Standards For The Use Of Cardiopulmonary Exercise Testing .

Review PaperStandards for the use of cardiopulmonary exercise testing forthe functional evaluation of cardiac patients: a report fromthe Exercise Physiology Section of the European Associationfor Cardiovascular Prevention and RehabilitationAlessandro Mezzania, Piergiuseppe Agostonib, Alain Cohen-Solald,Ugo Corràa, Anna Jegierf, Evangelia Kouidig, Sanja Mazich, Philippe Meurine,Massimo Piepolic, Attila Simoni, Christophe Van Laethemj and Luc VanheeskaS. Maugeri Foundation, Veruno Scientific Institute, Cardiology Division, Veruno (NO), bCentro CardiologicoMonzino, Institute of Cardiology, University of Milan, Milan, cHeart Failure Department, Cardiology Unit,Guglielmo da Saliceto Hospital, Piacenza, Italy, dDepartment of Cardiology, University Denis DiderotHospital Lariboisiere, Assistance Publique-Hôpitaux de Paris, Paris, eLes Grands Prés, CardiacRehabilitation Center, Villeneuve Saint Denis, France, fDepartment of Sports Medicine, Medical University,Lodz, Poland, gLaboratory of Sports Medicine, Aristotle University, Thessaloniki, Greece, hInstitute ofMedical Physiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia, iState Hospital forCardiology, Balatonfüred, Hungary, jCardiovascular Center, Onze Lieve Vrouw Ziekenhuis, Aalst andkDepartment of Rehabilitation Sciences-Biomedical Sciences, KU Leuven, Leuven, BelgiumReceived 6 November 2008 Accepted 4 January 2009Cardiopulmonary exercise testing (CPET) is a methodology that has profoundly affected the approach to patients’functional evaluation, linking performance and physiological parameters to the underlying metabolic substratum andproviding highly reproducible exercise capacity descriptors. This study provides professionals with an up-to-date review ofthe rationale sustaining the use of CPET for functional evaluation of cardiac patients in both the clinical and researchsettings, describing parameters obtainable either from ramp incremental or step constant-power CPET and illustrating thewealth of information obtainable through an experienced use of this powerful tool. The choice of parameters to bemeasured will depend on the specific goals of functional evaluation in the individual patient, namely, exercise toleranceassessment, training prescription, treatment efficacy evaluation, and/or investigation of exercise-induced adaptationsof the oxygen transport/utilization system. The full potentialities of CPET in the clinical and research setting still remainlargely underused and strong efforts are recommended to promote a more widespread use of CPET in the functionalc 2009 The European Society of Cardiologyevaluation of cardiac patients. Eur J Cardiovasc Prev Rehabil 16:249–267 European Journal of Cardiovascular Prevention and Rehabilitation 2009, 16:249–267Keyword: anaerobic threshold, cardiac disease, cardiopulmonary exercise testing, critcal power, functional evaluation, oxygen consumption, ventilationCorrespondence to Dr Alessandro Mezzani, MD, S. Maugeri Foundation, VerunoScientific Institute, IRCCS, Cardiology Division, Laboratory for the Analysis ofCardiorespiratory Signals, Via per Revislate 13, Veruno (NO) 28010, ItalyTel: 39 322 884711; fax: 39 322 830294; e-mail: amezzani@fsm.itA. M. and L. V. are current and past Chair, respectively, of the Exercise Physiology Section of the European Association of Cardiovascular Prevention andRehabilitation.Experts panel: S. Adamopoulos, Onassis Cardiac Surgery Center, 2ndDepartment of Cardiology, Athens, Greece; S. Gielen, Department ofCardiology, University of Leipzig, Leipzig Heart Center, Leipzig, Germany; M.Metra, Section of Cardiovascular Diseases, Department of Experimental andApplied Medicine, University of Brescia, Brescia, Italy; J-P. Schmid, Department ofCardiology, Cardiovascular Prevention and Rehabilitation, Inselspital, BernUniversity Hospital, and University of Bern, Bern, Switzerlandc 2009 The European Society of Cardiology1741-8267 IntroductionCardiopulmonary exercise testing (CPET) is a methodology that has profoundly changed the approach topatients’ functional evaluation, linking performance andphysiological parameters to the underlying metabolic substratum and providing highly reproducible exercisecapacity descriptors, for example, peak oxygen uptake(peakVO2) [1–3]. Moreover, CPET has dramaticallyincreased the mass of information obtainable from aDOI: 10.1097/HJR.0b013e32832914c8

250European Journal of Cardiovascular Prevention and Rehabilitation 2009, Vol 16 No 3Table 1Aims of cardiac patients functional evaluationReproducible assessment of patient’s exercise capacityPrescription of endurance training intensityEvaluation of response to endurance trainingEvaluation of response to therapeutic interventions (drugs, ventricularresynchronization, etc.) affecting exercise capacityEvaluation of the O2 transport and utilization system efficiency (ventilatory,hemodynamic, and metabolic components)relatively simple and inexpensive procedure such asexercise testing, furnishing an all-round vision of thesystems involved in both O2 transport from air tomitochondria and its utilization, and making it possibleto identify the link(s) limiting the exercise capacity inthe individual patient. However, during the last 20 years,the use of CPET for prognostic purposes [mainly inchronic heart failure (CHF) patients] has overshadowedits application for the functional evaluation of cardiacpatients, indeed its original one. This report aims toprovide professionals with an up-to-date review of therationale sustaining the use of CPET for the functionalevaluation of cardiac patients in both clinical and researchsettings (Table 1), describing parameters obtainableeither from ramp incremental or step constant-powerCPET, as specified in the respective paragraphs.Finally, as treatment of the use of CPET for differentiationof cardiac versus pulmonary causes of dyspnea and/orimpaired exercise capacity is not a specific goal of thisreport, readers interested in this topic are referred topreviously published reviews [4], as are those interestedin the use of CPET for prognostic stratification ofpatients with cardiac disease (in particular, CHF) [5].Use of cardiopulmonary exercise testing forthe evaluation of O2 transport and utilizationefficiencyVentilatory anaerobic thresholdDuring incremental exercise, an energy requirement isreached above which blood lactate concentration increasesat a progressively steeper rate [6]. This is because ofanaerobic glycolysis activation, that occurs as the oxygensupply rate is not rapid enough to reoxidize cytosolicNADH H [7]. Almost all of the H generated in thecell from lactic acid (La) dissociation is buffered bybicarbonate according to the following reaction: Hþ La þ HCO 3 () H2 O þ CO2 þ LaSuch a production of CO2, in excess of that producedby aerobic metabolism (excess CO2), makes the CO2production (VCO2) versus VO2 relationship becomesteeper. This has been labeled ‘anaerobic threshold’ oralso ‘aerobic threshold’ or ‘first lactate turn point’, withsome terminology disagreement in the scientific literature [8], and is a reliable index of aerobic fitness used fortraining prescription in both normal individuals andcardiac patients, especially for sustainable submaximalwork [9,10]. Interindividual variance, exercise protocol(e.g. fast versus slow work rate increments, step versusramp protocols) [11], blood sampling source (e.g. venous,capillary, arterial, arterialized) [12], and type of exercise(e.g. running, swimming, cycling, rowing, etc.) [13] canall affect blood lactate kinetics.By measuring gas exchange modifications induced bymetabolic changes at the mouth, the ‘ventilatoryanaerobic threshold’ (VAT) can be determined analyzingthe slope of the VCO2 versus VO2 (plotted on equalscales) relationship during ramp incremental exercise (Vslope method) [14], where VAT is the point of transitionof the VCO2 versus VO2 slope from less than 1 (activationof aerobic metabolism alone) to greater than 1 (anaerobicplus aerobic metabolism) (Fig. 1, upper panel). Moreover,the excess CO2 produced above VAT increases ventilatorydrive, which keeps the ventilation (VE) versus VCO2relationship linear and the end-tidal CO2 pressure(PETCO2) value constant (i.e. the individual does nothyperventilate with respect to the volume of CO2metabolically produced). However, an inversion of theVE versus VO2 relationship behavior (increase versusinitial decrease, i.e. hyperventilation with respect to O2)is observed above VAT; this makes both the VE versusVO2 ratio and end-tidal O2 pressure increase, in thepresence of a still decreasing or constant VE/VCO2 andPETCO2. VAT is thus also identifiable with the nadirof the VE versus VO2 relationship and with the pointwhere end-tidal O2 pressure begins to increase [2] (Fig. 1,lower panel). In the final phase of exercise, hyperventilation does occur also with respect to CO2 (respiratory compensation point), making VE/VCO2 increase andPETCO2 decrease [15] (Fig. 1, lower panel). VAT isusually expressed as a VO2 value relative to predictedmaximal oxygen uptake (VO2max), the lower limit ofnormality being 40% of predicted VO2max [16]. In the vastmajority of healthy individuals, VAT occurs at approximately 40–60% of VO2max (Table 2); in trained enduranceathletes, VAT can reach intensities as high as 80% oftheir VO2max [23].All cardiac diseases affecting the O2 transport chain(typically CHF) can determine a pathologic VAT (i.e. 40% predicted VO2max) [24], as can deconditioningfollowing bed rest for cardiac events, even in the presenceof normal left ventricular systolic function [25]. However,when expressed relative to measured peakVO2 (and not topredicted VO2max), VAT will still occur at approximately40–60% of peakVO2 in most cardiac patients, with a trendtoward higher percentages of peakVO2 in patients withCHF [7,16,24,26]. Notably, VAT may be not detectablein a variable percentage of patients [27], and especiallyin those with CHF because of exercise oscillatory VEand/or shortness of exercise time.