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Print version ISSN 1517-8692
Rev Bras Med Esporte vol.9 no.5 Niterói Sept./Oct. 2003
Fidelidad intra e interdiaria del test de ejercicio de 4 segundos
Claudio Gil Soares de AraújoI; Djalma Rabelo RicardoI; Marcos Bezerra de AlmeidaII
de Pós-Graduação em Educação Física
da Universidade Gama Filho Rio de Janeiro, RJ, CLINIMEX Clínica de Medicina
do Exercício Rio de Janeiro, RJ.
IIPrograma de Pós-Graduação em Educação Física da Universidade Gama Filho Rio de Janeiro, RJ.
The 4-second exercise test (T4s) is pharmacologically validated to assess cardiac vagal tone, and consists in pedaling, as fast as possible, a cycle-ergometer unloaded, from the 4th to the 8th second of a 12-second maximum inspiratory apnea. An dimensionless cardiac vagal index (CVI) is calculated from the ratio of the duration of the cardiac cycles (RR intervals at the electrocardiogram) from immediately before the exercise and the shorter of the exercise. Our objective was to determine T4s intra and interdays reliability, and the actual need for two trials, as described on the original protocol. In study 1, the interday reliability of the results was assessed prospectively from 15 asymptomatic subjects (28 ± 6 years) submitted to T4s for five consecutive days, being two trials carried out at each day. To determine CVI intraday reliability, in one of the five days, randomly selected, nine T4s consecutive trials were made. In study 2, the CVI intraday reliability was calculated from 1699 subjects (47 ± 17 years) in two trials. CVI presented high intraday and interday reliability (ri = 0.92; 95%CI = 0.84 to 0.97 and ri = 0.77; 95%CI = 0.49 to 0.92, respectively) for study 1 and for study 2 (ri = 0.89; 95%CI = 0.88 to 0.90). In spite of high reliability, there were some minor differences between the means (mean ± SEM = 1.32 ± 0.01 vs 1.37 ± 0.01; p < 0.001), and in only 15% of the cases this difference was higher than 0.20, thus not representing major clinical meaning. It was also observed that in 65% of the cases, the second trial was considered the best and, with only one trial, clinical misinterpretation could occur in 27% of the data. In summary, this study evidenced high CVI reliability assessed by T4s, and confirmed the need for two consecutive trials, as prescribed in its protocol.
Key words: 4-second exercise test. Physical exercise. Heart rate. Cardiac vagal tone. Reliability.
El test de 4 segundos (T4s) es validado farmacológicamente para la evaluación de la función vagal cardíaca y consiste en pedalear lo más rápido posible en cicloergómetro sin carga del cuatro al octavo segundo de una apnea inspiratoria máxima de 12 segundos de duración. Un índice vagal cardiaco (IVC) dimensionable, obtenido por el cociente entre la duración de dos ciclos cardíacos (intérvalo RR del electrocardiograma) inmediatamente antes y en lo mas corto del ejercicio. Objetivamos determinar la fidelidad inter e intradiaria del T4s y la necesidad de realizar las dos tentativas, conforme a lo descripto en el protocolo original. En el estudio 1, analizamos prospectivamente la fidelidad interdías de los resultados de 15 individuos asintomáticos (28 ± 6 años) sometidos al T4s por cinco días seguidos, realizándose dos tentativas cada día. Para determinar la fidelidad intradiaria del IVC, fueron realizadas ramdómizadamente en unos dos días, nueve tentativas consecutivas del T4s. En el estudio 2, calculamos retrospectivamente la fidelidad intradiaria del IVC de 1699 individuos (47± 7 años) en dos tentativas. El IVC presentó una elevada fidelidad intradiaria e interdiaria (ri = 0,92; IC 95% = 0,84 a 0,97 y ri = 0,77; IC 95%= 0,49 a 0,92, respectivamente) en el estudio 1, así como, en el estudio 2 (ri = 0,89; IC 95% = 0,88 a 0,90). A pesar de la elevada fidelidad, había mínimas diferencias entre las medias (media ± EPM = 1,32 ± 0,01 contra 1,37 ± 0,01; p < 0,001), siendo que en apenas 15% de los casos esta diferencia fué mayor que 0,20, no representando así, mayor relevancia clínica. Verificamos así que en el 65% de las observaciones, la segunda tentativa fué considerada la mejor y que la realización de apenas una tentativa induciría a un error de interpretación clínica en un 27% de los casos. En síntesis, este estudio demostró la elevada fidelidad del IVC evaluado por el T4s, además de justificar la necesidad de realizarse dos tentativas consecutivas en su protocolo.
Palabras clave: Test de 4 segundos. Ejercicio físico. Frecuencia cardíaca. Tono vagal cardíaco. Fidelidad.
The behavior of heart rate (HR) in exercises transient has been investigated in a number of studies over the past few years1-4, which shows the importance of its clinical and physiological investigations. HR modulation is mediated by the sympathetic and parasympathetic branches of the autonomous nervous system (ANS), and its integrity is associated to a decrease in mortality risk from cardiac events5,6.
In a study carried out by Nolan et al.7, it was seen that patients with heart failure (moderate and severe), with autonomic dysfunction, had a mortality rate 10-fold higher than their peers whose parasympathetic activity was closer to normal ranges. These results confirm the impression that cardiac vagal activity is a powerful and independent prognostic marker5.
A number of physiological and clinical procedures have been proposed to assess autonomic condition8-11. Among them, one can mention the 4-second exercise test (T4s), originally proposed by Araújo et al.12. The T4s is intended to indirectly assess cardiac vagal tone through the initial heart rate transient of a dynamic short term exercise performed in apnea13. This test was pharmacologically validated and has been applied in clinical trials and sports medicine, proving to be quite useful both as a diagnostic tool14,15, and longitudinal follow-up of cardiac parasympathetic activity16.
Thus, in order to consolidate this procedure, it is important to determine T4s consistency and reliability in assessing cardiac vagal autonomic activity of a heterogeneous sample. Therefore, the purposes of this study were to determine intra and interdays T4s reliability in measuring cardiac vagal tone, and the need for two measurements, as described in the original protocol.
Materials and Methods
To meet the intended purposes, the results from two different labs, presented separately, were assessed, looking for better understanding of the experimental procedures used. Furthermore, all tests and their measurements and interpretations were performed by experienced evaluators in the T4s protocol, and strictly followed its standards. The subjects submitted to the T4s read and signed an informed consent form before the procedures.
The 4-second Exercise Test-T4s
The purpose of the T4s is to assess exclusively the integrity of the parasympathetic branch of the autonomic nervous system through the initial HR transient at rest-exercise transition. The T4s consists in pedaling as quickly as possible a unloaded cycleergometer, from the 4th to the 8th second of a maximum inspiratory apnea of 12 seconds. Four consecutive commands are given at each four seconds: (a) a maximum and swift inhale through the mouth and then sustain apnea; (b) to pedal as fast as possible; (c) suddenly stop pedaling, and (d) normally exhale.
To minimize anticipatory responses to the commands, the subject should not see the chronometer nor the electrocardiograph, while a continuous trace is recorded from only one ECG lead (typically CC5 or CM5) for 35 seconds at a speed of 25 mm/s, started five seconds before the command for maximum inhale.
To determine the magnitude of the cardiac vagal tone, one must identify the immediately before or the first RR interval of the exercise (which is the longest) (RRB), and the shortest one during the exercise, usually the last (RRC). The quotient or ratio between these two intervals shows the cardiac vagal index (CVI), a T4s dimensionless index.
Two consecutive trials are made with a one-to-two-minute interval between them, which is typically enough for heart rate to return to resting level, being selected the highest of the two CVI values as representative of the subject's cardiac vagal tone.
Prior methodological studies with T4s showed that CVI value independs on the presence or absence of resistance opposing pedal movement17, if the exercise is performed actively or passively18, or if performed by lower or upper limbs19.
To assess T4s reliability, we made a prospective analysis of the results from 15 subjects (eight women), and 13 subjects (six women), for intra and interdays, respectively. The subjects were considered asymptomatic, aged 28 ± 6 (21 to 42) years, who volunteered for the study carried out in a lab.
Data were collected from a 380B electrocardiograph (Siemens, Germany), from a single lead (CC5), at a speed of 25 mm/s, and T4s was performed in a mechanic-breaking cycle-ergometer Monark. Measurement of the RR intervals on the recordings was made by a single evaluator, experienced in the test, with a 10 ms resolution.
The subjects were asked to rest in a room for about five minutes prior to the beginning of the test protocol. T4s was repeated for five days, always at the same time of the day, in order to measure interdays reliability. Intraday reliability was investigated in nine consecutive trials carried out in one of those five days, randomly selected for each subject.
In a second assessment, intraday reliability was retrospectively determined from the results of 1,699 subjects (613 women), aged 47 ± 17 (8 to 85) years, including subjects of different clinical and fitness conditions (even athletes), who spontaneously went for a detailed medical-functional assessment in one of the labs between 1994 and 2003.
For this analysis, a TEC 7100 electrocardiograph (Nihon-Kohden, Japan) was used in the tests carried out until 2001, and a digital electrocardiograph with a specific software (ErgoPC Elite version 220.127.116.11. Micromed, Brazil), in the tests from 2001 on, both in single lead (CC5 or CM5), recorded at a speed of 25 mm/s, and an electro-magnetic-break cycle-ergometer Cateye model Ergociser EC 1600 (CatEye, Japan). The measurement of the duration of the RR intervals on the electrocardiograph recordings were made by experienced evaluators, using a 10 ms resolution.
In order to assess T4s reliability in subjects with different magnitudes of vagal tone, we sorted the values as a function of the CVI from the second trial, and then used cut-off points arbitrarily defined in our database, of less than 1.20, between 1.20 and 1.70, and higher than 1.70 for vagal hypotonic, normal, and hypertonic (vagotonic), respectively (unpublished data).
Intraclass correlation coefficient was used in the studies to measure the degree of association between the trials. Furthermore, to compare the means, ANOVA for repeated measures, and paired t-test (for study 1 and study 2, respectively) were employed. Significance level of 5% and 95% confidence interval was used for all results.
Study 1 - The CVI obtained in the T4s showed high intra and interdays reliability, as one can see from the intraclass correlation coefficients (ri = 0.92; 95%CI = 0.84 to 0.97 and ri = 0.77; 95%CI = 0.49 to 0.92, respectively). These results were confirmed by ANOVA, and no differences between the trials were found (p > 0.10) (figures 1 and 2).
Study 2 In a larger and more heterogeneous sample, the CVI between the two T4s trials was considerably associated (ri = 0.89; 95%CI = 0.88 to 0.90), attesting once more its reliability (figure 3). However, the t-test showed differences between the means (mean ± SEM = 1.32 ± 0.01 vs 1.37 ± 0.01; p < 0.001), and in only 15% this difference was higher than 0.20 (figure 4). We also noticed that in 65% of the observations, the second trial had higher CVI results.
Likewise, by splitting the sample in three groups according to reference values from the second trial (selected for including most of CVI best results), we observed differences between the two trials for all groups (table 1). However, the number of cases in which the difference between trials was higher than 0.20 was lower than 1% for hypotonic, 9% for normals, and 5% for hypertonic subjects, being worth to mention that intraclass correlation coefficient had a significant association between the trials, in each group (p < 0.001). Moreover, 27% of the subjects would have been mistakenly classified if only one trial was to be made.
HR behavior is an important marker of the cardiac vagal activity, which, if decreased, is strongly associated to mortality risk2,3,6,20-22, showing an increase of cardiac vulnerability due to a potential and lethal risk of ventricular arrythmia5,23,24.
The clinical contributions of autonomic assessment in stratifying mortality risk from cardiovascular events and from all causes have been broadly used by the scientific community25-28, particularly because vagal activity is the main autonomic dysfunction marker29-32. Thus, it is interesting to stress the importance of a valid and reliable test to assess cardiac vagal tone.
As we could see from study 1, the measure of the vagal cardiac tone by T4s showed high intra and interdays reliability, evidencing T4s consistency to assess vagal cardiac function, expressed by CVI. It is also important to mention that ANOVA confirmed these results, with no differences found among the sample means.
Study 2 was based on a very large sample, and again CVI obtained in T4s was highly reliable, in spite of the diverse clinical conditions and populations (children, adolescents, adults, elders, athletes, even of Olympic levels, and asymptomatic non-athletes).
By confronting our results with those of other reliability studies on cardiovascular autonomic tests, we observed some important aspects that favored our T4s studies, such as: the size of the sample, as studies that investigate such topic have a significantly smaller number of subjects in their sample33,34; the characteristics of the sample (age group and clinical conditions)35,36; and the magnitude of intraclass correlation coefficients, similar to some and higher than others37,38.
One should also add that, regarding study 2, we observed differences between the first and second trial (t-test), for the whole sample and for the subgroups, even though these results do not indicate clinical or physiological relevance. This fact may be observed from the number of cases in which discrepancy between trials was higher than 0.20, particularly among subjects referred as vagal hypotonic, in whom a possible association with cardiovascular conditions and complex arrhythmias due to a lower vagal cardiac protection draws attention28,39-41.
In practice, the physician, when supervises the procedure, frequently advises the subject to correct minor distortions or errors from the first trial, so that better results from the second trial of study 2 are to be expected. In fact, about 2/3 of the subjects achieve higher CVI values in the second trial, probably because they are more familiar with the procedure, and thus perform it more appropriately. Furthermore, the second trial prevented more then 1/4 of the subjects to have their CVI wrongly classified or interpreted. These results prove the need for two trials, as described in the original protocol.
T4s seems to comply with scientific authenticity criteria (reliability and validity), considering the clinical conditions and the significant diversity of the sample, as we could see in this and in prior studies13,15. Moreover, the simplicity and applicability of this test should be stressed, in addition to its low operational cost.
Thus, incorporating T4s in the routine of pre-exercise test either conventional or with exhaled gases measurements42 -, has the potential ability to wide open the clinically relevant information to be obtained with the use of physical exercise in health or unhealthy subjects.
In summary, this study evidenced T4s reliability in assessing cardiac vagal tone, expressed by the CVI, and confirmed the need for two consecutive trials, as recommended in its protocol.
The authors thank Prof. Flavia Dias de Oliveira for her role in the data collection of study 1.
All the authors declared there is not any potential conflict of interests regarding this article.
1. Pierpont GL, Stolpman DR, Gornick CC. Heart rate recovery as an index of parasympathetic activity. J Auton Nerv Syst 2000;80:169-74. [ Links ]
2. Lauer MS, Francis GS, Okin PM, Pashkow FJ, Snader CE, Marwick TH. Impaired chronotropic response to exercise stress testing as a predictor of mortality. JAMA 1999;281:524-9. [ Links ]
3. Cole CR, Blackstone EH, Pashkow FJ, Snader CE, Lauer MS. Heart rate recovery immediately after exercise as a predictor of mortality. N Engl J Med 1999;341:1351-7. [ Links ]
4. Morshedi-Meibodi A, Larson MG, Levy D, O'Donnell CJ, Vasan RS. Heart rate recovery after treadmill exercise testing and risk of cardiovascular disease events (The Framingham Heart Study). Am J Cardiol 2002;90:848-52. [ Links ]
5. Buch AN, Coote JH, Townend JN. Mortality, cardiac vagal control and physical training What's the link? Exp Physiol 2002;87:423-35. [ Links ]
6. Tapanainen JM, Thomsen PE, Kober L, Torp-Pedersen C, Makikallio TH, Still AM, et al. Fractal analysis of heart rate variability and mortality after an acute myocardial infarction. Am J Cardiol 2002;90:347-52. [ Links ]
7. Nolan J, Batin PD, Andrews R, Lindsay SJ, Brooksby P, Mullen M, et al. Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-Heart). Circulation 1998;98:1510-6. [ Links ]
8. Marfella R, Guigliano D, di Maro G, Acampora R, Giunta R, D'Onofrio F. The squatting test. A useful tool to assess both parasympathetic and sympathetic involvement of the cardiovascular autonomic neuropathy in diabetes. Diabetes 1994;43:607-12. [ Links ]
9. Castro CLB, Nóbrega ACL, Araújo CGS. Testes autonômicos cardiovasculares. Uma revisão crítica. Parte I. Arq Bras Cardiol 1992;59:75-85. [ Links ]
10. Castro CLB, Nóbrega ACL, Araújo CGS. Testes autonômicos cardiovasculares. Uma revisão crítica. Parte II. Arq Bras Cardiol 1992;59:151-8. [ Links ]
11. European Society of Cardiology. Heart rate variability: standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing Electrophysiology. Circulation 1996;93:1043-65. [ Links ]
12. Araújo CGS, Nóbrega ACL, Castro CLB. Vagal activity: effect of age, sex and physical pattern. Braz J Med Biol Res 1989;22:909-11. [ Links ]
13. Araújo CGS, Nóbrega ACL, Castro CLB. Heart rate responses to deep breathing and 4-seconds of exercise before and after pharmacological blockade with atropine and propranolol. Clin Auton Res 1992;2:35-40. [ Links ]
14. Lazzoli JK, Castro CLB, Nóbrega ACL, Araújo CGS. Acurácia de critérios para vagotonia no eletrocardiograma de repouso de 12 derivações: uma análise com curvas ROC. Rev Bras Med Esporte 2002;8:50-8. [ Links ]
15. Lazzoli JK, da Silva Soares PP, da Nóbrega AC, de Araújo CG. Electrocardiographic criteria for vagotonia-validation with pharmacological parasympathetic blockade in healthy subjects. Int J Cardiol 2003;87:231-6. [ Links ]
16. Castro CLB, Nóbrega ACL, Araújo CGS. Cardiac vagal activity is still depressed two years after acute myocardial infarction. Med Sci Sports Exerc 1993;25:S106. [ Links ]
17. Araújo CGS. Fast "on" and "off" heart rate transients at different bicycle exercise levels. Int J Sports Med 1985;6:68-73. [ Links ]
18. Nóbrega ACL, Araújo CGS. Heart rate transient at the onset of active and passive dynamic exercise. Med Sci Sports Exerc 1993;25:37-41. [ Links ]
19. Araújo CGS, Nóbrega ACL, Castro CLB. Similarities between fast initial heart rate response to arm and leg cycling exercise. J Cardiopulm Rehabil 1993;13:348. [ Links ]
20. Cole CR, Foody JM, Blackstone EH, Lauer MS. Heart rate recovery after submaximal exercise testing as a predictor of mortality in a cardiovascularly healthy cohort. Ann Intern Med 2000;132:552-5. [ Links ]
21. Lauer MS, Okin PM, Larson MG, Evans JC, Levy D. Impaired heart rate response to graded exercise. Prognostic implications of chronotropic incompetence in the Framingham Heart Study. Circulation 1996;93: 1520-6. [ Links ]
22. Shelter K, Marcus R, Froelicher VF, Vora S, Kalisetti D, Prakash M, et al. Heart rate recovery: validation and methodological issues. J Am Coll Cardiol 2001;38:1980-7. [ Links ]
23. Nissinen SI, Makikallio TH, Seppanen T Tapanainen JM, Salo M, Tulppo MP, et al. Heart rate recovery after exercise as a predictor of mortality among survivors of acute myocardial infarction. Am J Cardiol 2003; 91:711-4. [ Links ]
24. Prakash M, Myers J, Froelicher VF, Marcus R, Do D, Kalisetti D, et al. Clinical and exercise test predictors of all-cause mortality. Results from > 6,000 consecutive referred male patients. Chest 2001;120:1003-13. [ Links ]
25. Makikallio T, Høiber S, Køber L, Torp-Pedersen C, Peng C, Goldberger AL, et al. Fractal analysis of heart rate dynamics as a predictor of mortality in patients with depressed left ventricular function after acute myocardial infarction. Am J Cardiol 1999;83:836-9. [ Links ]
26. Curtis B, O'Keefe JR J. Autonomic tone as a cardiovascular risk factor: the dangers of chronic fight or flight. Mayo Clin Proc 2002;77:45-54. [ Links ]
27. Sosnowski M, MacFarlane P, Czyz Z, Skrzypek-Wanha J, Boczkowska-Gaik E, Tendera M. Age-adjustment of HRV measures and its prognostic value for risk assessment in patients late after myocardial infarction. Int J Cardiol 2002;86:249-58. [ Links ]
28. Lombardi F, Makikallio T, Myerburg RJ, Huikuri H. Sudden cardiac death: role of heart rate variability to identify patients at risk. Cardiovasc Res 2001;50:210-7. [ Links ]
29. Robinson TG, Dawson SL, Eames PJ, Panerai RB, Potter JF. Cardiac baroreceptor sensitivity predicts long-term outcome after acute ischemic stroke. Stroke 2003;34:705-12. [ Links ]
30. Sevre K, Lefrandt JD, Nordby G, Os I, Mulder M, Gans RO, et al. Autonomic function in hypertensive and normotensive subjects: the importance of gender. Hypertension 2001;37:1351-6. [ Links ]
31. La Rovere MT, Bersano C, Gnemmi M, Specchia G, Schwartz PJ. Exercise-induced increase in baroreflex sensitivity predicts improved prognosis after myocardial infarction. Circulation 2002;106:945-9. [ Links ]
32. Braith RW, Edwards DG. Neurohormonal abnormalities in heart failure: impact of exercise training. Congest Heart Fail 2003;9:70-6. [ Links ]
33. Vardas P, Kochiadakis G, Orfanakis A, Kalaitzakis M, Manios E. Intraindividual reproducibility of heart rate variability before and during postural tilt in patients with syncope of unknown origin. Pacing Clin Electrophysiol 1994;17:2207-10. [ Links ]
34. Hartwig MS, Cardoso SS, Hathaway DK, Gaber AO. Reliability and validity of cardiovascular and vasomotor autonomic function tests. Diabetes Care 1994;17:1433-40. [ Links ]
35. Kim SY, Euler DE. Baroreflex sensitivity assessed by complex demodulation of cardiovascular variability. Hypertension 1997;29:1119-25. [ Links ]
36. Ziegler D, Laux G, Dannehl K, Spuler M, Muhlen H, Mayer P, et al. Assessment of cardiovascular autonomic function: age-related normal ranges and reproducibility of spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses. Diabet Med 1992;9:166-75. [ Links ]
37. Gerritsen J, TenVoorde BJ, Dekker JM, Kingma R, Kostense PJ, Bouter LM, et al. Measures of cardiovascular autonomic nervous function: agreement, reproducibility, and reference values in middle age and elderly subjects. Diabetologia 2003;46:330-8. [ Links ]
38. Amara CE, Wolfe LA. Reliability of noninvasive methods to measure cardiac autonomic function. Can J Appl Physiol 1998;23:396-408. [ Links ]
39. Bikkina M, Alpert M, Mukerji R, Mulekar M, Cheng B, Mukerji V. Diminished short-term heart rate variability predicts inducible ventricular tachycardia. Chest 1998;113:312-6. [ Links ]
40. Partington S, Myers J, Cho S, Froelicher V, Chun S. Prevalence and prognostic value of exercise-induced ventricular arrhythmias. Am Heart J 2003;145:139-46. [ Links ]
41. Frolkis J, Pothier CE, Blackstone EH, Lauer MS. Frequent ventricular ectopy after exercise as a predictor of death. N Engl J Med 2003;348: 781-90. [ Links ]
42. Araújo CGS. Teste de exercício: terminologia e algumas considerações sobre passado, presente e futuro baseadas em evidências. Rev Bras Med Esporte 2000;6:77-84. [ Links ]
Received in 12/7/03
Approved in 22/9/03