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Clinical and genetic predictors of major cardiac events in patients with Anderson–Fabry Disease
  1. Vimal Patel1,
  2. Constantinos O'Mahony1,
  3. Derralynn Hughes2,
  4. Mohammad Shafiqur Rahman3,
  5. Caroline Coats1,
  6. Elaine Murphy4,
  7. Robin Lachmann4,
  8. Atul Mehta2,
  9. Perry M Elliott1
  1. 1The Heart Hospital, University College London Hospitals NHS Foundation Trust, London, UK
  2. 2The Royal Free Hospital and University College Medical School, London, UK
  3. 3Institute of Statistical Research and Training, University of Dhaka, Dhaka, Bangladesh
  4. 4The National Hospital for Neurology and Neurosurgery, Charles Dent Metabolic Unit, London, UK
  1. Correspondence to Professor Perry M Elliott, The Heart Hospital, University College London Hospitals NHS Foundation Trust, 16-18 Westmoreland Street, London W1G 8PH, UK; perry.elliott{at}ucl.ac.uk

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.

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.

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