FASHION Fabry Disease Hypertrophic Cardiomyopathy and Infammation

Inflammation in Anderson-Fabry Disease and Hypertrophic Cardiomyopathy: A Comparative Study (FASHION STUDY)

In Fabry disease (FD) and hypertrophic cardiomyopathy (HCM) systemic inflammation recently gained attention as a possible key pathophysiologic process involved in the development of cardiac hypertrophy and progression of the disease. Differences in inflammatory profile between FD and HCM have never been investigated so far.

This study investigate whether partecipants with FD and HCM have a different inflammatory phenotype defined by plasma biomarkers, serum proteomic profile and transcriptomic analysis in peripheral blood mononuclear cells. Moreover, the investigators sought to explore if a correlation exists between the inflammatory phenotype and the severity of cardiac phenotype cardiovascular events during 24 months of follow up.

This will be a prospective, multicenter, observational study. Adult partecipants with a genetically-proven diagnosis of FD and age-matched patients with a diagnosis of sarcomeric HCM will be enrolled, according to the following exclusion criteria:

1. Diagnosis Autoinflammatory disorders;
2. history of recurrent infections;
3. HIV infection;
4. Active cancer;
5. History of organ transplantation needing chronic immunosuppressor treatment. For each patient, at the time of enrollment, a blood sample will be collected and plasma levels of markers of inflammation, oxidative stress and cardiac remodeling will be determined (C-reactive protein, interleukin [IL]-6, IL-1β, IL-2, soluble vascular cell adhesion molecule, tumor necrosis factor [TNF], TNF receptor 1 and 2, Myeloperoxidase, calprotectin, uric acid, asymmetric dimethyl arginine, symmetric dimethyl arginine, matrix metalloprotease [MMP]-2, MMP-8 and MMP-9, galectin-1, galectin-3, B-type natriuretic peptide, midregional pro-atrial natriuretic peptide, monocyte chemoattractant protein.

Serum proteomic analysis and transcriptomic analysis on peripheral blood mononuclear cells, investigating molecular mediators involved in inflammatory pathways will be also performed. Partecipants enrolled will also undergo a comprehensive 2D-echocardiography with Doppler, Tissue Doppler (TD) and speckle tracking analysis and 12-leads electrocardiogram.

Inclusion Criteria:

• Age ≥18 years;
• Patients with confirmed genetic diagnosis of FD19;
• Patients with a known diagnosis of sarcomeric HCM adult (with pathogenic mutation in sarcomeric genes identified);
• Signed informed consent.

Exclusion Criteria:

• Age <18 years;
• Diagnosis of Autoinflammatory disorders;
• History of recurrent infections;
• HIV infection;
• Active cancer;
• History of organ transplantation needing chronic immunosuppressor treatment;
• Pregnancy
• Refusal to sign informed consent to study participation.