Cardiomyopathy
Prevalence and Clinical Significance of Cardiac Arrhythmia in Anderson-Fabry Disease

https://doi.org/10.1016/j.amjcard.2005.05.033Get rights and content

Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by a deficiency in the enzyme α-galactosidase A. More than 60% of patients with AFD have evidence for cardiac involvement; the prevalence and clinical significance of arrhythmia in AFD are unknown. Seventy-eight consecutive patients (mean age 43.5 ± 15.0 years, range 13.0 to 83.0; 43 men) with AFD were studied for 1.9 years (range 0.25 to 10). All patients underwent clinical evaluation, 12-lead electrocardiography, and echocardiography. Sixty patients (76.9%) underwent 24-hour ambulatory electrocardiographic monitoring. Persistent atrial fibrillation (AF) was present in 3 of 78 patients (3.9%); 8 (13.3%) had paroxysmal AF, and 5 (8.3%) had nonsustained ventricular tachycardia (VT). Patients with nonsustained VT were all men, with a maximal left ventricular (LV) wall thickness >20 mm. Age (p <0.001), left atrial diameter (p = 0.001), maximal LV wall thickness (p = 0.003), LV mass index (p = 0.009), and angina (p = 0.02) were univariate predictors of AF or paroxysmal AF. Using these predictors in a stepwise logistic regression analysis model, age was the only independent predictor of AF or paroxysmal AF (odds ratio 1.2, 95% confidence interval 1.1 to 1.3, p = 0.001). During follow-up, there was 1 sudden cardiac death, 4 patients received pacemakers for bradyarrhythmia, and 1 received a biventricular pacemaker and an internal cardioverter defibrillator. In conclusion, arrhythmias are common in older patients with AFD. The high incidence of pacemaker implantation and sudden cardiac death suggests that arrhythmia has a significant impact on the natural history of AFD.

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Methods

From January 1993 to December 2003, 78 patients (43 men [55%]; mean age 43.5 ± 15.0 years, range 13 to 83) with AFD were assessed at The Heart Hospital, University College London, London, United Kingdom. The diagnosis of AFD was based on plasma α-galactosidase A levels and mutational analysis. Seven patients were identified during the screening of patients with unexplained left ventricular (LV) hypertrophy.3 The remainder were direct referrals for cardiac evaluation. Forty-one patients (6

Clinical evaluation

Seven patients (9%) were receiving β blockers, 2 were receiving sotolol for a history of paroxysmal AF, and 3 were receiving amiodarone for paroxysmal AF and 1 for nonsustained VT. Table 1 describes the prevalence of cardiac and AFD symptoms, and Table 2 lists baseline electrocardiographic and echocardiographic findings stratified by gender. There were no differences between men and women in the prevalence of cardiac symptoms. Men were more likely to have AFD symptoms and signs compared with

Discussion

AFD is an increasingly recognized cause of LV hypertrophy in middle-aged men and women.3, 9, 10 This study shows that arrhythmias are common in patients with AFD and that they are associated with significant morbidity.

Population-based studies have shown that the prevalence of AF in the normal population is <1%11; this prevalence is age dependant, with a prevalence of <1% in subjects <55 years old, increasing to ≥9% in those aged >80 years.11 In this study, the prevalence of AF was 4 times

Acknowledgment

We would like to thank Alan Milligan, RGJ, RGN, Linda Richfield, RGJ, RGN, Rebecca Bruce, RGN, Sian Goodwin, RGN, Melissa Blincoe, RGN, and Rebecca Bruce, RGN, from The Lysosomal Storage Disorders Unit and Amy Cole from The Charles Dent Metabolic Unit for their help in data collection.

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    Concentric left ventricular hypertrophy with an excessive left ventricular mass is the predominant structural finding in FD cardiomyopathy [18]. Complete atrioventricular blocks are rare in patients with FD, and it has been suggested that the accumulation of glycosphingolipids in and around the conduction system causes conduction disturbances in patients with FD [19–25]. Although information on cardiac pathology was not available in our case, there were no other identified causes for complete atrioventricular block, which strongly suggests that conduction disturbances are caused by FD.

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Dr. Shah and Dr. Hughes received an educational grant from Transkaryotic Therapies Europe-5S AB, Danderyd, Sweden. Dr. Ward and Dr. Tome are funded through a British Heart Foundation Junior Research Fellowship, London, United Kingdom.

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