Targeted screening of severe LVH patients with Anderson-Fabry Disease-related red flags diagnosed AFD in 6% of cases, enabling early detection and treatment.
Does targeted screening based on clinical and imaging red flags identify Anderson-Fabry Disease in patients with severe left ventricular hypertrophy of undetermined etiology?
Targeted screening for Anderson-Fabry Disease in patients with unexplained severe LVH and disease-related red flags yields a clinically meaningful diagnostic rate of 6%.
Absolute Event Rate: 0% vs 0%
Abstract Introduction Left ventricular hypertrophy (LVH) is a common finding in cardiovascular imaging. LVH may occasionally be due to rather uncommon, often concealed, yet precise mechanisms. Anderson-Fabry Disease (AFD), a lysosomal storage disease caused by decreased (or absence) of the α-galactosidase A enzyme activity (GLA), may underline LVH. Thus, we aimed to evaluate the prevalence of AFD in patients with LVH of undetermined aetiology and AFD-related ‘red-flags’ (RF). Methods Single-centre prospective study of consecutive patients with severe LVH defined as left ventricular (LV) thickness ≥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. Results Out of 256 patients identified with severe LVH, 162 (63%) without an identifiable cause were included 68±13 years, 65% male, left ventricular ejection fraction (LVEF) 57±14% and thickness (LVT) 18±3mm. The main exclusion criteria were cardiac amyloidosis (45%), sarcomeric hypertrophic cardiomyopathy (27%), and death prior to evaluation (15%). Of these, 107 had ≥1 AFD-related RF and were invited for AFD screening. The most common RF were ECG abnormalities and imaging findings – namely reduced global longitudinal strain (≥ -15%) in 47 (29%) patients and late gadolinium enhancement (LGE) in the basal infero-lateral wall in 46 (29%) patients – whereas clinical RF were less frequent (figure 1). Among those invited for screening, 86 (80%) accepted the invitation, resulting in a diagnosis of AFD in 5 (6%) patients. These patients 68±9years; 80% male; LVEF: 56±6%; LVT: 18±4mm had a mean of 3±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. Conclusion 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 such a routine screening should be considered, to improve AFD awareness, early detection, outcomes, prognosis and family counselling.
Pereira et al. (Sat,) reported a other. Targeted screening of severe LVH patients with Anderson-Fabry Disease-related red flags diagnosed AFD in 6% of cases, enabling early detection and treatment.