The Role of Cardiac MRI Stress Testing
1999; Lippincott Williams & Wilkins; Volume: 100; Issue: 16 Linguagem: Inglês
10.1161/01.cir.100.16.1676
ISSN1524-4539
AutoresGerald M. Pohost, Robert W Biederman,
Tópico(s)Cardiovascular Function and Risk Factors
ResumoHomeCirculationVol. 100, No. 16The Role of Cardiac MRI Stress Testing Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBThe Role of Cardiac MRI Stress Testing "Make a Better Mouse Trap … " Gerald M. Pohost and Robert W. W. Biederman Gerald M. PohostGerald M. Pohost From the Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Alabama. and Robert W. W. BiedermanRobert W. W. Biederman From the Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Alabama. Originally published19 Oct 1999https://doi.org/10.1161/01.CIR.100.16.1676Circulation. 1999;100:1676–1679Near the turn of the 20th century, Ralph Waldo Emerson said, "If a man can make a better mouse trap than his neighbor, the world will make a beaten path to his door." In the 1900s, we have seen particularly illuminating examples of this prediction: from the model T Ford, which in one decade eliminated the horse-and-buggy era, to the introduction of the heart-lung machine by John Gibbon, Jr, in 1953, which indelibly changed medicine, and, more recently, Andreas Gruentzig's intrepid introduction of intracoronary angioplasty, revolutionizing the treatment of coronary artery disease (CAD).We are now on the brink of another revolution, reaffirming Emerson's adage. Cardiac imaging has seen little to parallel its rapid advancement. In a short time, we have moved from x-ray methods for imaging coronary artery calcification in the 1950s by simple fluoroscopy, to the selective coronary arteriogram of Mason Sones in 1958, to the translation of postwar military ultrasound technology by Inge Edler and physicist C. Hellmuth Hertz into basic echocardiographic principles. In the early 1970s, a discovery was made that was little noticed in the medical profession, a formidable technology that would rise up to challenge the existing paradigms. From the adaptation of Lauterbur's work in 1973, investigators1 would set the stage for another challenger in the field of cardiac imaging: cardiovascular nuclear MRI. The improvements in resolution and contrast along with the ability for respiratory and cardiac gating generated diagnostic images of the highest quality, generating a wave of enthusiasm for this relatively new technology.Imaging techniques have become the workhorse of cardiologists for the diagnosis and risk stratification of patients with suspected ischemic heart disease. Two pathophysiological strategies have been coupled with imaging techniques for noninvasive detection of CAD. Generally, observations are made before, during, or after either exercise stress or dipyridamole/adenosine infusion to simulate the effects of exercise. Such strategies create myocardial perfusion defects and corresponding wall motion abnormalities in territories supplied by critically stenosed coronary arteries. To date, three imaging technologies have been coupled with "stress": (1) radionuclide imaging with 201Tl, 99mTc sestamibi, or similar agents to allow detection of perfusion defects and (2) 2D echocardiography to visualize abnormal wall motion or (3) first-pass or multigated radionuclide imaging. A new approach challenging these techniques has recently been recognized: the cardiac magnetic resonance (CMR) stress test.The reason the CMR stress test is becoming increasingly important is related to several factors. In large part, it is related to the fact that 2D stress echocardiography, although important and widely used, has several interrelated limitations. These include the requirement for an echocardiographic "window" and the effect that an inadequate window has on the ability to evaluate wall motion, substantial dependence on the skill of the sonographer, and the physical limitations inherent in ultrasound.Foremost among these limitations is the need for an adequate acoustic window. It is paradoxical that the very patient with a higher pretest probability for CAD frequently has other comorbidities (eg, obstructive pulmonary disease or obesity) that confound the search for a suitable window. Such a patient will suffer from the lack of an adequate acoustic window, which interferes with the ability to diagnose and prognose. Additionally, the window is essential for the adequate assessment of reversible left ventricular (LV) dysfunction. It is now clear that the detection of ischemia in the setting of either normal or abnormal systolic function is a crucial component of clinical practice. Given the convincing data in the literature to support the role of revascularization for the improvement of LV function in ischemic but viable myocardium, it is imperative to distinguish between reversible and irreversible myocardial dysfunction.234 A fundamental tenet exists: in order for stress-induced myocardial dysfunction to be revascularized, it must first be detected. As simplistic as this might sound, it is difficult to translate into clinical practice. Up to 15% of patients undergoing 2D stress echocardiography suffer from the lack of a suitable acoustic window.5 Moreover, the confidence for detecting and reporting myocardial dysfunction, even in the resting state, is notably reduced.6 One can safely assume that this problem would affect the results of stress echocardiography. In contrast, the problem of a window does not exist with MRI.Second, an expert sonographer is essential. The failure to detect regional abnormalities (which reduces sensitivity) is overshadowed only by the mistaken detection of abnormal wall motion where none exists (which reduces specificity), leading to inappropriate treatments and the morbidity associated with unnecessary interventions.78 Thus, we open a Pandora's box. On the one hand, an echocardiographic technique that is safe, is relatively easy to use, can be performed at the bedside, and is inexpensive9 is quite attractive, but on closer inspection, it suffers from technical variability related in large part to sonographer skill. This factor becomes even more critical when one realizes that not only is abnormal regional wall motion a harbinger of adverse prognosis, but it is the very situation that stands to improve the most if correctly identified.78 Conversely, MRI acquires images without operator dependence.Finally, the physical limitations of 2D echocardiography must be considered. All 2D echo images are formed as a result of the perturbation of an ultrasound beam that traverses the heart. It is the reflection of this beam from myocardial interfaces that results in the echocardiographic images. With MRI, a beam is neither created nor deflected. High-frequency radio waves excite protons within the heart, which are detected in 3 dimensions to give exquisite anatomic resolution. It is important to recognize that with MRI, the body habitus has no important effect on resultant images. Thus, with MRI, there is no euphemism of a "poor acoustic window."Accordingly, the use of MRI has increased over the past decade. However, several echocardiographic investigators have recently "upped the ante" by improving myocardial resolution, introducing the application of second harmonic imaging to overcome the nonlinear acoustic response from the endocardium. Second harmonic imaging involves the analysis of the returning acoustic signal at a frequency exactly twice that of the transmitted (fundamental) frequency.1011 Initially, this approach was used to improve the utility of echogenic contrast imaging. Even in the absence of contrast material, second harmonic imaging has resulted in considerable improvement in endocardial border recognition.511 The addition of contrast medium to second harmonic imaging has been of incremental value, with improved delineation in some patients with poor acoustic windows.12With such remarkable technical advancement in echocardiography, one might be very surprised by the substantial number of "rejects" reported by Hundley and colleagues in this issue of Circulation.13 The authors used an innovative methodological approach. Rather than a more conventional approach that compares 2 techniques in 1 patient group, they recognized that such direct comparisons would not materially contribute to the existing body of evidence supporting the role of the CMR stress test. Choosing a collection of low-quality echocardiographic studies due to the "poor acoustic window" leads one to the following statement: if stress MRI could be shown to be advantageous in that difficult cohort, it would provide compelling testimony for the potential utility of stress MRI in standard practice.From a group of >2500 patients referred for 2D echocardiography stress testing, Hundley and coworkers identified 163 in whom suitable images were unattainable, even with the most advanced echocardiographic techniques, including second harmonic imaging, used in all and with contrast agent administered in 10%. In 90% of this group of 163 patients, the echocardiographers were not able to recognize >50% of the endocardial segments. In the remaining patients, 25% to 50% could not be recognized. To be fair, it should be noted that only patients without contraindications for MRI (pacemaker, intracranial metal, or claustrophobia) were considered eligible for the study. Unfortunately, the number of patients with such contraindications was not provided. Likewise, the authors do not indicate the exact denominator on which the reference group was based. It is stated that commercially available MRI hardware with a standard phased-array surface coil, ECG gating, and an 8- to 12-second breathhold technique were used. It is interesting to note that although the best 2D echocardiographic technique was used, a less than state-of-the-art MRI approach was used for this comparison. Moreover, MRI has been soundly criticized for the incidence of claustrophobia, and dobutamine would be expected to accentuate this effect. Nevertheless, not only did 42 patients require the addition of atropine to reach maximal predicted heart rate, but only 4 patients were unable to complete the test because of anxiety. Interestingly, another criticism of MRI is the time required for image acquisition (with older systems). The authors completed the CMR stress study in an average of 53 minutes.The MRI study group was not ideal. Forty percent of the patients were markedly overweight (>150% of their ideal body weight); 32% had prior CABG; and 21% had chronic obstructive pulmonary disease. Additionally, 97 patients (58%) had preexisting wall motion abnormalities at rest, which makes it more difficult to detect changes with stress.14 Because echocardiographic images presently interrogate in 2D and MRI in 3D, it is not surprising that a third of the patients had a positive MRI stress test in an area that is traditionally poorly visualized by echocardiography (the apex of the posterolateral wall). With this in mind, one should wonder what the actual negative predictive value of a "normal" dobutamine stress echo is. This fact should send a message to the cardiovascular community. Closer inspection of this issue that focuses on interinstitutional agreement reveals that the reported sensitivity, specificity, and accuracy of dobutamine echocardiography versus coronary angiography at 5 centers were reasonable (76%, 87%, and 80%, respectively).14 On closer scrutiny, the results of stress echocardiography demonstrated agreement in at least 4 of 5 of the centers in only 73% of the patients. This provides a mean κ-value of 0.37, which indicates, at best, only fair interinstitutional agreement. Nevertheless, this result appears reasonable when agreement of stress test results, both positive and negative, was reported to be 100% only for patients with the highest image quality. However, agreement was only 43% for those with poor image quality. In fact, the highest yield was in the group at either extreme. A patient with either no CAD or advanced disease was much more likely to be correctly classified than if moderate disease was present. The authors of this multicenter analysis concluded that "The current heterogeneity in data acquisition and assessment criteria among different centers results in low interinstitutional agreement in interpretation of dobutamine stress echocardiograms."15Nonetheless, Hundley and coworkers13 identified 97 patients with abnormal and 56 patients with normal LV regional wall motion shortly after pharmacological stress testing. Thirty-six patients had inducible myocardial ischemia, whereas 103 did not. To the astute observer, this adds up to only 139. Adding 4 to this (the anxious patients) still leaves 10 patients unaccounted for. Ordinarily, this would be cause for alarm. Yet it is this group that serves to point out the fundamental advantages of MRI. Examination of this group of 10 patients illustrates the potential pitfalls with other imaging strategies for stress testing. MRI identified 1 patient with a previously unidentified aortic dissection and 2 patients with a mobile LV thrombus. These findings should be of considerable interest. If one estimates that 100 000 stress echoes are performed annually, such clinical discoveries would potentially translate into a substantial number of complications or even deaths. Indeed, it is remarkable that the outcomes of pharmacological stress testing, and even exercise testing, are not more disastrous.If there is a weakness in the study by Hundley et al,13 it is the lack of an overall comparison with the accepted standard, the coronary angiogram. Only 41 of 163 patients underwent coronary angiography. Yet, until 1999, there were, to the best of our knowledge, no larger studies comparing stress CMR with coronary angiography. Moreover, until early in 1999, no comparison had ever been performed between stress CMR and stress echocardiography. In February 1999, Nagel and coworkers15 directly compared >200 patients who had undergone coronary angiography (with a similar pretest probability as that in the present study) and demonstrated the diagnostic accuracy for the MR stress test (86%). From Hundley's group, the sensitivity and specificity for detecting an epicardial coronary artery lesion >50% narrowed were similar at 83% and 83%, respectively. Despite the high pretest probability for CAD, the small group used for comparison should not by itself provide an adequate study of sensitivity and specificity. However, the authors followed up these patients for an average of 8 months and noted that their cardiovascular occurrence–free survival was 97%.Should the results of Hundley and associates surprise us? The first study to report the application of the dobutamine MRI stress test was that of Pennell et al.16 Subsequently, additional studies have been reported.171819 As recently as February 1999, Circulation featured an elegant study by Nagel and colleagues.15 They performed the first simultaneous dobutamine stress comparison between 2D echocardiography and ultrafast MRI in 208 patients with suspected CAD. This study set the stage for the Hundley study, because the results of both 2D echocardiography and MRI were first prospectively compared with the "gold standard," coronary angiography. In the Nagel study, nearly 9% (18) patients could not be examined because of a poor acoustic window despite a similar use of second harmonic imaging. An equivalent number of patients could not be imaged by MRI (11 because of claustrophobia and 6 because of obesity). With a similar binary answer to whether the observed stenosis was greater or less than 50%, the authors showed that the use of stress CMR was not only comparable to that of stress echo, but in fact was superior. Both sensitivity and specificity were significantly greater with stress MRI than with stress echocardiography (86% versus 74% and 86% versus 70%, respectively; P<0.05 for both). The Nagel study served as a catalyst for the present study. Combined with its theoretical and physiological advantages, as well as its improved accuracy, results of these two studies indicate that stress MRI must be considered an important contender for diagnostic detection in patients with suspected ischemic heart disease detection.With data from more studies, the importance of the CMR stress test will continue to increase. This importance is not only based on its ability as a stress examination but is also related to documented improvements in the evaluation of mechanical function with myocardial tagging,20 its potential to assess regional myocardial perfusion,21 and the detection of myocardial ischemia and, potentially, viability with 31P-NMR spectroscopy.22The future of MRI is no longer just over the horizon. This insightful work by Hundley et al13 adds to the accumulating body of literature demonstrating the present ability and certain potential of a technology that will be the cornerstone for cardiovascular imaging in the next millennium. That mousetrap has been refined, and it is now at our doorstep.Reprint requests to Gerald M. Pohost, Mary Gertrude Waters Professor of Medicine, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Alabama, 1808 7th Ave S, Birmingham, AL 35294.The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association. References 1 Goldman MR, Pohost GM, Ingwall JS, Fossel ET. Nuclear magnetic resonance imaging: potential cardiac applications. Am J Cardiol.1980; 46:1278–1283.CrossrefMedlineGoogle Scholar2 Bonow RO, Dilsizian V. Thallium 201 for assessment of myocardial viability. Semin Nucl Med.1991; 21:230–241.CrossrefMedlineGoogle Scholar3 Pohost GM, Alpert NM, Ingwall JS, Strauss HW. Thallium redistribution: mechanics and clinical utility. Semin Nucl Med.1980; 10:70–93.CrossrefMedlineGoogle Scholar4 Brundage BH, Massie BM, Botvinick EH. Improved regional dysfunction after successful surgical revascularization. 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Circulation.1995; 92:9–10.CrossrefMedlineGoogle Scholar eLetters(0) eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate. Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page. Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited By Benza R, Biederman R, Murali S and Gupta H (2008) Role of Cardiac Magnetic Resonance Imaging in the Management of Patients With Pulmonary Arterial Hypertension, Journal of the American College of Cardiology, 10.1016/j.jacc.2008.08.033, 52:21, (1683-1692), Online publication date: 1-Nov-2008. Martin D and Semelka R (2007) Health effects of ionizing radiation from diagnostic CT imaging: Consideration of alternative imaging strategies, Applied Radiology, 10.37549/AR1492, (20-29) (2006) Ischemic Heart Disease: Stress and Vasodilator Testing Handbook of Cardiovascular Magnetic Resonance Imaging, 10.3109/9780203624371-13, (191-198) Sarma R and Pohost G (2006) Ischemic Heart Disease: Stress and Vasodilator Testing Handbook of Cardiovascular Magnetic Resonance Imaging, 10.3109/9780203624371.008, (171-178), Online publication date: 1-Oct-2006. Dymarkowski S, Bogaert J and Ni Y Ischemic Heart Disease Clinical Cardiac MRI, 10.1007/3-540-26997-5_8, (173-216) October 19, 1999Vol 100, Issue 16 Advertisement Article Information Metrics Copyright © 1999 by American Heart Associationhttps://doi.org/10.1161/01.CIR.100.16.1676 Originally publishedOctober 19, 1999 KeywordsEditorialsechocardiographymagnetic resonance imagingstress testingcoronary artery diseasePDF download Advertisement
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