RT Journal Article
SR Electronic
T1 Clinical and genetic predictors of major cardiac events in patients with Anderson–Fabry Disease
JF Heart
JO Heart
FD BMJ Publishing Group Ltd and British Cardiovascular Society
SP 961
OP 966
DO 10.1136/heartjnl-2014-306782
VO 101
IS 12
A1 Patel, Vimal
A1 O'Mahony, Constantinos
A1 Hughes, Derralynn
A1 Rahman, Mohammad Shafiqur
A1 Coats, Caroline
A1 Murphy, Elaine
A1 Lachmann, Robin
A1 Mehta, Atul
A1 Elliott, Perry M
YR 2015
UL http://heart.bmj.com/content/101/12/961.abstract
AB Background Anderson–Fabry Disease (AFD) is an X linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene. Some mutations are associated with prominent and, in many cases, exclusive cardiac involvement. The primary aims of this study were to determine the incidence of major cardiac events in AFD and to identify clinical and genetic predictors of adverse outcomes.Methods and results We studied 207 patients with AFD (47% male, mean age 44 years, mean follow-up 7.1 years). Fifty-eight (28%) individuals carried mutations that have been previously associated with a cardiac predominant phenotype. Twenty-one (10%) developed severe heart failure (New York Heart Association functional class (NYHA) ≥3), 13 (6%) developed atrial fibrillation (AF), 13 (6%) received devices for the treatment of bradycardia; there were a total of 7 (3%) cardiac deaths. The incidence of the primary endpoint (a composite of new onset AF, NYHA ≥ 3 symptoms, device insertion for bradycardia and cardiac death) was 2.64 per 100 person-years (CI 1.78 to 3.77). Age (HR 1.04, CI 1.01 to 1.08, p=0.004), Mainz Severity Score Index score (HR 1.05, CI 1.01 to 1.09, p=0.012) and QRS duration (HR 1.03, CI 1.00 to 1.05, p=0.020) were significant independent predictors of the primary endpoint. The presence of a cardiac genetic variant did not predict the primary end point.Conclusions AFD is associated with a high burden of cardiac morbidity and mortality. Adverse cardiac outcomes are associated with age, global disease severity and advanced cardiac disease but not the presence of cardiac genetic variants.