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Observational Study
. 2025 Jun 3;14(11):e041627.
doi: 10.1161/JAHA.124.041627. Epub 2025 May 23.

Evolution of Cardiac Damage Staged With Echocardiography in Fabry Disease

Rosa Lillo  1   2 , Maria Chiara Meucci  1 , Annamaria Del Franco  3 , Emanuele Monda  4 , Giulia Iannaccone  1   2 , Raffaello Ditaranto  5   6 , Federico Di Nicola  5   6 , Serena Serratore  7 , Antonella Lombardo  1   2 , Letizia Spinelli  8 , Guido Iaccarino  8   9 , Elena Biagini  5   6 , Francesco Cappelli  3 , Antonio Pisani  10 , Giuseppe Limongelli  4 , Iacopo Olivotto  3 , Maurizio Pieroni  3 , Francesco Burzotta  1   2 , Francesca Graziani  1
Affiliations
Observational Study

Evolution of Cardiac Damage Staged With Echocardiography in Fabry Disease

Rosa Lillo et al. J Am Heart Assoc. .

Abstract

Background: Fabry disease can be classified in 4 stages based on the extent of cardiac damage assessed with echocardiography. This staging is strongly associated with prognosis, with a doubled risk increase of cardiovascular events for each stage progression. The aims of the present study were to investigate the evolution of cardiac damage using this staging system during midterm follow-up and to identify predictors of stage worsening.

Methods and results: This is a retrospective, multicenter study, which included 168 patients with Fabry disease (38% men) categorized at baseline and follow-up in 4 stages, defined as follows: stage 0, no cardiac involvement; stage 1, left ventricular hypertrophy; stage 2, left atrial enlargement; and stage 3, ventricular impairment. After a median of 5 years, cardiac stage worsened of at least 1 class in 34 patients (24% of 143 patients in stage 0-2 at baseline), improved in 9 (12% of 73 patients in stages 1-3 at baseline), and remained stable in 125 (74% of the 168 patients enrolled). At multivariable logistic regression analysis, age (odds ratio, 1.05 [95% CI, 1.01-1.09]; P=0.006), male sex (odds ratio, 4.26 [95% CI, 1.54-11.79]; P=0.005), classic phenotype (odds ratio, 4.95 [95% CI, 1.30-18.72]; P=0.018), and renal failure (odds ratio, 10.40 [95% CI, 1.57-68.77]; P=0.015) emerged as independent predictors of cardiac damage stage deterioration.

Conclusions: Fabry disease is associated with a high rate of progression of cardiac damage during midterm follow-up, with ≈24% of patients experiencing cardiac stage worsening. Age, male sex, classic phenotype, and renal failure are independent predictors of stage progression.

Keywords: Fabry disease; cardiac damage; echocardiography; hypertrophic cardiomyopathy.

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Conflict of interest statement

Dr Lillo has received advisory board fees from Amicus Therapeutics, Sanofi Genzyme, Takeda, and Shire. Dr Biagini has received speaker fees from Amicus Therapeutics, Sanofi Genzyme, Takeda, and Bristol Myers Squibb. Dr Pieroni has received speaker and/or advisory board fees from Sanofi Genzyme, Pfizer, and Bristol Myers Squibb. Dr Limongelli has received advisory board fees from Amicus Therapeutics and an unrestricted grant from Sanofi. Dr Olivotto has received research grants from Bristol Myers Squibb, Cytokinetics, Sanofi Genzyme, Shire, Bayer, Amicus, Chiesi, and Menarini International; he has received also speaker and/or advisory board fees from Bristol Myers Squibb, Cytokinetics, Sanofi Genzyme, Amicus, Shire, Tenaya, and Rocket Pharma. Dr Graziani has received research grants from Takeda and Pfizer; she has also received advisory board fees from Amicus Therapeutics, Sanofi Genzyme, and Shire. Dr Pisani has received speaker fees from Amicus Therapeutics, Sanofi Genzyme, Takeda, and Shire. The remaining authors have no disclosures to report.

Figures

Figure 1
Figure 1. Criteria of the staging system based on echocardiographic signs of cardiac damage and the prevalence of each stage in the overall study population at baseline vs follow‐up (left panels). The central column reports histograms describing the distribution of each stage at baseline vs follow‐up in men (blue) and the right column in women (pink).
OR indicates odds ratio. Created with BioRender.com.
Figure 2
Figure 2. Sankey diagram illustrating changes of cardiac damage stage from baseline to follow‐up and the independent predictors of stage worsening.
Created with BioRender.com.
See this image and copyright information in PMC

References

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