title: Clinical and genetic predictors of major cardiac events in patients with Anderson-Fabry Disease.
abstract: 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.
  
  
  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.
authors: The Heart Hospital, University College London Hospitals NHS Foundation Trust, London, UK.
authors: Vimal
authors: V
authors: Patel
authors: The Heart Hospital, University College London Hospitals NHS Foundation Trust, London, UK.
authors: Constantinos
authors: C
authors: O'Mahony
authors: The Royal Free Hospital and University College Medical School, London, UK.
authors: Derralynn
authors: D
authors: Hughes
authors: Institute of Statistical Research and Training, University of Dhaka, Dhaka, Bangladesh.
authors: Mohammad Shafiqur
authors: MS
authors: Rahman
authors: The Heart Hospital, University College London Hospitals NHS Foundation Trust, London, UK.
authors: Caroline
authors: C
authors: Coats
authors: The National Hospital for Neurology and Neurosurgery, Charles Dent Metabolic Unit, London, UK.
authors: Elaine
authors: E
authors: Murphy
authors: The National Hospital for Neurology and Neurosurgery, Charles Dent Metabolic Unit, London, UK.
authors: Robin
authors: R
authors: Lachmann
authors: The Royal Free Hospital and University College Medical School, London, UK.
authors: Atul
authors: A
authors: Mehta
authors: The Heart Hospital, University College London Hospitals NHS Foundation Trust, London, UK.
authors: Perry M
authors: http://orcid.org/0000-0003-3383-3984
authors: PM
authors: Elliott
mesh_terms: D000328:Adult; D000367:Age Factors; D001281:Atrial Fibrillation / Q000209:etiology; D001919:Bradycardia / Q000209:etiology / Q000628:therapy; D017281:Cost of Illness; D003643:Death; D000795:Fabry Disease / Q000150:complications* / Q000235:genetics / Q000401:mortality; D005260:Female; D005544:Forecasting; D006331:Heart Diseases / Q000209:etiology*; D006333:Heart Failure / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010138:Pacemaker, Artificial; D012720:Severity of Illness Index