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DOI: 10.1055/a-0836-2723
Assessment of Cardiac Involvement in Fabry Disease (FD) with Native T1 Mapping
Natives T1-Mapping zur Beurteilung einer kardialen Beteiligung bei Morbus FabryPublication History
28 October 2017
16 January 2019
Publication Date:
12 February 2019 (online)
![](https://www.thieme-connect.de/media/roefo/201910/lookinside/thumbnails/roefo-2934_10-1055-a-0836-2723-1.jpg)
Abstract
Purpose Fabry disease (FD) is an X-linked multi-organ disorder of lysosomal metabolism with cardiac disease being the leading cause of death. Identifying early FD-specific pathologies is important in the context of maximum therapeutic benefit in these stages. Therefore, the aim of this study was to investigate the value of quantitative cardiac T1 mapping as a potential disease-specific surrogate.
Methods 16 consecutive FD patients (9 female, 7 male; median age: 54 years, IQR 17) and 16 control patients (9 female, 7 male; median age: 52 years, IQR 20) were investigated at 1.5 Tesla. Native T1 mapping was performed using a modified look locker inversion recovery sequence (MOLLI) and native T1 times were measured within the septal myocardium at the midventricular short-axis section. Also functional parameters, left ventricular morphology, presence of late-gadolinium enhancement, cTnI- and Lyso-Gb3-Levels were evaluated.
Results The median native septal T1 time for FD was 889.0 ms and 950.6 ms for controls (p < 0.003). LGE and positive cTnI values (0.26 ± 0.21) were present in 5 FD patients (31.25 %), and left ventricular hypertrophy (LVH) was present in 4 FD patients (25.00 %). The 4 cTnI and 8 Lyso-Gb3 positive FD patients had significantly lower native T1 values (p < 0.05, respectively p < 0.01). Assuming a T1 cut-off value of 900 ms for the identification of increased cardiac lipid deposit, 9 patients with FD (56.25 %) had pathologic values (4 patients cTnI and 8 patients Lyso-Gb3 positive). Moreover, native septal T1 showed a good negative correlation to Lyso-Gb3 (r = – 0.582; p = 0.018).
Conclusion A pathologic cardiac native T1 time obviously reflects cardiac involvement in the scope of FD at tissue level. In the future native T1 mapping as an imaging biomarker might allow identification of early stages of cardiac involvement in FD before morphological changes are obvious.
Key Points:
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Native T1 values are significantly decreased in Fabry disease.
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Native T1 shows promising correlation to cardiac and Fabry-specific biomarkers.
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Native T1 mapping might have great potential for early disease detection and therapy monitoring.
Citation Format
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Roller FC, Fuest S, Meyer M et al. Assessment of Cardiac Involvement in Fabry Disease (FD) with Native T1 Mapping. Fortschr Röntgenstr 2019; 191: 932 – 939
Zusammenfassung
Ziel Morbus Fabry (FD) ist eine X-chromosomale Multiorganerkrankung des lysosomalen Metabolismus, wobei die kardiale Beteiligung die Haupttodesursache der Erkrankung darstellt. Deswegen ist es wichtig, möglichst frühe Erkrankungsmanifestationen zu detektieren, um einen maximalen therapeutischen Nutzen zu erzielen. Das Ziel unserer Studie war es, die Wertigkeit des nativen T1-Mappings als krankheitsspezifisches Äquivalent zu untersuchen.
Material und Methoden 16 konsekutive FD-Patienten (9 weiblich, 7 männlich; Altersmedian 54 Jahre; IQR 17) und 16 Kontrollpatienten (9 weiblich, 7 männlich; Altersmedian 52 Jahre, IQR 20) wurden mit einem 1,5-Tesla MRT-System untersucht. Das native T1-Mapping wurde als modifizierte Look-Locker-Sequenz (MOLLI) durchgeführt, die Messungen erfolgten im septalen linksventrikulären Myokard auf mittventrikulären Kurzachsenschnitten. Zudem wurden die linksventrikuläre Funktion und Morphologie, das Vorhandensein einer Kontrastmittelspätanreicherung sowie cTnI- und Lyso-Gb3-Laborwerte ausgewertet.
Ergebnisse Die mediane native septale T1-Zeit bei FD-Patienten betrug 889,0 und 950,6 für die Kontrollgruppe (p < 0,003). 5 (31,25 %) Patienten hatten eine Kontrastmittelspätanreicherung und positive cTnI-Werte, 4 Patienten (25,0 %) eine linksventrikuläre Hypertrophie. Die 5 cTnI- und die 8 Lyso-Gb3-positiven Patienten hatten signifikant niedrigere native T1-Zeiten (p < 0,05, respektive p < 0,01). Unter der Annahme eines Grenzwertes von 900 ms für die Detektion eines erhöhten, zellulären Lipidgehalts zeigten 9 Patienten (56,25 %) pathologische Werte. Davon waren 8 Patienten Lyso-Gb3- und 4 Patienten cTnI-positiv. Zudem zeigte sich eine gute negative Korrelation der nativen T1-Zeit zu den Lyso-Gb3-Werten (r = – 0,582; p = 0,018).
Schlussfolgerung Offensichtlich reflektiert eine pathologische native T1-Zeit eine kardiale Beteiligung bei FD-Patienten. Zukünftig könnte natives T1-Mapping als Biomarker in der Bildgebung behilflich sein, frühe kardiale Beteiligungen im Rahmen des FD zu detektieren, bevor andere morphologische Veränderungen zu erkennen sind.
Kernaussagen:
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Die native T1-Zeit ist bei Patienten mit Morbus Fabry signifikant niedriger.
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Die native T1-Zeit korreliert zu kardialen und erkrankungsspezifischen Biomarkern.
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Das native T1-Mapping könnte großes Potenzial in Diagnostik und Therapie-Monitoring haben.
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References
- 1 MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinicalmanifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet 2001; 38: 750e60
- 2 Hoey ET, Neil-Gallagher E. Utility of gadolinium enhancedcardiovascular MRI to differentiate Fabry’s disease from other causes of hypertrophic cardiomyopathy. Postgrad Med J 2012; 88: 731-732
- 3 Eng CM, Guffon N, Wilcox WR. et al. Safety and efficacy of recombinant human alpha-galactosidase A-replacement therapy in Fabry’s disease. N Engl J Med 2001; 345: 9-16
- 4 Messalli G, Imbriaco M, Avitabile G. et al. Role of cardiac MRI in evaluating patients with Anderson-Fabry disease: assessing cardiac effects of long-term enzyme replacement therapy. Radiol Med 2012; 117: 19-28
- 5 Moon JC, Sachdev B, Elkington AG. et al. Gadolinium enhanced cardiovascularmagnetic resonance in Anderson-Fabry disease: evidence for a disease specific abnormality of the myocardial interstitium. Eur Heart J 2003; 24: 2151e5
- 6 Moon JC, Reed E, Sheppard MN. et al. The histologic basis of late gadolinium enhancement cardiovascular magnetic resonance in hypertrophic cardiomyopathy. J Am Coll Cardiol 2004; 43: 2260-2264
- 7 Reingold JS, McGavock JM, Kaka S. et al. Determination of triglyceride in the human myocardium by magnetic resonance spectroscopy: reproducibility and sensitivity of the method. Am J Physiol Endocrinol Metab 2005; 289: E935-E939
- 8 O’Connor RD, Xu J, Ewald GA. et al. Intramyocardial triglyceride quantification by magnetic resonance spectroscopy: In vivo and ex vivo correlation in human subjects. Magn Reson Med 2011; 65: 1234-1238
- 9 den Hollander JA, Evanochko WT, Pohost GM. Observation of cardiac lipids in humans by localized 1H magnetic resonance spectroscopic imaging. Magn Reson Med 1994; 32: 175-180
- 10 Petritsch B, Köstler H, Machann W. et al. Non-invasive Determination of Myocardial Lipid Content in Fabry Disease by 1H-MR Spectroscopy. Fortschr Röntgenstr 2012; 184: 1020-1025
- 11 Petritsch B, Köstler H, Weng AM. et al. Myocardial lipid content in Fabry disease: a combined 1H-MR spectroscopy and MR imaging study at 3 Tesla. BMC Cardiovasc Disord 2016; 16: 205
- 12 Sado DM, White SK, Piechnik SK. et al. Identification and assessment of Anderson-Fabry Disease by Cardiovascular Magnetic Resonance Non-contrast myocardial T1 mapping clinical perspective. Circ Cardiovasc Imaging 2013; 6: 392-398
- 13 Thompson RB, Chow K, Khan A. et al. T1 mapping with cardiovascular MRI is highly sensitive for Fabry disease independent of hypertrophy and sex. Circ Cardiovasc Imaging 2013; 6: 637-645
- 14 Arends M, Wijburg FA, Wanner C. et al. Favourable effect of early versus late start of enzyme replacement therapy on plasma globotriaosylsphingosine levels in men with classical Fabry disease. Mol Genet Metab 2017; 121: 157-161
- 15 Sueoka H, Ichihara J, Tsukimura T. et al. Nano-LC-MS/MS for Quantification of Lyso-Gb3 and Its Analogues Reveals a Useful Biomarker for Fabry Disease. PLoS One 2015; 10: e0127048
- 16 Lavoie P, Boutin M, Abaoui M. et al. Fabry Disease Biomarkers: Analysis of Urinary Lyso-Gb3 and Seven Related Analogs Using Tandem Mass Spectrometry. Curr Protoc Hum Genet 2016; 90: 17.22.1-17.22.12
- 17 Togawa T, Kodama T, Suzuki T. et al. Plasma globotriaosylsphingosine as a biomarker of Fabry disease. Mol Genet Metab 2010; 100: 257-261
- 18 Roller FC, Wiedenroth C, Breithecker A. et al. Native T1 mapping and extracellular volume fraction measurement for assessment of right ventricular insertion point and septal fibrosis in chronic thromboembolic pulmonary hypertension. Eur Radiol 2017; 27: 1980-1991
- 19 Messroghli DR, Radjenovic A, Kozerke S. et al. Modified Look-Locker inversion recovery (MOLLI) for high resolution T1 mapping of the heart. Magn Reson Med 2004; 52: 141-146
- 20 Tanislav C, Gündüz D, Liebetrau C. et al. Cardiac Troponin I: A Valuable Biomarker Indicating the Cardiac Involvement in Fabry Disease. PLOS One 2016; 11: e0157640
- 21 Rombach SM, Dekker N, Bouwman MG. et al. Plasma globotriaosylsphingosine: diagnostic value and relation to clinical manifestations of Fabry disease. Biochim Biophys Acta 2010; 1802: 741-748
- 22 Feustel A, Hahn A, Schneider C. et al. Continuous cardiac troponin I release in Fabry disease. PLoS One 2014; 9: e91757
- 23 Kilinc G, Dogan OT, Berk S. et al. Significance of serum cardiac troponin I levels in pulmonary embolism. J Thorac Dis 2012; 4: 588-593
- 24 Ries M, Clarke JT, Whybra C. et al. Enzyme-replacement therapy with agalisade alfa in children with Fabry disease. Pediatrics 2006; 118: 924e32
- 25 Germain DP, Waldek S, Banikazemi M. et al. Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease. J Am Soc Nephrol 2007; 18: 1547-1557
- 26 Frustaci A, Morgante E, Russo MA. et al. Pathology and function of conduction tissue in Fabry disease cardiomyopathy. Circ Arrhythm Electrophysiol 2015; 8: 799-805