Skip to main content
SpringerLink
Log in

Intravascular ultrasound assessment of coronary artery involvement in Fabry disease

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Summary

Aim

We used intravascular ultrasound (IVUS) to characterize coronary artery involvement in patients with Fabry disease (FD).

Methods

Nine FD patients (5 women) were matched to 10 control patients (5 women) chosen from our IVUS database. Standard volumetric IVUS analyses were performed along with assessment of plaque echodensity.

Results

Plaques in FD patients were diffuse and hypoechogenic compared with more focal and more echogenic lesions in control patients. Echogenicity of plaques was significantly lower in FD patients (median 30.7  ±  12.9 vs 55.9  ±  15.7, p  =  0.0052, mean 37.2  ±  15.6 vs 66.2  ±  13.3, p  =  0.0014). Diffusiveness was assessed as differences between mean and median plaque burden versus the plaque burden in each of the analysed cross-sections. These differences were lower in FD vs controls (5.8  ±  4.8 vs 8.7  ±  6.6, p  <  0.001 for mean, and 5.8  ±  4.9 vs 8.8  ±  7.3, p  <  0.001 for median) indicating a more diffuse involvement. The occurrence of lipid cores was significantly higher in FD patients than in controls (2.4  ±  1.5 vs 1.0  ±  0.94, p  =  0.02).

Conclusion

IVUS showed diffuse hypoechogenic plaques in patients with FD. The explanation may be higher lipid content in plaques and accumulation of glycosphingolipid in smooth-muscle and endothelial cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aerts JM, Groenr JE, Kuiper S, et al (2008) Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci U S A. 105: 2812–2817.

    Article  PubMed  CAS  Google Scholar 

  • Altarescu G, Moore DF, Pursley R, et al (2001) Enhanced endothelium-dependent vasodilatation in Fabry disease. Stroke 32: 1559–1562.

    PubMed  CAS  Google Scholar 

  • Barbey F, Brakch N, Linhart A, et al (2006a) Increased carotid intima-media thickness in the absence of atherosclerotic plaques in an adult population with Fabry disease. Acta Paediatr Suppl 95: 63–68. doi:10.1080/08035320600618924.

    Article  Google Scholar 

  • Barbey F, Brakch N, Linhart A, et al (2006b) Cardiac and vascular hypertrophy in Fabry disease. Evidence for a new mechanism independent of blood pressure and glycosphingolipid deposition. Arterioscler Thromb Vasc Biol 26: 839–844. doi:10.1161/01.ATV.0000209649.60409.38.

    Article  CAS  Google Scholar 

  • Boutouyrie P, Laurent S, Laloux B, Lidove O, Grunfeld JP, Germain DP (2001) Non-invasive evaluation of arterial involvement in patients affected with Fabry disease. J Med Genet 38: 629–631. doi:10.1136/jmg.38.9.629.

    Article  PubMed  CAS  Google Scholar 

  • Clarke JT, Stolz JM, Garner JB (1980) Stability of plasma low density lipoprotein with abnormal glycolipid composition from patients with Fabry’s disease. Atherosclerosis 35: 155–163. doi:10.1016/0021-9150(80)90081-7.

    Article  PubMed  CAS  Google Scholar 

  • Dobrovolny R, Dvorakova L, Ledvinova J, et al (2005) Relationship between X-inactivation and clinical involvement in Fabry heterozygotes. Eleven novel mutations in the alpha–galactosidase A gene in the Czech and Slovak population. J Mol Med 83: 647–654. doi:10.1007/s00109-005-0656-2.

    Article  PubMed  CAS  Google Scholar 

  • Elleder M (2003) Sequelae of storage in fabry disease—pathology and comparison with other lysosomal storage diseases. Acta Paediatr Suppl 443: 46–53.

    Google Scholar 

  • Elleder M, Bradová V, Smíd F, et al (1990) Cardiocyte storage and hypertrophy as a sole manifestation of Fabry’s disease. Report on a case simulating hypertrophic non-obstructive cardiomyopathy. Virchows Arch A Pathol Anat Histopathol 417: 449–455. doi:10.1007/BF01606034.

    Article  PubMed  CAS  Google Scholar 

  • Elliott PM, Kindler H, Shah JS, et al (2006) Coronary microvascular dysfunction in male patients with Anderson–Fabry disease and the effect of treatment with alpha galactosidase. Heart 92: 357–360. doi:10.1136/hrt.2004.054015.

    Article  Google Scholar 

  • Ficher EA, Desnick RJ, Gordon RE, Eng CM, Griepp R, Goldman ME (1992) Fabry disease: an unusual cause of severe coronary disease in a young man. Ann Intern Med 117: 221–223.

    Google Scholar 

  • Heltianu C, Costache G, Azibi K, Poenaru L, Simionescu M (2002) Endothelial nitric oxide synthase gene polymorphisms in Fabry’s disease. Clin Genet 61: 423–429. doi:10.1034/j.1399-0004.2002.610605.x.

    Article  PubMed  CAS  Google Scholar 

  • Hůlková H, Ledvinová J, Poupětová H, Bultas J, Zeman J, Elleder M (2000) [Postmortem diagnosis of fabry disease in a female heterozygote leading to the detection of undiagnosed manifest disease in the family]. Cas Lek Cesk 138: 660–664.

    Google Scholar 

  • Kalliokoski RJ, Kalliokoski KK, Sundell J, et al (2005) Impaired myocardial perfusion reserve but preserved peripheral endothelial function in patients with Fabry disease. J Inherit Metab Dis 28: 563–573. doi:10.1007/s10545-005-0563-2.

    Article  PubMed  CAS  Google Scholar 

  • Kalliokoski RJ, Kantola I, Kalliokoski KK, et al (2006) The effect of 12-month enzyme replacement therapy on myocardial perfusion in patients with Fabry disease. J Inherit Metab Dis 29: 112–118. doi:10.1007/s10545-006-0221-3.

    Article  PubMed  CAS  Google Scholar 

  • Kanda A, Nakao S, Tsuyama S, Murata F, Kanzaki T (2000) Fabry disease: ultrastructural lectin histochemical analyses of lysosomal deposits. Virchows Arch 436: 36–42. doi:10.1007/PL00008196.

    Article  PubMed  CAS  Google Scholar 

  • Kleinert J, Dehout F, Schwarting A, et al (2006) Prevalence of uncontrolled hypertension in patients with fabry disease. Am J Hypertens 19: 782–787. doi:10.1016/j.amjhyper.2006.01.011.

    Article  PubMed  Google Scholar 

  • Kovarnik T, Reznícek V, Novackova K, Horak J, Simek S, Aschermann M (2003) TREASURE study: intRavascular ultRasound Evaluation of Atherosclerosis regreSsion Using atoRvastatin thErapy. Am J Cardiol 92 (Suppl.197L). [Abstract].

  • Linhart A, Lubanda J-C, Palecek T, et al (2001) Cardiac manifestations in Fabry disease. J Inherit Metab Dis 24(Suppl 2): 75–83. doi:10.1023/A:1012428009627.

    Article  PubMed  Google Scholar 

  • Linhart A, Kampmann C, Zamorano JL, et al (2007) Cardiac manifestations of Anderson–Fabry disease: results from the international Fabry outcome survey. Eur Heart J 28: 1228–1235. doi:10.1093/eurheartj/ehm153.

    Article  PubMed  Google Scholar 

  • MacDermot KD, Holmes A, Miners AH (2001) Anderson–Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet 38: 750–760. doi:10.1136/jmg.38.11.750.

    Article  PubMed  CAS  Google Scholar 

  • Mintz GS, Nissen S (2001) American College of Cardiology Clinical Expert Consensus Document on Standards for Aquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS) A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 37: 1478–1492. doi:10.1016/S0735-1097(01)01175-5.

    Article  PubMed  CAS  Google Scholar 

  • Moore DF, Scott LT, Gladwin MT, et al (2001) Regional cerebral hyperperfusion and nitric oxide pathway dysregulation in Fabry disease: reversal by enzyme replacement therapy. Circulation 104: 1506–1512. doi:10.1161/hc3801.096352.

    Article  PubMed  CAS  Google Scholar 

  • Moore DF, Altarescu G, Ling GS, et al (2002) Elevated cerebral blood flow velocities in Fabry disease with reversal after enzyme replacement. Stroke 33: 525–531.

    Article  PubMed  Google Scholar 

  • Moore DF, Ye F, Brennan ML, et al (2004) Ascorbate decreases Fabry cerebral hyperperfusion suggesting a reactive oxygen species abnormality – an arterial spin tagging study. J Magn Reson Imaging 20: 674–683. doi:10.1002/jmri.20162.

    Article  PubMed  Google Scholar 

  • Ogawa T, Kawai M, Matsui T, et al (1996) Vasospastic angina in a patient with Fabry’s disease who showed normal coronary angiographic findings. Jpn Circ J 60: 315–318. doi:10.1253/jcj.60.315.

    Article  PubMed  CAS  Google Scholar 

  • Rasheed Q, Nair R, Sheehan H, McB Hodgson J (1994) Correlation of intracoronary ultrasound plaque characteristics in atherosclerotic coronary artery disease patients with clinical variables. Am J Cardiol 73: 753–758. doi:10.1016/0002-9149(94)90876-1.

    Article  PubMed  CAS  Google Scholar 

  • Shah JS, Hughes DA, Sachdev B, et al (2005) Prevalence and clinical significance of cardiac arrhythmias in Anderson–Fabry disease. Am J Cardiol 96: 842–846. doi:10.1016/j.amjcard.2005.05.033.

    Article  PubMed  Google Scholar 

  • Schiffmann R, Rapkiewitz A, Abu-Asab M, et al (2006) Pathological findings in a patient with Fabry disease who died after 2.5 years of enzyme replacement. Virchows Arch 448: 337–343. doi:10.1007/s00428-005-0089-x.

    Article  PubMed  Google Scholar 

  • Shirai T, Ohtake T, Kimura M, et al (2000) Atypical Fabry’s disease presenting with cholesterol crystal embolization. Intern Med 39: 646–649.

    Article  PubMed  CAS  Google Scholar 

  • von Scheidt W, Eng CM, Fitzmaurice TF, et al (1991) An atypical variant of Fabry’s disease with manifestation confined to the myocardium. N Engl J Med 324: 395–399.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Second Department of Internal Medicine, First Faculty of Medicine, Charles University, Prague, Czech Republic

    T. Kovarnik, D. Karetova, J. Horak, R. Skulec, H. Skalicka, M. Aschermann & A. Linhart

  2. Cardiovascular Research Foundation, New York, NY, USA

    G. S. Mintz

  3. Department of Pharmacology, Third Faculty of Medicine, Charles University, Prague, Czech Republic

    J. Bultas

  4. Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic

    M. Elleder

  5. II.interni klinika VFN, U Nemocnice 2, 128 08, Praha 2, Czech Republic

    T. Kovarnik

Authors
  1. T. Kovarnik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. S. Mintz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Karetova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Horak
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Bultas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. Skulec
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H. Skalicka
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Aschermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M. Elleder
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A. Linhart
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T. Kovarnik.

Additional information

Communicating editor: Robert Desnick

Competing interests: None declared

References to electronic databases: Fabry disease: OMIM +301500.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kovarnik, T., Mintz, G.S., Karetova, D. et al. Intravascular ultrasound assessment of coronary artery involvement in Fabry disease. J Inherit Metab Dis 31, 753–760 (2008). https://doi.org/10.1007/s10545-008-0794-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10545-008-0794-0

Keywords

Search

Navigation