1110 Imaging tehniques CARDIAC IMAGING IN CORONARY ARTERY DISEASE: DIFFERING MODALITIES Take the online multiple hoie questions assoiated with this artile (see page 1104) FUNCTIONAL See end of artile for authors affiliations Correspondene to: Dr Jeroen J Bax, Department of Cardiology, Leiden University Medial Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; jbax@knoware.nl C J D Shuijf, L J Shaw, W Wijns, H J Lamb, D Poldermans, A de Roos, E E van der Wall, J J Bax Heart 2005; 91:1110 1117. doi: 10.1136/hrt.2005.061408 oronary artery disease (CAD) remains one of the leading auses of morbidity and mortality worldwide. Moreover, the disease is reahing endemi proportions and will put an enormous strain on health are eonomis in the near future. Non-invasive testing is important to exlude CAD with a high ertainty on the one hand, and to detet CAD with its funtional onsequenes at an early stage, to guide optimal patient management, on the other hand. For these purposes, non-invasive imaging tehniques have been developed and used extensively over the last years. Currently, the main fous of non-invasive imaging for diagnosis of CAD is twofold: (1) funtional imaging, assessing the haemodynami onsequenes of obstrutive oronary artery disease; and (2) anatomial imaging, visualising non-invasively the oronary artery tree. For funtional imaging, nulear ardiology, stress ehoardiography, and magneti resonane imaging (MRI) are used, whereas for anatomial imaging or non-invasive angiography, MRI, multislie CT (MSCT), and eletron beam CT (EBCT) are used. This manusript will update the reader on the urrent status of non-invasive imaging, with a speial fous on funtional imaging versus anatomial imaging for the detetion of CAD. The auraies of the different imaging modalities are illustrated using pooled analyses of the available literature data when available. IMAGING What information does funtional imaging provide? The hallmark of funtional imaging is the detetion of CAD by assessing the haemodynami onsequenes of CAD rather than by diret visualisation of the oronary arteries. For this purpose, regional perfusion or wall motion abnormalities are indued (or worsened) during stress, refleting the presene of stress indued ishaemia. Ishaemia indution is based on the priniple that although resting myoardial blood flow in regions supplied by stenoti oronary arteries is preserved, the inreased flow demand during stress annot be met, resulting in a sequene of events referred to as the ishaemi asade. 1 Initially perfusion abnormalities are indued, followed by diastoli and (at a later stage) systoli dysfuntion; only at the very end of the asade do ECG hanges and angina our (fig 1). Aordingly, the ourrene of perfusion abnormalities during stress may be more sensitive for the detetion of CAD than the indution of systoli dysfuntion (wall motion abnormalities). Currently, funtional imaging an be performed using (gated) single photon emission omputed tomography (SPECT) or positron emission tomography (PET), (ontrast) stress ehoardiography, and MRI; all tehniques allow integrated assessment of perfusion and funtion, at rest and after stress, and are used linially aording to loal availability and expertise. Types of stress An inreased demand an be ahieved through physial (biyle or treadmill) exerise, or (in patients unable to exerise) pharmaologial stress an be applied inluding adrenergi stimulation and vasodilation. Dobutamine (a b1 speifi agonist) inreases heart rate, ontratility, and arterial blood pressure, resulting in inreased myoardial oxygen demand. Dobutamine is administered intravenously at inremental doses of 5, 10, 20, 30, and 40 mg/kg/min at intervals of approximately five minutes. When the target heart rate is not reahed, atropine (0.25 1.0 mg) an be added; b blokers an be used as antidote. The vasodilators inlude dipyridamole and adenosine. Adenosine is a diret vasodilator, while dipyridamole inhibits ellular uptake and breakdown of adenosine. Dipyridamole therefore has a slower onset, while its effet lasts longer. For adenosine, a stepwise infusion protool an be used, onsisting of three-minute stages of 0.10, 0.14, and 0.18 mg/kg/min. Dipyridamole is
Figure 1 The ishaemi asade represents the sequene of pathophysiologial events following ishaemia. administered intravenously over four minutes (dose 0.56 mg/ kg), followed by a seond dose of 0.28 mg/kg. Aminophylline an be used as antidote. Safety of all pharmaologial stressors has been investigated extensively and, although ontinuous patient monitoring is required, severe ompliations are rare. 2 3 Whih modalities are available for funtional imaging? SPECT: assessment of perfusion Most experiene for assessment of perfusion in daily linial pratie has been obtained with SPECT. Three radiopharmaeutials are used: thallium-201, tehnetium-99m sestamibi, and tehnetium-99m tetrofosmin. Currently, the tehnetium- 99m labelled traers are preferred for their higher photon energy resulting in less attenuation artefats. Two sets of images are obtained: after stress and at rest. In general, reversible and irreversible defets are onsidered indiative of CAD. While reversible (stress indued) defets reflet ishaemia, irreversible (fixed) defets mainly represent infarted myoardium (fig 2). Images are interpreted visually or using automated quantifiation. For segmentation of the left ventrile (LV), a 17 segment model is developed, that an be applied to all funtional imaging modalities (fig 3). 4 To assess the diagnosti auray of SPECT for detetion of CAD, Underwood et al pooled 79 studies (n = 8964 patients) showing a weighted mean sensitivity and speifiity of 86% and 74% 5 (fig 4). The lower speifiity of SPECT may be (partially) attributable to referral bias that is, among Figure 3 Shemati presentation of the 17 segment model (adapted from Cerqueira et al 4 ). Besides its appliation for evaluation of SPECT images, this model an be applied to ehoardiography and MRI as well. Figure 4 Sensitivities and speifiities of SPECT imaging for the detetion of oronary artery disease, using different stressors (data are based on Underwood et al 5 ). patients with normal SPECT studies, only those with a high suspiion for CAD are referred for oronary angiography. To overome this problem, the normaly rate has been introdued, whih is the perentage of normal SPECT studies in a Figure 2 Example of a reversible defet on tehnetium-99m tetrofosmin SPECT. Panels A and B show short axis slies following stress and at rest, respetively. A reversible defet is present in the anterior and anterolateral regions (white arrows), illustrating stress induible ishaemia. A fixed perfusion defet, most likely representing sar tissue, is present in the posterolateral and inferior region. 1111
1112 population with a low likelihood of CAD. Pooled analysis of 10 studies (n = 543 patients) showed a normaly rate of 89%. 5 SPECT: assessment of systoli funtion The introdution of ECG gated SPECT imaging has allowed assessment of global and regional LV funtion in addition to perfusion. Diret omparisons between gated SPECT and MRI (or ehoardiography) showed exellent orrelations for assessment of LV ejetion fration, volumes, and regional wall motion. 6 7 Addition of these systoli funtion parameters has improved diagnosti auray. In partiular, artefats aused by soft tissue attenuation ould be unmasked by the demonstration of normal wall motion. This resulted in a substantial redution of false positive test results. 8 Integration of perfusion and systoli funtion by SPECT resulted in a signifiant redution (from 31% to 10%) of inonlusive tests, with an inrease in normaly rate from 74% to 93%. 9 Ehoardiography: assessment of systoli funtion Stress ehoardiography is readily available for the routine evaluation of (stress induible) wall motion abnormalities (fig 5); both resting and stress indued (or worsened) wall motion abnormalities are indiative of CAD. While stress indued (or worsened) wall motion abnormalities reflet ishaemia, resting wall motion abnormalities mainly represent infarted myoardium. A total of 15 studies (n = 1849 patients) used exerise ehoardiography to detet CAD, with a weighted mean sensitivity and speifiity of 84% and 82%. 10 Pooled data from 28 dobutamine ehoardiography studies (n = 2246 patients) showed a weighted mean sensitivity and speifiity of 80% and 84% to detet CAD. 10 The auraies for the different forms of stress ehoardiography are summarised in fig 6. It has been demonstrated that the ontinuation of b blokers redued sensitivity, whih ould be improved by addition of atropine. Also, sensitivity inreased in parallel to the number of diseased vessels, from 74% for one vessel disease to 92% for three vessel disease. Disadvantages of stress ehoardiography in general inlude a suboptimal aousti window in up to 25% of patients and dropout of the anterior and lateral walls. Improved endoardial border delineation an be obtained by using seond harmoni imaging and administration of intravenous ontrast agents. Ehoardiography: assessment of perfusion At the same time the use of ontrast agents has allowed the assessment of myoardial perfusion. After ontrast injetion, the mirobubbles remain in the vasular spae until they dissolve, and thus reflet the mirovasular irulation. Aordingly, their relative onentrations in different regions of the myoardium (as measured by signal intensity) reflet the relative myoardial blood volume in those regions. Similar to SPECT, resting perfusion defets suggest infarted myoardium, whereas stress indued perfusion defets indiate ishaemia (fig 7). Currently, many modifiations of Figure 6 Diagnosti auray of stress (exerise and dobutamine) ehoardiography (data based on Bax et al 10 ). Figure 5 Example of a stress indued wall motion abnormality on dobutamine ehoardiography. Panels A, B, C, and D are obtained during rest, low dose (10 mg/kg/min) and high dose dobutamine (40 mg/kg/min), and reovery. In the septal region (white arrow), normal wall motion is present at rest and during low dose dobutamine infusion, whereas dyskinesia is indued at high dose dobutamine.
Figure 7 Representative myoardial ontrast ehoardiography (MCE) and SPECT images obtained in a patient with anterior myoardial infartion, showing a larger perfusion defet by SPECT than MCE: (top left) apial four hamber MCE; (bottom left) apial two hamber MCE; (top right) apial four hamber SPECT; (bottom right) apial two hamber SPECT. Arrows delineate the area of dereased opaifiation/traer uptake. Reprinted from Juquois et al, 14 with permission of BMJ Publishing Group Ltd. the tehnology have been introdued and real time assessment of perfusion by ontrast ehoardiography is now possible. 11 Reent studies from experiened entres showed an exellent agreement between SPECT and myoardial ontrast ehoardiography for detetion of perfusion abnormalities, with a omparable sensitivity/speifiity for the detetion of CAD. 12 13 In a head-to-head omparison, Juquois et al 14 demonstrated an agreement of 62% between SPECT and ontrast ehoardiography for detetion of perfusion defets; the disagreement between the two tehniques was related to attenuation artefats and when these segments were exluded, the onordane improved to 82%. The integration of assessment of perfusion and funtion by ontrast ehoardiography performed at rest and after stress should provide optimal information on the detetion of CAD. Moir et al reently performed myoardial ontrast ehoardiography in addition to ombined dipyridamole exerise ehoardiography in 85 patients. 15 In 70 of these patients, data ould be ompared to onventional oronary angiography. Sensitivity for the detetion of CAD was signifiantly improved by the addition of ontrast from 74% to 91%; speifiity on the other hand showed a (non-signifiant) derease from 81% to 70%. Pooled analysis of the seven urrently available studies (n = 245 patients) on the additive value of perfusion imaging with ontrast to standard wall motion imaging showed similar results: the weighted mean sensitivity for detetion of CAD was 89% with a speifiity of 63%. 15 21 MRI: assessment of perfusion A relatively new tehnique to evaluate myoardial perfusion is MRI. For this purpose, 5 8 slies in the short axis Figure 8 Magneti resonane perfusion images during rest (panel A) and stress (panel B) showing a fixed perfusion defet in the inferior wall (white arrows). Images were aquired using a breath hold sensitivity enoding imaging tehnique during the first pass of an intravenously administered bolus of gadolinium ontrast agent. orientation are imaged during the first pass of a bolus of a ontrast agent. Imaging is repeated during pharmaologial stress. The applied ontrast agent, gadolinium, temporarily hanges the T1 relaxation time and thereby inreases the signal intensity of the perfused myoardium. In ontrast, ishaemi regions are identified as areas with little or redued signal intensity (fig 8). Pooling of 17 MRI perfusion studies (n = 502 patients, using either dipyridamole or adenosine stress) revealed a weighted mean sensitivity and speifiity of 84% and 85% (fig 9). 10 22 24 The high spatial resolution (approximately 2 mm) enables distintion between subendoardial and transmural perfusion defets. This is an important advantage over SPECT imaging, sine the ourrene of subendoardial perfusion defets may indiate ompromised blood flow at an early stage. For linial routine, images are evaluated visually, although semi-quantitative assessment is possible by alulation of the myoardial perfusion reserve index. In the 25 26 future, absolute quantifiation of myoardial perfusion may be allowed by the use of new intravasular ontrast agents. At present, however, quantitative analysis is still time onsuming and in order to fully exploit this modality in Figure 9 Diagnosti auray of perfusion and wall motion imaging MRI (data are based on several studies 10 22 24 ). For the perfusion studies, adenosine or dipyridamole were used, while dobutamine was administered during the wall motion studies. 1113
1114 standard linial routine, automated quantifiation algorithms are needed. MRI: assessment of systoli funtion In addition to myoardial perfusion, global and regional systoli LV funtion an also be obtained with MRI. The most widely used steady state free preession tehnique allows lear identifiation of endoardial borders aused by a high blood pool signal. In addition, the tomographi approah allows measurement of volumes without geometri assumptions, resulting in aurate measurements in severely distorted ventriles as well. Global and regional LV funtion an be obtained at rest and during stress (mainly using dobutamine). Pooled data of 10 dobutamine MRI studies (n = 654 patients) revealed a weighted mean sensitivity and 10 22 speifiity of 89% and 84% (fig 9). The exellent endoardial blood pool ontrast is partiularly benefiial for patients with poor ehoardiographi windows. Unfortunately, MRI is still limited to highly speialised entres and aquisition protools are still time onsuming, making the tehnique urrently unsuitable for evaluation of larger populations. No MRI studies with integration of systoli wall motion and perfusion to detet CAD are urrently available. ANATOMICAL IMAGING Why is anatomial imaging needed? Although a safe and aurate evaluation of patients with known or suspeted CAD is offered by funtional imaging, in a substantial number of patients anatomial imaging is needed. First, in patients with abnormal stress tests, diret visualisation of the oronary tree is still required for the definite diagnosis of CAD. Moreover, deisions on treatment strategy for example, whether the observed oronary lesions will be treated onservatively (medially) or more aggressively by means of perutaneous oronary intervention (PCI) or oronary artery bypass graft surgery (CABG) are based to a large extent on the findings of onventional oronary angiography. Also, in ertain subpopulations for example, diabetes funtional imaging may be less reliable. In these patients, diffuse atheroslerosis in all major epiardial vessels is frequently present, resulting in the absene of detetable perfusion abnormalities. Considering the fat that if CAD is present, prognosis is substantially worse ompared to non-diabeti individuals, knowledge of oronary anatomy is needed. Thus, besides detetion of haemodynami onsequenes, diret visualisation of the oronary anatomy is frequently needed. What is the urrent gold standard for anatomial imaging? At present, onventional x ray angiography with seletive ontrast injetion through ardia atheterisation remains the referene standard for the evaluation of the oronary arteries. Both spatial (0.2 mm) and temporal resolution (5 ms) of the tehnique are extremely high. In addition, the degree of luminal narrowing an be preisely measured using quantitative oronary angiography. Also, when during the diagnosti proedure the presene of one or more signifiant lesions is onfirmed, diret intervention is possible. Currently, approximately 3000 invasive diagnosti proedures per million inhabitants have been performed in Europe in 2001, whih resulted in perutaneous transluminal oronary angioplasty (PTCA) in only one out of three. 27 The development of non-invasive imaging of the oronary arteries would potentially failitate the aess to anatomial imaging and expand the indiations for revasularisation. What are the available modalities for non-invasive anatomial imaging? Currently, three tehniques are being developed for noninvasive angiography: MRI, MSCT, and EBCT. Although results are promising, all tehniques still have shortomings and limitations, hampering implementation in routine linial pratie. Sine the oronary arteries are small, tortuous, and show rapid movement during the ardia yle, demands on spatial and temporal resolution of the tehniques are tremendous. However, all tehniques are developing at a rapid pae and, as a result, image quality and diagnosti auray are ontinuously improving. Non-invasive angiography with MRI More than 10 years ago, the first results of non-invasive angiography were reported by Manning and olleagues. 28 The authors performed a omparison between two dimensional MRI and onventional angiography in 39 patients and observed a sensitivity and speifiity of 90% and 92%, respetively. With these first generation tehniques, data were aquired during onseutive breath holds, requiring substantial patient ooperation. To enable free breathing, navigator tehniques, that allow real time monitoring of diaphragm motion, have been developed. In ombination with the development of three dimensional aquisition tehniques, superior visualisation of oronary anatomy was ahieved. In fig 10, examples of non-invasive oronary angiography with three dimensional MR aquisition tehniques are provided. Pooled data from 28 studies (n = 903 patients) diretly omparing MRI with invasive angiography showed a weighted mean sensitivity of 72% with a speifiity of 87% (fig 11). 29 However, the perentage of interpretable segments is still insuffiient and exlusion of up to 30% of all segments has been reported, even with newer aquisition tehniques. Thus, full overage of the oronary arteries within a reasonable amount of time still annot be ahieved. Future developments in the area of oronary MR angiography, inluding higher field strengths (3T) and improved ontrast tehniques, suh as balaned steady state free preession tehniques and the development of blood pool Figure 10 Non-invasive oronary angiography with MRI. In panel A, a native right oronary artery (blak arrow) and a venous oronary bypass (white arrow) on the left anterior desending oronary artery an be observed. In ontrast, panel B depits the right oronary artery (white arrows) of a healthy volunteer. Images were aquired with a 1.5 T system, using T 2 preparation for bakground suppression during respiratory gating.
Figure 11 Diagnosti auray of non-invasive oronary angiography with MRI in the detetion of signifiant stenoses (data based on Shuijf et al 29 ). ontrast agents, will improve diagnosti auray. Moreover, extensive researh is direted towards assessment of plaque omposition as well as assessment of oronary flow, whih may potentially enable the tehnique to provide a omprehensive evaluation of both the presene and extent, as well as the funtional signifiane, of CAD. Non-invasive angiography with MSCT More reently, MSCT has emerged as a potential modality for non-invasive angiography. Initial studies with four slie tehnology showed promising results, with sensitivities and speifiities ranging from 66 90% and from 71 99%, respetively. 29 However, the tehnique was still hampered by the high perentage of segments (approximately 25%) with nondiagnosti quality. Modern systems have an x ray gantry rotation time of 400 ms or less while data are aquired using 16 or more parallel detetors with submillimetre ollimation (fig 12). At present, 11 studies with 16 slie tehnology have been reported. 29 As expeted, onsiderably more segments were available for evaluation, approximately 96% of segments. Furthermore, an inrease in sensitivity from (on average) 80% to 88% ould also be observed with no loss in sensitivity (fig 13). With 64 slie systems that have reently beome available, both the perentage evaluable segments and sensitivity are expeted to improve further. Sine data are aquired during onseutive heartbeats, a stable heart rate is important in order to obtain good image quality. Similar to MRI, the tehnique has therefore limited value in patients with atrial fibrillation or frequent extrasystoli ontrations, although for the latter raw data an sometimes be manually orreted. Other ontraindiations to MSCT inlude renal failure or pregnany due to the administration of ontrast agent and the use of ionising radiation, respetively. Moreover, the radiation dose assoiated with an MSCT examination is still onsiderably high and remains an important limitation of the tehnique. To redue radiation dose, prospetive x ray tube modulation or more dediated filtering may be applied while other dose redution strategies are urrently investigated. Non-invasive angiography with EBCT The first experienes with oronary angiography with EBCT were desribed in 1995. 30 Instead of a mehanially rotating tube, x rays are reated through an eletron beam that is guided along a 210 tungsten target ring in the gantry. As a result, a high resolution image is aquired in 50 100 ms. The aquisition of serial overlapping ross setional images with a 1.5 or 3.0 mm slie thikness is performed during the administration of an iodinated ontrast agent, using Figure 12 Non-invasive oronary angiography with 16 slie MSCT. In panel A, a urved multiplanar reonstrution of a left anterior desending oronary artery is depited. A proximal stenosis an be observed (white arrow), whih was onfirmed by invasive angiography (panel B, blak arrow). An example of a patent right oronary artery is provided in panel C. In panel D, the orresponding oronary angiogram is shown. Figure 13 Diagnosti auray of non-invasive oronary angiography with four and 16 slie MSCT in the detetion of signifiant stenoses (data based on Shuijf et al 29 ). prospetive ECG triggering. To over the whole heart, 40 50 slies are neessary, typially requiring a breath hold of 30 40 seonds, depending on the heart rate. Pooled analysis of the 10 available studies (n = 583 patients) omparing ontrast enhaned EBCT angiography with onventional angiography demonstrated a weighted mean sensitivity and speifiity of 87% and 91%, respetively 31 ; 16% of the oronary arteries were non-interpretable (fig 14). Similar to other non-invasive oronary angiography tehniques, distal oronary segments are relatively more diffiult to image, while oronary artery motion and breathing artefats also frequently our. Coronary artery alium soring Another, more frequently performed appliation of EBCT is the quantifiation of alium in the oronary arteries. The presene of alium serves as a marker of atheroslerosis. The absene of alium virtually exludes atheroslerosis, and no further analysis is needed. This is also supported by the very 1115
1116 Figure 14 Image quality and diagnosti auray of EBCT (data based on Budoff et al 31 ). low rate of ardia events in patients without alium on EBCT; Raggi et al 32 demonstrated in 4800 patients without diabetes and no oronary alium that the five year survival was 99.4%. By multivariate analysis, the presene of oronary alium ontributed to the predition of all ause mortality in 9474 asymptomati and non-diabeti subjets to the same extent as age, hyperlipidaemia, hypertension, and ative smoking. Moreover, Berman et al 33 showed that, 1% of patients with minimal oronary alium had ishaemia on SPECT imaging. However, the presene of oronary alium only indiates atheroslerosis in general and requires additional evaluation. In partiular, no relation between the extent of oronary alium and stenosis severity has been shown. 31 CONCLUSION As disussed in this manusript, the emphasis of noninvasive imaging is on funtional imaging (assessing the haemodynami onsequenes of obstrutive CAD that is, Cardia imaging in oronary artery disease: key points In the presene of a signifiant oronary artery stenosis, a sequene of events alled the ishaemi asade ours during stress: first perfusion abnormalities our, followed by wall motion abnormalities, while ECG hanges and angina our at a later stage Non-invasive imaging to assess oronary artery disease an be divided into funtional imaging and anatomial imaging Funtional imaging aims at assessment of the haemodynami onsequenes of obstrutive oronary artery disease; the available tehniques are nulear imaging (mainly SPECT), stress ehoardiography (with the optional use of intravenous ontrast agents), and magneti resonane imaging (MRI) Currently, all three funtional imaging modalities allow omprehensive evaluation inluding assessment of both perfusion and wall motion For non-invasive anatomial imaging, or non-invasive oronary angiography, MRI, multislie CT (MSCT) and eletron beam CT (EBCT) are used. These modalities do not yet assess the haemodynami onsequenes of oronary artery disease In the future, integrated anatomial and funtional imaging may eventually result in superior detetion and evaluation of patients with suspeted and known oronary artery disease ishaemia) and anatomi imaging (non-invasive angiography). Over the past deades, non-invasive imaging for the detetion of CAD has mainly relied on SPECT and stress ehoardiography, funtional imaging tehniques to assess perfusion or wall motion abnormalities (as markers of CAD), respetively. Over time, these tehniques were onsidered omplementary, rather than ompetitive, sine they provided different information. At present, however, both SPECT and ehoardiography have developed into omprehensive imaging tehniques, and eah an assess both perfusion and wall motion. Similarly, MRI an also assess both perfusion and wall motion. Still, for proper patient management, knowledge on oronary anatomy is frequently needed and patients are subsequently referred for invasive angiography. More reently, emphasis has shifted to anatomi imaging using MRI, MSCT, and EBCT allowing non-invasive angiography. These tehniques an adequately rule out CAD, but do not provide any information on the haemodynami onsequenes of the oronary artery stenoses if present. Therefore, it is likely that in the near future emphasis will shift to integration of funtional and anatomial imaging. For this purpose, the diagnosti performane of PET-CT is urrently being evaluated, whih integrates non-invasive angiography with perfusion imaging (to visualise the haemodynami onsequenes of the anatomi abnormalities). Although PET allows absolute quantifiation of perfusion, SPECT may be more pratial in daily linial routine, and it is antiipated that MSCT integrated with SPECT systems will beome available in the future. Similarly, fusion of non-invasive angiography by MRI with funtional imaging by MRI (assessment of perfusion and/or wall motion) an potentially provide similar information. Future studies should assess the additional linial value of integrated anatomial and funtional imaging, whih may eventually result in superior detetion and evaluation of patients with suspeted and known CAD.... Authors affiliations J D Shuijf*, E E van der WallÀ, J J Bax, Department of Cardiology, Leiden University Medial Center, Leiden, the Netherlands H J Lamb, A de Roos, Department of Radiology, Leiden University Medial Center, Leiden, the Netherlands L J Shaw, Atlanta Cardiovasular Researh Institute, Atlanta, USA W Wijns, Cardiovasular Center, Aalst, Belgium D Poldermans, The Thorax Center, Erasmus Medial Centre, Rotterdam, the Netherlands *Also at the Department of Radiology, Leiden University Medial Center, Leiden, and the Interuniversity Cardiology Institute of the Netherlands, Utreht, the Netherlands ÀAlso at the Interuniversity Cardiology Institute of the Netherlands, Utreht, the Netherlands In ompliane with EBAC/EACCME guidelines, all authors partiipating in Eduation in Heart have dislosed potential onflits of interest that might ause a bias in the artile This work was finanially supported by The Netherlands Heart Foundation, grant number 2002B105. 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