Anatomic and Functional Assessment of Coronary Artery Disease
2009; Lippincott Williams & Wilkins; Volume: 2; Issue: 3 Linguagem: Inglês
10.1161/circimaging.109.873489
ISSN1942-0080
AutoresJames K. Min, Daniel S. Berman,
Tópico(s)Acute Myocardial Infarction Research
ResumoHomeCirculation: Cardiovascular ImagingVol. 2, No. 3Anatomic and Functional Assessment of Coronary Artery Disease Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBAnatomic and Functional Assessment of Coronary Artery DiseaseConvergence of 2 Aims in a Single Setting James K. Min, MD and Daniel Berman, MD James K. MinJames K. Min From the Department of Medicine and Radiology, Weill Medical College of Cornell University, The New York Presbyterian Hospital, New York, NY; the Departments of Imaging (Division of Nuclear Medicine), Department of Medicine (Division of Cardiology), and CSMC Burns & Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, Calif; and the Department of Medicine, University of California at Los Angeles, School of Medicine, Los Angeles, Calif. and Daniel BermanDaniel Berman From the Department of Medicine and Radiology, Weill Medical College of Cornell University, The New York Presbyterian Hospital, New York, NY; the Departments of Imaging (Division of Nuclear Medicine), Department of Medicine (Division of Cardiology), and CSMC Burns & Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, Calif; and the Department of Medicine, University of California at Los Angeles, School of Medicine, Los Angeles, Calif. Originally published1 May 2009https://doi.org/10.1161/CIRCIMAGING.109.873489Circulation: Cardiovascular Imaging. 2009;2:163–165Between two worlds life hovers like a star, twixt night and morn, upon the horizon's verge.— —Lord ByronConventional noninvasive methods of evaluation of individuals with suspected coronary artery disease (CAD) have relied on functional testing by an array of modalities, including exercise treadmill testing, stress echocardiography and myocardial perfusion imaging (MPI) with single-photon emission computed tomography (SPECT),1 or positron-emission tomography (PET).2 In their most commonly used applications, these modalities are useful for assessing myocardial perfusion and function at rest and in response to exercise or pharmacological intervention, providing valuable information regarding the presence or absence of obstructive CAD, future cardiac events, and predicting benefit from appropriate therapies.Article see p 174Among the wide range of functional imaging tests, SPECT-MPI has emerged as the most commonly used modality—accounting for nearly 90% of imaging stress tests performed in the United States each year.3 Early studies examining SPECT indicate that myocardial perfusion is reduced in the presence of a ≥70% intraluminal epicardial stenosis.4 Beyond its diagnostic potential, the widespread use of SPECT-MPI stems from its robust ability for prognostic risk stratification, such that individuals with normal SPECT have very low rates of near- and intermediate-term adverse CAD events, whereas those with severely abnormal SPECT-MPI have high rates of adverse CAD events.5 Further, SPECT may identify patients who may most benefit from invasive coronary angiography (ICA) and coronary revascularization in addition to medical therapy versus those who would benefit from medical therapy alone.6,7After early validation as a sensitive method for assessing reduction in coronary flow reserve,8 PET-MPI has also become a clinically useful method for the same applications as SPECT-MPI, adding higher resolution imaging and the ability to image ventricular function during peak stress.9,10 Given its ability for high count-rate dynamic studies, PET promises a noninvasive assessment of coronary flow reserve and absolute coronary flow.11Although SPECT and PET function-based evaluations for flow-limiting CAD lesions have become the standard, these approaches are costly. Additionally, SPECT misclassifies a significant proportion of patients as low risk12,13 and has a false-positive rate such that the proportion of patients undergoing ICA after SPECT, in whom no obstructive CAD is identified, remains substantial. Recent estimates indicate that >50% of individuals referred for elective ICA do not have obstructive CAD; patients with equivocal or positive SPECT studies constitute a large proportion of these patients.14Recently, coronary computed tomography angiography (CCTA) has emerged as an accurate anatomic method for detection of CAD.15,16,17 Particularly for individuals without known CAD, the sensitivity to detect as well as the negative predictive value to exclude obstructive CAD at both the 50% and 70% intraluminal stenosis thresholds approaches 100%. However, specificity and positive predictive value of current-generation CCTA interpretation have been less robust, reflecting a higher than desirable rate of false-positives. In this regard, prior reports have suggested that interpretation of CCTA is commonly associated with a general overestimation of CAD stenosis severity, and recent data suggest an inability to differentiate between slight differences in stenosis severity (eg, 50% to 69% versus ≥70%).18 Because anatomic definitions of CAD significance are generally defined at the 70% stenosis threshold, some have contended that the use of CCTA may simply increase rates of unnecessary ICA and coronary revascularization.19 Furthermore, dense coronary calcification often makes it impossible to evaluate luminal stenosis in patients with CAD. Thus, there is concern that CCTA will also result in an increase in the rate of unnecessary ICA.Thus, there are strengths and limitations of both the SPECT and PET functional approaches and the anatomic approach of CCTA. It has become common practice to begin an evaluation with one of these modalities and to perform imaging with the complementary modality when the results of the first test are in question.20 Alternatively, several recent studies have evaluated the feasibility of hybrid imaging by SPECT-CT or PET-CT, with aims to maximize the advantages of both functional and anatomic imaging methods.21,22 These early studies suggest enhanced diagnostic test performance by hybrid imaging, as compared with functional or anatomic imaging alone, for the detection of "functionally significant" stenoses. It is very difficult, however, to know a priori that a patient will need both the PET or SPECT and CCTA, and performance of both tests increases radiation burden and costs. Thus, an active area of scientific pursuit has been to identify a "1-stop shop" that is capable of concurrently evaluating coronary artery stenosis presence and severity and myocardial perfusion by a single modality during a single examination.23In this issue of Circulation: Cardiovascular Imaging, George et al24 examine single-modality imaging by CCTA for assessment of both anatomic coronary artery stenosis severity and functional myocardial perfusion. In this pilot study of 40 patients with abnormal SPECT undergoing rest and adenosine stress CCTA by either 64- or 256-detector-row CCTA, diagnostic performance of CCTA and CT perfusion (CTP) (CCTA/CTP) was compared for 27 individuals undergoing ICA, using the combination of quantitative coronary angiography (QCA) and SPECT-MPI (QCA/SPECT) as a reference standard. Per-patient diagnostic sensitivity, specificity, positive predictive value, and negative predictive value were good, with values of 86%, 92%, 92%, and 85%, respectively. These preliminary results are consistent with data derived from a canine model from the same group, in which the transmural perfusion ratio (TPR) of subendocardial to subepicardial attenuation density correlated with myocardial blood flow as measured by microspheres.25This study represents a large step forward for the field of CCTA, demonstrating the potential feasibility of myocardial perfusion imaging by CCTA using the TPR. Nevertheless, this study is not unlike many early "proof of principle" studies, which tend to raise as many questions as they seek to answer.In the present analysis, the study cohort represented a selective population of individuals prechosen because of an abnormal SPECT. This criterion alone probably contributed to the escalation of the diagnostic performance of CCTA/CTP caused by referral bias. Further, the overall study population was small. Indeed, only 43 patients underwent CCTA/CTP, and, among these, less than two thirds of patients eventually underwent ICA for diagnostic confirmation. Diagnostic performance of the CCTA/CTP technique was based solely on patients undergoing ICA, thus further exacerbating referral bias. Compounding these biases was a heterogeneous mixture of individuals both with and without known CAD.In the study, the definition of a normal TPR was based on 14 patients who underwent CCTA/CTP who did not exhibit >30% stenosis by CCTA. This ratio in "normal" individuals was 1.12, and an abnormal TPR was then designated as <0.99, which represented only 1 standard deviation below that considered normal. A number of potential limitations arise from these definitions, including a lack of a validation cohort for the derived normal patients, inclusion of the 14 normal patients into the overall cohort, and the classification of a sizable proportion of patients within 2 standard deviations from the mean 1.12 ratio as abnormal.Although the TPR may theoretically enhance detection of subendocardial ischemia, it is unclear how it would perform for transmural ischemia. In this scenario, a subendocardial to subepicardial ratio may be decreased, which may result in a falsely elevated TPR. It is this issue of per–myocardial segment balanced reduction of perfusion that may result in discordance between CCTA/CTP and QCA/SPECT.The issue of balanced reduction of perfusion that has been described with SPECT12 was addressed by the authors, but only as it related to SPECT. For patients with QCA-confirmed 3-vessel or left main disease, perfusion deficits identified by the CCTA/CTP strategy were considered true-positives—even if SPECT perfusion was normal—in an attempt to avoid "penalizing" CCTA/CTP for SPECT misdiagnosis of balanced ischemia. This type of analysis is problematic because QCA/SPECT had been defined a priori as the reference standard and probably serves to falsely elevate the diagnostic performance of CCTA/CTP. Just as artifacts are well known with SPECT, CTP can produce artifactual perfusion defects. CTP performed during adenosine infusion increases heart rate and thus the likelihood of artifactual reductions in CT attenuation densities caused by heart motion, partial volume effects, and beam-hardening artifacts. The authors used a beam-hardening correction software, although the performance of CCTA/CTP with and without the software was not discussed in the study results.A potentially interesting analysis would have been a comparison of the results of CCTA/CTP versus QCA/SPECT for both 64- and 256-detector-row CT. The wide-area 256-detector CT permits single axial image acquisition of the heart in less than a single heartbeat. Whether simultaneous imaging of all myocardial segments renders different diagnostic performance as compared with sequential imaging of the heart in 4 to 7 heartbeats, as is required by 64-detector-row CT, remains unknown because this analysis was not performed (probably because of the small numbers of patients). Finally, in keeping with prior studies, it would have been valuable to determine the incremental value of CTP to CCTA alone for the diagnosis of QCA/SPECT-defined obstructive CAD.Despite its limitations, this study represents a significant advance for the field of CCTA. Criticisms of CCTA have focused on the inability of CCTA to assess the "functional" significance of an identified stenosis. In their pilot study, George et al demonstrated that this assessment can be accomplished without additional testing modalities. Clearly, a great deal of work in refining and validating the approach is needed before this approach becomes a clinical reality. Nonetheless, this pilot study provides important early evidence that CCTA may hold the potential to serve as a single modality for the concurrent assessment of both anatomic coronary stenoses and their functional physiological significance.The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.DisclosuresDr Berman has received grant/research from Lantheus (formerly BMS), Astellas Healthcare, GE/Amersham, and Siemens; consulting fees/honoraria from Astellas, Flouro Pharma, and Magellan; royalty income from CSMC (software royalties); and equity interest from Spectrum Dynamics.FootnotesCorrespondence to Daniel S. Berman, MD, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Room 1258, Los Angeles, CA 90048. E-mail [email protected] References 1 Berman DS, Shaw LJ, Hachamovitch R, Friedman JD, Polk DM, Hayes SW, Thomson LE, Germano G, Wong ND, Kang X, Rozanski A. Comparative use of radionuclide stress testing, coronary artery calcium scanning, and noninvasive coronary angiography for diagnostic and prognostic cardiac assessment. Semin Nucl Med. 2007; 37: 2–16.CrossrefMedlineGoogle Scholar2 Di Carli MF, Hachamovitch R. New technology for non-invasive evaluation of coronary artery disease. Circulation. 2007; 115: 1464–1480.LinkGoogle Scholar3 IMV 2007 Nuclear Medicine Market Summary Report. 2007.Google Scholar4 Gould KL, Lipscomb K. Effects of coronary stenoses on coronary flow reserve and resistance. Am J Cardiol. 1974; 34: 48–55.CrossrefMedlineGoogle Scholar5 Berman DS, Hachamovitch R, Shaw LJ, Friedman JD, Hayes SW, Thomson L, Fieno DS, Germano G, Slomka P, Wong ND, Kang X, Rozanski A. Roles of nuclear cardiology, cardiac computed tomography, and cardiac magnetic resonance: assessment of patients with suspected coronary artery disease. J Nuc Med. 2006; 47: 74–82.MedlineGoogle Scholar6 Hachamovitch R, Berman DS, Shaw LJ, Kiat H, Cohen I, Cabico JA, Friedman J, Diamond GA. Incremental prognostic value of myocardial perfusion single photon emission computed tomography for the prediction of cardiac death: differential stratification for risk of cardiac death and myocardial infarction. Circulation. 1998; 97: 535–543.CrossrefMedlineGoogle Scholar7 Shaw LJ, Berman DS, Maron DJ, Mancini GB, Hayes SW, Hartigan PM, Weintraub WS, O'Rourke RA, Dada M, Spertus JA, Chaitman BR, Friedman J, Slomka P, Heller GV, Germano G, Gosselin G, Berger P, Kostuk WJ, Schwartz RG, Knudtson M, Veledar E, Bates ER, McCallister B, Teo KK, Boden WE. Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy. Circulation. 2008; 117: 1283–1291.LinkGoogle Scholar8 Demer LL, Gould KL, Goldstein RA, Kirkeeide RL, Mullani NA, Smalling RW, Nishikawa A, Merhige ME. Assessment of coronary artery disease severity by positron emission tomography. Comparison with quantitative arteriography in 193 patients. Circulation. 1989; 79: 825–835.CrossrefMedlineGoogle Scholar9 Di Carli MF, Asgarzadie F, Schelbert HR, Brunken RC, Rokhsar S, Maddahi J. Relation of myocardial perfusion at rest and during pharmacologic stress to the PET patterns of tissue viability in patients with severe left ventricular dysfunction. J Nucl Cardiol. 1998; 5: 558–566.CrossrefMedlineGoogle Scholar10 Bateman TM, Heller GV, McGhie AI, Friedman JD, Case JA, Bryngelson JR, Hertenstein GK, Moutray KL, Reid K, Cullom SJ. Diagnostic accuracy of rest/stress ECG-gated Rb-82 myocardial perfusion PET: comparison with ECG-gated Tc-99m sestamibi SPECT. J Nucl Cardiol. 2006; 13: 24–33.CrossrefMedlineGoogle Scholar11 Campisi R, Di Carli MF. Assessment of coronary flow reserve and microcirculation: a clinical perspective. J Nucl Cardiol. 2004; 11: 3–11.CrossrefMedlineGoogle Scholar12 Berman DS, Kang X, Slomka PJ, Gerlach J, Yang L, Hayes SW, Friedman JD, Thomson LEJ, Germano G. Underestimation of extent of ischemia by gated SPECT myocardial perfusion imaging in patients with left main coronary artery disease. J Nucl Cardiol. 2007; 14: 521–528.CrossrefMedlineGoogle Scholar13 Lima RS WD, Goode AR, Siadaty MS, Ragosta M, Beller GA, Samady H. Incremental value of combined perfusion and function over perfusion alone by gated SPECT myocardial perfusion imaging for detection of severe three-vessel coronary artery disease. J Am Coll Cardiol. 2003; 42: 64–70.CrossrefMedlineGoogle Scholar14 IMV 2006 Cardiac Catheterization Lab Market Summary Report. 2006.Google Scholar15 Budoff MJ, Dowe D, Jollis JG, Gitter M, Sutherland J, Halamert E, Scherer M, Bellinger R, Martin A, Benton R, Delago A, Min JK. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol. 2008; 52: 1724–1732.CrossrefMedlineGoogle Scholar16 Meijboom WB, Meijs MF, Schuijf JD, Cramer MJ, Mollet NR, van Mieghem CA, Nieman K, van Werkhoven JM, Pundziute G, Weustink AC, de Vos AM, Pugliese F, Rensing B, Jukema JW, Bax JJ, Prokop M, Doevendans PA, Hunink MG, Krestin GP, de Feyter PJ. Diagnostic accuracy of 64-slice computed tomography coronary angiography: a prospective, multicenter, multivendor study. J Am Coll Cardiol. 2008; 52: 2135–2144.CrossrefMedlineGoogle Scholar17 Miller JM, Rochitte CE, Dewey M, Arbab-Zadeh A, Niinuma H, Gottlieb I, Paul N, Clouse ME, Shapiro EP, Hoe J, Lardo AC, Bush DE, de Roos A, Cox C, Brinker J, Lima JA. Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med. 2008; 359: 2324–2336.CrossrefMedlineGoogle Scholar18 Cheng V, Gutstein A, Wolak A, Suzuki Y, Dey D, Gransar H, Thomson LEJ, Hayes SW, Friedman JD, Berman DS. Moving beyond binary grading of coronary arterial stenoses on coronary CT angiography: insights for the imager and referring clinician. JACC Cardiovasc Imaging. 2008; 1: 460–471.CrossrefMedlineGoogle Scholar19 Redberg RF, Walsh J. Pay now, benefits may follow–the case of cardiac computed tomographic angiography. N Engl J Med. 2008; 359: 2309–2311.CrossrefMedlineGoogle Scholar20 Berman DS. Fourth annual Mario S. Verani MD Memorial Lecture: noninvasive imaging in coronary artery disease: changing roles, changing players. J Nucl Cardiol. 2006; 13: 457–473.CrossrefMedlineGoogle Scholar21 Rispler S, Keidar Z, Ghersin E, Roguin A, Soil A, Dragu R, Litmanovich D, Frenkel A, Aronson D, Engel A, Beyar R, Israel O. Integrated single-photon emission computed tomography and computed tomography coronary angiography for the assessment of hemodynamically significant coronary artery lesions. J Am Coll Cardiol. 2007; 49: 1059–1067.CrossrefMedlineGoogle Scholar22 Sampson UK, Dorbala S, Limaye A, Kwong R, Di Carli MF. Diagnostic accuracy of rubidium-82 myocardial perfusion imaging with hybrid positron emission tomography/computed tomography in the detection of coronary artery disease. J Am Coll Cardiol. 2007; 49: 1052–1058.CrossrefMedlineGoogle Scholar23 Becker CR. Cardiac CT: a one-stop-shop procedure? Eur Radiol. 2006; 16 (Suppl 7): M65–M70.CrossrefMedlineGoogle Scholar24 George RT, Arbab-Zadeh A, Miller JM, Kitagawa K, Chang HJ, Bluemke DA, Becker L, Yousuf O, Texter J, Lardo AC, Lima JAC. Adenosine stress 64- and 256-row detector computed tomography angiography and perfusion imaging: a pilot study evaluating the transmural extent of perfusion abnormalities to predict atherosclerosis causing myocardial ischemia. Circ Cardiovasc Imaging. 2009; 2: 174–182.LinkGoogle Scholar25 George RT, Silva C, Cordeiro MA, DiPaula A, Thompson DR, McCarthy WF, Ichihara T, Lima JA, Lardo AC. Multidetector computed tomography myocardial perfusion imaging during adenosine stress. J Am Coll Cardiol. 2006; 48: 153–160.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Xaplanteris P, Barbato E and De Bruyne B (2016) Catheter-based functional metrics of the coronary circulation, Journal of Nuclear Cardiology, 10.1007/s12350-016-0652-7, 24:4, (1178-1189), Online publication date: 1-Aug-2017. Pang C, Alcock R, Pilkington N, Reis T and Roobottom C (2016) Determining the haemodynamic significance of arterial stenosis: the relationship between CT angiography, computational fluid dynamics, and non-invasive fractional flow reserve, Clinical Radiology, 10.1016/j.crad.2016.03.001, 71:8, (750-757), Online publication date: 1-Aug-2016. Toth G, Ntalianis A, Ntarladimas Y, de Booij M, De Winter O, Barbato E, Pilet B, Van Mieghem C, Wijns W and De Bruyne B (2014) Effective radiation doses associated with non-invasive versus invasive assessment of coronary anatomy and physiology, Catheterization and Cardiovascular Interventions, 10.1002/ccd.25729, 85:7, (1173-1181), Online publication date: 1-Jun-2015. Bamberg F (2012) Why Are We Interested in Myocardial Perfusion? CT Imaging of Myocardial Perfusion and Viability, 10.1007/174_2012_765, (45-55), . Xu Y, Nakazato R, Hayes S, Hachamovitch R, Cheng V, Gransar H, Miranda-Peats R, Hyun M, Shaw L, Friedman J, Germano G, Berman D and Slomka P (2011) Prognostic value of automated vs visual analysis for adenosine stress myocardial perfusion SPECT in patients without prior coronary artery disease: A case-control study, Journal of Nuclear Cardiology, 10.1007/s12350-011-9449-x, 18:6, (1003-1009), Online publication date: 1-Dec-2011. Xu Y, Hayes S, Ali I, Ruddy T, Wells R, Berman D, Germano G and Slomka P (2010) Automatic and visual reproducibility of perfusion and function measures for myocardial perfusion SPECT, Journal of Nuclear Cardiology, 10.1007/s12350-010-9297-0, 17:6, (1050-1057), Online publication date: 1-Dec-2010. May 2009Vol 2, Issue 3 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCIMAGING.109.873489PMID: 19808586 Originally publishedMay 1, 2009 KeywordsEditorialsimagingPDF download Advertisement SubjectsChronic Ischemic Heart DiseaseComputerized Tomography (CT)Nuclear Cardiology and PET
Referência(s)