Themyocardial phenotype of Fabry disease pre-hypertrophy and pre-detectable storage

Joao Augusto; Nicolas Johner; Dipen  Shah; Sabrina Nordin; Kristopher Knott; Stefania Rosmini; Clement Lau; Mashael  Alfarih; Rebecca Hughes; Andreas Seraphim; Ravi Vijapurapu; Anish Bhuva; Linda Lin; Natalia Ojrzynska; Tarekegn Geberhiwot; Gabriella Captur; Uma Ramaswami; Richard Steeds; Rebecca Kozor; Derralynn A Hughes; James C Moon; Mehdi Namdar

doi:10.1093/ehjci/jeaa101

Themyocardial phenotype of Fabry disease pre-hypertrophy and pre-detectable storage

Joao Augusto, Nicolas Johner, Dipen Shah, Sabrina Nordin, Kristopher Knott, Stefania Rosmini, Clement Lau, Mashael Alfarih, Rebecca Hughes, Andreas Seraphim, Ravi Vijapurapu, Anish Bhuva, Linda Lin, Natalia Ojrzynska, Tarekegn Geberhiwot, Gabriella Captur, Uma Ramaswami, Richard Steeds, Rebecca Kozor, Derralynn A HughesJames C Moon, Mehdi Namdar

Cardiovascular Sciences

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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 (T_onset – T_peak; 104 ± 28 vs. 115 ± 20 ms, P = 0.015), resulting in a more symmetric T wave with lower T-wave time ratio (T_onset – T_peak)/(T_peak – T_end) (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.

Original language	English
Journal	European Heart Journal Cardiovascular Imaging
Early online date	8 Jun 2020
DOIs	https://doi.org/10.1093/ehjci/jeaa101
Publication status	E-pub ahead of print - 8 Jun 2020

Keywords

Fabry disease
cardiovascular magnetic resonance
electrocardiogram
microvascular dysfunction
global longitudinal strain

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Augusto, J., Johner, N., Shah, D., Nordin, S., Knott, K., Rosmini, S., Lau, C., Alfarih, M., Hughes, R., Seraphim, A., Vijapurapu, R., Bhuva, A., Lin, L., Ojrzynska, N., Geberhiwot, T., Captur, G., Ramaswami, U., Steeds, R., Kozor, R., ... Namdar, M. (2020). Themyocardial phenotype of Fabry disease pre-hypertrophy and pre-detectable storage. European Heart Journal Cardiovascular Imaging. Advance online publication. https://doi.org/10.1093/ehjci/jeaa101

@article{8081bf7b06cf49c7b268215c8781a21f,

title = "Themyocardial phenotype of Fabry disease pre-hypertrophy and pre-detectable storage",

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, microvascular dysfunction, global longitudinal strain",

author = "Joao Augusto and Nicolas Johner and Dipen Shah and Sabrina Nordin and Kristopher Knott and Stefania Rosmini and Clement Lau and Mashael Alfarih and Rebecca Hughes and Andreas Seraphim and Ravi Vijapurapu and Anish Bhuva and Linda Lin and Natalia Ojrzynska and Tarekegn Geberhiwot and Gabriella Captur and Uma Ramaswami and Richard Steeds and Rebecca Kozor and Hughes, {Derralynn A} and Moon, {James C} and Mehdi Namdar",

year = "2020",

month = jun,

day = "8",

doi = "10.1093/ehjci/jeaa101",

language = "English",

journal = "European Heart Journal Cardiovascular Imaging",

issn = "2047-2404",

publisher = "Oxford University Press",

}

Augusto, J, Johner, N, Shah, D, Nordin, S, Knott, K, Rosmini, S, Lau, C, Alfarih, M, Hughes, R, Seraphim, A, Vijapurapu, R, Bhuva, A, Lin, L, Ojrzynska, N, Geberhiwot, T, Captur, G, Ramaswami, U, Steeds, R, Kozor, R, Hughes, DA, Moon, JC & Namdar, M 2020, 'Themyocardial phenotype of Fabry disease pre-hypertrophy and pre-detectable storage', European Heart Journal Cardiovascular Imaging. https://doi.org/10.1093/ehjci/jeaa101

TY - JOUR

T1 - Themyocardial phenotype of Fabry disease pre-hypertrophy and pre-detectable storage

AU - Augusto, Joao

AU - Johner, Nicolas

AU - Shah, Dipen

AU - Nordin, Sabrina

AU - Knott, Kristopher

AU - Rosmini, Stefania

AU - Lau, Clement

AU - Alfarih, Mashael

AU - Hughes, Rebecca

AU - Seraphim, Andreas

AU - Vijapurapu, Ravi

AU - Bhuva, Anish

AU - Lin, Linda

AU - Ojrzynska, Natalia

AU - Geberhiwot, Tarekegn

AU - Captur, Gabriella

AU - Ramaswami, Uma

AU - Steeds, Richard

AU - Kozor, Rebecca

AU - Hughes, Derralynn A

AU - Moon, James C

AU - Namdar, Mehdi

PY - 2020/6/8

Y1 - 2020/6/8

N2 - 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.

AB - 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.

KW - Fabry disease

KW - cardiovascular magnetic resonance

KW - electrocardiogram

KW - microvascular dysfunction

KW - global longitudinal strain

U2 - 10.1093/ehjci/jeaa101

DO - 10.1093/ehjci/jeaa101

M3 - Article

SN - 2047-2404

JO - European Heart Journal Cardiovascular Imaging

JF - European Heart Journal Cardiovascular Imaging

ER -

Themyocardial phenotype of Fabry disease pre-hypertrophy and pre-detectable storage

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Keywords

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