were collected through a low-resistance3-way valve (Hans Rudolph) for 1 to 2 minutes at rest, and continuously during exercise. VO2, carbon dioxide production (VCO3 and minute ventilation were continuously monitored on a breath-by-breath basis (Medical Graphics 2001). Becauseno plateau in VOz at end-exercisewas observedin patients, peak VOZ was defined as the aver-
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16
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.
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1566
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THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 69
agevalue of VOz in the last 30 secondsof exercisewhen the respiratory exchangeratio was >1.05. Detemhation of anaembic thresholdz Anaerobic threshold was determined by both arterial blood lactate concentrations (lactate threshold) and analysis of expired gases(ventilatory threshold). LACTATE THRESHOLD: Arterial blood lactate concentration was determined by a spectrophotometricmethod in mmol/liter (Sigma Kit). Lactate threshold was determined by the following 2 methods: (1) visual inspection of the plot of arterial lactate concentrationsversusVO2, and (2) log-log transformation of the lactate and VO2 data, as describedby Beaver et all2 A sharp inflection point, if present, was chosen by visual inspection, and lactate threshold was determined by a 2-segmentlinear regressionmodel. VENTILATORY THRESHOLD: Ventilatory threshold was determined by both subjective interpretation of respiratory gas exchange data (VT standard) and by a computerized method (VT-V slope). VT standard was determined independently by 2 investigators familiar with the criteria for anaerobic threshold detection, as describedby Wasserman.15VO2, VCO2, minute ventilation, respiratory exchange ratio (R), ventilatory equivalents of VOZ and VCO2 (VE/ VO2 and VE/VC02, respectively), and end-tidal partial pressuresof oxygen and carbon dioxide (Pet02 and Pet COz, respectively) were plotted versustime, using an 8breath moving averagefilter. Ventilatory threshold was considered present when: (1) the VE/V02 curve reached a minimum and began to rise, while the VE/ VCO2 curve remained flat, (2) the Pet02 curve began to rise, while the PetCO2 curve remained flat, and (3) the slopeof the R curve beganto rise more sharply during exercise.Ventilatory threshold was chosenfrom the plot that most clearly satisfied Wasserman’scriteria. Values for ventilatory threshold determined independently by each observer were highly correlated (r = 0.92, p
JUNE 15, 1992
Scheffe test for post hoc determination of statistical significance. Single linear regressionanalysis was also performed using the least-squaresmethod. Statistical significance was acceptedat the 95% confidence limit (2tailed p value <0.05). RESULTS L8&te threrhdd: Arterial lactate concentration increasedcurvilinearly as a function of VOz in 7 patients in whom a clear threshold point was detected by a loglog transformation of the data (Figure 1). Arterial lactate increasedlinearly as a function of VO2 in 9 patients in whom no clear lactate threshold could be detected even with a log-log transformation of the data (Figure 2).
Peak VO2 was significantly lower in patients without detectable lactate threshold than in those in whom lactate threshold was present (Table I). A specific lactate threshold point was not detectedin any patient with severe CHF (peak VO2 <12 ml/kg/min), but was present in all with mild to moderate CHF (>14 ml/kg/ min). For patients with peak VO2 between 12 and 14 ml/kg/min, lactate threshold was detectedin 2 and not detectedin 1. Arterial lactate concentrationsat rest and after 2 minutes of exercise (corresponding to a work load of 10 to 20 W), and percentageof peak VOX after 2 minutes of exercise were significantly greater in patients without detectable lactate threshold. (T&e II): Ventilatory threshv-old was detected from examination of standard plots in 12 patients and by the computerized V-slope method in 14. Ventilatory threshold was detectedby both methods in the 7 patients in whom lactate threshold was present. In 9 patients without detectablelactate threshold, ventilatory threshold was determined by standard plots in 5 and by the V-slope method in 7. In the remaining patients, no clear threshold point was evident on plots of respiratory gas exchange. Compvkon of m Lactate threshold (when detected) significantly correlated with both VT standard (r = 0.79, p <0.05) and VT-V slope (r = 0.78, p <0.05; Figure 3). Lactate threshold occurred at a significantly lower VO2 and arterial lactate concentration than did ventilatory anaerobic threshold determined by standard plots or the V-slope method (p <0.05; Table II and Figure 4). VT-V slope tended to occur earlier in exercise than did VT standard and was closer to the lactate threshold.
rapid early increasein lactate concentration in 15 of 48 patients studied when exercise capacity was <6 minutes, correspondingto a peak work load of <60 W on a cycle ergometer.Simonton et aL7Matsumura et al8 and TABLE I Clinical Characteristics of Patients With and Without Detectable Lactate Threshold
Age (yr) Left ventricular ejection fraction (%) Exercise duration (set) Peak VOz (ml/kg/min) Peak work rate(W) Resting lactate (mmol) Lactate at 2 minutes of exercise (mmol) % peak VOz at 2 minutes of exercise
Lactate Threshold Present
Lactate Threshold Absent
p Value
58 + 6 23 2 7
62 t 8 25 -t 8
NS NS
663 15.9 95 0.8 1.0
+ + f f 2
126 2.7 18 0.2 0.3
541 10.5 54 1.0 1.5
53 k 6
156 1.4 16 0.3 0.4
NS
77 f 9
<0.05
NS = not significant; VOa = oxygen uptake.
4
5
6
7
OXYGEN
6
9
UPTAKE
10
11
12
(mbkglmin.)
B
0.7
n +: n
0.5
n
I n
0.3
DISCUSSION In patients with severe CHF (peak VO2 <12 ml/ kg/m@, lactate threshold could not be detected with the methods used in this study. In patients with mild to moderate CHF (peak VOz >14 ml/kg/min), ventilatory threshold determined by analysis of gas exchange data was closely related to the lactate threshold. Our findings in patients with severe CHF are in agreement with previous reports. Weber and Janicki5 described a rapid linear increase in blood lactate concentration in patients with severe aerobic impairment (peak VOz
+ + f f k
n
n
0.1
i n
-0.1
I 0.6
0.7
-
I
0.8
*
I
-
I
0.9
.
,
1.0
1.1
FAILURE
1567
LOG OXYGEN UPTAKE
ANAEROBIC
THRESHOLD
IN HEART
TABLE II Comparison of Methods for Detection of Anaerobic Threshold Lactate Threshold Pt.
Peak VO2
Peak Lactate
vo2
VT-V Slope
Lactate
vo2
VT Standard Lactate
vo2
Lactate
Lactate Threshold Present (n = 7)
1 2 3 4 5 6 7
3.3 5.2 4.7 6.1 2.8 4.0 6.0 4.6 t 1.3
12.0
13.5 14.4 19.4 17.0 18.1 16.7
Mean 2 SD
15.9 + 2.7*
8 9 10 11 12 13 14 15 16 Mean 2 SD
9.5 10.3 12.6 9.0 10.5 13.2 10.3 9.9 9.5
5.9 9.0 10.8 11.9 11.0 12.0 9.1 10.0 ‘- 2.2’1
1.1 1.6 1.5 1.3 0.9 1.1 1.9 1.3 + 0.47
8.5 9.2 10.3 14.2 11.0 13.8 12.2 1 1.3 + 2.2
1.8 1.7 1.6 3.0 0.9 1.5 2.6 1.9 r 0.7
9.3 9.9 11.4 14.0 10.6 13.7 12.5 11.6 i 1.8
2.3 2.4 2.1 2.6 1.1 1.6 3.4 2.2 i- 0.7
Lactate Threshold Absent (n = 9)
5.2 3.7 6.2 4.4 4.9 3.0 3.3 4.6 2.6 4.2 k 1.2
10.5 z 1.4
-
-
l p ~0.05 vs patients without lactate threshold; tp < 0.05 vs VT-V slope and VT standard. VO? = oxygen uptake; VT Standard = subjective analysis of gas exchange; VT-V slope = computerized
6
6
10
12
Oxygen
uptake
at lactate (ml/kg/min.)
threshold
Oxygen
uptake
mt lactate (ml/kglmln.)
threshold
15 1
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THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 69
10.0 10.0 10.9 9.4 10.3 8.1 8.1 9.5 2 1.1 analysis of respimtoly
4.3 1.7 4.6 3.6 4.0 2.4 1.7 3.2 k 1.2
9.4 7.3 8.9 10.9 9.1 9.2 f 1.3
1.7 2.5 3.5 1.6 2.6 2.4 Z!I0.8
gas exchange date.
Rajfer et al9 also identified subsetsof patients with severe aerobic impairment in whom anaerobic threshold could not be detected. The inability to detect lactate threshold in severeCHF is related to the extremely limited work load capacity in these patients. Despite extremely low work loads, patients with severeCHF demonstrated anaerobic metabolism from the onset of exercise. In patients with mild to moderate CHF in whom lactate threshold was detected,the relation betweenlactate and ventilatory threshold was similar to that of previous reports. The correlation coefficients of 0.78 and 0.79 for the V-slope and standard methods of determination of ventilatory threshold, respectively, compare favorably with the r value of 0.81 reported by Wilson et a1,6but are below the r value of 0.96 reported by Matsumura et a1.8As reported in normal subjects,r2the ventilatory threshold determined by the V-slope method is closer to the lactate threshold than is ventilatory threshold determined by standard plots. Whereasarterial lactate concentration increasedlinearly from the onset of exercise, ventilatory threshold could still be detectedin approximately 50% of patients with severe CHF. The point of respiratory compensation, rather than anaerobic threshold, may have been detectedin thesepatients. This explanation is consistent with high relative VOz at ventilatory threshold determined in this group. Factors other than blood lactate concentration may have also affected the ventilatory response during exercise. Patients with McArdle’s syndrome (a congenital metabolic myopathy in which skeletal muscle lacks the ability to produce lactate) may still manifest criteria for detecting ventilatory threshold determination during graded exercise.l6 Similarly, gly-
JUNE 15, 1992
I
fiz .E
*
_
P 2 0 5
l-
2 E E Q
oLT
cogen depletion in normal subjectsdecreasesblood lactate concentration, but increasesminute ventilation during exercise.” Our findings demonstratethat in patients with severeCHF, criteria for ventilatory threshold were present even in the absence of a detectable lactate threshold. Clinkal implkatiam An objective measureof functional impairment is needed in patients with severe CHF, because they are most likely to be involved in therapeutic drug trials. A power-assistedbicycle ergometer that provides extremely low work loads may allow detection of anaerobic threshold in severely impaired patients. Submaximal steady-stateexerciseprotocols to assessVOz or lactate kinetics may provide an alternative means of assessingfunctional capacity in patients with severeCHF.18 In patients with mild to moderate CHF (peak VOZ >14 ml/kg/mm), the computerized V-slope method is preferable to standard plots, becausethe values for ventilatory threshold are determined objectively and are closer to the lactate threshold point than are those determined by subjective interpretation of gas exchange data.
REFERENCES
1. LeJemtel TH, Mancini D, Gumbardo D, Chadwick B. Pitfalls and limitations of maximal oxygen uptake as an index of cardiovascular functional capacity in patients with chronic heart failure. Heart Failure 1985;1:112-124. 2. WassermanK, McIlroy MB. Detecting the thresholdof anaerobicmetabolism in cardiac patient. Am J Cardiol 1964;14:844-852. 3. Davis JA. Anaerobic threshold: review of the conceptand direction for future
VT-VSLOPE
VT-STAND
2
research.Med Sci Sports Exert 1985;17:6-18. 4. Caiozxo VJ, Davis JA, Ellis JF, Azus JL, Vandagriff R, Prietto CA, McMaster WC. A comparisonof gasexchangeindicesusedto detectthe anaerobicthreshold. J Appl fhysiol 1982;53:1184-1189. 5. Weber KT, Janicki JS. Lactate production during maximal and submaximal exercisein patientswith chronicheart failure. JAm Co11Cardioll985;6:7 17-724. 6. Wilson JR, Fink LI, Ferraro N, Dunkman WB, JonesRA. Use of maximal bicycle exercisetesting with respiratory gas exchangeanalysisto assessexercise performancein patientswith congestiveheart failure secondaryto coronary artery diseaseor to idiopathic dilated cardiomyopathy.Am J Cardiol 1986;58:601-606. 7. SimontonCA, Higginbotham MB, Cobb FR. The ventilatory threshold:Quantitative analysisof reproducibility and relation to arterial lactate concentrationin normal subjectsand in patients with chronic congestive heart failure. Am J Cardiol 1988;62:100-107. 6. Matsumura N, Nishijima H, Kojima S, Hashimoto F, Minami M, Yasuda H. Determinationof anaerobicthresholdfor assessment of functional statein patients with chronic heart failure. Circulation 1983;68:360-367. 9. Rajfer SI, Nemanich JW, Shurman AJ, RossenJD. Metabolic responsesto exercisein patientswith heart failure. Circularion 1987;76(supplVl):VI46-V153. 10. Yeh MP, Gardner RM, Adams TD, Yanowits FG, Craps RO. “Anaerobic threshold”: problemsof determination and validation. J App/ Physiol 1983;55: 1178-1186. 11. Gladden LB, Yates JW, Stremel RW, Stamford BA. Gas exchangeand lactate anaerobicthresholds:inter- and intraevaluator agreement.J Appl Physiol 1985;58:2082-2089. 12. BeaverWL, WassermanK, Whipp BJ. Improveddetectionof lactate threshold during exercise using a log-log transformation. J App/ Physic4 1985;59: 1936- 1940. 13. Beaver WL, WassermanK, Whipp BJ. A new method for detectinganaerobic threshold by gas exchange.J Appl Physiol 1986;60:2020-2027.
14. Weber KT, Kinasewitz GT, Janicki JS, FishmanAP. Oxygen utilization and ventilation during exercise in patients with chronic cardiac failure. Circularion 1982;65:1213-1223. IS. WassermanK. Determinantsanddetectionof anaerobicthresholdandconsequencesof exercise above it. Circulation 1987;76(supplVl):VI29-VI39. 16. Hagberg J, Coyle EM, Carroll JE, Miller JM, Martin WH, Brooke MH. Exercise hyperventilation in patients with McArdle’s disease.J Appl Pfiysiol 1982;52:991-994. 17. Segal SS, Brooks GA. Effect of glycogendepletion and workload on post exercise02 consumptionand bleed lactate. J Appl Physiol 1979;47:512-514. 16. WassermanK. New conceptsin assessingcardiovascularfunction. Circulorim 1988;78:1060-1071.
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