Related Experiment Video

Updated: Dec 18, 2025

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
03:45

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

Published on: August 8, 2022

4.0K

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

João B Augusto1,2, Nicolas Johner3, Dipen Shah3

  • 1Institute of Cardiovascular Science, University College London, London, UK.

European Heart Journal. Cardiovascular Imaging
|June 10, 2020
PubMed

Insights

Cardiac involvement in Fabry disease (FD) shows measurable changes even before left ventricular hypertrophy (LVH) or detectable sphingolipid storage. These early signs include microvascular dysfunction and subtle electrocardiogram (ECG) alterations, indicating a pre-clinical myocardial phenotype.

Area of Science:

  • Cardiology
  • Genetics
  • Biochemistry

Background:

  • Fabry disease (FD) is a genetic disorder causing sphingolipid accumulation.
  • Cardiac involvement, including left ventricular hypertrophy (LVH), is a major complication of FD.
  • Current understanding suggests cardiac involvement manifests with low myocardial T1 on cardiovascular magnetic resonance (CMR) and electrocardiogram (ECG) changes, reflecting sphingolipid storage.

Purpose of the Study:

  • To investigate if a myocardial phenotype in FD exists prior to detectable sphingolipid storage and LVH.
  • To identify early cardiac changes in FD patients using advanced CMR and ECG analysis.

Main Methods:

  • Conducted same-day ECG with advanced analysis and multiparametric CMR (cines, GLS, T1/T2 mapping, stress perfusion, LGE) in 114 FD patients and 76 controls.
  • Compared pre-LVH FD patients with normal T1 values to controls and FD patients with low T1.

Main Results:

  • Pre-LVH FD patients with normal T1 showed reduced global longitudinal strain (GLS), microvascular dysfunction (lower myocardial blood flow), subtle T2 elevation, and minimal LGE compared to controls.
  • ECG abnormalities in this group included shorter P-wave duration and altered T-wave morphology, indicating changes in atrial depolarization and ventricular repolarization.
  • FD patients with low T1 (indicating storage) exhibited more pronounced ECG and functional abnormalities.

Conclusions:

  • Fabry disease exhibits a measurable myocardial phenotype even before LVH and detectable myocyte storage.
  • Early FD cardiac involvement is characterized by microvascular dysfunction, subtly impaired GLS, and altered atrial and ventricular electrical activity.
  • These findings suggest that advanced CMR and ECG analysis can detect cardiac changes in FD at a very early stage.
Abstract

Keywords:
Fabry diseasecardiovascular magnetic resonanceelectrocardiogramglobal longitudinal strainmicrovascular dysfunction

More Related Videos

Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix10:21

Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix

Published on: June 14, 2016

10.5K
Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model06:22

Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model

Published on: November 29, 2024

1.2K

Related Concept Videos

Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
263
Cardiomyopathy I: Introduction and Classification01:25

Cardiomyopathy I: Introduction and Classification

Cardiomyopathy, or CMP, is a group of diseases affecting the myocardial structure, impairing its ability to pump blood effectively. This condition can lead to arrhythmias, heart failure, or sudden cardiac death.Cardiomyopathies are classified into primary and secondary categories:Primary Cardiomyopathy refers to conditions involving only the heart muscle that are often idiopathic (of unknown cause) or genetic. They primarily affect the myocardium without the involvement of other systemic...
383
Cardiomyopathy II: Dilated Cardiomyopathy01:30

Cardiomyopathy II: Dilated Cardiomyopathy

Dilated cardiomyopathy, or DCM, is a progressive myocardial disorder characterized by ventricular chamber dilation and contractile dysfunction.EtiologyVarious factors can cause DCM, including hypertension and heavy alcohol intake, which contribute to the weakening and enlargement of the heart muscle. Viral infections, such as Coxsackievirus B, adenoviruses, and influenza, can lead to DCM by causing inflammation and damage to heart tissue. Certain chemotherapeutic agents, including daunorubicin,...
319
Cardiomyopathy IV: Restrictive Cardiomyopathy01:29

Cardiomyopathy IV: Restrictive Cardiomyopathy

Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...
337