European Journal of Applied Physiology

, Volume 118, Issue 8, pp 1547–1553 | Cite as

Characteristics of patients with a relatively greater minimum VE/VCO2 against peak VO2% and impaired exercise tolerance

  • Taisuke NakadeEmail author
  • Hitoshi Adachi
  • Makoto Murata
  • Shigeru Oshima
Original Article



Cardiopulmonary exercise testing (CPX) is used to evaluate functional capacity and assess prognosis in cardiac patients. Ventilatory efficiency (VE/VCO2) reflects ventilation–perfusion mismatch; the minimum VE/VCO2 value (minVE/VCO2) is representative of pulmonary arterial blood flow in individuals without pulmonary disease. Usually, minVE/VCO2 has a strong relationship with the peak oxygen uptake (VO2), but dissociation can occur. Therefore, we investigated the relationship between minVE/VCO2 and predicted peak VO2 (peak VO2%) and evaluated the parameters associated with a discrepancy between these two parameters.


A total of 289 Japanese patients underwent CPX using a cycle ergometer with ramp protocols between 2013 and 2014. Among these, 174 patients with a peak VO2% lower than 70% were enrolled. Patients were divided into groups based on their minVE/VCO2 [Low group: minVE/VCO2 < mean − SD (38.8–5.6); High group: minVE/VCO2 > mean + SD (38.8 + 5.6)]. The characteristics and cardiac function at rest, evaluated using echocardiography, were compared between groups.


The High group had a significantly lower ejection fraction, stroke volume, and cardiac output, and higher brain natriuretic peptide, tricuspid regurgitation pressure gradient, right ventricular systolic pressure, and peak early diastolic LV filling velocity/peak atrial filling velocity ratio compared with the Low group (p’s < 0.01). In addition, the Low group had a significantly higher prevalence of pleural effusion than did the High group (26 vs 11%, p < 0.01).


Patients with a relatively greater minVE/VCO2 in comparison with peak VO2 had impaired cardiac output as well as restricted pulmonary blood flow increase during exercise, partly due to accumulated pleural effusion.


Peak VO2 min VE/VCO2 Cardiopulmonary exercise test Cardiac output 



Angiotensin-converting enzyme/angiotensin receptor blockers


Anaerobic threshold


Body fat mass


Body mass index


Brain natriuretic peptide


Cardiopulmonary exercise testing


Deceleration time


Early diastolic mitral annular motion at the septum


Ratio of E to E


Inferior vena cava


Left ventricular ejection fraction


Mean right atrial pressure


Minimum ventilatory efficiency


Respiratory compensation point


Right ventricular systolic pressure


Standard deviation


Dead-space gas volume to tidal gas volume ratio


Ventilatory efficiency


Oxygen uptake


Author contributions

TN, HA and MM conceived and designed the study. TN, MM and SO extracted and analysed the data. TN and HA drafted the manuscript, and reviewed and revised the manuscript. TN: Taisuke Nakade, HA: Hitoshi Adachi, MM: Makoto Murata, SO: Shigeru Oshima.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. Adachi H (2017) Cardiopulmonary exercise test. Int Heart J 58:654–665. CrossRefPubMedGoogle Scholar
  2. Adachi H, Nguyen PH, Belardinelli R, Hunter D, Jung T, Wasserman K (1997) Nitric oxide production during exercise in chronic heart failure. Am Heart J 134:196–202CrossRefGoogle Scholar
  3. Adachi H, Oshima S, Sakurai S, Toyama T, Hoshizaki H, Taniguchi K, Ito H (2003) Nitric oxide exhalation correlates with ventilatory response to exercise in patients with heart disease. Eur J Heart Fail 5:639–643CrossRefGoogle Scholar
  4. Allen SJ, Laine GA, Drake RE, Gabel JC (1988) Superior vena caval pressure elevation causes pleural effusion formation in sheep. Am J Physiol 255(3 Pt 2):H492–H495PubMedGoogle Scholar
  5. American Thoracic Society; American College of Chest Physicians (2003) ATS/ACCP statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med 167:211–277. CrossRefGoogle Scholar
  6. Anker SD, Ponikowski P, Varney S, Chua TP, Clark AL, Webb-Peploe KM, Harrington D, Kox WJ, Poole-Wilson PA, Coats AJ (1997) Wasting as independent risk factor for mortality in chronic heart failure. Lancet 349:1050–1053. CrossRefPubMedGoogle Scholar
  7. Arena R, Myers J, Williams MA, Gulati M, Kligfield P, Balady GJ, Collins E, Fletcher G, American Heart Association Committee on Exercise, Rehabilitation, and Prevention of the Council on Clinical Cardiology; American Heart Association Council on Cardiovascular Nursing (2007) Assessment of functional capacity in clinical and research settings: a scientific statement from the American Heart Association Committee on Exercise, Rehabilitation, and Prevention of the Council on Clinical Cardiology and the Council on Cardiovascular Nursing. Circulation 116:329–343. CrossRefPubMedGoogle Scholar
  8. Arena R, Myers J, Abella J, Pinkstaff S, Brubaker P, Moore B, Kitzman D, Peberdy MA, Bensimhon D, Chase P, Forman D, West E, Guazzi M (2009) Determining the preferred percent-predicted equation for peak oxygen consumption in patients with heart failure. Circ Heart Fail 2(2):113–120CrossRefGoogle Scholar
  9. Armstrong DW, Tsimiklis G, Matangi MF (2010) Factors influencing the echocardiographic estimate of right ventricular systolic pressure in normal patients and clinically relevant ranges according to age. Can J Cardiol 26:e35–e39CrossRefGoogle Scholar
  10. Borlaug BA, Nishimura RA, Sorajja P, Lam CS, Redfield MM (2010) Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. Circ Heart Fail 3:588–595. CrossRefPubMedPubMedCentralGoogle Scholar
  11. Buchfuhrer ML, Hartsen JE, Robinson TE, Sue DY, Wasserman K, Whipp BJ (1983) Optimizing the exercise protocol for cardiopulmonary assessment. J Appl Physiol Respir Environ Exerc Physiol 55:1558–1564PubMedGoogle Scholar
  12. Deboeck G, Niset G, Lamotte M, Vachiéry JL, Naeije R (2004) Exercise testing in pulmonary arterial hypertension and in chronic heart failure. Eur Respir J 23:747–751CrossRefGoogle Scholar
  13. Fonarow GC, Srikanthan P, Costanzo MR, Cintron GB, Lopatin M; ADHERE Scientific Advisory Committee and Investigators (2007) An obesity paradox in acute heart failure: analysis of body mass index and inhospital mortality for 108,927 patients in the Acute Decompensated Heart Failure National Registry. Am Heart J 153:74–81. CrossRefPubMedGoogle Scholar
  14. Francis DP, Shamim W, Davies LC, Piepoli MF, Ponikowski P, Anker SD, Coats AJ (2000) Cardiopulmonary exercise testing for prognosis in chronic heart failure: continuous and independent prognostic value from VE/VCO(2)slope and peak VO(2). Eur Heart J 21:154–161. CrossRefPubMedGoogle Scholar
  15. Gazetopoulos N, Salonikides N, Davies H (1974) Cardiopulmonary function in patients with pulmonary hypertension. Br Heart J 36:19–28CrossRefGoogle Scholar
  16. Guazzi M, Myers J, Peberdy MA, Bensimhon D, Chase P, Arena R (2010) Cardiopulmonary exercise testing variables reflect the degree of diastolic dysfunction in patients with heart failure-normal ejection fraction. J Cardiopulm Rehabil Prev 30:165–172. CrossRefPubMedGoogle Scholar
  17. Hadano Y, Murata K, Yamamoto T, Kunichika H, Matsumoto T, Akagawa E, Sato T, Tanaka T, Nose Y, Tanaka N, Matsuzaki M (2006) Usefulness of mitral annular velocity in predicting exercise tolerance in patients with impaired left ventricular systolic function. Am J Cardiol 97:1025–1028. CrossRefPubMedGoogle Scholar
  18. Hansen JE, Sue DY, Wasserman K (1984) Predicted values for clinical exercise testing. Am Rev Respir Dis 129:S49–S55. CrossRefPubMedGoogle Scholar
  19. Janicki JS, Weber KT, Likoff MJ, Fishman AP (1984) Exercise testing to evaluate patients with pulmonary vascular disease. Am Rev Respir Dis 129(2 Pt 2):S93–S95CrossRefGoogle Scholar
  20. Kemper HC, Twisk JW, van Mechelen W (2013) Changes in aerobic fitness in boys and girls over a period of 25 years: data from the Amsterdam Growth and Health Longitudinal Study revisited and extended. Pediatr Exerc Sci 25:524–535CrossRefGoogle Scholar
  21. Kleber FX, Vietzke G, Wernecke KD, Bauer U, Opitz C, Wensel R, Sperfeld A, Gläser S (2000) Impairment of ventilatory efficiency in heart failure: prognostic impact. Circulation 101:2803–2809CrossRefGoogle Scholar
  22. Lang RM, Bierig M, Devereux RB et al (2006) Recommendations for chamber quantification. Eur J Echocardiogr 7:79–108. CrossRefPubMedGoogle Scholar
  23. Matsumoto A, Itoh H, Eto Y, Kobayashi T, Kato M, Omata M, Watanabe H, Kato K, Momomura S (2000) End-tidal CO2 pressure decreases during exercise in cardiac patients: association with severity of heart failure and cardiac output reserve. J Am Coll Cardiol 36:242–249CrossRefGoogle Scholar
  24. Melenovsky V, Kotrc M, Borlaug BA, Marek T, Kovar J, Malek I, Kautzner J (2013) Relationships between right ventricular function, body composition, and prognosis in advanced heart failure. J Am Coll Cardiol 62:1660–1670. CrossRefPubMedGoogle Scholar
  25. Miyazaki A, Adachi H, Oshima S, Taniguchi K, Hasegawa A, Kurabayashi M (2007) Blood flow redistribution during exercise contributes to exercise tolerance in patients with chronic heart failure. Circ J 71:370–465CrossRefGoogle Scholar
  26. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, Evangelisa A (2009) Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr 10:165–193. CrossRefPubMedGoogle Scholar
  27. Ohwada M, Igarashi M (1983) Evaluation of measurement of maternal symphysis-fundus length as fetal growth screening method. Nihon Sanka Fujinka Gakkai Zasshi 35:637–644. (In Japanese) PubMedGoogle Scholar
  28. Podolec P, Rubis P, Tomkiewicz-Pajak L, Kopeć G, Tracz W (2008) Usefulness of the evaluation of left ventricular diastolic function changes during stress echocardiography in predicting exercise capacity in patients with ischemic heart failure. J Am Soc Echocardiogr 21:834–840. CrossRefPubMedGoogle Scholar
  29. Robbins M, Francis G, Pashkow FJ, Snader CE, Hoercher K, Young JB, Lauer MS (1999) Ventilatory and heart rate responses to exercise: better predictors of heart failure mortality than peak oxygen consumption. Circulation 100:2411–2417CrossRefGoogle Scholar
  30. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, Solomon SD, Louie EK, Schiller NB (2010) Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr 23:685–713. CrossRefPubMedGoogle Scholar
  31. Shim CY, Kim SA, Choi D, Yang WI, Kim JM, Moon SH, Lee HJ, Park S, Choi EY, Chung N, Ha JW (2011) Clinical outcomes of exercise- induced pulmonary hypertension in subjects with preserved left ventricular ejection fraction: implication of an increase in left ventricular filling pressure during exercise. Heart 97:1417–1424. CrossRefPubMedGoogle Scholar
  32. Sun XG, Hansen JE, Oudiz RJ, Wasserman K (2001) Exercise pathophysiology in patients with primary pulmonary hypertension. Circulation 104:429–435CrossRefGoogle Scholar
  33. Taguchi T, Adachi H, Hoshizaki H, Oshima S, Kurabayashi M (2014) Effect of physical training on ventilator patterns during exercise in patients with heart failure. J Cardiol 65:343–348. CrossRefPubMedGoogle Scholar
  34. Wasserman K, Hansen JE, Sue DY, Stringer W, Whipp BJ (2005) Normal values. In: Weinberg R (ed) Principles of exercise testing and interpretation, 4th edn. Lippincott Williams and Wilkins, Philadelphia, pp 160–182Google Scholar
  35. Weber KT, Janicki JS (1985) Cardiopulmonary exercise testing for evaluation of chronic heart failure. Am J Cardiol 55:22A–31ACrossRefGoogle Scholar
  36. Weber KT, Kinasewitz GT, Janicki JS, Fishman AP (1982) Oxygen utilization and ventilation during exercise in patients with chronic heart failure. Circulation 65:1213–1223CrossRefGoogle Scholar
  37. Wong CL, Holroyd-Leduc J, Straus SE (2009) Does this patient have a pleural effusion? JAMA 301:309–317. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Cardiovascular Medicine, Department of CardiologyGunma Prefectural Cardiovascular CenterMaebashiJapan
  2. 2.Department of Medicine and Biological Science, Graduate School of MedicineGunma University School of MedicineMaebashiJapan

Personalised recommendations