Subclinical myocardial inflammation and diffuse fibrosis are common in systemic sclerosis – a clinical study using myocardial T1-mapping and extracellular volume quantification

Journal of Cardiovascular Magnetic Resonance

Theodoros D Karamitsos¹  Stefan Neubauer¹  Paul B Wordsworth⁴  James Moon³  Matthew D Robson¹  Paul M Matthews²  Aitzaz BS Rai¹  Vanessa M Ferreira¹  Jane M Francis¹  Stefan K Piechnik¹  Ntobeko AB Ntusi¹ 

[1] Radcliffe Department of Medicine, Division of Cardiovascular Medicine, Level 0, John Radcliffe Hospital, University of Oxford Centre for Clinical Magnetic Resonance Research, Oxford OX3 9DU, United Kingdom;Division of Brain Sciences, Department of Medicine, Imperial College, London, UK;Institute of Cardiovascular Science, University College London & Heart Hospital, London, UK;Nuffield Department of Orthopaedics & NIHR Oxford Musculoskeletal Biomedical Research Unit, Rheumatology and Musculoskeletal Sciences, University of Oxford, Nuffield Orthopaedic Centre and John Radcliffe Hospital, Oxford, UK

关键词: Gadolinium;    Extracellular volume estimation;    T1 mapping;    Cardiovascular magnetic resonance;    Scleroderma;   

Others  :  801608
DOI  :  10.1186/1532-429X-16-21

 received in 2013-11-11, accepted in 2014-02-17,  发布年份 2014

【 摘 要 】

Background

Systemic sclerosis (SSc) is characterised by multi-organ tissue fibrosis including the myocardium. Diffuse myocardial fibrosis can be detected non-invasively by T1 and extracellular volume (ECV) quantification, while focal myocardial inflammation and fibrosis may be detected by T2-weighted and late gadolinium enhancement (LGE), respectively, using cardiovascular magnetic resonance (CMR). We hypothesised that multiparametric CMR can detect subclinical myocardial involvement in patients with SSc.

Methods

19 SSc patients (18 female, mean age 55 ± 10 years) and 20 controls (19 female, mean age 56 ± 8 years) without overt cardiovascular disease underwent CMR at 1.5T, including cine, tagging, T1-mapping, T2-weighted, LGE imaging and ECV quantification.

Results

Focal fibrosis on LGE was found in 10 SSc patients (53%) but none of controls. SSc patients also had areas of myocardial oedema on T2-weighted imaging (median 13 vs. 0% in controls). SSc patients had significantly higher native myocardial T1 values (1007 ± 29 vs. 958 ± 20 ms, p < 0.001), larger areas of myocardial involvement by native T1 >990 ms (median 52 vs. 3% in controls) and expansion of ECV (35.4 ± 4.8 vs. 27.6 ± 2.5%, p < 0.001), likely representing a combination of low-grade inflammation and diffuse myocardial fibrosis. Regardless of any regional fibrosis, native T1 and ECV were significantly elevated in SSc and correlated with disease activity and severity. Although biventricular size and global function were preserved, there was impairment in the peak systolic circumferential strain (-16.8 ± 1.6 vs. -18.6 ± 1.0, p < 0.001) and peak diastolic strain rate (83 ± 26 vs. 114 ± 16 s-1, p < 0.001) in SSc, which inversely correlated with diffuse myocardial fibrosis indices.

Conclusions

Cardiac involvement is common in SSc even in the absence of cardiac symptoms, and includes chronic myocardial inflammation as well as focal and diffuse myocardial fibrosis. Myocardial abnormalities detected on CMR were associated with impaired strain parameters, as well as disease activity and severity in SSc patients. CMR may be useful in future in the study of treatments aimed at preventing or reducing adverse myocardial processes in SSc.

【 授权许可】

   
2014 Ntusi et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Steen VD, Medsger TA Jr: Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis Rheum 2000, 43:2437-44.
• [2]Heine J: Uber ein eigenartiges Krankheitsbild von deiffuser Sklerosis der haut and inner organe (Peculiar disease profile of diffuse sclerosis of the skin and inner organs). Virchows Arch 1926, 262:1.
• [3]Champion HC: The heart is scleroderma. Rheum Dis Clin North Am 2008, 34:181-90.
• [4]Follansbee WP, Curtis EI, Medsger TA Jr, Steen VD, Uretsky BF, Owens GR, Rodnan GP: Physiologic abnormalities of cardiac function in progressive systemic sclerosis with diffuse scleroderma. N Eng J Med 1984, 310:142-8.
• [5]Clements PJ, Lachenbruch PA, Furst DE, Paulus HE, Sterz MG: Cardiac score: a semiquantitative measure of cardiac involvement that improves prediction of prognosis in systemic sclerosis. Arthritis Rheum 1991, 34:1371-80.
• [6]Kahan A, Allanore Y: Primary myocardial involvement in systemic sclerosis. Rheumatology 2006, 45(Suppl. 4):s14-7.
• [7]D’Angelo WA, Fries JF, Masi AT, Shulman LE: Pathologic observations in systemic sclerosis (scleroderma). A study of fifty-eight autopsy cases and fifty-eight matched controls. Am J Med 1969, 46:428-40.
• [8]Bulkley BH, Ridolfi RL, Salyer WR, Hutchins GM: Myocardial lesions of progressive systemic sclerosis. A cause of cardiac dysfunction. Circulation 1976, 53:483-90.
• [9]Kahaleh B: The microvascular endothelium in scleroderma. Rheumatology 2008, 47(Suppl 5):s14-5.
• [10]Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U, Levine GN, Narula J, Starling RC, Towbin J, Virmani R: The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of cardiology and the European Society of Cardiology. Eur Heart J 2007, 28:3076-93.
• [11]Hachulla AL, Launay D, Gaxotte V, de Groote P, Lamblin N, Devos P, Hatron PY, Beregi JP, Hachulla E: Cardiac magnetic resonance imaging in systemic sclerosis: a cross-sectional observational study of 52 patients. Ann Rheum Dis 2009, 68:1878-84.
• [12]Tzelepis GE, Kelekis NL, Plastiras SC, Mitseas P, Economopoulos N, Kampolis C, Gialafos EJ, Moyssakis I, Moutsopoulos HM: Pattern and distribution of myocardial fibrosis in systemic sclerosis: a delayed enhanced magnetic resonance imaging study. Arthritis Rheum 2007, 56:3827-36.
• [13]Friedrich MG, Sechtem U, Schulz-Menger J, Holmvang G, Alakija P, Cooper LT, White JA, Abdel-Aty H, Gutberlet M, Prasad S, Aletras A, Laissy JP, Paterson I, Filipchuk NG, Kumar A, Pauschinger M, Liu P, International Consensus Group on Cardiovascular Magnetic Resonance in Myocarditis: Cardiovascular magnetic resonance in myocarditis: A JACC White Paper. J Am Coll Cardiol 2009, 53:1475-87.
• [14]Ferreira VM, Piechnick SK, Dall’Armellina E, Karamitsos TD, Francis JM, Ntusi N, Holloway C, Choudhury RP, Kardos A, Robson MD, Friedrich MG, Neubauer S: T1 mapping for the diagnosis of acute myocarditis using cardiovascular magnetic resonance – comparison to T2-weighted and late gadolinium enhanced imaging. J Am Coll Cardiol Cardiovasc Imaging 2013. doi:pii:S1936-878X(13)00539-1.10-1016/jcmg.2013.03.008. Epub ahead off print
• [15]Won S, Davies-Venn C, Liu S, Bleumke DA: Noninvasive imaging of myocardial extracellular matrix for assessment of fibrosis. Curr Opin Cardiol 2013, 28:282-9.
• [16]Mewton N, Liu CY, Croiselle P, Bluemke D, Lima JA: Assessment of myocardial fibrosis with cardiovascular magnetic resonance. J Am Coll Cardiol 2011, 57:891-903.
• [17]Ferreira VM, Piechnik SK, Dall’Armellina E, Karamitsos TD, Francis JM, Choudhury RP, Friedrich MG, Robson MD, Neubauer S: Non-contrast T1-mapping detects acute myocardial edema with high diagnostic accuracy: a comparison to T2-weighted cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2012, 14:42. BioMed Central Full Text
• [18]Messroghli DR, Radjenovic A, Kozerke S, Higgins DM, Sivanantham MU, Ridgway JP: Modified Look-Locker Inversion recovery (MOLLI) for high-resolution T1 mapping of the heart. Magn Res Med 2004, 52:141-6.
• [19]Piechnik S, Ferreira VM, Dall’Armellina E, Cochlin LE, Greiser A, Neubauer S, Robson MD: Shortened Modified look-locker inversion recovery (ShMOLLI) for clinical myocardial T1-mapping at 1.5 And 3T within a 9 heartbeath breathhold. J Cardiovasc Magn Res 2010, 12:69. BioMed Central Full Text
• [20]Iles L, Pfluger H, Phrommintikul A, Cherayath J, Aksit P, Gupta SN, Kaye DM, Taylor AJ: Evaluation of diffuse myocardial fibrosis in heart failure with cardiac magnetic resonance contrast-enhanced T1 mapping. J Am Coll Cardiol 2008, 52:1574-80.
• [21]Bull S, White SK, Piechnik SK, Flett AS, Ferreira VM, Loudon M, Francis JM, Karamitsos TD, Prendegrast BD, Robson MD, Neubauer S, Moon JC, Myerson SG: Human non-contrast T1 values and correlation with histology in diffuse fibrosis. Heart 2013, 99:932-7.
• [22]Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee: Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 1980, 23:581-90.
• [23]Payne AR, Casey M, McClure J, McGeoch R, Murphy A, Woodward R, Saul A, Bi X, Zeuhlsdorff S, Oldroyd KG, Tzemos N, Berry C: Bright-blood T2-weighted MRI has higher diagnostic accuracy than dark-blood short tau inversion recovery MRI for detection of acute myocardial infarction and for assessment of the ischemic area at risk and myocardial salvage. Circ Cardiovasc Imaging 2011, 4:210-9.
• [24]Young AA, Imai H, Cheng-Ning C, Axel L: Two-dimensional left ventricular deformation during systole using magnetic resonance imaging with spatial modulation of magnetization. Circulation 1994, 89:740-52.
• [25]Kellman P, Arai AE, McVeigh ER, Aletras AH: Phase-sensitive inversion recovery for detecting myocardial infarction using gadolinium-delayed hyperenhancement. Magn Reson Med 2002, 47:372-83.
• [26]White SK, Sado DM, Fontana M, Banypersad SM, Maestrini V, Flett AS, Piechnik SK, Robson MD, Hausenloy DJ, Sheikh AM, Hawkins PN, Moon JC: T1 mapping for myocardial extracellular volume measurement by CMR: bolus only versus primed infusion technique. J Am Coll Cardiol Cardiovasc Imaging 2013. doi:pii:S1936-878X(13)00229-5. 10.1016/j.jcmg.2013.01.011. Epub ahead of print
• [27]Jerosh-Herold M, Sheridan DC, Kushner JD, Nauman D, Burgess D, Dutton D, Alharethi R, Li D, Hershberger RE: Cardiac magnetic resonance imaging of myocardial contrast uptake and blood flow in patients affected with idiopathic or familial dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 2008, 295(Suppl H):H1234-42.
• [28]Coelho-Filho OR, Mongeon FP, Mitchell R, Moreno H Jr, Nadrz W Jr, Kwong R, Jerosch-Herold M: Role of transcytolemmal water-exchange in magnetic resonance measurements of diffuse myocardial fibrosis in hypertensive disease. Circ Cardiovasc Imaging 2013, 6:134-41.
• [29]Valentini G, Della Rossa A, Bombardieri S, Bencivelli W, Silman AJ, D’Angelo S, Cerinic MM, Belch JF, Black CM, Bruhlmann P, Czirjak L, de Luca A, Drosos AA, Ferri C, Gabrielli A, Giacomelli R, Hayem G, Inanc M, McHugh NJ, Nielsen H, Rosada M, Scorza R, Stork J, Sysa A, van den Hoogen FH, Vlachoyiannopoulos PJ: European multicenter study to define disease activity criteria for systemic sclerosis. Identification of disease activity variables and development of preliminary activity indexes. Ann Rheum Dis 2001, 60:592-8.
• [30]Clements P, Lachenbruch P, Siebold J, White B, Weiner S, Martin R, Weinstein A, Weisman M, Mayes M, Collier D, Wigley F, Medsger T Jr, Steen V, Moreland L, Dixon M, Massa M, Lally E, McCloskey D, Varga J: Inter and intraobserver variability of total skin thickness core (modified Rodnan TSS) in systemic sclerosis. J Rheumatol 1995, 22:1281-5.
• [31]Weber KT, Janicki JS, Shroff SG, Pick R, Chen RM, Bashey RI: Collagen remodeling of the pressure-overloaded, hypertrophied nonhuman primate myocardium. Circ Res 1988, 62:757-65.
• [32]Beltrami CA, Finato N, Rocco M, Feruglio GA, Puricelli C, Cigola E, Quaini F, Sonnenblick EH, Olivetti G, Anversa P: Structural basis of end-stage failure in ischemic cardiomyopathy in humans. Circulation 1994, 89:151-63.
• [33]Ling LH, Kistler PM, Ellims AH, Iles LM, Lee G, Hughes GL, Kalman JM, Kaye DM, Taylor AJ: Diffuse ventricular fibrosis in atrial fibrillation: noninvasive evaluation and relationships with aging and systolic dysfunction. J Am Coll Cardiol 2012, 60:2402-8.
• [34]Dall’Armellina E, Piechnik SK, Ferreira VM, Si QL, Robson MD, Francis JM, Cuculi F, Kharbanda RK, Banning AP, Choudhury RP, Karamitsos TD, Neubauer S: Cardiovascular magnetic resonance by non contrast T1-mapping allows assessment of severity of injury in acute myocardial infarction. J Cardiovasc Magn Res 2012, 15:15.
• [35]Karamitsos TD, Piechnik SK, Banypersad SM, Fontana M, Ntusi NB, Ferreira VM, Whelan CJ, Myerson SG, Robson MD, Hawkins PN, Neubauer S, Moon JC: Non-contrast T1 mapping for the diagnosis of cardiac amyloidosis. J Am Coll Cardiol Cardiovasc Imaging 2013, 6:488-97.
• [36]Moon J, Messroghli D, Kellman P, Piechnik S, Robson M, Ugander M, Gatehouse P, Arai A, Friedrich M, Neubauer S, Schulz-Menger J, Schelbert E: Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement. J Cardiovasc Magn Reson 2013, 15:92. BioMed Central Full Text
• [37]Liu S, Han J, Nacif MS, Jones J, Kawel N, Kellman P, Sibley CT, Buemke DA: Diffuse myocardial fibrosis evaluation using cardiac magnetic resonance T1 mapping: sample size considerations for clinical trials. J Cardiovasc Magn Reson 2012, 14:90. BioMed Central Full Text
• [38]Wong TC, Piehler K, Meier CG, Testa SM, Klock AM, Aneizi AA, Shakesprere J, Kellman P, Shroff SG, Schwartzman DS, Mulukutla SR, Simon MA, Schelbert EB: Association between expansion of extracellular matrix expansion quantified by cardiovascular magnetic resonance and short-term mortality. Circulation 2012, 126:1206-16.
• [39]Valentini G, Vitale DF, Giunta A, Malone S, Gerundo G, Arnese M, Tirri E, Pelaggi N, Giacummo A, Tirri G, Condorelli M: Diastolic abnormalities in systemic sclerosis: evidence for associated defective cardiac function reserve. Ann Rheum Dis 1996, 55:455-60.
• [40]Jellis C, Martin J, Narula J, Marwick TH: Assessment of nonischemic myocardial fibrosis. J Am Coll Cardiol 2010, 56:89-97.
• [41]Moreo A, Ambrosio G, de Chiara B, Pu M, Tran T, Mauri F, Raman SV: Influence of myocardial fibrosis on left ventricular diastolic function: noninvasive assessment by cardiac magnetic resonance and echo. Circ Cardiovasc Imaging 2009, 2:437-43.
• [42]Mottram PM, Haluska B, Leano R, Cowley D, Stowasser M, Marwick TH: Effect of aldosterone antagonism on myocardial dysfunction in hypertensive patients with diastolic heart failure. Circulation 2004, 110:558-65.
• [43]Tayebjee MH, Lim HS, Nadar S, MacFayden RJ, Lip GY: Tissue inhibitor of metalloproteinase-1 is a marker of diastolic dysfunction using tissue Doppler in patients with type 2 diabetes and hypertension. Eur J Clin Invest 2005, 35:8-12.
• [44]Knobelsdorff-Brenkenhoff F, Prothmann M, Dieringer M, Wassmuth R, Greiser A, Schwenke C, Niendorf T, Schulz-Menger J: Myocardial T1 and T2 mapping at 3 T: reference values, influencing factors and implications. J Cardiovasc Magn Reson 2013, 15:53. BioMed Central Full Text
• [45]Thavendiranathan P, Walls M, Giri S, Verhaert D, Rajagopalan S, Moore S, Simonetti OP, Raman SV: Improved detection of myocardial involvement in acute inflammatory cardiomyopathies using T2 mapping. Circ Cardiovasc Imaging 2011, 5:102-10.