Lupus (2014) 23, 337–341 http://lup.sagepub.com
REVIEW
Tomography and blood vessels in Hughes syndrome L Stojanovich and A Djokovic Internal Medicine, ‘‘Bezanijska Kosa,’’ University Medical Center, Belgrade, Serbia
Antiphospholipid antibody syndrome (APS) or Hughes syndrome is a multisystem autoimmune disorder that is characterized by venous and arterial thrombosis and/or pregnancy complications (miscarriage and fetal death, preeclampsia, placental insufficiency, and fetal growth restriction), and positive serologic tests for anticardiolipin antibodies (aCL), lupus anticoagulant (LA), or antibodies against beta2-glycoprotein I (anti-ß2GPI) either of IgG or IgM isotype. APS is characterized by accelerated atherosclerosis that, together with an increased tendency toward thrombosis, leads to the occurrence of various vascular events. Timely diagnosis of vascular changes, preferably in the subclinical phase, is required both because of their severity and the high mortality rate. Detection of arterial and venous changes is performed by various invasive and noninvasive diagnostic methods. Computed tomographic angiography (CTA) seems to be the most precise method with low exposure time, giving clinicians an opportunity for early diagnosis and timely treatment of APS patients. Lupus (2014) 23, 337–341. Key words: Antiphospholipid syndrome (Hughes syndrome); vascular manifestations; computed tomographic angiography
Knowing the ropes—vascular manifestations in Hughes syndrome Antiphospholipid syndrome (APS) or Hughes syndrome represents a systemic autoimmune disorder characterized by arterial and/or venous thrombosis, multiple and recurrent fetal losses, often accompanied by thrombocytopenia and elevated levels of antiphospholipid antibodies (aPL), such as lupus anticoagulant (LA), anticardiolipin antibodies (aCL) and beta2-glycoprotein I (anti-ß2GPI) antibodies.1,2 Data from the multicenter EuroPhospholipid project, which includes 1000 unselected patients who met the criteria for APS, revealed that 53% of the cohort had primary APS, while 41% had APS with systemic lupus erythematosus (SLE) or lupus-like conditions.3 The range of clinical features of APS continues to broaden, with descriptions of renal artery stenosis, metatarsal fractures, avascular necrosis, and abnormalities of vascular function.4 Although many clinical associations are explicable on the Correspondence to: A. Djokovic, Autoput b.b. Novi Beograd, Belgrade, 11080, Serbia. Email: [email protected] Received 4 December 2013; accepted 18 December 2013
basis of thrombotic occlusions of not only large vessels but also predominantly small vessels, many others are not. And although aPL are typically held to evoke microvascular changes primarily in the context of vascular thrombosis, it is becoming increasingly apparent that these antibodies may be associated with direct endothelial cell injury via acceleration of endothelial cell apoptosis and/or in the context of the endothelium as immunogenic.5–7 Vascular manifestations in Hughes syndrome present in a variety of clinical forms, including asymptomatic ones.8,9 Considering atherosclerosis as a systematic chronic disease, we can distinguish two phases in its course: subclinical, which starts in youth with a stable fibrolipid plaque, and clinical, which has a vulnerable, ulcerated, active plaque with a thrombotic mass.10 Patients with autoimmune diseases have premature and accelerated atherosclerosis, which can later result in serious complications.11 The fact that these patients are of younger age and that, as part of their primary disease, they are already faced with very serious disabilities, places on the clinician a strong demand for early diagnosis, which would then enable timely and adequate treatment.12
! The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
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10.1177/0961203313520061
Computed tomographic angiography in Hughes syndrome L Stojanovich and A Djokovic
338
Water under the bridge? Well-known diagnostic tools for vascular manifestations in Hughes syndrome Physical examination The techniques of inspection, palpation and auscultation are used for vascular diseases assessment. The arterial pulses may be classified simply as being present or absent, or they may be evaluated on a scale from 0 to 4 (0: pulse absent; 1: pulse markedly diminished; 2: pulse moderately diminished; 3: pulse slightly diminished; 4: normal pulse). Venous systems of the limbs are inspected with the patient in the supine and dependent positions. Following inspection a gentle systematic palpitation is performed, and the skin temperature, presence of edemas, sensitivity to pressure, and consistency of the superficial tissues are assessed. X-ray diagnosis of the chest Roentgen diagnosis is the fastest and cheapest method, but it also gives us the least amount of information regarding the state of thoracic organs after acute thrombosis. Thrombosis can be manifested as effusion or infiltration of the lung parenchyma, arising due to artery embolism. Often, X-ray cardiomegaly can be present as a result of pulmonary hypertension after a pulmonary embolism, or as a result of a sudden heart failure. Vascular ultrasonography (Doppler) A variety of noninvasive ultrasound techniques have been developed during recent years. Continuous-wave (CW) and pulsed-wave (PW) methods are used for examining the vessels. However, lesions of less than 40% lumen narrowing are not reliably detectable by Doppler ultrasonography alone. The diagnostic accuracy in the vertebrobasilar system is lower than in the carotid system. Furthermore, Doppler ultrasonography in diagnostics of renal artery stenosis (RAS), with presumed sensitivity and specificity of 95%, can give a false-positive diagnosis in more than 50% of patients.13 The reliability of detection of RAS and of other types of vascular stenosis appears to be determined by the experience and skill of the operator, the type of the pathologic substrate, the location of the stenosis (e.g. distal part of vessels, lumen diameter), and the presence of accessory arteries, collateral arteries, etc.14
Peripheral angiography in patients with Hughes syndrome Digital subtraction angiography (DSA) was until recently the ‘‘gold standard‘‘ in diagnostics of vascular diseases. However, DSA is not used as a diagnostic tool in daily practice because of its invasive character and the risk of complications.15,16 Moreover, meta-analyses have shown both that computed tomography angiography (CTA) and contrast enhanced magnetic resonance angiography (CE-MRA) are highly accurate noninvasive imaging techniques.17 Relevant data on complications related to the adverse reaction to contrast media, puncture site, catheter, and guidewire manipulations are already discussed in the literature.18–20 Furthermore, long fluoroscopic time and high exposure (which requires the use of very effective radiation protection for the examiner), as well as the lack of protection for the patient, make this procedure a less favorable one. Exposure time depends on several factors, and while it can range from 1.5 minutes to five minutes or more, it exceeds the recommended time in very few cases.21 As distal artery diameters are small, it is likely that they are more difficult to assess, especially with concomitant proximal disease. Bearing all this in mind, state-of-the-art angiographic imaging technology is nowadays aided by CT and MRA, which allow simultaneous display of all relevant data on one viewing station.22
A picture is worth a thousand words: CTA in patients with Hughes syndrome Visualization of the vessel lumen (lumenography) plays a central role in determining the site and severity of vascular stenosis before an intervention. Atherosclerosis develops within the arterial wall, which is not imaged by lumenography, and hence this method provides no information regarding the underlying processes that may lead to complications, such as plaque rupture. CT reconstructs an image based on the differing X-ray attenuation of body tissue.23 The addition of intravenous X-ray contrast medium allows visualization of the coronary lumen, supporting reliable exclusion of significant stenosis with high negative predictive values (97%–99%). This has led to widespread acceptance of the utility of coronary CTA. Importantly, CT has the capacity to visualize the vessel wall in addition to the lumen. This opens up the potential for
Lupus Downloaded from lup.sagepub.com at UNIV OF PITTSBURGH on March 15, 2015
Computed tomographic angiography in Hughes syndrome L Stojanovich and A Djokovic
339
more precise quantification and characterization of atherosclerotic plaque. During the exam, X-rays are used, which are harmful by their nature. A spiral 64-multi-slice CT (64MSCT) was developed with the goal of reducing examination time, and allows for shorter X-ray exposure compared to angiographic examination. Using 64MSCT, a scan of coronary arteries (CAs) takes 12–15 seconds, while whole body angiography (WBA) takes 26–35 seconds, less than a minute in total. This also allows us to diagnose subclinical changes in other arteries. On the other hand, the development of electron beam CT (EBCT) allowed quantification of calcified plaque on noncontrast imaging—the Agatston score.24 Coronary artery calcium (CAC) scoring has well-validated prognostic implications.25 The recently introduced multidetector computed tomography coronary angiography (MDCT-CA) allows a reliable noninvasive evaluation of the coronary tree in patients with non-acute cardiac disease, reaching a diagnostic accuracy close to 100%, compared with conventional coronary angiography in the evaluation of CA stenosis. Nevertheless, the evaluation of CAs in MDCTCA is basically visual, so the problem of subjectivity in the evaluation of the vessels remains. Quantitative computed analysis of the vessel aims to remove the implicit subjectivity of the visual score. To this end, software was developed to estimate the percentage of stenosis in the culprit vessel.
Taking into account that there are virtually no complications associated with using CTA, except allergic reactions to contrast (which can also occur during other diagnostic methods), CTA is considered a low-risk method. Unlike with MRA, the acquired resolution of the blood vessel is identical to the images obtained through the use of conventional arteriography. Also, the possibility of artifacts is lower than with MRA. With 64MSCT angiography, the possibility of interpretation error is significantly lower than with ultrasound examination, which has a high degree of error, especially while examining blood vessels (Doppler) (Figure 1). 64MSCT supports excellent visualization of all major and minor blood vessels, showing changes in all blood vessels in one pass. This feature is of special importance for the evaluation of the course and treatment of patients with Hughes syndrome (Figure 2).26
Icing on the cake: combination of CTA with functional imaging Since anatomic imaging does not predict the functional significance of atherosclerotic lesions, a fusion of anatomic and functional imaging provides more accurate information for identifying functionally significant lesions, especially in CAs. High incidence of artery disease (CAD) among APS patients is well known. Recent studies noted
Figure 1 Patient P.Z., 56 years old, female, with Hughes syndrome and diffuse stenosis of the right renal artery (white arrows) and abdominal artery (black arrow), as accidental findings on spiral 64-multi-slice computed tomography (64MSCT). Lupus Downloaded from lup.sagepub.com at UNIV OF PITTSBURGH on March 15, 2015
Computed tomographic angiography in Hughes syndrome L Stojanovich and A Djokovic
340
Figure 2 Diffuse stenosis of the brachocephalic trunk (white arrows) and left arteria subclavia (black arrow) in patient M.A., 50 years old, female, with Hughes syndrome, visualized on spiral 64-multi-slice computed tomography (64MSCT).
elevated levels of aCL and anti-ß2GPI in patients with CAD compared with controls.27,28 RochaFilho et al. showed that adenosine-induced stress-MDCT myocardial perfusion imaging (MPI) has good diagnostic accuracy for the detection of ischemic myocardium, a higher level of reader confidence and improved inter-observer agreement.29 Using dual-source CT with dualenergy mode, a ‘‘perfusion-weighted color-coded iodine map’’ permits the assessment of myocardial perfusion status by analyzing the iodine volume within the myocardium on the basis of the specific absorption characteristics of iodine for radiographs, obtained at high- and low-energy levels.30–32
Go the extra mile: future developments of CTA in vascular diagnostics Although CTA is a promising technique, it still raises concerns over radiation exposure.33 Multiple dose-reduction strategies have been devised, and doses of 1 mSv are now possible using prospective-gating and high-pitch protocols.34 In the end, tissue differentiation by CTA is limited by the overlap of the attenuation ranges between plaque components, especially between necrotic core and fibrous tissues, which can be
transcended by multi-energy CT.35 Plaque has also been interrogated at multiple energies using spectral CT or ‘‘photon counting,’’ and this has been shown to permit differentiation of contrast from other tissue types.36 Finally, new contrast agents may be able to target inflammatory components in areas of potential vulnerability. N1177 or gold nanoparticles have been shown to track macrophage accumulation in plaque in an animal model.37
Take-home messages . Vascular changes in patients with Hughes syndrome, resulting from premature atherosclerosis or thrombophilia, should not be underestimated. It is of high importance to reveal their presence in the subclinical phase. Comprehensive understandings of the vascular system’s condition, and of the severity of the changes, enable timely treatment. . Available noninvasive diagnostic procedures such as Doppler ultrasound of blood vessels or MRA, can give important information, but with a high percentage of false-positive or false-negative findings, or with a limitation in presenting the whole vasculature clearly. . Computed tomographic angiography (CTA) is a safe, noninvasive diagnostic procedure with short exposure time that is as accurate as standard arteriography.
Lupus Downloaded from lup.sagepub.com at UNIV OF PITTSBURGH on March 15, 2015
Computed tomographic angiography in Hughes syndrome L Stojanovich and A Djokovic
341
Funding This work was supported by research grant number 175041 for 2011-2014, issued by the Ministry of Science of the Republic of Serbia.
Conflict of interest The authors have no conflicts of interest to declare.
References 1 Hughes GR. The antiphospholipid syndrome: Ten years on. Lancet 1993; 342: 341–344. 2 Khamashta MA. Hughes syndrome: History. In: Khamashta MA (ed.), Hughes syndrome: Antiphospholipid syndrome, 2nd ed. London: Springer, 2006. 3 Cervera R, Piette JC, Font J, Khamashta MA, Campo MT. Antiphospholipid syndrome: Clinical and immunologic manifestations and patterns of disease expression in a cohort of 1000 patients. Arthritis Rheum 2002; 46: 1019–1027. 4 Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA. Antiphospholipid syndrome. Lancet 2010; 376: 1498–1509. 5 Hughes GR. Migraine, memory loss, and ‘‘multiple sclerosis’’. Neurological features of the antiphospholipid (Hughes’) syndrome. Postgrad Med J 2003; 79: 81–83. 6 Rauch J, Subang R, D’Agnillo P, Koh JS, Levine JS. Apoptosis and the antiphospholipid syndrome. J Autoimmun 2000; 15: 231–235. 7 Levine JS, Koh J, Subang R, Rauch J. Apoptotic cells as immunogen and antigen in the antiphospholipid syndrome. Exp Mol Pathol 1999; 66: 82–98. 8 Nair S, Khamashta MA, Hughes GR. Syndrome X and Hughes syndrome. Lupus 2002; 11: 332–339. 9 Stojanovich L, Markovic O, Marisavljevic D, Elezovic I, Ilijevski N, Stanisavljevic N. Influence of antiphospholipid antibody levels and type on thrombotic manifestations: Results from the Serbian National Cohort Study. Lupus 2012; 21: 338–345. 10 Djokovic A, Stojanovich L, Stanisavljevic N, et al. Does the presence of secondary antiphospholipid syndrome in patients with systemic lupus erythematodes accelerate carotid arteries intima-media thickness changes? Rheumatol Int. Epub ahead of print 15 November 2013. DOI: 10.1007/s00296-013-2903-0. 11 Jime´nez S, Garcı´ a-Criado A, Ta`ssies D, et al. Preclinical vascular disease in systemic lupus erythematosus and primary antiphospholipid syndrome. Rheumatology 2005; 44: 756–761. 12 Cuadrado MJ, Bertolaccini ML, Seed PT, et al. Low-dose aspirin vs. low-dose aspirin plus low-intensity warfarin in thromboprophylaxis: A prospective, multicentre, randomized, open, controlled trial in patients positive for antiphospholipid antibodies (ALIWAPAS). Rheumatology (Oxford). Epub ahead of print 4 October 2013. 13 Liu YQ. Radiology of aortoarteritis. Radiol Clin North Am 1985; 23: 671–688. 14 Lanzer P, Ro¨sch J (eds), Vascular diagnostics: Noninvasive and invasive techniques. Berlin: Springer-Verlag; New York: Heidelberg, 1994. 15 Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg 2007; 45: S5–S67. 16 Singh H, Cardella JF, Cole PE, et al. Quality improvement guidelines for diagnostic arteriography. J Vasc Interv Radiol 2003; 14(9 Pt 2): S283–S288.
17 Medina G, Casaos D, Jara LJ, et al. Increased carotid artery intima-media thickness may be associated with stroke in primary antiphospholipid syndrome. Ann Rheum Dis 2003; 62: 607–610. 18 Takaro T, Peasley ED, McKeel MF, Wilkerson JL. Aortic dissection due to translumbar aortography, with recovery following surgery. Arch Surg 1959; 79: 1023–1027. 19 Scheinberg P, Zunker E. Complications in direct percutaneous carotid arteriography. Arch Neurol 1963; 9: 676–684. 20 Abdelrazeq AS, Saleem TB, Nejim A, Leveson SH. Massive hemoperitoneum caused by rupture of an aneurysm of the marginal artery of Drummond. Cardiovasc Intervent Radiol 2008; 31: 108–110. 21 Beregi JP, Djabbari M, Desmoucelle F, Willoteaux S, Wattinne L, Louvegini S. Popliteal vascular disease: Evaluation with spiral CT angiography. Radiology 1997; 203: 477–483. 22 Tasaneem AL, Jeffery PK, Gregory AH. Imaging findings in systemic lupus erythematosus. RadioGraphics 2004; 24: 1069–1086. 23 Hounsfield GN. Computerized transverse axial scanning (tomography). 1. Description of system. Br J Radiol 1973; 46: 1016–1022. 24 Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990; 15: 827–832. 25 Budoff MJ, Shaw LJ, Liu ST, et al. Long-term prognosis associated with coronary calcification: Observations from a registry of 25,253 patients. J Am Coll Cardiol 2007; 49: 1860–1870. 26 Kaushik S, Federle M, Schur PH, Krishnan M, Silverman SG, Ros PR. Abdominal thrombotic and ischemic manifestations of the antiphospholipid antibody syndrome: CT findings in 42 patients. Radiology 2001; 218: 768–771. 27 Bruce IN, Urowitz MB, Gladman DD, Iban˜ez D, Steiner G. Risk factors for coronary heart diseases in women with systemic lupus erythematosus: The Toronto Risk Factor Study. Arthritis Rheum 2003; 48: 3159–3167. 28 Ruffatti A, Del Ross T, Ciprian M, et al. Risk factors for a first thrombotic event in antiphospholipid antibody carriers. A multicentre, retrospective follow-up study. Ann Rheum Dis 2008; 68: 397–399. 29 Rocha-Filho JA, Blankstein R, Shturman LD, et al. Incremental value of adenosine-induced stress myocardial perfusion imaging with dual-source CT at cardiac CT angiography. Radiology 2010; 254: 410–441. 30 Ruzsics B, Lee H, Zwerner PL, Gebregziabher M, Costello P, Schoepf UJ. Dual-energy CT of the heart for diagnosing coronary artery stenosis and myocardial ischemia: Initial experience. Eur Radiol 2008; 18: 2414–2424. 31 Schwarz F, Ruzsics B, Schoepf UJ, et al. Dual-energy CT of the heart—principles and protocols. Eur J Radiol 2008; 68: 423–433. 32 Ruzsics B, Schwarz F, Schoepf UJ, et al. Comparison of dualenergy computed tomography of the heart with single photon emission computed tomography for assessment of coronary artery stenosis and of the myocardial blood supply. Am J Cardiol 2009; 104: 318–326. 33 Brenner DJ, Hall EJ. Computed tomography—an increasing source of radiation exposure. N Engl J Med 2007; 357: 2277–2284. 34 Achenbach S, Marwan M, Ropers D, et al. Coronary computed tomography angiography with a consistent dose below 1 mSv using prospectively electrocardiogram-triggered high-pitch spiral acquisition. Eur Heart J 2010; 31: 340–346. 35 Barreto M, Schoenhagen P, Nair A, et al. Potential of dual-energy computed tomography to characterize atherosclerotic plaque: Ex vivo assessment of human coronary arteries in comparison to histology. J Cardiovasc Comput Tomogr 2008; 2: 234–242. 36 Feuerlein S, Roessl E, Proksa R, et al. Multienergy photon-counting K-edge imaging: Potential for improved luminal depiction in vascular imaging. Radiology 2008; 249: 1010–1016. 37 Cormode DP, Roessl E, Thran A, et al. Atherosclerotic plaque composition: Analysis with multicolor CT and targeted gold nanoparticles. Radiology 2010; 256: 774–782.
Lupus Downloaded from lup.sagepub.com at UNIV OF PITTSBURGH on March 15, 2015
REVIEW
Tomography and blood vessels in Hughes syndrome L Stojanovich and A Djokovic Internal Medicine, ‘‘Bezanijska Kosa,’’ University Medical Center, Belgrade, Serbia
Antiphospholipid antibody syndrome (APS) or Hughes syndrome is a multisystem autoimmune disorder that is characterized by venous and arterial thrombosis and/or pregnancy complications (miscarriage and fetal death, preeclampsia, placental insufficiency, and fetal growth restriction), and positive serologic tests for anticardiolipin antibodies (aCL), lupus anticoagulant (LA), or antibodies against beta2-glycoprotein I (anti-ß2GPI) either of IgG or IgM isotype. APS is characterized by accelerated atherosclerosis that, together with an increased tendency toward thrombosis, leads to the occurrence of various vascular events. Timely diagnosis of vascular changes, preferably in the subclinical phase, is required both because of their severity and the high mortality rate. Detection of arterial and venous changes is performed by various invasive and noninvasive diagnostic methods. Computed tomographic angiography (CTA) seems to be the most precise method with low exposure time, giving clinicians an opportunity for early diagnosis and timely treatment of APS patients. Lupus (2014) 23, 337–341. Key words: Antiphospholipid syndrome (Hughes syndrome); vascular manifestations; computed tomographic angiography
Knowing the ropes—vascular manifestations in Hughes syndrome Antiphospholipid syndrome (APS) or Hughes syndrome represents a systemic autoimmune disorder characterized by arterial and/or venous thrombosis, multiple and recurrent fetal losses, often accompanied by thrombocytopenia and elevated levels of antiphospholipid antibodies (aPL), such as lupus anticoagulant (LA), anticardiolipin antibodies (aCL) and beta2-glycoprotein I (anti-ß2GPI) antibodies.1,2 Data from the multicenter EuroPhospholipid project, which includes 1000 unselected patients who met the criteria for APS, revealed that 53% of the cohort had primary APS, while 41% had APS with systemic lupus erythematosus (SLE) or lupus-like conditions.3 The range of clinical features of APS continues to broaden, with descriptions of renal artery stenosis, metatarsal fractures, avascular necrosis, and abnormalities of vascular function.4 Although many clinical associations are explicable on the Correspondence to: A. Djokovic, Autoput b.b. Novi Beograd, Belgrade, 11080, Serbia. Email: [email protected] Received 4 December 2013; accepted 18 December 2013
basis of thrombotic occlusions of not only large vessels but also predominantly small vessels, many others are not. And although aPL are typically held to evoke microvascular changes primarily in the context of vascular thrombosis, it is becoming increasingly apparent that these antibodies may be associated with direct endothelial cell injury via acceleration of endothelial cell apoptosis and/or in the context of the endothelium as immunogenic.5–7 Vascular manifestations in Hughes syndrome present in a variety of clinical forms, including asymptomatic ones.8,9 Considering atherosclerosis as a systematic chronic disease, we can distinguish two phases in its course: subclinical, which starts in youth with a stable fibrolipid plaque, and clinical, which has a vulnerable, ulcerated, active plaque with a thrombotic mass.10 Patients with autoimmune diseases have premature and accelerated atherosclerosis, which can later result in serious complications.11 The fact that these patients are of younger age and that, as part of their primary disease, they are already faced with very serious disabilities, places on the clinician a strong demand for early diagnosis, which would then enable timely and adequate treatment.12
! The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
Downloaded from lup.sagepub.com at UNIV OF PITTSBURGH on March 15, 2015
10.1177/0961203313520061
Computed tomographic angiography in Hughes syndrome L Stojanovich and A Djokovic
338
Water under the bridge? Well-known diagnostic tools for vascular manifestations in Hughes syndrome Physical examination The techniques of inspection, palpation and auscultation are used for vascular diseases assessment. The arterial pulses may be classified simply as being present or absent, or they may be evaluated on a scale from 0 to 4 (0: pulse absent; 1: pulse markedly diminished; 2: pulse moderately diminished; 3: pulse slightly diminished; 4: normal pulse). Venous systems of the limbs are inspected with the patient in the supine and dependent positions. Following inspection a gentle systematic palpitation is performed, and the skin temperature, presence of edemas, sensitivity to pressure, and consistency of the superficial tissues are assessed. X-ray diagnosis of the chest Roentgen diagnosis is the fastest and cheapest method, but it also gives us the least amount of information regarding the state of thoracic organs after acute thrombosis. Thrombosis can be manifested as effusion or infiltration of the lung parenchyma, arising due to artery embolism. Often, X-ray cardiomegaly can be present as a result of pulmonary hypertension after a pulmonary embolism, or as a result of a sudden heart failure. Vascular ultrasonography (Doppler) A variety of noninvasive ultrasound techniques have been developed during recent years. Continuous-wave (CW) and pulsed-wave (PW) methods are used for examining the vessels. However, lesions of less than 40% lumen narrowing are not reliably detectable by Doppler ultrasonography alone. The diagnostic accuracy in the vertebrobasilar system is lower than in the carotid system. Furthermore, Doppler ultrasonography in diagnostics of renal artery stenosis (RAS), with presumed sensitivity and specificity of 95%, can give a false-positive diagnosis in more than 50% of patients.13 The reliability of detection of RAS and of other types of vascular stenosis appears to be determined by the experience and skill of the operator, the type of the pathologic substrate, the location of the stenosis (e.g. distal part of vessels, lumen diameter), and the presence of accessory arteries, collateral arteries, etc.14
Peripheral angiography in patients with Hughes syndrome Digital subtraction angiography (DSA) was until recently the ‘‘gold standard‘‘ in diagnostics of vascular diseases. However, DSA is not used as a diagnostic tool in daily practice because of its invasive character and the risk of complications.15,16 Moreover, meta-analyses have shown both that computed tomography angiography (CTA) and contrast enhanced magnetic resonance angiography (CE-MRA) are highly accurate noninvasive imaging techniques.17 Relevant data on complications related to the adverse reaction to contrast media, puncture site, catheter, and guidewire manipulations are already discussed in the literature.18–20 Furthermore, long fluoroscopic time and high exposure (which requires the use of very effective radiation protection for the examiner), as well as the lack of protection for the patient, make this procedure a less favorable one. Exposure time depends on several factors, and while it can range from 1.5 minutes to five minutes or more, it exceeds the recommended time in very few cases.21 As distal artery diameters are small, it is likely that they are more difficult to assess, especially with concomitant proximal disease. Bearing all this in mind, state-of-the-art angiographic imaging technology is nowadays aided by CT and MRA, which allow simultaneous display of all relevant data on one viewing station.22
A picture is worth a thousand words: CTA in patients with Hughes syndrome Visualization of the vessel lumen (lumenography) plays a central role in determining the site and severity of vascular stenosis before an intervention. Atherosclerosis develops within the arterial wall, which is not imaged by lumenography, and hence this method provides no information regarding the underlying processes that may lead to complications, such as plaque rupture. CT reconstructs an image based on the differing X-ray attenuation of body tissue.23 The addition of intravenous X-ray contrast medium allows visualization of the coronary lumen, supporting reliable exclusion of significant stenosis with high negative predictive values (97%–99%). This has led to widespread acceptance of the utility of coronary CTA. Importantly, CT has the capacity to visualize the vessel wall in addition to the lumen. This opens up the potential for
Lupus Downloaded from lup.sagepub.com at UNIV OF PITTSBURGH on March 15, 2015
Computed tomographic angiography in Hughes syndrome L Stojanovich and A Djokovic
339
more precise quantification and characterization of atherosclerotic plaque. During the exam, X-rays are used, which are harmful by their nature. A spiral 64-multi-slice CT (64MSCT) was developed with the goal of reducing examination time, and allows for shorter X-ray exposure compared to angiographic examination. Using 64MSCT, a scan of coronary arteries (CAs) takes 12–15 seconds, while whole body angiography (WBA) takes 26–35 seconds, less than a minute in total. This also allows us to diagnose subclinical changes in other arteries. On the other hand, the development of electron beam CT (EBCT) allowed quantification of calcified plaque on noncontrast imaging—the Agatston score.24 Coronary artery calcium (CAC) scoring has well-validated prognostic implications.25 The recently introduced multidetector computed tomography coronary angiography (MDCT-CA) allows a reliable noninvasive evaluation of the coronary tree in patients with non-acute cardiac disease, reaching a diagnostic accuracy close to 100%, compared with conventional coronary angiography in the evaluation of CA stenosis. Nevertheless, the evaluation of CAs in MDCTCA is basically visual, so the problem of subjectivity in the evaluation of the vessels remains. Quantitative computed analysis of the vessel aims to remove the implicit subjectivity of the visual score. To this end, software was developed to estimate the percentage of stenosis in the culprit vessel.
Taking into account that there are virtually no complications associated with using CTA, except allergic reactions to contrast (which can also occur during other diagnostic methods), CTA is considered a low-risk method. Unlike with MRA, the acquired resolution of the blood vessel is identical to the images obtained through the use of conventional arteriography. Also, the possibility of artifacts is lower than with MRA. With 64MSCT angiography, the possibility of interpretation error is significantly lower than with ultrasound examination, which has a high degree of error, especially while examining blood vessels (Doppler) (Figure 1). 64MSCT supports excellent visualization of all major and minor blood vessels, showing changes in all blood vessels in one pass. This feature is of special importance for the evaluation of the course and treatment of patients with Hughes syndrome (Figure 2).26
Icing on the cake: combination of CTA with functional imaging Since anatomic imaging does not predict the functional significance of atherosclerotic lesions, a fusion of anatomic and functional imaging provides more accurate information for identifying functionally significant lesions, especially in CAs. High incidence of artery disease (CAD) among APS patients is well known. Recent studies noted
Figure 1 Patient P.Z., 56 years old, female, with Hughes syndrome and diffuse stenosis of the right renal artery (white arrows) and abdominal artery (black arrow), as accidental findings on spiral 64-multi-slice computed tomography (64MSCT). Lupus Downloaded from lup.sagepub.com at UNIV OF PITTSBURGH on March 15, 2015
Computed tomographic angiography in Hughes syndrome L Stojanovich and A Djokovic
340
Figure 2 Diffuse stenosis of the brachocephalic trunk (white arrows) and left arteria subclavia (black arrow) in patient M.A., 50 years old, female, with Hughes syndrome, visualized on spiral 64-multi-slice computed tomography (64MSCT).
elevated levels of aCL and anti-ß2GPI in patients with CAD compared with controls.27,28 RochaFilho et al. showed that adenosine-induced stress-MDCT myocardial perfusion imaging (MPI) has good diagnostic accuracy for the detection of ischemic myocardium, a higher level of reader confidence and improved inter-observer agreement.29 Using dual-source CT with dualenergy mode, a ‘‘perfusion-weighted color-coded iodine map’’ permits the assessment of myocardial perfusion status by analyzing the iodine volume within the myocardium on the basis of the specific absorption characteristics of iodine for radiographs, obtained at high- and low-energy levels.30–32
Go the extra mile: future developments of CTA in vascular diagnostics Although CTA is a promising technique, it still raises concerns over radiation exposure.33 Multiple dose-reduction strategies have been devised, and doses of 1 mSv are now possible using prospective-gating and high-pitch protocols.34 In the end, tissue differentiation by CTA is limited by the overlap of the attenuation ranges between plaque components, especially between necrotic core and fibrous tissues, which can be
transcended by multi-energy CT.35 Plaque has also been interrogated at multiple energies using spectral CT or ‘‘photon counting,’’ and this has been shown to permit differentiation of contrast from other tissue types.36 Finally, new contrast agents may be able to target inflammatory components in areas of potential vulnerability. N1177 or gold nanoparticles have been shown to track macrophage accumulation in plaque in an animal model.37
Take-home messages . Vascular changes in patients with Hughes syndrome, resulting from premature atherosclerosis or thrombophilia, should not be underestimated. It is of high importance to reveal their presence in the subclinical phase. Comprehensive understandings of the vascular system’s condition, and of the severity of the changes, enable timely treatment. . Available noninvasive diagnostic procedures such as Doppler ultrasound of blood vessels or MRA, can give important information, but with a high percentage of false-positive or false-negative findings, or with a limitation in presenting the whole vasculature clearly. . Computed tomographic angiography (CTA) is a safe, noninvasive diagnostic procedure with short exposure time that is as accurate as standard arteriography.
Lupus Downloaded from lup.sagepub.com at UNIV OF PITTSBURGH on March 15, 2015
Computed tomographic angiography in Hughes syndrome L Stojanovich and A Djokovic
341
Funding This work was supported by research grant number 175041 for 2011-2014, issued by the Ministry of Science of the Republic of Serbia.
Conflict of interest The authors have no conflicts of interest to declare.
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