SPC365

Screening for Anderson-Fabry Disease in patients with left ventricular hypertrophy and disease-related “red flags”

Session: SESSÃO DE POSTERS 57 - MIOCARDIOPATIA HIPERTRÓFICA
Speaker: Joana Certo Pereira

Congress: CPC 2025
Topic: F. Valvular, Myocardial, Pericardial, Pulmonary, Congenital Heart Disease
Theme: 17. Myocardial Disease
Subtheme: 17.3 Myocardial Disease – Diagnostic Methods
Session Type: Cartazes
FP Number: ---
Authors: Joana Certo Pereira; Maria Rita Lima; Rita Amador; Sérgio Maltês; Manuel Costa; Pedro Freitas; João Abecasis; Marisa Trabulo; António M. Ferreira; Carlos Aguiar; Regina Ribeiras; Bruno Rocha

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><strong>Introduction:</strong></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif">Left ventricular hypertrophy (LVH) is a common finding in cardiovascular imaging. It might sometimes result from rare, often subtle, but specific underlying causes. &ldquo;LVH&rdquo; is a key feature of Anderson-Fabry Disease (AFD), a lysosomal storage disease caused by decreased (or absence) of the &alpha;-galactosidase A enzyme activity (GLA). We aimed to assess the prevalence of AFD in patients with LVH of undetermined aetiology and AFD-related &lsquo;red-flags&rsquo; (RF).</span></span></p>

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<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><strong>Methods:</strong></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif">Single-centre prospective study of consecutive patients with severe LVH [defined as left ventricular (LV) thickness &ge;15 mm on cardiac magnetic resonance (CMR)] without an identifiable cause (i.e. confirmed cardiomyopathies or severe aortic stenosis). CMR studies from 2019 to May 2023 were reviewed, and patients presenting with at least one AFD-related RF (clinical, ECG, or cardiac imaging) were invited for screening with GLA activity testing (men) or genetic testing (women) starting in November 2023.</span></span></p>

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<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><strong>Results:</strong></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif">Out of 256 patients identified with severe LVH, 162 (63%) without an identifiable cause were included [68&plusmn;13 years, 65% male, left ventricular ejection fraction (LVEF) 57&plusmn;14% and thickness (LVT) 18&plusmn;3mm]. The main exclusion criteria were cardiac amyloidosis (45%), sarcomeric hypertrophic cardiomyopathy (27%), and death prior to evaluation (15%). Of these, 107 had &ge;1 AFD-related RF and were invited for AFD screening. The most common RF were ECG abnormalities and imaging findings &ndash; namely reduced global longitudinal strain (&ge; -15%) in 47 (29%) patients and late gadolinium enhancement (LGE) in the basal infero-lateral wall in 46 (29%) patients &ndash; whereas clinical RF were less frequent (<strong><span style="color:#0070c0">figure 1</span></strong>).</span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif">Among those invited for screening, 86 (80%) accepted the invitation, resulting in a diagnosis of AFD in 5 (6%) patients. These patients [68&plusmn;9years; 80% male; LVEF: 56&plusmn;6%; LVT: 18&plusmn;4mm] had a mean of 3&plusmn;1 RF, with the most frequent being basal infero-lateral LGE (80%). Two patients had classical AFD and the other three exhibited non-classical AFD. Four patients were referred for targeted therapy, of which two are already receiving treatment. Their families were referred for genetic counselling, having identified 2 obligate carriers, while the remainder of the individuals are undergoing further evaluation. </span></span></p>

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<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><strong>Conclusion:</strong></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif">Targeted screening in patients with severe LVH and AFD-related RF identified AFD in 6% in our cohort, thus yielding a high positive rate compared to other well-established organized screening programmes. Our findings suggests that a structured routine screening should be considered in patients with severe LVH and AFD-related RF, promoting disease awareness, early detection, targeted treatment and family counselling, contributing to the improvement of prognosis and outcomes.</span></span></p>