Electrocardiogram analysis in Anderson-Fabry disease: a valuable tool for progressive phenotypic expression tracking

Anderson-Fabry disease is a lysosomal* storage disorder caused by mutations in the gene GLA (mapping on the X-chromosome). These genetic variants reduce the activity of an enzyme called α-galactosidase A. This results in a progressive accumulation of a group of lipids known as sphingolipids in various tissues (including the heart, kidneys, vessels, nervous system, and skin), causing dysfunction of affected organs.

Cardiac involvement in Anderson-Fabry disease presents with unexplained thickening of the cardiac muscle (referred to as left ventricular hypertrophy, LVH), mimicking the more common other inherited forms of hypertrophic cardiomyopathy (HCM). Symptoms are slow and fast heart rate and chest pain. Heart disease is the most important factor influencing the outcome in this condition, and increasing attention has been given to improving diagnostic accuracy due to the availability of specific treatment (which relates to enzyme replacement therapy).

In this context, the traditional electrocardiogram (ECG) remains the first diagnostic tool when assessing patients with LVH. Anderson-Fabry disease exhibits peculiar ECG features, and a recent Italian multicentre study showed that ECG provides useful clues for discriminating between Anderson-Fabry disease and other genetic forms of HCM.

The paper presented here is a multicentre study (including five centers from Italy and Spain), led by the IRCCS Azienda Ospedaliero-Universitaria di Bologna (Italy). It has the purpose of determining if the ECG can track cardiac disease progression in Anderson-Fabry disease by comparing ECG findings with disease severity expressed as the maximal thickness of the wall of the left cardiac chamber: maximal wall thickness (MWT) measured by echocardiogram. The study cohort includes 189 AFD patients, mainly female (61%), with a median age of 47 years, divided into four groups according to MWT (≤9 mm; 10–14 mm; 15–19 mm; ≥20 mm).

The paper reports that ECG parameters show a delay in the time it takes for the electrical impulse to traverse the cardiac chambers (atria and ventricles), parallel to the increase in myocardial wall thickness. Interestingly, these abnormalities don’t occur in isolation but tend to occur in certain patterns, in association with findings indicating electrocardiographic LVH, that can aid in recognizing Anderson-Fabry disease. Furthermore, some patients exhibit initial abnormal ECG results even when their echocardiogram appears normal.

Therefore, the study highlight that the electrocardiogram is not only useful for suggesting the diagnosis of Anderson-Fabry disease but also to track disease progression over time.

* The lysosomes are cellular organelles that are responsible for breaking down and recycling waste materials to keep the cell tidy and functioning properly.


Link to full article


Prepared by Elena Biagini Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. Confirmed by Ruth Biller (ARVC Selbsthillfe, Germany)

Front Cardiovasc Med. 2023 Jun 21;10:1184361. doi: 10.3389/fcvm.2023.1184361.