DEBATE ARTICLE Computed tomography: The optimal imaging method for differentiation of ischemic vs non-ischemic cardiomyopathy Ibrahim Danad, MD,a,b and James K. Min, MD, FACC, FSCCTa,b a
Department of Radiology, Weill Cornell Medical College and The NewYork-Presbyterian Hospital, New York, NY b Dalio Institute of Cardiovascular Imaging, Weill Cornell Medical College and The NewYorkPresbyterian Hospital, New York, NY Received Apr 1, 2015; accepted Apr 1, 2015 doi:10.1007/s12350-015-0146-z
Case history: 57-year-old woman presents with 8 month history of shortness of breath on exertion. She has no chest pain. She has history of hypertension and type 2 diabetes and both are well controlled with oral medications. The HR is 74 bpm and regular, BP140/ 85 mm Hg. The cardiac examination is normal. The ECG shows NSR and voltage criteria of LVH. The renal function is normal. TTE shows mildly enlarged LV, EF of 35%, and mild diffuse wall motion abnormality with trivial MR. The RV is normal. The PAS pressure is estimated at 35 mm Hg. Cardiomyopathies are diseases of the heart muscle and represent a heterogeneous group of disorders affecting the myocardium and ultimately resulting in heart failure. The primary diagnostic strategy is to determine the underlying cause of cardiomyopathy. Notably, there are causes that are treatable and may to some extent be reversible. Ischemic cardiomyopathy is the most common cause of dilated cardiomyopathy in the Western world and is associated with a worse adverse outcome. The differentiation between ischemic and non-ischemic cardiomyopathy is challenging, and has both important therapeutic and prognostic implications as patients with ischemia may benefit from coronary revascularization. In those patients with extensive coronary atherosclerotic disease (CAD), the cardiomyopathy is likely ischemic in etiology. Therefore, a
Reprint requests: ames K. Min, MD, FACC, FSCCT, Dalio Institute of Cardiovascular Imaging, Weill Cornell Medical College and The NewYork-Presbyterian Hospital, 413 East 69th Street, Suite 108, New York, NY 10021; [email protected] J Nucl Cardiol 2015;22:961–7. 1071-3581/$34.00 Copyright Ó 2015 American Society of Nuclear Cardiology.
diagnostic strategy for the differentiation between ischemic and non-ischemic cardiomyopathy relies primarily on the evaluation of coronary anatomy for the presence of coronary atherosclerosis. Coronary artery calcium (CAC) is a marker of vascular injury and its presence is pathognomonic for the presence of coronary atherosclerosis. A non-contrast coronary CT, referred to as a CAC scan, allows for the visualization and quantification of calcium in the coronary arteries. The deposit of coronary calcium is highly correlated to the extent and severity of the coronary atherosclerotic burden. As such, CAC-scanning has been used to identify those patients at high risk for obstructive disease. The complete absence of coronary calcium deposits rules out obstructive CAD with near to absolute certainty,1 implying a non-ischemic etiology to the cardiomyopathy. Of note, Budoff et al found an accuracy of 92% to differentiate between ischemic and non-ischemic cardiomyopathy by using a non-contrast CT scan, obviating the need of invasive procedures in those patients with a negative CAC-scan.2 Nevertheless, the presence of coronary calcium deposits warrants further testing, since the CAC-score has poor predictive values for obstructive CAD.3 In this regard calcium scoring may serve as a gatekeeper to CT-based coronary angiography. In contrast to conventional coronary angiography, coronary computed tomography angiography (CCTA) provides a non-invasive alternative for visualizing coronary anatomy. There is a large body of literature on the diagnostic performance of CCTA, unambiguously portraying the same picture of an unequaled high sensitivity and negative predictive value (NPV) of 96% and 94%, respectively.4 Notably, studies have demonstrated that its accuracy remained high even in patients with tachycardia and/or irregular heart rhythms, recipients of heart transplants, and dilated cardiomyopathy of 961
HCM is caused by mutations in one of the sarcomere genes. HCM is characterized by left ventricular hypertrophy of various morphologies. Prevalence in the general population is 0.2% LVNC is a rare genetic cardiomyopathy resulting from an arrest of the normal myocardial compaction process during the embryonic development. Prevalence is 0.014%–1.3% among patients undergoing echocardiography ARVC cardiomyopathy is a predominantly genetic disorder, which is considered to be autosomal dominant. Characterized by structural and functional abnormalities of the right ventricle. Prevalence in the general population is 0.02%–0.05% Takotsubo is a stress cardiomyopathy also referred to as apical ballooning or broken heart syndrome. Characterized by transient LV dysfunction. Prevalence 1.2%–2.2% of patients with a troponin-positive acute coronary syndrome
Left ventricular non-compaction (LVNC)
Arrhythmogenic RV cardiomyopathy (ARVC)
Takotsubo cardiomyopathy
Characteristics
Hypertrophic cardiomyopathy (HCM)
Type of cardiomyopathies
Measurement at enddiastole
Volume measurement at end-diastole
Thin compacted epicardial layer and an extensive non-compacted endocardial layer of trabecular meshwork Non-compacted layer/compacted myocardium [ 2.3
Fibrofatty replacement of the right ventricular myocardium Bulging/scalloped appearance of RV wall RV volume indexed [ 110 mLm-2 for males and [ 100 mLm-2 for females RVEF \ 40%
LV apical ballooning involving all LV walls with a hyperdynamiccontracting base Wall motion abnormalities not limited to any single vascular territory RV involvement in almost 25% of patients
Measurement at enddiastole
Comments
Typically asymmetric LV wall thickening. Diffuse or segmented LV wall thickening C15 mm (any segment) thickness
Typical CT-based characteristics
Table 1. Types of cardiomyopathies that may be diagnosed with coronary computed tomography angiography
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Wall thickness is measured Combination LV mass and relative at the level of the LV wall thickness (RWT) to differentiate minor axis, approximately between: at the mitral leaflet tips. (1) concentric hypertrophy; (2) (10 mm is upper limit of eccentric; and (3) concentric normal) remodeling RWT = 2 * posterior wall (1) RWT [ 0.42 ? increased LV thickness at end-diastole/ mass LV internal diameter (LVID) (2) RWT B 0.42 ? increased LV at end-diastole mass LVID is measured at the (3) RWT [ 0.42 ? normal LV mass mitral valve leaflets at the level of the minor axis Hypertensive cardiomyopathy is caused by pressure and/or volume overload and is the most common cardiomyopathy affecting 1 billion people worldwide Hypertensive cardiomyopathy
Type of cardiomyopathies
Table 1. continued
Characteristics
Typical CT-based characteristics
Comments
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unknown etiology.5-7 In these specific patient cohorts, CCTA’s NPV was greater than 95%, emphasizing the feasibility of CCTA for the evaluation of coronary anatomy even in patients with atrial fibrillation, tachycardia, cardiac allograft vasculopathy, and new-onset heart failure with reduced ejection fraction.5-7 In addition, CCTA appears also to be helpful in patients with known CAD, exhibiting a high sensitivity of 90% for the detection of coronary in-stent restenosis against a background of invasive coronary angiography.8 Therefore, CCTA enables the rule out of obstructive CAD with close to absolute certainty, which is not achieved by any other non-invasive cardiac imaging modality. Furthermore, data from the CONFIRM registry showed that CT-based angiography may also play an important role in the management of patients with obstructive CAD by identifying those patients who will potentially benefit from coronary revascularization as compared to optimal medical therapy alone.9 Nevertheless, evidence of CAD does not necessarily imply an ischemic etiology, since angiographic severity of stenosis does not always equate with its functional significance.10 Although conventional CCTA-graded stenosis correlates favorably with invasive coronary angiography, both, on the other hand, are unable to determine the hemodynamic significance of epicardial disease. Therefore, functional testing is often considered in the presence of a CT-deemed obstructive stenosis. In this regard, recent advances in cardiac CT have enabled myocardial perfusion imaging with CT. Stress myocardial CT perfusion (CTP) is feasible and allows for a comprehensive evaluation of CAD, providing both anatomical and physiological information on stenosis severity. Recent studies have demonstrated the incremental diagnostic value of myocardial CTP to CCTA, mainly by reducing the number of false-positive scans and thus, affording high diagnostic accuracy in patients with naı¨ve CAD and stented coronary arteries.11,12 However, similar to nuclear-based myocardial perfusion imaging, CTP does not depict lesion-specific ischemia and cannot differentiate between diffuse epicardial disease and ischemia-causing stenoses that may be targets for revascularization. At present, invasive fractional flow reserve (FFR) is considered the gold standard for detection of lesionspecific flow-limiting CAD. Although elegant in its simplicity, namely the measurement of high flow transstenotic pressure gradients as a surrogate for myocardial perfusion,13 its invasive nature limits its application to broader populations. Recently, a novel method has been described that applies computational fluid dynamics to derive FFR values from traditional CCTA images [FFRCT] (Figure 1), obviating the need of additional imaging, modifications of CT acquisition
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Figure 1. Non-invasive fractional flow reserve derived from conventional CCTA. Although both patients have obstructive coronary artery disease by computed tomographic angiography (CT), FFRCT identified myocardial ischemia in one patient (A), whereas FFRCT revealed no ischemia in the other patient (B). Multiplanar reformat of a CT angiogram demonstrating obstructive stenosis of the proximal portion of the left anterior descending artery (LAD) and an FFRCT value of 0.62, indicating vessel ischemia. Invasive coronary angiogram demonstrates obstructive stenosis of the proximal portion of the LAD and measured FFR values of 0.65, indicating vessel ischemia. B CT angiogram demonstrating obstructive stenosis of the mid portion of the right coronary artery (RCA) and an FFRCT value of 0.87, indicating no vessel ischemia. Invasive coronary angiogram demonstrates obstructive stenosis of the mid portion of the RCA and a measured FFR value of 0.88, indicating no vessel ischemia (Reprinted with permission of the American Medical Association from Ref. [16]).
protocols, or administration of medications. The diagnostic performance of FFRCT was first reported in the prospective multicenter DISCOVER-FLOW trial, which demonstrated that FFRCT augmented the diagnostic accuracy of CCTA, mainly by reducing the rate of falsepositive lesions incorrectly classified by anatomical stenosis severity alone.14 These results were confirmed by the DeFACTO and NXT trial, all showing FFRCT to be more accurate than CCTA alone.15,16 The NXT trial,
the most recent of the FFRCT studies, reported FFRCT to improve accuracy of CT angiography, largely by enhancing its specificity from 60% to 86%.15 FFRCT shows an excellent correlation with invasive FFR and is at the same time the only non-invasive imaging modality that allows the depiction of lesion-specific ischemia. As such, CCTA is a tool that provides detailed information on coronary anatomy, myocardial perfusion, and lesionspecific physiological significance of CAD, rendering it
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Figure 2. Diagnostic algorithm for differentiation between ischemic and non-ischemic cardiomyopathy using cardiac CT. CT, Computed tomography; CAC, coronary artery calcium; CAD, coronary artery disease; LM, left main; FFR, fractional flow reserve; DCE, delayed contrast enhancement.
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a true ‘‘one-stop shop’’ imaging tool for the evaluation of CAD. Left ventricular volume and function are fundamental aspects of the diagnosis, disease progression, therapeutic strategies, effect of therapy, and prognosis of both ischemic and non-ischemic cardiomyopathy. Ventricular function and volumes can accurately be depicted from cardiac CT imaging.17 Notably, loss of myocardium as a result of infarcted tissue is considered the largest cause underlying ischemic cardiomyopathy. As such, the distinction between viable, albeit dysfunctional, myocardium, and non-viable myocardium allows one to assess the magnitude of ischemic injury and predict recovery of left ventricular dysfunction after myocardial infarction. The assessment of myocardial viability by delayed contrast enhancement (DCE) using magnetic resonance imaging (MRI) has been well validated and is currently considered the clinical standard for the assessment of infarct size and prediction of recovery. However, due to recent advances in CT hardware, detection of infarcted myocardial tissue using DCE-CT, analogous to delayed enhancement MRI, has become a clinical reality. Data have reported excellent agreement between the area of DCE on CT and MRI infarct imaging.18 In a study by Sato et al, myocardial DCE size gleaned from CT was shown to add incremental prognostic value above TIMI risk score and even left ventricular ejection fraction in patients who have suffered an acute myocardial infarction.19 Moreover, DCE imaging with CT allows not only for assessment of myocardial viability, but is also helpful to reveal other causes of cardiomyopathy such as myocarditis and sarcoidosis. Anecdotal reports have shown the feasibility of CT-based DCE imaging for the diagnosis of cardiac sarcoidosis.20 Moreover, it has been shown that CT DCE images provide similar information to MRI in both localization and extent of DCE abnormalities. Noteworthy, although CT is not routinely used for the assessment of DCE, it has important advantages over MRI. For instance, CT is widely available at low cost, easy to use in clinical practice, allows for shorter scanning acquisitions, and is less operator dependent than MRI. Moreover, CT-based DCE imaging is feasible in patients with a pacemaker or implantable cardioverter defibrillator. A diagnostic algorithm is provided (Figure 2) based on cardiac CT for the differentiation between ischemic and non-ischemic cardiomyopathy. In dilated cardiomyopathy, right ventricle (RV) involvement owing to left ventricle (LV) diastolic impairment has been observed. RV-dysfunction has been demonstrated to contribute to an adverse outcome in patients with heart failure of both ischemic and nonischemic etiology.21 However, given its complex shape and location in the chest, which is obliquely placed in
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the thorax immediately behind the body of the sternum, rendering imaging of the RV particularly challenging. As a consequence, being an operator-dependent imaging tool and highly reliant on good acoustic windows, RV imaging by echocardiography is difficult, whereas nuclear imaging modalities lack anatomical information, and are limited by a low spatial resolution as compared to CT. In addition, imaging of the RV using SPECT or PET comes at a cost of less tracer activity, and therefore poorer image quality, due to its relatively thin wall and low metabolic state as compared to the LV. Studies have demonstrated cardiac CT to provide accurate and reproducible information on RV volume, wall motion, and function, compared to MRI as a reference standard, indicating the robustness of CT for this purpose.17 This is of clinical importance, since RV dysfunction is present in almost one-third of non-ischemic dilated cardiomyopathy patients. Noteworthy, RV function contains important prognostic information, which goes beyond established markers of adverse outcome such as LV function and NYHA functional class.22 Finally, CT allows for the direct visualization of the myocardium and enables the assessment of ventricle size, morphology, wall thickness, and compaction, providing incremental information that will assist the cardiologist in determining the cause of heart failure. Dilated non-ischemic cardiomyopathy, ischemic cardiomyopathy, hypertensive cardiomyopathy, LV noncompaction syndrome, arrhythmogenic right ventricular cardiomyopathy, and Takotsubo cardiomyopathy are identifiable at CCTA (Table 1).23 Altogether, cardiac CT provides a wealth of comprehensive information on coronary atherosclerosis, myocardial perfusion, lesion-specific ischemia, myocardial structure, and cardiac function and geometry of both left and right ventricle that will allow the cardiologist to determine the etiology of the cardiomyopathy with unequaled diagnostic accuracy that is not achieved by any other imaging modality. Disclosure The authors have indicated that they have no financial conflict of interest.
References 1. Mouden M, Timmer JR, Reiffers S, Oostdijk AH, Knollema S, Ottervanger JP, et al. Coronary artery calcium scoring to exclude flow-limiting coronary artery disease in symptomatic stable patients at low or intermediate risk. Radiology 2013;269:77-83. 2. Budoff MJ, Shavelle DM, Lamont DH, Kim HT, Akinwale P, Kennedy JM, et al. Usefulness of electron beam computed tomography scanning for distinguishing ischemic from nonischemic cardiomyopathy. J Am Coll Cardiol 1998;32:1173-8.
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3. Budoff MJ, Jollis JG, Dowe D, Min J, Group VCTS. Diagnostic accuracy of coronary artery calcium for obstructive disease: Results from the ACCURACY trial. Int J Cardiol 2013;166:505-8. 4. Danad I, Raijmakers PG, Knaapen P. Diagnosing coronary artery disease with hybrid PET/CT: It takes two to tango. J Nucl Cardiol 2013;20:874-90. 5. Andreini D, Pontone G, Bartorelli AL, Agostoni P, Mushtaq S, Bertella E, et al. Sixty-four-slice multidetector computed tomography: An accurate imaging modality for the evaluation of coronary arteries in dilated cardiomyopathy of unknown etiology. Circ Cardiovasc Imaging 2009;2:199-205. 6. Wever-Pinzon O, Romero J, Kelesidis I, Wever-Pinzon J, Manrique C, Budge D, et al. Coronary computed tomography angiography for the detection of cardiac allograft vasculopathy: A meta-analysis of prospective trials. J Am Coll Cardiol 2014;63:1992-2004. 7. Sun G, Li M, Jiang ZW, Xu L, Peng ZH, Ding J, et al. Diagnostic accuracy of dual-source CT coronary angiography in patients with atrial fibrillation: Meta analysis. Eur J Radiol 2013;82:1749-54. 8. Sun Z, Almutairi AM. Diagnostic accuracy of 64 multislice CT angiography in the assessment of coronary in-stent restenosis: A meta-analysis. Eur J Radiol 2010;73:266-73. 9. Min JK, Berman DS, Dunning A, Achenbach S, Al-Mallah M, Budoff MJ, et al. All-cause mortality benefit of coronary revascularization vs. medical therapy in patients without known coronary artery disease undergoing coronary computed tomographic angiography: Results from CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter Registry). Eur Heart J 2012;33:3088-97. 10. Tonino PA, Fearon WF, De Bruyne B, Oldroyd KG, Leesar MA, Ver Lee PN, et al. Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography in multivessel evaluation. J Am Coll Cardiol 2010;55:2816-21. 11. Wong DT, Ko BS, Cameron JD, Leong DP, Leung MC, Malaiapan Y, et al. Comparison of diagnostic accuracy of combined assessment using adenosine stress computed tomography perfusion ? computed tomography angiography with transluminal attenuation gradient ? computed tomography angiography against invasive fractional flow reserve. J Am Coll Cardiol 2014;63:1904-12. 12. Rief M, Zimmermann E, Stenzel F, Martus P, Stangl K, Greupner J, et al. Computed tomography angiography and myocardial computed tomography perfusion in patients with coronary stents: Prospective intraindividual comparison with conventional coronary angiography. J Am Coll Cardiol 2013;62:1476-85.
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13. Pijls NH, De Bruyne B, Peels K, van der Voort PH, Bonnier HJ, Bartunek J, et al. Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. N Engl J Med 1996;334:1703-8. 14. Koo BK, Erglis A, Doh JH, Daniels DV, Jegere S, Kim HS, et al. Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve) study. J Am Coll Cardiol 2011;58:1989-97. 15. Norgaard BL, Leipsic J, Gaur S, Seneviratne S, Ko BS, Ito H, et al. Diagnostic performance of noninvasive fractional flow reserve derived from coronary computed tomography angiography in suspected coronary artery disease: The NXT trial (Analysis of coronary blood flow using CT angiography: Next steps). J Am Coll Cardiol 2014;63:1145-55. 16. Min JK, Leipsic J, Pencina MJ, Berman DS, Koo BK, van Mieghem C, et al. Diagnostic accuracy of fractional flow reserve from anatomic CT angiography. J Am Med Assoc 2012;308:1237-45. 17. Raman SV, Shah M, McCarthy B, Garcia A, Ferketich AK. Multidetector row cardiac computed tomography accurately quantifies right and left ventricular size and function compared with cardiac magnetic resonance. Am Heart J 2006;151:736-44. 18. Gerber BL, Belge B, Legros GJ, Lim P, Poncelet A, Pasquet A, et al. Characterization of acute and chronic myocardial infarcts by multidetector computed tomography: Comparison with contrastenhanced magnetic resonance. Circulation 2006;113:823-33. 19. Sato A, Nozato T, Hikita H, Akiyama D, Nishina H, Hoshi T, et al. Prognostic value of myocardial contrast delayed enhancement with 64-slice multidetector computed tomography after acute myocardial infarction. J Am Coll Cardiol 2012;59:730-8. 20. Kim JS, Judson MA, Donnino R, Gold M, Cooper LT, Prystowsky EN, et al. Cardiac sarcoidosis. Am Heart J 2009;157:9-21. 21. Meluzin J, Spinarova L, Hude P, Krejcı´ J, Kincl V, Panovsky´ R, et al. Prognostic importance of various echocardiographic right ventricular functional parameters in patients with symptomatic heart failure. J Am Soc Echocardiogr 2005;18:435-44. 22. Gulati A, Ismail TF, Jabbour A, Alpendurada F, Guha K, Ismail NA, et al. The prevalence and prognostic significance of right ventricular systolic dysfunction in nonischemic dilated cardiomyopathy. Circulation 2013;128:1623-33. 23. Troupis JM, Singh-Pasricha S, Gunaratnam K, Nasis A, Cameron J, Seneviratne S. Cardiomyopathy and cardiac computed tomography: What the radiologist needs to know. Clin Radiol 2013;68:e49-58.
Department of Radiology, Weill Cornell Medical College and The NewYork-Presbyterian Hospital, New York, NY b Dalio Institute of Cardiovascular Imaging, Weill Cornell Medical College and The NewYorkPresbyterian Hospital, New York, NY Received Apr 1, 2015; accepted Apr 1, 2015 doi:10.1007/s12350-015-0146-z
Case history: 57-year-old woman presents with 8 month history of shortness of breath on exertion. She has no chest pain. She has history of hypertension and type 2 diabetes and both are well controlled with oral medications. The HR is 74 bpm and regular, BP140/ 85 mm Hg. The cardiac examination is normal. The ECG shows NSR and voltage criteria of LVH. The renal function is normal. TTE shows mildly enlarged LV, EF of 35%, and mild diffuse wall motion abnormality with trivial MR. The RV is normal. The PAS pressure is estimated at 35 mm Hg. Cardiomyopathies are diseases of the heart muscle and represent a heterogeneous group of disorders affecting the myocardium and ultimately resulting in heart failure. The primary diagnostic strategy is to determine the underlying cause of cardiomyopathy. Notably, there are causes that are treatable and may to some extent be reversible. Ischemic cardiomyopathy is the most common cause of dilated cardiomyopathy in the Western world and is associated with a worse adverse outcome. The differentiation between ischemic and non-ischemic cardiomyopathy is challenging, and has both important therapeutic and prognostic implications as patients with ischemia may benefit from coronary revascularization. In those patients with extensive coronary atherosclerotic disease (CAD), the cardiomyopathy is likely ischemic in etiology. Therefore, a
Reprint requests: ames K. Min, MD, FACC, FSCCT, Dalio Institute of Cardiovascular Imaging, Weill Cornell Medical College and The NewYork-Presbyterian Hospital, 413 East 69th Street, Suite 108, New York, NY 10021; [email protected] J Nucl Cardiol 2015;22:961–7. 1071-3581/$34.00 Copyright Ó 2015 American Society of Nuclear Cardiology.
diagnostic strategy for the differentiation between ischemic and non-ischemic cardiomyopathy relies primarily on the evaluation of coronary anatomy for the presence of coronary atherosclerosis. Coronary artery calcium (CAC) is a marker of vascular injury and its presence is pathognomonic for the presence of coronary atherosclerosis. A non-contrast coronary CT, referred to as a CAC scan, allows for the visualization and quantification of calcium in the coronary arteries. The deposit of coronary calcium is highly correlated to the extent and severity of the coronary atherosclerotic burden. As such, CAC-scanning has been used to identify those patients at high risk for obstructive disease. The complete absence of coronary calcium deposits rules out obstructive CAD with near to absolute certainty,1 implying a non-ischemic etiology to the cardiomyopathy. Of note, Budoff et al found an accuracy of 92% to differentiate between ischemic and non-ischemic cardiomyopathy by using a non-contrast CT scan, obviating the need of invasive procedures in those patients with a negative CAC-scan.2 Nevertheless, the presence of coronary calcium deposits warrants further testing, since the CAC-score has poor predictive values for obstructive CAD.3 In this regard calcium scoring may serve as a gatekeeper to CT-based coronary angiography. In contrast to conventional coronary angiography, coronary computed tomography angiography (CCTA) provides a non-invasive alternative for visualizing coronary anatomy. There is a large body of literature on the diagnostic performance of CCTA, unambiguously portraying the same picture of an unequaled high sensitivity and negative predictive value (NPV) of 96% and 94%, respectively.4 Notably, studies have demonstrated that its accuracy remained high even in patients with tachycardia and/or irregular heart rhythms, recipients of heart transplants, and dilated cardiomyopathy of 961
HCM is caused by mutations in one of the sarcomere genes. HCM is characterized by left ventricular hypertrophy of various morphologies. Prevalence in the general population is 0.2% LVNC is a rare genetic cardiomyopathy resulting from an arrest of the normal myocardial compaction process during the embryonic development. Prevalence is 0.014%–1.3% among patients undergoing echocardiography ARVC cardiomyopathy is a predominantly genetic disorder, which is considered to be autosomal dominant. Characterized by structural and functional abnormalities of the right ventricle. Prevalence in the general population is 0.02%–0.05% Takotsubo is a stress cardiomyopathy also referred to as apical ballooning or broken heart syndrome. Characterized by transient LV dysfunction. Prevalence 1.2%–2.2% of patients with a troponin-positive acute coronary syndrome
Left ventricular non-compaction (LVNC)
Arrhythmogenic RV cardiomyopathy (ARVC)
Takotsubo cardiomyopathy
Characteristics
Hypertrophic cardiomyopathy (HCM)
Type of cardiomyopathies
Measurement at enddiastole
Volume measurement at end-diastole
Thin compacted epicardial layer and an extensive non-compacted endocardial layer of trabecular meshwork Non-compacted layer/compacted myocardium [ 2.3
Fibrofatty replacement of the right ventricular myocardium Bulging/scalloped appearance of RV wall RV volume indexed [ 110 mLm-2 for males and [ 100 mLm-2 for females RVEF \ 40%
LV apical ballooning involving all LV walls with a hyperdynamiccontracting base Wall motion abnormalities not limited to any single vascular territory RV involvement in almost 25% of patients
Measurement at enddiastole
Comments
Typically asymmetric LV wall thickening. Diffuse or segmented LV wall thickening C15 mm (any segment) thickness
Typical CT-based characteristics
Table 1. Types of cardiomyopathies that may be diagnosed with coronary computed tomography angiography
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Wall thickness is measured Combination LV mass and relative at the level of the LV wall thickness (RWT) to differentiate minor axis, approximately between: at the mitral leaflet tips. (1) concentric hypertrophy; (2) (10 mm is upper limit of eccentric; and (3) concentric normal) remodeling RWT = 2 * posterior wall (1) RWT [ 0.42 ? increased LV thickness at end-diastole/ mass LV internal diameter (LVID) (2) RWT B 0.42 ? increased LV at end-diastole mass LVID is measured at the (3) RWT [ 0.42 ? normal LV mass mitral valve leaflets at the level of the minor axis Hypertensive cardiomyopathy is caused by pressure and/or volume overload and is the most common cardiomyopathy affecting 1 billion people worldwide Hypertensive cardiomyopathy
Type of cardiomyopathies
Table 1. continued
Characteristics
Typical CT-based characteristics
Comments
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unknown etiology.5-7 In these specific patient cohorts, CCTA’s NPV was greater than 95%, emphasizing the feasibility of CCTA for the evaluation of coronary anatomy even in patients with atrial fibrillation, tachycardia, cardiac allograft vasculopathy, and new-onset heart failure with reduced ejection fraction.5-7 In addition, CCTA appears also to be helpful in patients with known CAD, exhibiting a high sensitivity of 90% for the detection of coronary in-stent restenosis against a background of invasive coronary angiography.8 Therefore, CCTA enables the rule out of obstructive CAD with close to absolute certainty, which is not achieved by any other non-invasive cardiac imaging modality. Furthermore, data from the CONFIRM registry showed that CT-based angiography may also play an important role in the management of patients with obstructive CAD by identifying those patients who will potentially benefit from coronary revascularization as compared to optimal medical therapy alone.9 Nevertheless, evidence of CAD does not necessarily imply an ischemic etiology, since angiographic severity of stenosis does not always equate with its functional significance.10 Although conventional CCTA-graded stenosis correlates favorably with invasive coronary angiography, both, on the other hand, are unable to determine the hemodynamic significance of epicardial disease. Therefore, functional testing is often considered in the presence of a CT-deemed obstructive stenosis. In this regard, recent advances in cardiac CT have enabled myocardial perfusion imaging with CT. Stress myocardial CT perfusion (CTP) is feasible and allows for a comprehensive evaluation of CAD, providing both anatomical and physiological information on stenosis severity. Recent studies have demonstrated the incremental diagnostic value of myocardial CTP to CCTA, mainly by reducing the number of false-positive scans and thus, affording high diagnostic accuracy in patients with naı¨ve CAD and stented coronary arteries.11,12 However, similar to nuclear-based myocardial perfusion imaging, CTP does not depict lesion-specific ischemia and cannot differentiate between diffuse epicardial disease and ischemia-causing stenoses that may be targets for revascularization. At present, invasive fractional flow reserve (FFR) is considered the gold standard for detection of lesionspecific flow-limiting CAD. Although elegant in its simplicity, namely the measurement of high flow transstenotic pressure gradients as a surrogate for myocardial perfusion,13 its invasive nature limits its application to broader populations. Recently, a novel method has been described that applies computational fluid dynamics to derive FFR values from traditional CCTA images [FFRCT] (Figure 1), obviating the need of additional imaging, modifications of CT acquisition
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Figure 1. Non-invasive fractional flow reserve derived from conventional CCTA. Although both patients have obstructive coronary artery disease by computed tomographic angiography (CT), FFRCT identified myocardial ischemia in one patient (A), whereas FFRCT revealed no ischemia in the other patient (B). Multiplanar reformat of a CT angiogram demonstrating obstructive stenosis of the proximal portion of the left anterior descending artery (LAD) and an FFRCT value of 0.62, indicating vessel ischemia. Invasive coronary angiogram demonstrates obstructive stenosis of the proximal portion of the LAD and measured FFR values of 0.65, indicating vessel ischemia. B CT angiogram demonstrating obstructive stenosis of the mid portion of the right coronary artery (RCA) and an FFRCT value of 0.87, indicating no vessel ischemia. Invasive coronary angiogram demonstrates obstructive stenosis of the mid portion of the RCA and a measured FFR value of 0.88, indicating no vessel ischemia (Reprinted with permission of the American Medical Association from Ref. [16]).
protocols, or administration of medications. The diagnostic performance of FFRCT was first reported in the prospective multicenter DISCOVER-FLOW trial, which demonstrated that FFRCT augmented the diagnostic accuracy of CCTA, mainly by reducing the rate of falsepositive lesions incorrectly classified by anatomical stenosis severity alone.14 These results were confirmed by the DeFACTO and NXT trial, all showing FFRCT to be more accurate than CCTA alone.15,16 The NXT trial,
the most recent of the FFRCT studies, reported FFRCT to improve accuracy of CT angiography, largely by enhancing its specificity from 60% to 86%.15 FFRCT shows an excellent correlation with invasive FFR and is at the same time the only non-invasive imaging modality that allows the depiction of lesion-specific ischemia. As such, CCTA is a tool that provides detailed information on coronary anatomy, myocardial perfusion, and lesionspecific physiological significance of CAD, rendering it
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Figure 2. Diagnostic algorithm for differentiation between ischemic and non-ischemic cardiomyopathy using cardiac CT. CT, Computed tomography; CAC, coronary artery calcium; CAD, coronary artery disease; LM, left main; FFR, fractional flow reserve; DCE, delayed contrast enhancement.
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a true ‘‘one-stop shop’’ imaging tool for the evaluation of CAD. Left ventricular volume and function are fundamental aspects of the diagnosis, disease progression, therapeutic strategies, effect of therapy, and prognosis of both ischemic and non-ischemic cardiomyopathy. Ventricular function and volumes can accurately be depicted from cardiac CT imaging.17 Notably, loss of myocardium as a result of infarcted tissue is considered the largest cause underlying ischemic cardiomyopathy. As such, the distinction between viable, albeit dysfunctional, myocardium, and non-viable myocardium allows one to assess the magnitude of ischemic injury and predict recovery of left ventricular dysfunction after myocardial infarction. The assessment of myocardial viability by delayed contrast enhancement (DCE) using magnetic resonance imaging (MRI) has been well validated and is currently considered the clinical standard for the assessment of infarct size and prediction of recovery. However, due to recent advances in CT hardware, detection of infarcted myocardial tissue using DCE-CT, analogous to delayed enhancement MRI, has become a clinical reality. Data have reported excellent agreement between the area of DCE on CT and MRI infarct imaging.18 In a study by Sato et al, myocardial DCE size gleaned from CT was shown to add incremental prognostic value above TIMI risk score and even left ventricular ejection fraction in patients who have suffered an acute myocardial infarction.19 Moreover, DCE imaging with CT allows not only for assessment of myocardial viability, but is also helpful to reveal other causes of cardiomyopathy such as myocarditis and sarcoidosis. Anecdotal reports have shown the feasibility of CT-based DCE imaging for the diagnosis of cardiac sarcoidosis.20 Moreover, it has been shown that CT DCE images provide similar information to MRI in both localization and extent of DCE abnormalities. Noteworthy, although CT is not routinely used for the assessment of DCE, it has important advantages over MRI. For instance, CT is widely available at low cost, easy to use in clinical practice, allows for shorter scanning acquisitions, and is less operator dependent than MRI. Moreover, CT-based DCE imaging is feasible in patients with a pacemaker or implantable cardioverter defibrillator. A diagnostic algorithm is provided (Figure 2) based on cardiac CT for the differentiation between ischemic and non-ischemic cardiomyopathy. In dilated cardiomyopathy, right ventricle (RV) involvement owing to left ventricle (LV) diastolic impairment has been observed. RV-dysfunction has been demonstrated to contribute to an adverse outcome in patients with heart failure of both ischemic and nonischemic etiology.21 However, given its complex shape and location in the chest, which is obliquely placed in
Journal of Nuclear CardiologyÒ September/October 2015
the thorax immediately behind the body of the sternum, rendering imaging of the RV particularly challenging. As a consequence, being an operator-dependent imaging tool and highly reliant on good acoustic windows, RV imaging by echocardiography is difficult, whereas nuclear imaging modalities lack anatomical information, and are limited by a low spatial resolution as compared to CT. In addition, imaging of the RV using SPECT or PET comes at a cost of less tracer activity, and therefore poorer image quality, due to its relatively thin wall and low metabolic state as compared to the LV. Studies have demonstrated cardiac CT to provide accurate and reproducible information on RV volume, wall motion, and function, compared to MRI as a reference standard, indicating the robustness of CT for this purpose.17 This is of clinical importance, since RV dysfunction is present in almost one-third of non-ischemic dilated cardiomyopathy patients. Noteworthy, RV function contains important prognostic information, which goes beyond established markers of adverse outcome such as LV function and NYHA functional class.22 Finally, CT allows for the direct visualization of the myocardium and enables the assessment of ventricle size, morphology, wall thickness, and compaction, providing incremental information that will assist the cardiologist in determining the cause of heart failure. Dilated non-ischemic cardiomyopathy, ischemic cardiomyopathy, hypertensive cardiomyopathy, LV noncompaction syndrome, arrhythmogenic right ventricular cardiomyopathy, and Takotsubo cardiomyopathy are identifiable at CCTA (Table 1).23 Altogether, cardiac CT provides a wealth of comprehensive information on coronary atherosclerosis, myocardial perfusion, lesion-specific ischemia, myocardial structure, and cardiac function and geometry of both left and right ventricle that will allow the cardiologist to determine the etiology of the cardiomyopathy with unequaled diagnostic accuracy that is not achieved by any other imaging modality. Disclosure The authors have indicated that they have no financial conflict of interest.
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