Reproducibility of native myocardial T1 mapping in the assessment of Fabry disease and its role in early detection of cardiac involvement by cardiovascular magnetic resonance

Silvia Pica, Daniel M Sado, Viviana Maestrini, Marianna Fontana, Steven K White, Thomas Treibel, Gabriella Captur, Sarah Anderson, Stefan K Piechnik, Matthew D Robson, Robin H Lachmann, Elaine Murphy, Atul Mehta, Derralyn Hughes, Peter Kellman, Perry M Elliott, Anna S Herrey, James C Moon, Silvia Pica, Daniel M Sado, Viviana Maestrini, Marianna Fontana, Steven K White, Thomas Treibel, Gabriella Captur, Sarah Anderson, Stefan K Piechnik, Matthew D Robson, Robin H Lachmann, Elaine Murphy, Atul Mehta, Derralyn Hughes, Peter Kellman, Perry M Elliott, Anna S Herrey, James C Moon

Abstract

Background: Cardiovascular magnetic resonance (CMR) derived native myocardial T1 is decreased in patients with Fabry disease even before left ventricular hypertrophy (LVH) occurs and may be the first non-invasive measure of myocyte sphingolipid storage. The relationship of native T1 lowering prior to hypertrophy and other candidate early phenotype markers are unknown. Furthermore, the reproducibility of T1 mapping has never been assessed in Fabry disease.

Methods: Sixty-three patients, 34 (54%) female, mean age 48±15 years with confirmed (genotyped) Fabry disease underwent CMR, ECG and echocardiographic assessment. LVH was absent in 25 (40%) patients. Native T1 mapping was performed with both Modified Look-Locker Inversion recovery (MOLLI) sequences and a shortened version (ShMOLLI) at 1.5 Tesla. Twenty-one patients underwent a second scan within 24 hours to assess inter-study reproducibility. Results were compared with 63 healthy age and gender-matched volunteers.

Results: Mean native T1 in Fabry disease (LVH positive), (LVH negative) and healthy volunteers was 853±50 ms, 904±46 ms and 968±32 ms (for all p<0.0001) by ShMOLLI sequences. Native T1 showed high inter-study, intra-observer and inter-observer agreement with intra-class correlation coefficients (ICC) of 0.99, 0.98, 0.97 (ShMOLLI) and 0.98, 0.98, 0.98 (MOLLI). In Fabry disease LVH negative individuals, low native T1 was associated with reduced echocardiographic-based global longitudinal speckle tracking strain (-18±2% vs -22±2%, p=0.001) and early diastolic function impairment (E/E'=7 [6-8] vs 5 [5-6], p=0.028).

Conclusion: Native T1 mapping in Fabry disease is a reproducible technique. T1 reduction prior to the onset of LVH is associated with early diastolic and systolic changes measured by echocardiography.

Figures

Figure 1
Figure 1
Native T1 mapping in Fabry disease using ShMOLLI at 1.5 T. Top left: normal. Top right: a Fabry disease subject without LVH but clear myocardial T1 reduction – the myocardium is blue. Bottom left: Typical T1 when LVH present: the myocardial T1 is lower than without LVH and the basal infero-lateral wall has T1 elevation with a normal (pseudonormal?) surrounding area. Bottom right: rarely (4 patients), Fabry disease has a normal T1.
Figure 2
Figure 2
Mean septal T1 in LVH negative patients (n = 25), LVH positive patients (n = 38) and healthy volunteers (n = 63). Red solid line indicates -2SD below the mean native T1 of females healthy volunteers. Blue solid line indicates -2SD below the mean native T1 of males healthy volunteers.
Figure 3
Figure 3
Systolic and diastolic function in LVH negative Fabry disease patients. Global longitudinal speckle tracking strain of LVH negative-T1↓ subjects vs LVH negative-T1N subjects (left); E/E’ of LVH negative-T1↓ subjects vs LVH negative-T1N subjects (right).
Figure 4
Figure 4
Reproducibility of ShMOLLI sequences. ShMOLLI inter-study correlation (upper pannel) and Bland Altman analysis (lower pannel).

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