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. 2021 Jun 22;22(7):790-799.
doi: 10.1093/ehjci/jeaa101.

The myocardial phenotype of Fabry disease pre-hypertrophy and pre-detectable storage

João B Augusto  1   2 , Nicolas Johner  3 , Dipen Shah  3 , Sabrina Nordin  1   2 , Kristopher D Knott  1   2 , Stefania Rosmini  2 , Clement Lau  2   4 , Mashael Alfarih  1   2 , Rebecca Hughes  1   2 , Andreas Seraphim  1   2 , Ravi Vijapurapu  5 , Anish Bhuva  1   2 , Linda Lin  2 , Natalia Ojrzyńska  2   6 , Tarekegn Geberhiwot  7 , Gabriella Captur  2 , Uma Ramaswami  8 , Richard P Steeds  5 , Rebecca Kozor  9 , Derralynn Hughes  8 , James C Moon  1   2 , Mehdi Namdar  3
Affiliations

The myocardial phenotype of Fabry disease pre-hypertrophy and pre-detectable storage

João B Augusto et al. Eur Heart J Cardiovasc Imaging. .

Abstract

Aims: Cardiac involvement in Fabry disease (FD) occurs prior to left ventricular hypertrophy (LVH) and is characterized by low myocardial native T1 with sphingolipid storage reflected by cardiovascular magnetic resonance (CMR) and electrocardiogram (ECG) changes. We hypothesize that a pre-storage myocardial phenotype might occur even earlier, prior to T1 lowering.

Methods and results: FD patients and age-, sex-, and heart rate-matched healthy controls underwent same-day ECG with advanced analysis and multiparametric CMR [cines, global longitudinal strain (GLS), T1 and T2 mapping, stress perfusion (myocardial blood flow, MBF), and late gadolinium enhancement (LGE)]. One hundred and fourteen Fabry patients (46 ± 13 years, 61% female) and 76 controls (49 ± 15 years, 50% female) were included. In pre-LVH FD (n = 72, 63%), a low T1 (n = 32/72, 44%) was associated with a constellation of ECG and functional abnormalities compared to normal T1 FD patients and controls. However, pre-LVH FD with normal T1 (n = 40/72, 56%) also had abnormalities compared to controls: reduced GLS (-18 ± 2 vs. -20 ± 2%, P < 0.001), microvascular changes (lower MBF 2.5 ± 0.7 vs. 3.0 ± 0.8 mL/g/min, P = 0.028), subtle T2 elevation (50 ± 4 vs. 48 ± 2 ms, P = 0.027), and limited LGE (%LGE 0.3 ± 1.1 vs. 0%, P = 0.004). ECG abnormalities included shorter P-wave duration (88 ± 12 vs. 94 ± 15 ms, P = 0.010) and T-wave peak time (Tonset - Tpeak; 104 ± 28 vs. 115 ± 20 ms, P = 0.015), resulting in a more symmetric T wave with lower T-wave time ratio (Tonset - Tpeak)/(Tpeak - Tend) (1.5 ± 0.4 vs. 1.8 ± 0.4, P < 0.001) compared to controls.

Conclusion: FD has a measurable myocardial phenotype pre-LVH and pre-detectable myocyte storage with microvascular dysfunction, subtly impaired GLS and altered atrial depolarization and ventricular repolarization intervals.

Keywords: Fabry disease; cardiovascular magnetic resonance; electrocardiogram; global longitudinal strain; microvascular dysfunction.

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Figures

Figure 1
Figure 1
Schematic illustration of ECG intervals of interest.
Figure 2
Figure 2
Boxplots of maximum Q-wave amplitude (A), R-wave amplitude in V1 (B), Cornell index (C), Sokolow–Lyon index (D), and R-wave duration in V5 (E) according to T1 status in pre-hypertrophic Fabry patients. SL, Sokolow–Lyon.
Figure 3
Figure 3
Receiver-operator characteristic curves and corresponding AUCs for detection of cardiac involvement in pre-hypertrophic normal T1 Fabry disease. AUC, area under the curve; CI, confidence interval; GLS, global longitudinal strain.
Figure 4
Figure 4
Multiparametric cardiovascular magnetic resonance and electrocardiographic assessment in patients with FD and healthy controls. Left to right—steady-state free precession cines, native T1 mapping, stress MBF mapping, GLS, P-wave duration, and T-wave ratio. (A) Healthy control, no LVH, normal T1, MBF, GLS, P-wave time, and T-wave ratio. (B) FD with normal T1 and without LVH; MBF and GLS are mildly reduced, P wave is short and T-wave ratio reduced. (C) FD with low T1 and without LVH, low MBF and GLS, P-wave duration, and T-wave ratio are no different from control. (D) FD with LVH; T1 is low, MBF and GLS are significantly impaired, P wave is long and T-wave ratio increased.
Figure 5
Figure 5
Proposed stages of cardiac involvement in Fabry disease. A new pre-storage stage is proposed.
See this image and copyright information in PMC

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