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Reduced coronary flow reserve in Anderson-Fabry disease measured by transthoracic Doppler echocardiography

Cardiovascular Ultrasound volume 3, Article number: 11 (2005) Cite this article

Abstract

Coronary flow reserve was assessed in a patient with Anderson-Fabry disease complicated by symmetric left ventricular hypertrophy. Coronary flow reserve was measurable in all three major coronary arteries providing an opportunity to compare regional coronary flow reserve from different vascular beds. In this patient all the three vascular beds supplied diffusely hypertrophied myocardium. Coronary flow disturbances in small intramyocardial perforating arteries were visible. The coronary flow reserve was reduced to a similar level (around to 2.0) in all three major arteries. In our patient with Anderson-Fabry disease, the coronary vasodilatation was blunted in a diffuse pattern corresponding to the myocardial hypertrophy distribution. In small intramyocardial arteries coronary flow was also disturbed. Accordingly, retrograde systolic flow and accelerated anterograde diastolic flow were documented.

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Background

Anderson-Fabry disease is an X-linked, multisystem, lysosomal storage disease (deficiency of enzyme α-galactosidase A), characterized by the accumulation of glycosphingolipids in various tissues and organs [1, 2], including skin, vascular endothelium, heart, kidneys, liver, lungs, pancreas and ganglion cells of the peripheral nervous system. The incidence is 1:117000. However, the rate may be underestimated because a common cardiac manifestation is myocardial hypertrophy that mimics hypertrophic cardiomyopathy. Abnormal storage in the cardiovascular system may also involve cardiac conduction system, valvular apparatus and endothelial cells in coronary vessels [1–3].

To assess coronary flow abnormalities in a patient with Anderson-Fabry disease, we performed transthoracic Doppler echocardiography. Using this method, coronary flow reserve is effectively measurable [4] and all three major coronary arteries are accessible in some patients [5, 6]. In a large series of 658 patients [6], coronary flow reserve was contemporarily recorded in left anterior descending (LAD) coronary artery (98% of patients), right coronary artery (RCA) (66% of patients) and circumflex (Cx) coronary artery (43% of patients). Additionally, flow disturbances in small intramyocardial perforating arteries were assessed as blood flow abnormalities at this level of coronary circulation were previously reported in left ventricular (LV) hypertrophy [7].

Case presentation

This 49-year-old male patient with Anderson-Fabry disease was referred to our hospital. He did not complain of anginal symptoms or dyspnea. As a part of an overall clinical evaluation, transthoracic echocardiography was performed, revealing a diffusely distributed myocardial hypertrophy, i.e. involving both (LV) free walls and the septum (the myocardial thickness at diastole was measured in the short parasternal-axis: the anterior segment of the septum- 19.6 mm; the posterior segment of the septum – 20.8 mm; the LV posterior wall – 20.7 mm; and the anterolateral wall 16.8 mm). Left ventricular systolic function was preserved (LV ejection fraction 68%). A precise assessment of myocardial hypertrophy by magnetic resonance imaging confirmed increased LV mass to 386 grams.

Methods

Using noninvasive, inexpensive and widely accessible method, B-mode and color Doppler transthoracic echocardiography, the segments of three major coronary arteries: LAD, Cx and right posterior descending (RPD) coronary artery or RCA were visualized (Figure 1,2). High quality recordings of flow velocity in all these coronary arteries were obtained using spectral Doppler.

Figure 1
figure1

Parasternal short axis view, color Doppler examination at the heart base level. Left main, left anterior descending (LAD) and origin of left circumflex (Cx) coronary arteries are seen. Blood flow within the left main coronary artery and proximal LAD is depicted in red, while in the Cx – in blue.

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Figure 2
figure2

Modified apical four-chamber view, color Doppler examination. Flow detected in long segment of the right posterior descending (RPD) coronary artery is depicted in red.

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Results

The coronary flow reserve in response to intravenous adenosine (140 μg/kg/min) was homogeneously reduced to a similar value in the major coronary arteries (LAD – 2.07; Cx- 2.18; RPD/RCA- 1.91). Small, intramyocardial branches of epicardial coronary arteries were visualized [intramyocardial perforators originated from LAD (Figure 3) and branches from RPD (Figure 4)]. Increased resistance to flow (probably due to myocardial hypertrophy and increased extravascular compressive forces) was demonstrated by the detection of flow with high velocity in spectral Doppler (figure 5, 6, 7) and color Doppler (Figures 3, 4, 5) in these penetrating vessels. The peak diastolic flow velocity was higher in the LAD perforator (41 cm/s – figure 6) than in the distal portion of LAD (25 cm/s – figure 7). The systolic flow in the LAD perforator was abnormally retrograde (figure 6).

Figure 3
figure3

Modified apical 2-chamber view, apical area, color Doppler examination. The LAD and the penetrating intramyocardial arteries (vertical perforators branching of the LAD) are seen.

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Figure 4
figure4

Modified apical 2-chamber view, middle segment of the inferior wall on color Doppler examination. Small (arch-shaped) arteries branching of the right posterior descending (RPD) coronary artery are seen.

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Figure 5
figure5

The orientation of Doppler gate within the LAD perforator.

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Figure 6
figure6

The flow velocity spectrum in the LAD perforator visualized in figure 5. In diastole the flow velocity is negative (towards ventricular chamber) and during systole the retrograde flow (towards epicardium) results in positive value of velocity.

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Figure 7
figure7

Diastolic flow velocity spectrum in distal portion of LAD.

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Discussion

Prevalence of Anderson-Fabry disease in patients with late-onset hypertrophic cardiomyopathy is about 6.3% in males [8] and 12% in females [9]. In contrast, among males with hypertrophic cardiomyopathy diagnosed at <40 years of age, the rate of appropriate verification of the diagnosis to Anderson-Fabry disease was lower i.e. 1.4% [8]. If properly recognized, Anderson-Fabry disease is treatable by enzyme replacement therapy and both cardiac and non-cardiac abnormalities may be reversed/reduced by substitution of α-galactosidase (especially in the early stage) [10]. Therefore, it is important to consider Anderson-Fabry disease in the differential diagnosis of hypertrophic cardiomyopathy. Anderson-Fabry disease is hardly indistinguishable from hypertrophic cardiomyopathy by echocardiography [9, 11, 12], however we made an attempt to identify potential differences (mainly quantitative) in table 1. Recently [13], the findings of magnetic resonance imaging have appeared useful in differential diagnosis (table 1). Clinical findings may be more helpful in differential diagnosis and we recommend to evaluate the presence or absence of all non-cardiac manifestations (dermatological, nephrological, neurological, ophthamological) of Anderson-Fabry disease in patients diagnosed as having hypertrophic cardiomyopathy.

Table 1 Comparison of echocardiography and MRI findings between Anderson-Fabry and hypertrophic cardiomyopathy.
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Conclusion

In our patient with Anderson-Fabry disease, the coronary vasodilatation was blunted in a diffuse pattern corresponding to the myocardial hypertrophy distribution. In small intramyocardial arteries coronary flow was disturbed. Accordingly, retrograde systolic flow and accelerated anterograde diastolic flow were documented. Transthoracic Doppler echocardiography is now the only method available to evaluate blood flow characteristics in small intramyocardial arteries.

Abbreviations

LAD:

left anterior descending coronary artery

RCA:

right coronary artery

RPD:

right posterior descending coronary artery

Cx:

circumflex coronary artery

References

  1. 1.

    Linhart A, Palecek T, Bultas J, Ferguson JJ, Hrudova J, Karetova D, Zeman J, Ledvinova J, Poupetova H, Elleder M, Aschermann M: New insights in cardiac structural changes in patients with Fabry's disease. Am Heart J 2000, 139: 1101-1108. 10.1067/mhj.2000.105105

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Kampmann C, Wiethoff CM, Perrot A, Beck M, Dietz R, Osterziel KJ: The heart in Anderson Fabry disease. Z Kardiol 2002, 91: 786-795. 10.1007/s00392-002-0848-5

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Doi Y, Toda G, Yano K: Sisters with atypical Fabry's disease with complete atrioventricular block. Heart 2003, 89: e2. 10.1136/heart.89.1.e2

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Dimitrow PP: Transthoracic Doppler echocardiography- noninvasive diagnostic window for coronary flow reserve assessment. Cardiovasc Ultrasound 2003, 1: 4. 10.1186/1476-7120-1-4

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Krzanowski M, Bodzon W, Dimitrow PP: Imaging of all three coronary arteries by transthoracic echocardiography: an illustrated guide. Cardiovasc Ultrasound 2003, 1: 16. 10.1186/1476-7120-1-16

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Rigo F: Coronary flow reserve in stress-echo lab. From pathophysiologic toy to diagnostic tool. Cardiovasc Ultrasound 2005, 3: 8. 10.1186/1476-7120-3-8

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Watanabe N, Akasaka T, Yamaura Y, Akiyama M, Kaji S, Saito Y, Yoshida K: Intramyocardial coronary flow characteristics in patients with hypertrophic cardiomyopathy: non-invasive assessment by transthoracic Doppler echocardiography. Heart 2003, 89: 657-658. 10.1136/heart.89.6.657

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Sachdev B, Takenaka T, Teraguci H, Tei C, Lee P, McKenna WJ, Elliott P: Prevalence of Anderson-Fabry disease in male patients with late onset of hypertrophic cardiomyopathy. Circulation 2002, 105: 1407-1411. 10.1161/01.CIR.0000012626.81324.38

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Chimenti C, Pieroni M, Morgante E, Antuzzi D, Russo A, Russo MA, Maseri A, Frustaci A: Prevalence of Fabry disease in female patients with late-onset hypertrophic cardiomyopathy. Circulation 2004, 110: 1047-1053. 10.1161/01.CIR.0000139847.74101.03

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Weidemann F, Breunig F, Beer M, Sandstede J, Turschner O, Voelker W, Ertl G, Knoll A, Wanner C, Strotmann JM: Improvement of cardiac function during enzyme replacement therapy in patients with Fabry disease: a prospective strain rate imaging study. Circulation 2003, 108: 1299-1301. 10.1161/01.CIR.0000091253.71282.04

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Nagueh SF: Fabry disease. Heart 2003, 89: 819-820. 10.1136/heart.89.8.819

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Pieroni M, Chimenti C, Ricci R, Sale P, Russo MA, Frustaci A: Early detection of Fabry cardiomyopathy by tissue Doppler imaging. Circulation 2003, 107: 1978-1984. 10.1161/01.CIR.0000061952.27445.A0

    Article  PubMed  Google Scholar 

  13. 13.

    Moon JC, Sachdev B, Elkington AG, McKenna WJ, Mehta A, Pennell DJ, Leed PJ, Elliott PM: Gadolinium enhanced cardiovascular magnetic resonance in Anderson-Fabry disease. Evidence for a disease specific abnormality of the myocardial interstitium. Eur Heart J 2003, 24: 2151-2155. 10.1016/j.ehj.2003.09.017

    Article  PubMed  Google Scholar 

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Affiliations

  1. 2nd Department of Cardiology, Collegium Medicum Jagiellonian University, Cracow, Poland

    Paweł Petkow Dimitrow

  2. 2nd Department of Internal Medicine, Collegium Medicum Jagiellonian University, Cracow, Poland

    Marek Krzanowski & Anetta Undas

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  1. Paweł Petkow Dimitrow
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  2. Marek Krzanowski
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Correspondence to Paweł Petkow Dimitrow.

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The author(s) declare that they have no competing interests.

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Dimitrow, P.P., Krzanowski, M. & Undas, A. Reduced coronary flow reserve in Anderson-Fabry disease measured by transthoracic Doppler echocardiography. Cardiovasc Ultrasound 3, 11 (2005). https://doi.org/10.1186/1476-7120-3-11

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Keywords

  • Left Anterior Descend
  • Coronary Flow
  • Hypertrophic Cardiomyopathy
  • Enzyme Replacement Therapy
  • Right Coronary Artery

Cardiovascular Ultrasound

ISSN: 1476-7120

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