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provided by Elsevier - Publisher Connector 1184 Letters to the Editor JACC: CARDIOVASCULAR IMAGING, VOL. 5, NO. 11, 2012 NOVEMBER 2012:1181–6

valve leaflets was restricted by the prosthetic stent resulting in 5. Astarci P, Desiron Q, Glineur D, et al. Transapical explantation of an severe central regurgitation stopping at the competent biopros- embolized transcatheter valve. Interact Cardiovasc Thorac Surg 2011; 13:1–2. thetic leaflets. An urgent valve-in-valve TAVI was planned but repeat TEE demonstrated further valve migration into LVOT APPENDIX that precluded safe implantation of the second overlapping For supplementary videos and their legends, please see the online version of this article. prosthesis. The patient underwent an emergent open- surgery during which the TAVI valve was found sitting in Effective Dose of PET/CT in LVOT in an unstable position. The native valve leaflets had 3 relatively flexible cusps with moderate calcification (Fig. 1E). Informed Consent Forms The aortic annulus had only trivial amount of calcium. The AV was replaced with 23-mm Perimount Magna (Edwards Life- The recent article by Terranova et al. (1) made important points sciences) tissue valve. The patient tolerated the surgery well. about informed consent. We agree with their conclusions that “the Valve dislodgment may occur in patients with less-than-severe development of simpler and more informative informed consent AV and root calcification that may be insufficient for anchoring the models and forms will gently force the doctor to be more aware of prosthesis (1,2), which was likely the case in our patient. Other what he/she does and the patient more aware of what he/she potential causes include stent malposition (3,4) and selection of an undergoes, enabling both to make more responsible choices” (1). undersized valve (5). In the present case, the correct 26-mm valve However, the authors might have begun with the correct facts to was selected based on 23-mm annulus, and its optimal position was avoid the gross error shown in Figure 3. At the bottom right of that confirmed with aortogram and TEE. Forces from the peripros- figure, the dose for rest/stress myocardial perfusion positron emis- thetic and central AV regurgitation, and from the residual over- sion (PET) is shown as approximately 1,000 “equiva- hanging native AV leaflets (2) likely contributed to the progression lent number of chest x-rays.” For a visual representation, the of valve migration. authors reproduced Figure 2A from our prior publication, featured This case demonstrates that routine 24-h follow-up echocardi- on the cover of that issue of the Journal of (2). As ography is essential to confirm correct TAVI valve position and we described in the middle of the second column on page 1,113 of function in order to prevent adverse consequences of delayed that paper (2), with further detail in Table 2 of a subsequent paper mechanical complications. In addition, it demonstrates that TAVI (3), the dose equivalent from our rest/stress cardiac PET scan using should be used with caution in patients with less-than-severe AV computed tomography (CT) attenuation correction is approxi- calcification. mately 7.5 mSv (using a low-dose helical CT at rest and a single post-stress cine CT in addition to the rubidium-82 tracer for PET). Ryoji Iida, MD, Robert C. Welsh, MD, Assuming a standard 0.02-mSv effective dose for a chest x-ray, Steven R. Meyer, MD, PhD, Benjamin D. Tyrrell, MD, our PET/CT scan equals roughly 375 chest x-rays, almost one- Dylan A. Taylor, MD, Miriam Shanks, MD* third of the value suggested in their Figure 3 (1). As such, PET/CT delivers less radiation than other modalities in their Table 3: *Division of Cardiology, University of Alberta Hospital, 8440-112 Street, single-photon emission computed tomography (SPECT) (using 2C2 Walter Mackenzie Health Sciences Centre, Edmonton, Alberta, either technetium-99m or thallium-201), CT angiogram, or per- T6G 2B7 Canada. E-mail: [email protected] cutaneous coronary intervention. As an additional error, the dose- http:dx.doi.org/10.1016/j.jcmg.2012.04.012 based order of tests on the x-axis of Figure 3 (invasive angiogram, SPECT, CT angiogram, PET) differs from their order in Table 3 Please note: Dr. Meyer is his site’s local investigator for Boehringer Ingelheim’s ReAlign trial investigating the use dabigatran in the anticoagulation of mechanical above it (SPECT with technetium-99m, CT angiogram, invasive heart valves. He personally receives no money for this trial. His site does receive stenting, SPECT with thallium-201). Therefore, Figure 3 was money to support their research coordinator for this trial. Dr. Shanks serves on the factually incorrect and failed the authors’ words for “simpler and advisory board for Servier Canada and has received honorarium from Astra Zeneca. All other authors have reported that they have no relationships relevant to the more informative informed consent.” contents of this paper to disclose. Moreover, quantitative PET perfusion imaging is a powerful guide to avoid the higher-dose procedures like SPECT imaging REFERENCES and CT or invasive by quantitatively defining physio- logical stenosis severity before these procedures are undertaken and 1. Clavel MA, Dumont E, Pibarot P, et al. Severe valvular regurgitation and identifying who will optimally benefit from them (4) at the lowest late prosthesis embolization after percutaneous aortic valve implantation. Ann Thorac Surg 2009;87:618–21. total radiation dose. 2. Pang PYK, Chiam PTL, Chua YL, et al. A survivor of late prosthesis migration and rotation following percutaneous transcatheter aortic valve Nils P. Johnson, MD, K. Lance Gould, MD* implantation. Eur J Cardiothorac Surg 2012;41:1195–6. 3. Ali AMA, Altwegg L, Horlick EM, et al. Prevention and management of transcatheter balloon-expandable aortic valve malposition. Catheter *Weatherhead PET Center for Preventing and Reversing Atheroscle- Cardiovasc Interv 2008;72:573–8. rosis, University of Texas Medical School at Houston, 6431 Fannin 4. Erdoes G, Wenaweser P, Kadner A, et al. Ventricular prosthesis Street, Room 4.256 MSB, Houston, Texas 77030. E-mail: embolization during transapical aortic valve implantation: the role of transesophageal in diagnosis and management. J Am [email protected] Soc Echocardiogr 2011;24:227.e1-4. http:dx.doi.org/10.1016/j.jcmg.2012.07.012 JACC: CARDIOVASCULAR IMAGING, VOL. 5, NO. 11, 2012 Letters to the Editor 1185 NOVEMBER 2012:1181–5

REFERENCES 3. Picano E, Vano E. The radiation issue in cardiology: the time for action is now. Cardiovasc Ultrasound 2011;9:35. 1. Terranova G, Ferro M, Carpeggiani C, et al. Low quality and lack of 4. Picano E. Stress echocardiography: a historical perspective. Am J Med clarity of current informed consent forms in cardiology: how to improve 2003;114:126–30. them. J Am Coll Cardiol Img 2012;5:649–55. 5. Picano E. Sustainability of . Education and debate. BMJ 2. Gould KL, Pan T, Loghin C, Johnson NP, Guha A, Sdringola S. 2004;328:578–80. Frequent diagnostic errors in cardiac PET/CT due to misregistration of CT attenuation and emission PET images: a definitive analysis of causes, consequences, and corrections. J Nucl Med 2007;48:1112–21. Intraplaque Hemorrhage, 3. Gould KL, Pan T, Loghin C, Johnson NP, Sdringola S. Reducing radiation dose in rest-stress cardiac PET/CT by single poststress cine CT RBC-Derived Cholesterol, for attenuation correction: quantitative validation. J Nucl Med 2008;49: 738–45. 4. Johnson NP, Gould KL. Physiological basis for angina and ST-segment and Plaque Progression change PET-verified thresholds of quantitative stress myocardial perfu- sion and coronary flow reserve. J Am Coll Cardiol Img 2011;4:990–8. Time to Move From Conjecture to Evidence? The interesting study by Sun et al. (1) in a recent issue of iJACC REPLY adds important new insights into the role of intraplaque hemor- rhage (IPH) in the natural history of carotid atherosclerosis. Serial We thank Drs. Johnson and Gould for their interest in our paper magnetic resonance imaging (MRI) over an extended period of (1). The “factually incorrect” doses reported in Figure 3 are indeed observation demonstrated that plaque growth after the occurrence correct. Positron emission tomography (PET) scans are usually of IPH was on average higher compared with the period before coupled with angiogram computed tomography (CT) and lead IPH (1). Notably, however, the rate of individual plaque growth ϩ precisely to a cumulative (CT angiogram PET scan) dose of differed substantially after the occurrence of IPH; some plaques approximately 20 mSv (1,000 chest x-rays) (2). PET scan alone actually showed regression despite evidence of new IPH, as shown (without CT) totals 2 mSv with 13-ammonia, and 3 mSv with in Figure 4 of Sun et al. (1). Thus, this study strongly links IPH to 82-rubidium. Obviously, reported doses are only reference doses, accelerated atherosclerosis, but it also raises a key issue: detection of and lower doses can be achieved with state-of-the-art CT technol- IPH alone may be a suboptimal predictor of the exact rate and ogy. On the other hand, for each test (from CT to single-photon magnitude of subsequent plaque growth. Therefore, identification emission computed tomography [SPECT] to coronary angiogra- of other factors that modulate the proatherogenic effect of IPH phy), substantially (up to 5-fold) higher doses can be recorded in might enhance the potential of MRI to accurately predict which the real world—especially when no systematic dose audit is imple- lesions with IPH will exhibit most pronounced and rapid growth. mented in the imaging laboratory (3). Based on the pathobiological sequelae of IPH (2), we suggest that We agree that a major advantage of PET myocardial perfusion differences in the cholesterol contents of erythrocyte membranes imaging is the lower radiation dose when compared with SPECT (2 mSv vs. 8 to 10 mSv). Obviously, this advantage may apply (CEM) are very likely to account, at least in part, for the observed mainly in cost-insensitive settings in which there is no technology differential plaque growth after IPH (1). or expertise for zero-dose cardiac testing with magnetic resonance The driving mechanisms of plaque progression and the main imaging or stress echocardiography—which provide similar diag- source of cholesterol that is accumulated in the developing plaque nostic and prognostic results at much lower cost using radiation- differ fundamentally in lesions without versus those with IPH. In free techniques (4). Only an explicit, systematic discussion of costs lesions without IPH, cholesterol in the plaque is derived mainly and risks would facilitate the identification of appropriate, sustain- from circulating blood lipoproteins; hence, higher blood cholesterol able medical imaging strategies (5), avoiding the use of high-cost, levels amplify the proatherogenic stimulus of adverse local hemo- high-risk techniques instead of low-cost, low-risk methods with dynamics, which is a major driving force of focal plaque develop- comparable benefit. ment in this setting (3). In contrast, in lesions with IPH extrava- sated erythrocytes contain abundant free cholesterol that is Giuseppina Terranova, MD, Eugenio Picano, MD, PhD* absorbed into the necrotic core and is conjectured to contribute centrally to plaque enlargement (2). Accordingly, in lesions with *Istituto di Fisiologia Clinica CNR, Via Moruzzi, 1, Pisa, Italy IPH, it seems highly plausible that increasing levels of CEM might 56124. E-mail: [email protected]. amplify the proatherogenic stimulus of IPH per se. http:dx.doi.org/10.1016/j.jcmg.2012.08.008 Of clinical importance, the CEM can be measured in the clinic (4,5) and is positively related to coronary plaque burden (4) and REFERENCES plaque instability (5). We hereby propose that the combination of CEM measurement with serial MRI may substantiate our current 1. Terranova G, Ferro M, Carpeggiani C, et al. Low quality and lack of clarity of current informed consent forms in cardiology: how to improve understanding of the role of IPH in plaque biology and, conse- them. J Am Coll Cardiol Img 2012;5:649–55. quently, may enhance risk-stratification of patients with evidence of 2. Kajander S, Joutsiniemi E, Saraste M, et al. Cardiac positron emission IPH. First, a finding of greatest plaque progression after IPH in tomography/computed tomography imaging accurately detects anatomi- cally and functionally significant . Circulation patients with higher compared with those with lower CEM levels 2010;122:603–13. would lend definitive mechanistic support to the long-standing