Heart Inflammation Prevalent in Fabry Disease Patients with Cardiomyopathy, Study Reports

Inflammation of the heart, known as myocarditis, is found in more than half of patients with Fabry disease cardiomyopathy — a consequence of fat molecule accumulation in the cells of the heart — and is associated with disease severity, a study has found.

Myocarditis may also limit the impact of enzyme replacement therapy (ERT).

The study, “Immune-mediated myocarditis in Fabry disease cardiomyopathy,” was published in the Journal of the American Heart Association.

Fabry disease patients are unable to produce an enzyme called alpha-galactosidase A, which is responsible for breaking down a type of fat called globotriaosylceramide (Gb3 or GL-3).

The buildup of Gb3 in different cells of the body, including the muscles, kidneys, and heart, results in a wide range of symptoms, such as kidney diseases, stroke, heart attack, and other heart diseases, or cardiomyopathies.

Researchers had already shown that Gb3 accumulation could promote inflammation and influence disease progression and responsiveness to enzyme replacement therapy. However, until now, myocarditis was poorly characterized, and its impact on Fabry disease was not clearly understood.

From January 2000 to May 2016, a team of Italian researchers investigated the incidence, mechanism, and impact of myocarditis in Fabry disease patients with cardiomyopathy by analyzing heart biopsies from 78 patients.

Myocarditis was identified if the heart tissue contained a high number of CD3+ T lymphocytes, a type of white blood cell involved in inflammation.

The severity of patients’ cardiac involvement was based on the thickness of the heart wall, a parameter known as maximal wall thickness (MWT): The higher the MWT value, the more severe the cardiomyopathy.

All clinical and pathological data were obtained at the time of diagnosis before patients were on ERT.

Analysis of heart tissues, by a technique known as histology, revealed myocarditis in 48 of the 78 patients. Magnetic resonance imaging (MRI) analysis showed that 24 of the patients (31%), mainly those with the highest MWT values, had a myocardial edema, which is an accumulation of excess fluid in certain compartments within the heart.

Importantly, researchers found that an increased number of CD3+ T lymphocytes correlated with the degree of MWT, severity of cell death, and serum biomarkers, all indicators of disease severity.

Researchers believe that myocarditis is immune-mediated and correlates with disease severity, with Gb3 accumulation leading to the activation of a parallel immune response and proportional immune-mediated heart damage.

“Myocarditis … can be disclosed by serum anti-heart or anti-myosin autoantibodies [serum biomarkers] and, in the advanced stage, by cardiac magnetic resonance. It may contribute to disease progression and ERT resistance,” the researchers concluded.