5. Barbey F, Oliver L, Schwarting A. Fabry nephropathy: 5 years of enzyme replacement therapy—a short review. NDT Plus. 2008;1:11–19.

6. Sanchez-Niño MD, Sanz AB, Carrasco S, et al. Globotriaosylsphingosine actions on human glomerular podocytes: implicationsfor Fabry nephropathy. Nephrol Dial Transplant. 2011;26:1797–1802.

7. National Institute for Health and Clinical Excellence. Chronic Kidney Disease: National Clinical Guideline for Early Identificationand Management in Adults in Primary and Secondary Care. Clinical Guideline 73. http://www.nice.org.uk/nicemedia/live/12069/42117/42117.pdf. Accessed 2010.

8. Lamb EJ, Stevens PE. Proteinuria or albuminuria? Nephrol Dial Transplant. 2010;25:3454–3455.9. Tøndel C, Bostad L, Hirth A, Svartstad E. Renal biopsy findings in children and adolescents with Fabry disease and minimal

albuminuria. Am J Kidney Dis. 2008;51:767–776.10. Fogo AB, Bostad L, Svarstad E, et al. Scoring system for renal pathology in Fabry disease: report of the international study group of

Fabry nephropathy (ISGFN). Nephrol Dial Transplant. 2010;25:2168–2177.

New Techniques for Assessing the Heart (Cardiac Imaging)Dr. Matthias Schmitt

South Manchester University Hospital, Manchester, United Kingdom

It is estimated that 1% of patients with unexplained left ventricular hypertrophy (LVH) seen in cardiovascularclinics have Fabry disease, totaling possibly 5000 undiagnosed patients in Europe at any given time. While Fabrydisease is not an imaging diagnosis, advanced imaging technologies are increasingly applied to phenotyping and riskstratification of patients with unexplained LVH. Furthermore, imaging technologies may help to select patients,guide timing for the initiation of enzyme-replacement therapy, and aid as a valuable tool in monitoring both diseaseprogression and therapy.

Because the confidence limits of imaging-based measurements are a function of the variability of the measure-ment, including the sum of intraobserver and interobserver variability and the imaging variability itself, cardiacmagnetic resonance (CMR) is able to reliably detect abnormalities and changes in ventricular structure and functionthat conventional 2D echocardiography cannot. As such, 2D transthoracic echocardiography (TTE) is suboptimalfor disease monitoring and assessment of treatment response. However, 2D TTE is the most widely available andapplied technology in patients with suspected or confirmed LVH and is perfectly capable of confirming or ruling outa diagnosis of LVH. In this respect, its role will remain unchallenged.

In contrast, strain rate imaging, and in particular a specific strain rate pattern termed the double peak sign(postsystolic shortening with a postsystolic peak of �50% of the height of the early systolic peak), has previouslybeen demonstrated to have excellent diagnostic characteristics for the detection of localized myocardial fibrosis.Importantly, it appears that the double peak sign present in unenhanced segments in patients with Fabry diseasemay be a marker of presence of diffuse background fibrosis.

The major drawback of echo-based strain and strain rate imaging is the need for time-consuming postprocessingand its fair reproducibility.

The major difference between Doppler- and MRI-based strain technologies is that CMR-based strain uses theposition of tags to describe motion of fixed points within the myocardium itself. Doppler-based strain measures thevelocity at 2 locations (gradient) along the Doppler sample beam. Therefore, Doppler-based strain technologies areinherently 1-dimensional, whereas CMR-based techniques are 2- and 3-dimensional. The major advantage ofDoppler-based strain as compared to CMR-based strain is the higher temporal resolution, allowing extraction ofmore meaningful strain rate data.

The major challenge for imaging technologies in general is to demonstrate that their application is impacting onclinical decision making and ideally on patients’ quality of life and outcomes. The best example for such anachievement at present is the role of CMR-based T2* imaging in patients with thalassemia major.

With this in mind, CMR-based technologies may have a role to play in the management of patients with Fabrydisease beyond late enhancement imaging. In this context, 3 promising applications—T1 mapping, T2 mapping,and equilibrium contrast CMR for the measurement and quantification of diffuse myocardial fibrosis—will bediscussed.

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FURTHER READINGFlett AS, Hayward MP, Ashworth MT, et al. Equilibrium contrast cardiovascular magnetic resonance for the measurement of diffuse

myocardial fibrosis: preliminary validation in humans. Circulation. 2010;122:138–144.Iles L, Pfluger H, Phrommintikul A, et al. Evaluation of diffuse myocardial fibrosis in heart failure with cardiac magnetic resonance

contrast-enhanced T1 mapping. J Am Coll Cardiol. 2008;52:1574–1580.Wansapura JP, Hor KN, Mazur W, et al. Left ventricular T2 distribution in Duchenne muscular dystrophy. J Cardiovasc Magn Reson.

2010;12:14.Beer M, Weidemann F, Breunig F, et al. Impact of enzyme replacement therapy on cardiac morphology and function and late

enhancement in Fabry’s cardiomyopathy. Am J Cardiol. 2006;97:1515–1518.Weidemann F, Niemann M, Sommer C, et al. Females with Fabry’s disease—an interdisciplinary diagnostic and therapeutic challenge

[in German]. Med Klin (Munich). 2010;105:627–634.Weidemann F, Niemann M, Breunig F, et al. Long-term effects of enzyme replacement therapy on Fabry cardiomyopathy: evidence for a

better outcome with early treatment. Circulation. 2009;119:524–529.Weidemann F, Niemann M, Herrmann S, et al. A new echocardiographic approach for the detection of non-ischaemic fibrosis in

hypertrophic myocardium. Eur Heart J. 2007;28:3020–3026.Weidemann F, Strotmann JM. Use of tissue Doppler imaging to identify and manage systemic diseases. Clin Res Cardiol.

2008;97:65–73.Weidemann F, Breunig F, Beer M, et al. The variation of morphological and functional cardiac manifestation in Fabry disease: potential

implications for the time course of the disease. Eur Heart J. 2005;26:1221–1227.Weidemann F, Breunig F, Beer M, et al. Improvement of cardiac function during enzyme replacement therapy in patients with Fabry

disease: a prospective strain rate imaging study. Circulation. 2003;108:1299–1301.Ho CY, Lopez B, Coelho-Filho OR, et al. Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy. N Engl J Med.

2010;363:552–563.

The Vessels: Focusing on the AortaElie Mousseaux, MD, PhD

Department of Cardiovascular Imaging, Institut National de la Santé et de la Recherche Médicale, Paris, France

Since accumulation of globotriaosylceramide (GL-3) in lysosomes of parenchymal and interstitial cells inmultiple organs of the body is further associated with major storage in endothelial cells and smooth cellproliferation in the arterial media, Fabry disease (FD) has to be considered as a specific vasculopathy.1 Severalstudies indicate that these vascular lesions occur as a result of vascular dysfunction with major endothelialalteration, modification of perfusion at the basal state and/or in response to stimuli, and prothrombic state dueto capillary damage. Although enzyme-replacement therapy has shown significant improvement in clearing theendothelium of stored GL-3, the more complex alterations in vascular function may not be influenced bytherapeutic intervention.

Using echo Doppler, increased intima-medial thickness has been found within carotid arteries in several studies,but without significant atherosclerotic plaque composed of a combination of fibrous tissue and cholesterol-richlipids. Concerning endothelial function, authors have suggested that the abnormal vascular response is not nitricoxide dependent, but that the nitric oxide pathway should be downregulated. Since no significant endothelialstorage was found in females and atypical cardiac variants are histopathologic findings, smooth muscle cellinvolvement with stored GL-3 has to be considered as the most prominent and probably as the earliest feature inFabry arteries. After Barbey et al2 found that Fabry plasma was capable of inducing proliferation of vascularsmooth cells and cardiomyocyte hypertrophy, 2 circulating compounds (sphingosine-1 phosphate and lyso-globot-riaosylceramide [lyso-Gb-3]) have now been described to induce such proliferation.

Despite a marked peripheral artery hypertrophy in patients with FD, only limited data are available on thestructural properties of the thoracic aorta. In the recent study by Barbey et al2 in 106 patients with FD from 3European centers, the diameter of the thoracic aorta was assessed using echocardiography and cardiovascularmagnetic resonance imaging (MRI). Aortic dilatation at the sinus of Valsalva was found in 32.7% of males and

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