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

Shah, Jaymin; Hughes, D.A.; Sachdev, Bhavesh; Tomé, Maite; Ward, Deirdre; Lee, Philip; Mehta, Atul; Elliott, Perry

doi:10.1016/j.amjcard.2005.05.033

Cited by 186 publications

(171 citation statements)

References 16 publications

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“…In addition, these results are in agreement with a recent report that patients with replacement fibrosis can die because of malignant arrhythmias (Kr€ amer et al 2014). Thus, together with other data (Shah et al 2005), the current findings emphasize the importance of regular Holter-ECG heart rhythm surveillance in patients with FD, particularly given that clinically relevant arrhythmias are not detectable on resting ECG. From a clinical perspective, the threshold of ventricular arrhythmias justifying the implantation of an automatic cardioverter defibrillator is still under debate but should be regarded as a prioritized research topic.…”

Section: Holter Ecgsupporting

confidence: 92%

Electrical Changes in Resting, Exercise, and Holter Electrocardiography in Fabry Cardiomyopathy

et al. 2015

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Background: In Fabry cardiomyopathy, little is known about the interaction between its key feature of myocardial replacement fibrosis and changes in resting, Holter, and exercise electrocardiography (ÀECG).Methods and Results: Resting ECG, 24-h Holter ECG, and exercise ECG were performed in 95 patients (50 women) with Fabry disease, staged using cardiac magnetic resonance imaging to measure left ventricular fibrosis. With resting ECG, T alterations were seen in patients with cardiac fibrosis, while time intervals and rhythm were unchanged (except for a longer QRS duration in patients with severe fibrosis). All patients with severe fibrosis showed T inversion, ST alteration, or both. With Holter ECG, maximum and minimum heart rate did not differ with fibrosis severity. Patients without fibrotic tissue showed less ventricular premature beats (VPB) (median 5/24 h) compared to those with mild (median 11/24 h) or severe fibrosis (median 115/24 h; P < 0.05, respectively). Fibrosis was a strong predictor of VPB burden (r 2 ¼ 0.5; P < 0.001). During exercise, patients with severe fibrosis had the least increase in systolic blood pressure (sBP) (47 AE 22 mmHg vs. 62 AE 25 mmHg, P < 0.05) and the lowest maximum heart rate (113 AE 18/min; P < 0.05). Patients with mild fibrosis had a high sBP during exercise (198 AE 37 mmHg; P < 0.05). Decreased diastolic blood pressure (>10 mmHg) occurred in some patients with no (3/41) or mild fibrosis (3/ 34) but not in patients with severe fibrosis (0/20; P < 0.01).Conclusions: Our data suggest that cardiac replacement fibrosis is responsible for repolarization abnormalities on resting ECG and increased VPB with Holter ECG. During exercise ECG, advanced cardiomyopathy is characterized by chronotropic incompetence with limitations on blood pressure and heart rate increase.

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Section: Holter Ecgsupporting

confidence: 92%

Electrical Changes in Resting, Exercise, and Holter Electrocardiography in Fabry Cardiomyopathy

et al. 2015

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“…This is in contrast with findings described in adults with FD who present with high incidence of paroxysmal atrial fibrillation, non-sustained ventricular tachycardia, AVB and sinus node dysfunction (Shah et al 2005;Frustaci and Chimenti 2007).…”

Section: -H Ecg Monitorscontrasting

confidence: 55%

“…Left ventricular hypertrophy (LVH) is the most frequent and well-recognised cardiac manifestation in adults (Linhart et al 2000;Kampmann et al 2002;Sachdev et al 2002;Elliott et al 2011). Other frequent complications and changes in adult patients with FD include atrial fibrillation, non-sustained ventricular tachycardia, QRS broadening, shortening of PR interval or atrio-ventricular blocks (AVBs) and sinus node dysfunction (Mehta et al 1977;Pochis et al 1994;Shah et al 2005). Several patients may develop mild to moderate valve insufficiencies, dilatation of the proximal aorta, arterial hypertension and coronary artery disease (Linhart et al 2000;Kampmann et al 2002;Nagueh 2003;Kleinert et al 2006;Elliott et al 2006;Barbey et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Early Cardiac Changes in Children with Anderson–Fabry Disease

et al. 2013

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Objective: Limited evidence is available about the early cardiac manifestation of Fabry disease (FD) in children. We aimed to evaluate cardiac involvement in children with FD by analysing serial structural and electrocardiographic changes.Methods: The data were acquired from 22 children with FD [11 males; median age 9.8 (ranging 2.5-16) years]. Seven patients (5 males) were on enzyme replacement therapy (ERT) with Agalasidase alpha. Echocardiography, ECG and 24-h ECG monitoring recordings were acquired during routine annual clinical controls. ECG data were compared to a group of age-and gender-matched controls.Results: At baseline, ECG and ECHO parameters of left ventricular mass were similar in both males and females. Three boys (all were on ERT) developed left ventricular hypertrophy (LVH) during two-year follow-up. The progression to LVH was accompanied by the appearance of frequent ventricular premature beats in two cases and supraventricular premature beats (SPBs) with T wave inversion in one case. T wave inversion and SPBs were detected in two younger relatives of a patient with LVH, in the absence of detectable LVH. Seven out of 22 patients had T wave abnormalities. Five of them were males (p ¼ 0.03) all carrying the N215S mutation (p ¼ 0.03). At baseline, median PR intervals were prolonged in FD subjects compared to controls [143 (122-177) vs. 122 (82-165) ms; p < 0.0001].Conclusions: Cardiac complications of FD become apparent in childhood as subtle changes with slow but detectable progression over time, with males more frequently affected than females. Progression of LVH was apparent in three children despite ERT.

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“…[4][5][6][7] The cardiovascular manifestations of FD can include leftventricular hypertrophy (LVH), atrial and left-ventricular arrhythmias, heart block, valvular dysfunction, angina, and arterial wall thickening. 4,5,[8][9][10][11][12][13] As the disease progresses, the hypertrophy becomes more severe, including the development of myocardial fibrosis and serious cardiac events including cardiac-related death. 4,5,8,11 Agalsidase-β, a recombinant form of human α-galactosidase A (Fabrazyme, Genzyme a Sanofi Company, Cambridge, MA), is approved for use as enzyme replacement therapy (ERT) for FD.…”

mentioning

confidence: 99%

“…4,5,[8][9][10][11][12][13] As the disease progresses, the hypertrophy becomes more severe, including the development of myocardial fibrosis and serious cardiac events including cardiac-related death. 4,5,8,11 Agalsidase-β, a recombinant form of human α-galactosidase A (Fabrazyme, Genzyme a Sanofi Company, Cambridge, MA), is approved for use as enzyme replacement therapy (ERT) for FD. In clinical studies, agalsidase-β at a dose of 1 mg/kg/2 weeks cleared microvascular endothelial glycosphingolipid deposits from the heart, as well as from kidney and skin, within 5 months.…”

mentioning

confidence: 99%

Analysis of left ventricular mass in untreated men and in men treated with agalsidase-β: data from the Fabry Registry

Germain

Weidemann

Abiose

et al. 2013

Genetics in Medicine

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Fabry disease (FD) (OMIM 301500) is a rare disorder in which globotriaosylceramide and other glycosphingolipids accumulate within lysosomes because of insufficient activity of α-galactosidase A. 1,2 Over time, the glycosphingolipid substrate progressively accumulates within blood vessels and various other cell types throughout the body. The initial signs and symptoms of FD frequently include neuropathic pain in the extremities, hypohidrosis, angiokeratomas, and gastrointestinal discomfort. 3 Over a period of decades, the accumulation of glycosphingolipids impairs vital organ function, putting patients at risk of developing renal failure, stroke, and cardiovascular dysfunction. [4][5][6] Because it is an X-linked disorder, hemizygous males typically experience the most severe manifestations of FD, 1 but heterozygous females can also develop serious complications. [4][5][6][7] The cardiovascular manifestations of FD can include leftventricular hypertrophy (LVH), atrial and left-ventricular arrhythmias, heart block, valvular dysfunction, angina, and arterial wall thickening. 4,5,[8][9][10][11][12][13] As the disease progresses, the hypertrophy becomes more severe, including the development of myocardial fibrosis and serious cardiac events including cardiac-related death. 4,5,8,11 Agalsidase-β, a recombinant form of human α-galactosidase A (Fabrazyme, Genzyme a Sanofi Company, Cambridge, MA), is approved for use as enzyme replacement therapy (ERT) for FD. In clinical studies, agalsidase-β at a dose of 1 mg/kg/2 weeks cleared microvascular endothelial glycosphingolipid deposits from the heart, as well as from kidney and skin, within 5 months. 14 It also provided long-term stabilization of renal function in patients with mild renal involvement 15 and delayed time to renal, cardiovascular, and cerebrovascular events in patients with more advanced FD. 16 Because it is a rare disorder, the randomized clinical trials of agalsidase-β included a relatively limited number of subjects with FD. 14,16 Several prospective, observational studies have reported cardiac data from patients treated with agalsidase-β, but these also involved only small numbers of patients. 17,18 Purpose: The aim of this study was to evaluate the progression of left ventricular hypertrophy in untreated men with Fabry disease and to assess the effects of agalsidase-β (recombinant human α-galactosidase A) on left ventricular hypertrophy. Methods:Longitudinal Fabry Registry data were analyzed from 115 men treated with agalsidase-β (1 mg/kg/2 weeks) and 48 untreated men. Measurements included baseline left-ventricular mass and at least one additional left-ventricular mass assessment over ≥2 years. Patients were grouped into quartiles, based on left-ventricular mass slopes. Multivariate logistic regression analyses identified factors associated with left ventricular hypertrophy progression.Results: For men in whom treatment was initiated at the age of 18 to <30 years, mean left ventricular mass slope was −3.6 g/year (n = 31) compared with +9.5 g/year in untr...

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

Cited by 186 publications

References 16 publications

Electrical Changes in Resting, Exercise, and Holter Electrocardiography in Fabry Cardiomyopathy

Electrical Changes in Resting, Exercise, and Holter Electrocardiography in Fabry Cardiomyopathy

Early Cardiac Changes in Children with Anderson–Fabry Disease

Analysis of left ventricular mass in untreated men and in men treated with agalsidase-β: data from the Fabry Registry

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