Onset and progression of the Anderson–Fabry disease related cardiomyopathy

Kampmann, Christoph; Linhart, Aleš; Baehner, Frank; Paleček, Tomáš; Wiethoff, Christiane M.; Miebach, E; Whybra, Catharina; Gal, Andreas; Bultas, Jan; Beck, Michael

doi:10.1016/j.ijcard.2008.03.007

Cited by 145 publications

(130 citation statements)

References 57 publications

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“…24 The current findings are also generally similar to those of a previous study of LVMI slope in 39 untreated men and 39 untreated women with FD. 25 Among the untreated men, LVMI increased over time in all age categories, with the greatest increases reported in men over the age of 40 years at baseline. 25 It should be noted that the studies of Weidemann et al 18 and Imbriaco et al 23 used cardiac magnetic resonance imaging (MRI), which provides higher spatial resolution than the standard echocardiographic data reported here.…”

Section: Discussionmentioning

confidence: 87%

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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Section: Discussionmentioning

confidence: 87%

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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“…agala agalsidase alfa, Gb 3 globotriaosylceramide, lyso-Gb 3 globotriaosylsphingosine, naïve treatment naïve prior to baseline, SE standard error, switch patients formerly treated with agalsidase beta. *Mean values significantly different from baseline based on 95% confidence intervals long-term outcomes and is relevant to both groups in this study, given that the annual mean increase in cardiac mass for untreated Fabry patients is 4.07 g/m 2.7 in males and 2.31 g/m 2.7 in females and even higher (6.59 g/m 2.7 in males and 3.77 g/m 2.7 in females) in those with LVH at baseline (Kampmann et al 2008).…”

Section: Discussionmentioning

confidence: 89%

Effect and Tolerability of Agalsidase Alfa in Patients with Fabry Disease Who Were Treatment Naïve or Formerly Treated with Agalsidase Beta or Agalsidase Alfa

et al. 2015

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Objectives: In a multicenter, open-label, treatment protocol (HGT-REP-059; NCT01031173), clinical effects and tolerability of agalsidase alfa (agala; 0.2 mg/ kg every other week) were evaluated in patients with Fabry disease who were treatment naïve or switched from agalsidase beta (switch). Over 24 months, data were collected on the safety profile; renal and cardiac parameters were assessed using estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMI), and midwall fractional shortening (MFS).Results (AEs) were consistent with the known safety profile of agala. Two switch patients had hospitalization due to possibly/probably drug-related serious AEs (one with transient ischemic attack, one with infusion-related AEs). One switch and two treatment-naïve patients discontinued treatment because of AEs. Three patients (one each switch, treatment naïve, and previous agala) died; no deaths were considered drug-related. There was no significant change from baseline in LVMI or MFS in either group. Similarly, eGFR remained stable; mean AE standard error annualized change in eGFR (mL/min/ 1.73 m 2 ) was À2.40 AE 1.04 in switch and À1.68 AE 2.21 in treatment-naïve patients.Conclusions: This is the largest cohort of patients with Fabry disease who were started on or switched to agala in an FDA-accepted protocol during a worldwide supply shortage of agalsidase beta. Because this protocol was primarily designed to provide access to agala, there were limitations, including not having stringent selection criteria and the lack of a placebo group.

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“…Renal involvement is progressive, eventually leading to end-stage renal disease (ESRD) by the fourth and fifth decades of life if untreated; prior to the advent of dialysis and renal transplantation, ESRD was the leading cause of death (Branton et al 2002). Cardiac manifestations include left ventricular (LV) hypertrophy, valvular disease, conduction abnormalities leading to arrhythmias, congestive heart failure, and coronary artery disease (Weidemann et al 2005;Linhart and Elliott 2007;Kampmann et al 2008;Linhart 2008;Morrissey et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Effects of Switching from Agalsidase Beta to Agalsidase Alfa in 10 Patients with Anderson-Fabry Disease

et al. 2012

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Onset and progression of the Anderson–Fabry disease related cardiomyopathy

Cited by 145 publications

References 57 publications

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

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

Effect and Tolerability of Agalsidase Alfa in Patients with Fabry Disease Who Were Treatment Naïve or Formerly Treated with Agalsidase Beta or Agalsidase Alfa

Effects of Switching from Agalsidase Beta to Agalsidase Alfa in 10 Patients with Anderson-Fabry Disease

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