Schmid, J.-P

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EditorialDetection of exercise induced ischaemia: a newrole for cardiopulmonary exercise testingJ.-P. Schmid*Swiss Cardiovascular Center Bern, Cardiovascular Prevention & Rehabilitation, University Hospital(Inselspital), 3010 Bern, SwitzerlandReceived 9 May 2003; revised 9 May 2003; accepted 16 May 2003See doi:10.1016/S1095-668X(03)00210-0, for thearticle to which this editorial refersThe exercise stress test has been used for decades asa diagnostic tool in the work-up of patients withsuspected coronary artery disease. Even though thetraditional exercise electrocardiogram is a widelyaccepted and well-validated diagnostic tool, itsuffers from low sensitivity, which neverthelessdepends strongly on the population tested. Whena work-up bias is avoided (that means, the test isapplied to individuals not already known to havecoronary artery disease), the sensitivity can be aslow as 45% with a specificity of 85%.1 In patients withan angiographically significant coronary artery dis-ease and a horizontal or downsloping ST-depressionof 1 mV (1 mm), in a meta-analysis a mean sensitivityof 66% has been described with a range between40% and 90% for 1-vessel to 3-vessel disease and acorresponding mean specificity of 84%.2Because of the low sensitivity of the exercisestress test, a lot of specialists risk to be misled toapply more expensive, time-consuming and poten-tially risky diagnostic procedures. In this issue ofthe European Heart Journal, to overcome the dis-advantages of the standard exercise stress test,Belardinelli et al.3 report about the application ofa new element to detect exercise–induced is-chaemia, namely the analysis of respiratory gasduring the exercise stress test. In their effort toameliorate the diagnostic accuracy of exercisestress testing, they take advantage of the conceptof the ischaemic cascade, which has already beenrecognized for several decades and describes theimpact of the pathophysiologic manifestations ofischaemia on left ventricular function. After reduc-tion in myocardial blood flow sufficient to resultin ischaemia, a predictable sequence of eventsoccurs. The first mechanical consequence of themetabolic changes at the onset of ischaemia isdiastolic dysfunction, followed by wall motionabnormalities and a subsequent rise in left ven-tricular filling pressure. This occurs well beforeECG changes are registered or chest pain isreported.The increase of VO2 with incremental work loadis linear in the normal subject and a function ofheart rate, stroke volume and the difference ofarterio-venous oxygen concentration. According toFick’s law (VO2 = cardiac output × arterio-venousO2 difference), the non-invasive measurement ofoxygen uptake allows conclusions about cardiacoutput. Therefore, a decline of the ejection frac-tion and consequently the cardiac output duringexercise, will lower the rate of increase of VO2 andcardiopulmonary exercise testing (CPET) shouldallow the detection of ischaemia, even in case of anon-conclusive ECG and/or silent ischaemia.In their study, Belardinelli et al. report about202 consecutive patients with documented cor-onary artery disease, in whom an incremental exer-cise stress test with breath-by-breath gas exchangeanalysis, followed by a 2 day stress/rest gatedSPECT myocardial scintigraphy was effectuated.Two variables were found to improve the sensi-tivity of the stress test: the decline in the rate ofincrease of VO2 proportional to work load change* Corresponding author. Tel.: +41-316-328-972;fax: +41-316-328-977E-mail address: jean-paul.schmid@insel.ch (J.-P. Schmid).European Heart Journal (2003) 24, 1285–12860195-668X/03/$ - see front matter © 2003 Published by Elsevier Ltd on behalf of The European Society of Cardiology.doi:10.1016/S0195-668X(03)00280-X(∆VO2/∆work) and O2 pulse flattening duration,calculated from the onset of myocardial ischaemiato peak exercise. That way the sensitivity of stan-dard ECG stress testing in identifying exercise-induced myocardial ischaemia increased from 46%to 87%, and the specificity from 66% to 74% (64% forwomen respectively).Thus, the authors were able to combine thewell known physiologic law of linear increase inoxygen consumption during exercise with thepathophysiologic steps of the ischaemic cascadeand to correlate it successfully with an imagingtechnique. This translation of profound under-standing of pathophysiologic mechanisms and thetechnical possibilities of CPET into a new investiga-tional concept could serve as a landmark studyin the exercise-testing domain concerning thedetection of ischaemia. Hopefully, this study willpromote the application of CPET as a non-invasivetool in the work up of patients with suspectedcoronary artery disease and thus valorise this test.During the last years, cardiopulmonary stresstesting has already gained more and more interestamong cardiologists. By means of O2 uptake andCO2 production together with minute ventilationmeasurement, it allows an integrative assessmentof cardiovascular performance, pulmonary functionand peripheral muscular condition, which has ledto an extension of the diagnostic possibilities.Actually, CPET in cardiology is applied mainly inpatients with heart failure where it has been shownto be of great value in the appreciation of prognos-tically important parameters (for example VE/VCO2slope and peak VO2) or in the setting of cardiacrehabilitation, where the assessment of maximalphysical work capacity, determination of theanaerobic threshold and evaluation of exertionaldyspnoea are in the foreground.The great prognostic information offered by theexercise stress test compared with other tech-niques in the evaluation of stress induced myocar-dial ischaemia is a big advantage. Exercise capacityhas been shown to be one of the most potentpredictors of mortality4 and also heart rate recov-ery has consistently shown its prognostic useful-ness.5 Furthermore, chronotropic incompetence,that is an attenuated rise in heart rate duringexercise, is at least as prognostically ominous as anuclear perfusion abnormality,6 while ST-segmentchanges alone have not emerged as an independentrisk predictor.7The prognostic and diagnostic value of the exer-cise test is maximized, when multiple exercise find-ings are considered and it seems, that respiratorygas analysis offers new perspectives in this sense.Cardiologists should realise that with CPET we havean enormously powerful tool to our disposal. Whenwe evaluate a patient without a revascularizationhistory, one of the most important tasks is to assesshis risk.8 It makes no sense to institute invasivetherapeutic procedures in patients who are alreadyat low risk. On the other hand in front of a patientwith known coronary artery disease who has under-gone an angioplasty with stent implantation andcomplains about rather atypical chest pain severalmonths later, the course of the ∆VO2/∆work slopeand/or the presence of an O2 pulse flatteningduring the exercise stress test will be of greathelp when to decide, whether conservative man-agement and reassurance is appropriate or if arestenoses has to be excluded by angiography.As Belardinelli and coworkers state in the intro-duction of their article, until now there has beensome reluctance to use CPET, mainly because oflacking routine in interpretation of the results,the time requirements of the test and technicalaspects. This will remain a barrier to introduceCPET into clinical routine, but further simplifi-cation of the system’s handling and growingpopularity of CPET will certainly change this cir-cumstance and pave the way to success, assumedthat the new indication will assert itself.References1. Froelicher VF, Lehmann KG, Thomas R et al. The electro-cardiographic exercise test in a population with reducedworkup bias: diagnostic performance, computerized in-terpretation, and multivariable prediction. Veterans AffairsCooperative Study in Health Services #016 (QUEXTA) StudyGroup. Quantitative Exercise Testing and Angiography. AnnIntern Med 1998;128:965–74.2. Gianrossi R, Detrano R, Mulvihill D et al. Exercise-induced STdepression in the diagnosis of coronary artery disease. Ameta-analysis. Circulation 1989;80:87–98.3. Bellardinelli R, Lacalaprice F, Carle F et al. Exercise-inducedmyocardial ischaemia detected by cardiopulmonaryexercise-testing. Eur Heart Jnl 2003;24:1304–13.4. Myers J, Prakash M, Froelicher V et al. Exercise capacity andmortality among men referred for exercise testing. N Engl JMed 2002;346:793–801.5. Cole CR, Blackstone EH, Pashkow FJ et al. Heart-rate recov-ery immediately after exercise as a predictor of mortality.N Engl J Med 1999;341:1351–7.6. Lauer MS, Francis GS, Okin PM et al. Impaired chronotropicresponse to exercise stress testing as a predictor of mortality.Jama 1999;281:524–9.7. Goraya TY, Jacobsen SJ, Pellikka PA et al. Prognostic value oftreadmill exercise testing in elderly persons. Ann Intern Med2000;132:862–70.8. Califf RM, Armstrong PW, Carver JR et al. 27th BethesdaConference: matching the intensity of risk factor manage-ment with the hazard for coronary disease events. Task Force5. Stratification of patients into high, medium and low risksubgroups for purposes of risk factor management. J Am CollCardiol 1996;27:1007–19.1286 Editorial

Detection of exercise induced ischaemia: a new role for cardiopulmonary exercise testing

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