SPECIAL ARTICLES

Stress Echocardiography: A Historical Perspective

Eugenio Picano, MD, PhD

Stress echocardiography is a popular cardiac imaging techniquethat provides similar diagnostic and prognostic accuracy as ra-dionuclide stress perfusion imaging. Similar accuracy, however,should not be synonymous with being “clinically interchange-able.” Because of economic cost, environmental impact, andindividual biohazard exposure, a nuclear examination shouldbe performed only when it cannot be replaced by other tech-niques that do not employ ionizing radiation. Nuclear medicalimaging procedures, of which cardiological procedures are animportant part, account for 4% of the annual effective radiationdose received by the average person in the United States. At the

individual level, the radiological exposure of a single nuclearcardiology procedure conveys a low, but measurable, risk offatal cancer, which varies from 1 in 1000 to 1 in 10,000, depend-ing on the type of examination (higher for thallium scans; lowerfor technetium 99m methoxyisobutylisonitrile scans). Becausethe information provided by stress echocardiography and stressradionuclide perfusion imaging are similar, the choice of testshould be made in the context of the environmental, biological,and economic effects of that choice. Am J Med. 2003;114:126 –130. ©2003 by Excerpta Medica Inc.

Like many scientific innovations (1,2), stress echo-cardiography has evolved from the status of a“promising innovation” embraced by a few enthu-

siastic supporters amid general scepticism, to an “estab-lished technology” that is accepted by the great majorityof cardiologists (3– 6). Twenty years ago, stress echocar-diography was a research tool (7–9); even the few labora-tories whose results had been published in widely readjournals had not yet implemented the test in routine clin-ical practice. Today, stress echocardiography has becomecommonplace in clinical practice, as just another diag-nostic test for myocardial ischemia (10). Established im-aging techniques (e.g., nuclear cardiology, echocardiog-raphy) and more recent developments (e.g., magneticresonance imaging, ultrafast computed tomography) al-low a noninvasive insight into myocardial function andperfusion. Not infrequently, the complex nature of a pa-tient’s problems is reduced to a transient perfusion defector reversible hypokinesia, and technological output re-places integrated clinical reasoning. It may be time toreassess our diagnostic strategies.

The Information Content of Nuclear Cardiologyand Stress EchocardiographyNuclear cardiology has had a dominant position in thediagnosis of coronary artery disease for more than 20years. In the first edition of Braunwald’s textbook (11),

there were 60 pages about nuclear cardiology and noneabout stress echocardiography, which was still experi-mental. In the 2001 edition, nuclear cardiology is dis-cussed for more than 50 pages, with less than one page onstress echocardiography (12), which in the meantime hascompleted the full circle of scientific validation from ini-tial feasibility (7–9) to large-scale multicenter studies in-volving thousands of patients (13–15).

Nuclear cardiology is the time-honored offspring ofthe marriage between nuclear technology and coronaryphysiology. Several imaging paradigms were developedand popularized by nuclear cardiology: the merit of im-aging cardiac function during stress, in lieu of the simpleelectrocardiogram; the value of pharmacological alterna-tives to physical exercise for stressing the heart; the needto assess viability in segments with resting dysfunction;the advantage of digital data acquisition, storage, and dis-play; and the prognostic importance of the extent andseverity of stress-induced ischemia (11,12). The mainmerit of stress echocardiography has been its proven abil-ity to reproduce the nuclear imaging paradigms in a sim-pler and more cost-effective fashion (10).

Modern cardiac evaluation involves both an anatomi-cal and a physiological approach. In the physiological ap-proach, the cardiologist gains knowledge of the heteroge-neity underlying similar anatomical conditions: not allresting dysfunction is irreversible, not all coronary steno-ses can provoke ischemia, and not all technically success-ful revascularizations yield a physiological or prognosticbenefit (15). In this approach to coronary artery disease,the stress test is the “gatekeeper” for referral to coronaryangiography, filtering out patients who are not likely tobenefit from revascularization (16). For this purpose,

From the Institute of Clinical Physiology, Consiglio Nazionale delleRicerche, Pisa, Italy.

Requests for reprints should be addressed to Eugenio Picano, MD,PhD, Institute of Clinical Physiology, Consiglio Nazionale delleRicerche, Via Moruzzi 1, 56124 Pisa, Italy; or picano@ifc.cnr.it.

Manuscript submitted February 28, 2002, and accepted in revisedform September 4, 2002.

126 ©2003 by Excerpta Medica Inc. 0002-9343/03/$–see front matterAll rights reserved. PII S0002-9343(02)01427-4

Table 1. Studies That Have Reviewed the Diagnostic and Prognostic Information of Cardiac Stress Imaging Techniques

Type of InformationFirst Author(Reference)

Number of Studies(Number of Patients) Techniques Results

Diagnostic accuracy forcoronary artery disease

O’Keefe (17) 11 studies Stress echocardiography Sensitivity � 78%(n � 808) Specificity � 86%

Perfusion imaging Sensitivity � 85%Specificity � 77%

Fleischmann (18) 44 studies Exercise echocardiography Sensitivity � 85%(n � 5974) Specificity � 77%

Exercise SPECT Sensitivity � 87%Specificity � 64%

Prognostic value Gibbons (5) 9 studies Stress echocardiography Positive predictive value: 14%–66%(n � 3497) Negative predictive value: 81%–98%12 studies Stress myocardial imaging Positive predictive value � 3.8%–41%

(n � 12,589) Negative predictive value � 81.2%–100%Diagnostic value of viability Bax (19) 37 studies F-18 fluorodeoxyglucose Specificity significantly lower for 201

thallium(n � 1341) Thallium perfusion imaging Specificity significantly higher for low-

dose dobutamineDobutamine echocardiographyPrognostic value of viability Allman (20) 24 studies F-18 fluorodeoxyglucose No measurable difference for predicting

revascularization benefit between thethree testing techniques

(n � 3089) Thallium perfusion imagingDobutamine echocardiography

SPECT � single photon emission computed tomography.

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nuclear cardiology and stress echocardiography havesimilar diagnostic accuracy for the noninvasive detectionof coronary artery disease, the identification of myocar-dial viability, and prognostic stratification (Table 1)(5,6,17–21). In recent guidelines (5,6), the advantages ofstress echocardiography include higher specificity,greater versatility, greater convenience, and lower cost.The advantages of stress perfusion imaging include ahigher technical success rate, higher sensitivity (especiallyfor single-vessel disease involving the left circumflex),better accuracy when multiple resting left ventricular wallmotion abnormalities are present, and a more extensivedatabase for the evaluation of prognosis (5). The Ameri-can College of Cardiology/American Heart AssociationTask Force concluded that “the choice of which test toperform depends on issues of local expertise, availablefacilities and considerations of cost-effectiveness” (5).

Cardiac Stress Testing and Nuclear Scanning:the Effects of Ionizing RadiationSeven million nuclear cardiology studies are performedeach year in the United States, accounting for 35% of allnuclear imaging (22). The total effective dose (expressedin milliSievert [mSv]) received by an average person inthe United States is 2.8 mSv per year: 2.4 mSv from nat-ural sources and 0.4 mSv from man-made sources. In1987, the National Council of Radiation Protection andMeasurements estimated that nuclear medicine tests ac-counted for 4% of the total radiation exposure of theaverage person in the United States (23). Since 1987, thenumber of nuclear cardiology studies has more than dou-bled in the country (22).

At the patient level, the effective dose of a single nuclearcardiology stress procedure ranges from 23 mSv from a thal-lium scan to 10 mSv from a technetium 99m methoxyisobu-tylisonitrile scan (24,25). According to data provided by theInternational Commission on Radiological Protection, thisexposure dose corresponds to an additional risk of cancerthat is between 1 in 1000 and 1 in 10,000 (24–29). The ex-posure doses from cardiac imaging procedures—and theassociated risks—are substantially greater than those forother common radiological tests (Table 2; Figure). A single

exposure to 0.01 mSv (a chest radiograph, for instance) cor-responds to an average loss of 2 minutes of life expectancy,whereas a single exposure to 10 mSv corresponds to 2 days oflost life expectancy (24,28,29).

These biological burdens might be acceptable if thereare no alternative means to obtaining the informationprovided by the technique. The same burden may be-come too great when similar information can be obtainedwith alternative techniques of widespread availability thathave no known biohazards and environmental impact.This is especially true given the frequent need for re-peated stress imaging testing in the same patient. Theseconsiderations are also somewhat mirrored in the guide-lines developed by the International Commission on Ra-diological Protection, whose recommendations form thebasis of legislation in many countries (29), and of theInternational Basic Safety Standards issued by the Inter-national Atomic Energy Agency (30). In Italy, a 2000 law(art. 3, DL187/26 May 2000) states that a nuclear exami-nation may be performed only when “it cannot be re-placed by other techniques that do not employ ionizingradiation.” In the European Community (31), a 97/43Euratom directive for nuclear medicine establishes thatindication and execution of diagnostic proceduresshould follow three basic principles: the justificationprinciple (article 3: “if an exposure cannot be justified, itshould be prohibited”), the optimization principle (arti-cle 4: “according to the ALARA principle, all doses due tomedical exposures must be kept As Low As ReasonablyAchievable”), and the responsibility principle (article 5:“both the referring physician ordering the nuclear medi-cine test [the prescriber] and the nuclear medicine phy-sician [the practitioner] are responsible for the justifica-tion of the test exposing the patient to ionizing radia-tion”). Any responsible prescription of a nuclearcardiology test today should follow these principles. Thepatient, the cardiologist, and the referring physicianshould be aware of the risks, costs, and environmentalimpact of this “subjective” choice, even if quantificationof these negative effects of low-level radiation remains achallenge (32).

Table 2. Radiation Doses and Estimated Cancer Risk from Common Radiological Examinations and Isotope Scans

Type of TestEffective Radiation

Dose (mSv)Equivalent Period of Natural

Background RadiationLifetime Additional Risk of

Cancer per Examination

Chest radiograph 0.01 A few days Negligible riskSkull radiograph 0.1 A few weeks Minimal risk

(1 in 100,000 to 1 in 1,000,000)Breast (mammography) 1 A few months to a year Very low riskLung isotope scan (1 in 10,000 to 1 in 100,000)Cardiac gated study 10 A few years Low riskCardiac thallium scan (1 in 1000 to 1 in 10,000)

mSv � milliSievert.

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Stress Echocardiography: Some Potential PitfallsEasy access to ultrasound technology can become a prob-lem in clinical practice; even though an echocardiogramis simple to obtain, skill in interpretation cannot be ac-quired in a few days or weeks. With a handheld echocar-diographic machine and an inexpensive drug, any physi-cian can become a stress echocardiographer (10). Order-ing patterns might be distorted by financial incentivesbecause the test can be performed in a physician’s office.In the absence of a strict system of credentialing and qual-ity control, we may soon experience a backlash of distrustabout the technique. Moreover, after a technique be-comes an “established technology,” it may suffer the tran-sition from selective to large-scale application (2).

Cardiac Stress Imaging without BiohazardsPrescribing physicians should be aware that their choicesplace economic and biohazard burdens on the planet andthe patient. Although ultrasound technology is improv-

ing steadily, an alternative technique is needed for acous-tically hostile patients. For these patients, fast magneticresonance imaging, which incorporates the best aspectsof nuclear and echocardiographic scanning, can providean accurate second-line choice (33). Like nuclear scan-ning, it is operator independent, digital, and quantitative;like echocardiography, it is nonionizing and versatile. In-deed, fast magnetic resonance imaging is likely to have agrowing role in nonionizing cardiac stress testing in thenext decade.

ACKNOWLEDGMENTI am grateful to Ms. Manuella Walker who edited the manu-script.

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Figure. Simplified effective dose ranges for diagnostic nuclear medicine and radiological procedures. The benchmark of backgroundradiation for an average person in the United States (2 to 3 milliSievert [mSv] per year) is shown as a shaded area. MIBI �methoxyisobutylisonitrile; Tc � technetium. Adapted from references 26 and 29.

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