Aktueller Stellenwert der MSCTA in der Koronargefäßdiagnostik (2011): Klinischer Leitfaden der Österreichischen Gesellschaften für Kardiologie und Radiologie

Präambel

Der 2007 publizierte klinische Leitfaden für die Anwendung der kardialen MSCT war das Ergebnis einer intensiven interdisziplinären Zusammenarbeit zwischen Radiologie und Kardiologie in Österreich. Die nun vorliegende Aktualisierung soll die kontinuierliche klinische und technische Weiterentwicklung widerspiegeln. Die zeitliche und räumliche Auflösung der CT haben sich erheblich verbessert, sodass eine Abbildung der Koronararterien in unter einer Sekunde in hoher diagnostischer Qualität möglich geworden ist. Dabei hat sich die Strahlenbelastung reduziert und liegt derzeit, unter Anwendung der modernsten Gerätetechnologie, im Bereich einer diagnostischen Katheterangiografie. Die Liste der Indikationen der kardialen MSCT-Untersuchung hat sich zudem erweitert: So kann sie zum Beispiel in der Vorbereitung komplexer kardiologischer Interventionen hilfreich sein. Darüber hinaus schränken höhergradige Verkalkungen der Koronararterien die Untersuchungsqualität weniger ein als bisher angenommen. Auf der anderen Seite hat die Bedeutung des Ca-Score nicht den erwarteten Stellenwert in der individuellen Prognose der koronaren Herzerkrankung erreicht, demnach handelt es sich um keine allgemein zu empfehlende Screening-Methode.

Der vorliegende aktualisierte Leitfaden trägt auch der wachsenden Expertise der Radiologen und Kardiologen auf dem Gebiet der nicht invasiven kardiologischen Abklärung Rechnung und unterstreicht die positive Entwicklung der Kooperation beider Fachgruppen. Qualität und Indikationsspektrum der Herz-CT sowie fachliche Expertise und interdisziplinäre Kooperation haben zu einer breiteren Anwendung geführt.

Der aktualisierte Leitfaden informiert über derzeit sinnvolle Anwendungen der MSCT bei Patienten mit Verdacht auf oder bereits bekannter koronarer Herzkrankheit, wie sie aus zahlreichen Originalpublikationen abzulesen sind. Der Leitfaden wurde analog zur Publikation von 2007 evidenzbasiert erstellt, wo notwendig wurden Ergänzungen oder Korrekturen vorgenommen, die auf einem interdisziplinärem Konsensus beruhen.

Literatur

• 1 Einstein A J, Henzlova M J, Rajagopalan S. Estimating risk of cancer associated with radiation exposure from 64-slice computed tomography coronary angiography.  JAMA. 2007;  298 317-323
• 2 Smith-Bindman R, Lipson J, Marcus R et al. Radiation dose associated with common CT examinations and the associated lifetime attributable risk of cancer.  ArchIntMed. 2009;  169 2078-2086
• 3 Rumberger J A, Schwartz R S, Simons D B et al. Relation of coronary calcium determined by electron beam computed tomography and lumen narrowing determined by autopsy.  Am J Cardiol. 1994;  73 1169-1173
• 4 Budoff M J, Georgiou D, Brody A et al. Ultrafast computed tomography as a diagnostic modality in the detection of coronary artery disease: a multicenter study.  Circulation. 1996;  93 898-904
• 5 Sangiorgi G, Rumberger J A, Severson A et al. Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: a histologic study of 723 coronary artery segments using nondecalcifying methodology.  J Am Coll Cardiol. 1998;  31 126-133
• 6 Rumberger J A, Simons D B, Fitzpatrick L A et al. Coronary artery calcium area by electron beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative study.  Circulation. 1995;  92 2157-2162
• 7 Gschnitzer H, Stöger A, Friedrich G et al. Electron beam computed tomography detects calcifications but not plaque burden: an in vitro comparison with intravascular ultrasound.  Circulation. 1999;  100 I-230
• 8 Rumberger J A, Behrenbeck T, Breen J F et al. Coronary calcification by electron beam computed tomography and obstructive coronary artery disease: a model for costs and effectiveness of diagnosis as compared with conventional cardiac testing methods.  J Am Coll Cardiol. 1999;  33 453-462
• 9 Rumberger J A, Sheedy P F, Breen J F et al. Electron beam computed tomographic coronary calcium score cut-points and severity of associated angiographic lumen stenosis.  J Am Coll Cardiol. 1997;  29 1542-1548
• 10 Gottlieb I, Miller J M, Arbab-Zadeh A et al. The absence of coronary calcification does not exclude obstructive coronary artery disease or the need for revascularization in patients referred for conventional coronary angiography.  J Am Coll Cardiol. 2010;  55 627-634
• 11 Haberl R, Becker A, Leber A et al. Correlation of coronary calcification and angiographically documented stenoses in patients with suspected coronary artery disease: results of 1,764 patients.  J Am Coll Cardiol. 2001;  37 451-457
• 12 Schmermund A, Möhlenkamp S, Berenbein S et al. Population-based assessment of subclinical coronary atherosclerosis using electron-beam computed tomography.  Atherosclerosis. 2006;  185 177-182
• 13 Rumberger J A, Sheedy P F, Breen J F et al. EBCT coronary calcium score cutpoints and severity of associated angiographic lumen stenosis.  J Am Coll Cardiol. 1997;  29 1542-1548
• 14 Budoff M J, Daimond G A, Raggi P et al. Continous probalistic prediction of angiographically significant coronary artery disease using EBT.  Circulation. 2002;  105 1791-1796
• 15 Möhlenkamp S, Lehmann N, Schmermund A et al. EBT-based coronary calcium quantities predict future hard events in symptomatic males with advanced coronary artery disease – a 5 year follow-up study.  Eur Heart J. 2003;  24 845-854
• 16 He Z X, Hedrick T D, Pratt C M et al. Severity of coronary artery calcification by EBCT predicts silent myocardial ischemia.  Circulation. 2000;  101 244-251
• 17 Möhlenkamp S, Schmermund A, Kerkhoff G et al. Prognostischer Nutzen der nicht-invasive bestimmten koronaren Plaquelast bei Patienten mit Risikofaktoren.  Z Kardiol. 2003;  92 351-361
• 18 Schmermund A, Bailey K, Rumberger J A et al. An algorithm for non-invasive identification of angiographic three-vessel and/or left main coronary artery disease in symptomatic patients on the basis of cardiac and EBCT calcium scores.  J Am Coll Cardiol. 1999;  33 444-452
• 19 Schmermund A, Baumgart D, Adamzik M et al. Comparison of EBCT and IVUS in detecting calcified and non-calcified plaques in patients with acute coronary syndromes and no or minimal to moderate angiographic coronary artery disease.  Am J Cardiol. 1998;  81 141-146
• 20 Sarwar A, Shaw L J, Shapiro M D et al. Diagnostic and prognostic value of absence of coronary calcification.  JACC Cardiovasc Imaging. 2009;  2 675-688
• 21 Michos E D, Nasir K, Braunstein J B et al. Framingham risk equation underestimates subclinical atherosclerosis risk in asymptomatic women.  Atherosclerosis. 2006;  184 201-206
• 22 Lakoski S G, Greenland P, Wong N D et al. Coronary artery calcium scores and risk for cardiovascular events in women classified as ’low risk’ based on Framingham risk score: the multi-ethnic study of atherosclerosis (MESA).  Arch Intern Med. 2007;  167 2437-2442
• 23 Greenland P, LaBree L, Azen S P et al. Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals.  JAMA. 2004;  291 210-215
• 24 McClelland R L, Chung H, Detrano R et al. Distribution of coronary artery calcium by race, gender and age: results from the Multi-Ethnic Study of Atherosclerosis (MESA).  Circulation. 2006;  113 30-37
• 25 Oudkerk M, Stillman A E, Halliburton S S et al. Coronary artery calcium screening: current status and recommendations from the European Society of Cardiac radiology and North American Society for Cardiovascular Imaging.  Int J Cardiovasc imaging. 2008;  24 645-671
• 26 Blaha M, Budoff M J, Shaw L J et al. Absence of coronary artery calcification and all-cause mortality.  JACC Cardiovasc Imaging. 2009;  2 692-700
• 27 Detrano R, Guerci A D, Carr J J et al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups.  N Engl J Med. 2008;  358 1336-1345
• 28 Greenland P, Bonow R O, Brundage B H et al. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in the evaluation of patients with chest pain.  J Am Coll Cardiol. 2007;  49 378-402
• 29 Mc Cullough P A, Chinnaiyan K M. Annual progression of coronary calcification in trials of preventive therapies: a systematic review.  Arch Intern Med. 2009;  169 2064-2070
• 30 Maintz D, Seifarth H et al. 64-slice multidetector coronary CT angiography: in vitro evaluation of 68 different stents.  Eur Radiol. 2006;  16  818-826
• 31 Cademartiri F, Mollet N R et al. Improving diagnostic accuracy of MDCT coronary angiography in patients with mild heart rhythm irregularities using ECG editing.  AJR. 2006;  186 634-638
• 32 Ropers U, Ropers D, Pflederer T et al. Influence of heart rate on the diagnostic accuracy of dual-source CT coronary angiography.  J Am Coll Cardiol. 2007;  50 2393-2398
• 33 Achenbach S, Ropers D, Kuettner A et al. Contrast-enhanced coronary artery visualization by dual-source computed tomography – Initial experience.  European Journal of Radiology. 2006;  57 331-335
• 34 Leber A W, Johnson T, Becker A. Diagnostic accuracy of dual-source multi-slice CT-coronary angiography in patients with an intermediate pretest likelihood for coronary artery disease.  Eur Heart J. 2007;  28 2354-2360
• 35 Artmann A, Enayati S, Ratzenböck M et al. Bildqualität von CT-Angiografien der Koronararterien in Abhängigkeit vom Ausmaß der Koronarverkalkungen bei Einsatz eines Dual-Source-CTs.  Fortschr Röntgenstr. 2009;  181 863-869
• 36 Scheffel H, Alkadhi H, Leschka S et al. Low-dose CT coronary angiography in the step-and-shoot mode: diagnostic performance.  Heart. 2008;  94 1132-1137
• 37 Leschka L, Stolzmann P, Desbiolles L et al. Diagnostic accuracy of high-pitch dual sourceCT for the assessment of coronary stenoses: first experience.  Eur Radiol. 2009;  19 2896-2903
• 38 Alkadhi H, Scheffel H, Desbiolles L et al. Dual-source computed tomography coronary angiography: influence of obesity, calcium load, and heart rate on diagnostic accuracy.  Eur Heart J. 2008;  29 766-776
• 39 Mowatt G, Cook J A, Hillis G S et al. 64-Slice computed tomography angiography in the diagnosis and assessment of coronary artery disease: systematic review and meta-analysis.  Heart. 2008;  94 1386-1393
• 40 Budoff M J, Achenbach S, Blumenthal R S et al. Assessment of coronary artery disease by cardiac computed tomography: a statement from the American Heart Association Committee on Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology.  Circulation. 2006;  114 1761-179
• 41 Patel M R, Hendel R C, Kramer C M et al. ACCF/ACR/SCCT/SCMR/ASNC/NASCI/SCAI/SIR 2006 appropriateness criteria for cardiac computed tomography and cardiac magnetic resonance imaging.  J Am Coll Cardiol. 2006;  48 1475-1497
• 42 Pugliese F, Mollet N R et al. Diagnostic accuracy of non-invasive 64-slice CT coronary angiography in patients with stable angina pectoris.  Eur Radiol. 2006;  16 575-582
• 43 Nikolaou K, Knez A et al. Accuracy of 64-MDCT in the diagnosis of ischemic heart disease.  AJR. 2006;  186 1659-1668
• 44 Leschka S, Wildermuth S et al. Noninvasive coronary angiography with 64-section CT: effect of average heart rate and heart rate variability on image quality.  Radiology. 2006;  241 378-385
• 45 Pannu H K, Jacobs J E et al. Coronary CT angiography with 64-MDCT: assessment of vessel visibility.  AJR. 2006;  186 341-345
• 46 Nieman K, Pattynama P M, Rensing B J. Evaluation of patients after coronary artery bypass surgery: angiographic assessment of grafts and coronary arteries.  Radiology. 2003;  229 749-756
• 47 Frazier A A, Qureshi F et al. Coronary artery bypass grafts: assessment with multidetector CT in the early and late postoperative settings.  Radiographics. 2005;  25 881-896
• 48 Moore R, Sampson C et al. Coronary artery bypass graft imaging using ECG-gated multislice computed tomography: comparison with catheter angiography.  Clin Radiol. 2005;  60 990-998
• 49 Budoff M J, Dowe D, Jollis J et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease.  J Am Coll Cardiol. 2008;  52 1724-1732
• 50 Dewey M, Vavere A L, Arbab-Zadeh A et al. Patient characteristic as predictors of image quality and diagnostic accuracy of MDCT compared with conventional coronary angiography for detecting coronarystenoses: CORE-64 multicenter international trail.  AJR. 2010;  194 93-10
• 51 Leschka S, Alkadhi H, Plass A et al. Accuracy of MSCT coronary angiography with 64-slice technology: first experience.  Eur Heart J. 2005;  26 1482
• 52 Leber A W, Knez A, Ziegler von F et al. Quantification of obstructive and nonobstructive coronary lesions by 64-slice computed tomography: a comparative study with quantitative coronary angiography and intravascular ultrasound.  J Am Coll Cardiol. 2005;  46 147
• 53 Raff G L, Gallagher M J, O’Neill W W et al. Diagnostic accuracy of noninvasive coronary angiography using 64-slice spiral computed tomography.  J Am Coll Cardiol. 2005;  46 552
• 54 Kopp A F, Schroeder S, Kuettner A et al. Non-invasive coronary angiography with high resolution multidetector-row CT. Results in 102 patients.  Eur Heart J. 2002;  23 1714-1725
• 55 Budoff M J, Dowe D, Jollis J G et al. (ACCURACY trial): Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease.  J Am Coll Cardiol. 2008;  52 1724-32
• 56 Miller J M, Rochitte C E, Dewey M et al. Diagnostic performance of coronary angiography by 64-row CT (Core 64).  N Engl J Med. 2008;  359 2324-36
• 57 Dewey M, Zimmermann E, Deissenrieder F et al. Noninvasive coronary angiography by 320-row CT with lower radiation exposure and maintained diagnostic accuracy.  Circulation. 2009;  120 867-875
• 58 Meijboom W B, Meijs M FL, Schuijf J D et al. Diagnostic accuracy of 64-slice CT coronary angiography.  J Am Coll Cardiol. 2008;  52 2135-2144
• 59 Maffei E, Palumbo A, Martini C et al. Diagnostic accuracy of 64-slice CT coronary angiography in a large population of patients without revascularization: registry data and review of multicenter trial.  Radiol med. 2010;  115 368-384
• 60 Raff G L, Abidov A, Achenbach S et al. SCCT guidelines for the interpretation and reporting of coronary CT angiography.  Journal of Cardiovascular Computed Tomography. 2009;  3 122-136
• 61 Achenbach S. Assessing the prognostic value of coronary CT angiography.  J Am Coll Cardiol. 2008;  52 1344-1346
• 62 Min J K, Hachamovitch R, Rozanski A et al. Clinical benefits of non-invasive testing:coronary computed tomography angiography as a test case.  JACC Cardiovasc Imaging. 2010;  3 305-315
• 63 Tamarappoo B K, Dey D, Nakazato R et al. Comparison of the extent and severity of myocardial perfusion defects measured by CT coronary angiography and SPECT myocardial perfusion imaging.  JACC Cardiovasc Imaging. 2010;  3 1010-1019
• 64 Kirsch J, Araoz P A, Steinberg F B et al. Prevalence and significance of incidental extracardiac findings at 64-multidetector coronary CTA.  J Thorac Imaging. 2007;  22 330-334
• 65 Hoffmann U, Bamberg F, Chae C U et al. Coronary computed tomography for early triage of patients with acute chest pain (ROMICAT trial).  J Am Coll Cardiol. 2009;  53 1642-1650
• 66 Roguin A, Abadi S, Engel A et al. Novel method for real-time hybrid cardiac CT and coronary angiography image registration: visualising beyond luminology, proof-of-concept.  Eurointervention. 2009;  4 648-53
• 67 Litmanovich D, Zamboni G A, Hauser T H et al. ECG-gated chest CT angiography with 64-MDCT and triphasic IV contrast administration regimen in patients with acute non-specific chest pain.  Eur Radiol. 2008;  18 308-317
• 68 Rubinshtein R, Halon D A, Caspar T et al. Impact of 64-slice cardiac CT angiography on clinical decision-making in emergency department patients with chest pain of possible myocardial ischemic origin.  Am J Cardiol. 2007;  100 1522-1526
• 69 Schertler T, Scheffel H, Frauenfelder T et al. Dual-source computed tomography in patients with acute chest pain:feasibility and image quality.  Eur Radiol. 2007;  17 3179-3188
• 70 Vrachliotis T G, Bis K G, Haidary A et al. Atypical chest pain: coronary, aortic, and pulmonary vasculature enhancement at biphasic single-injection 64-section CT angiography.  Radiology. 2007;  243 368-376
• 71 Kim S Y, Seo J B et al. Coronary artery anomalies: classification and ECG-gated multidetector row CT findings with angiographic correlation.  Radiographics. 2006;  26 317-334
• 72 Cademartiri F, La Grutta L, Malago R et al. Prevalence of anatomical variants and coronary anomalies in 543 consecutive patients studied with 64-slice CT coronary angiography.  Radiol Med. 2008;  113 363-375
• 73 Pichler P, Loewe C, Roedler S et al. Detection of high-grade stenoses with multislice computed tomography in heart transplant patients.  J Heart Lung Transplant. 2008;  27 310-316
• 74 Feuchtner G M, Dichtl W, Muller S et al. 64-MDCT for diagnosis of aortic regurgitation in patients referred to CT coronary angiography.  Am J Roentgenol. 2008;  191 W1-W7
• 75 Alkadhi H, Desbiolles L, Husmann L et al. Aortic regurgitation: assessment with 64-section CT.  Radiology. 2007;  245 111-121
• 76 Jassal D S, Shapiro M D, Neilan T G et al. 64-slice MDCT for detection of aortic regurgitation and quantification of severity.  Invest Radiol. 2007;  42 507-512
• 77 Blanke P, Siepe M, Reinöhl J et al. Assessment of aortic annulus dimensions for Edwards SAPIEN transapical heart valve implantation by computed tomography: calculating average diameter using a virtual ring method.  Eur J Cardiothorac Surg. 2010;  38 750-758
• 78 Ben-Dor I, Waksman R, Hanna N N et al. Utility of radiologic review for noncardiac findings on MSCT in patients with severe aortic stenosis evaluated for transcatheter aortic valve implantation.  Am J Cardiol. 2010;  105 1461-1464
• 79 Koos R, Mahnken A H, Dohmen G et al. Association of aortic valve calcification severity with the degree of aortic regurgitation after transcatheter aortic valve implantation.  Int J Cardiol. 2010;  (in press)
• 80 Schuijf J D, Pundziute G, Jukema J W et al. Evaluation of patients with previous coronary stent implantation with 64-section CT.  Radiology. 2007;  245 416-423
• 81 Carbone I, Francone M, Algeri E et al. Non-invasive evaluation of coronary artery stent patency with retrospectively ECG-gated-64-slice CT angiography.  Eur Radiol. 2008;  18 234-243
• 82 Carraba N, Bamoshmoosh M, Carusi L M et al. Usefulness of 64-slice MDCT for detecting drug eluting in-stent restenosis.  Am J Cardiol. 2007;  100 1754-1758
• 83 Das K M, El-Menyar A A, Salm A M et al. Contrast-enhanced 64-section coronary MDCT angiography versus conventional coronary angiography for stent assessment.  Radiology. 2007;  245 424-432
• 84 Hecht H S, Zaric M, Jelnin V et al. Usefulness of 64-detector CT angiography for diagnosing in-stent restenosis in native coronary arteries.  Am J Cardiol. 2008;  101 820-824
• 85 Manghat N, Van Lingen R, Hewson P et al. Usefulness of 64-detector row CT for evaluation of intracoronary stents in symptomatic patients with suspected in-stent restenosis.  Am J Cardiol. 2008;  101 1567-1573
• 86 Feuchtner G, Jodocy D, Klauser A et al. radiation dose reduction by using 100-kVtube voltage in cardiac 64-slice computed tomography: a comparative study.  European J of Radiology. 2010;  75 e51-e56
• 87 The 2007 Recommendations of the International Commission on Radiological Protection. ICRP publication 103.  Ann ICRP. 2007;  37 1-332
• 88 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
• 89 Alkadhi H, Stolzmann P, Scheffel H et al. Radiation dose of cardiac dual-source CT: the effect of tailoring the protocol to patient-specific parameters.  Eur J Radiol. 2008;  68 385-391
• 90 Einstein A J, Elliston C D, Arai A E et al. Radiation dose from single-heartbeat coronary CT angiography performed with a 320-detector row volume scanner.  Radiology. 2010;  254 698-706
• 91 Faulkner K, Werduch A. An estimate of the collective dose to the European population from cardiac X-ray procedures.  Br J Radiol. 2008;  81 955-962
• 92 Goetti R, Leschka S, Baumuller S et al. Low dose high-pitch spiral acquisition 128-slice dual-source computed tomography for the evaluation of coronary artery bypass graft patency.  Invest Radiol. 2010;  45 324-330
• 93 Hausleiter J, Meyer T, Hermann F et al. Estimated radiation dose associated with cardiac CT angiography.  JAMA. 2009;  301 500-507
• 94 Hirai N, Horiguchi J, Fujioka C et al. Prospective versus retrospective ECG-gated 64-detector coronary CT angiography: assessment of image quality, stenosis, and radiation dose.  Radiology. 2008;  248 424-430
• 95 Leschka S, Stolzmann P, Schmid F T et al. Low kilovoltage cardiac dual-source CT: attenuation, noise, and radiation dose.  Eur Radiol. 2008;  18 1809-1817
• 96 Leschka L, Stolzmann P, Desbiolles L et al. Diagnostic accuracy of high-pitch dual-source CT for the assessment of coronary stenoses: first experience.  Eur Radiol. 2009;  19 2896-2903
• 97 Lell M, Marwan M, Schepis T et al. Prospectively ECG-triggered high-pitch spiral acquisition for coronary CT angiography using dual source CT: technique and initial experience.  Eur Radiol. 2009;  19 2576-2583
• 98 Arnoldi E, Johnson T R, Rist C et al. Adequate image quality with reduced radiation dose in prospectively triggered coronary CTA compared with retrospective techniques.  Eur Radiol. 2009;  19 2147-2155
• 99 Rybicki F J, Otero H J, Steigner M L et al. Initial evaluation of coronary images from 320-detector row computed tomography.  Int J Cardiovasc Imaging. 2008;  24 535-546
• 100 Scheffel H, Alkadhi H, Leschka S et al. Low-dose CT coronary angiography in the step-and-shoot mode: diagnostic performance.  Heart. 2008;  94 1132-1137
• 101 Stolzmann P, Leschka S, Betschart T et al. Radiation dose values for various coronary calcium scoring protocols in dual-source CT.  Int J Cardiovasc Imaging. 2009;  25 443-451
• 102 Stolzmann P, Leschka S, Scheffel H et al. Dual-source CT in step-and-shoot mode: noninvasive coronary angiography with low radiation dose.  Radiology. 2008;  249 71-80
• 103 Zimmermann E, Dewey M. Whole heart 320-row computed tomography: reducton of radiation dose via prior coronary calcium scanning.  Fortschr Röntgenstr. 2011;  183 54-59
• 104 Ketelsen D, Buchgeister M, Fenchel M et al. Estamation of radiation exposure of prospectively triggered 128-slice computed tomography coronary angiography.  Fortschr Röntgenstr. 2010;  182 1105-1109