Assessment of Cardiac Involvement in Fabry Disease (FD) with Native T1 Mapping

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: 

• Native T1 values are significantly decreased in Fabry disease.

• Native T1 shows promising correlation to cardiac and Fabry-specific biomarkers.

• Native T1 mapping might have great potential for early disease detection and therapy monitoring.

Citation Format

• 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: 

• Die native T1-Zeit ist bei Patienten mit Morbus Fabry signifikant niedriger.

• Die native T1-Zeit korreliert zu kardialen und erkrankungsspezifischen Biomarkern.

• Das native T1-Mapping könnte großes Potenzial in Diagnostik und Therapie-Monitoring haben.

Key words

cardiac - technical aspects - MR imaging

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