Abstract
Background
Morphology and function of Fabry cardiomyopathy has been previously studied by echocardiography and cardiac magnetic resonance (CMR). However, the value of electrocardiography (ECG) in relation to these two techniques remains largely unknown.
Methods
One hundred fifty genetically confirmed Fabry patients were investigated using a comprehensive clinical workup comprising 12-lead ECG, echocardiography, and CMR.
Results
ECG parameters at rest [PR, P wave, QT, QTc, QT dispersion and time interval from the peak to the end of the T wave (Tpeak to Tend)] were normal in the entire cohort and did not distinguish between males and females or stages of cardiomyopathy. A significant positive correlation was found between left ventricular (LV) mass on CMR and both the QRS duration and the LV Sokolow index, with the highest values in male patients with an advanced cardiomyopathy stage. No prediction of late enhancement on CMR (a sign for replacement fibrosis) was possible by a single ECG parameter. However, the absence of ST or T alterations (in 37 of 38 patients) specifically excluded late enhancement on CMR.
Conclusion
Our data in a large cohort of Fabry patients, including all cardiomyopathy stages, show, in contrast to former assumptions, that ECG parameters are not suitable to stage Fabry cardiomoypathy. Most ECG parameters were normal in the complete cohort. However, the absence of ST or T alterations seems to almost exclude late enhancement on CMR in these patients.
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References
Alfakih K, Reid S, Jones T, Sivananthan M (2004) Assessment of ventricular function and mass by cardiac magnetic resonance imaging. Eur Radiol 10:1813–1822
Breunig F, Weidemann F, Beer M et al (2003) Fabry disease: diagnosis and treatment. Kidney Int Suppl 84:S181–S185
Cain PA, Ahl R, Hedstrom E et al (2009) Age and gender specific normal values of left ventricular mass, volume and function for gradient echo magnetic resonance imaging: a cross sectional study. BMC medical imaging 2.
Chimenti C, Morgante E, Tanzilli G et al (2008) Angina in fabry disease reflects coronary small vessel disease. Circ Heart Fail 3:161–169
Desnick R, Ionnou Y, Eng C (1995) Fabry disease: alpha galactosidase A deficiency. In: Scriver C, Beaudet A, Sly W, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw Hill, New York, pp 2741–2784
Eng CM, Banikazemi M, Gordon RE et al (2001) A phase 1/2 clinical trial of enzyme replacement in fabry disease: pharmacokinetic, substrate clearance, and safety studies. Am J Hum Genet 3:711–722
Eng CM, Germain DP, Banikazemi M et al (2006) Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med 9:539–548
Hughes DA, Elliott PM, Shah J et al (2008) Effects of enzyme replacement therapy on the cardiomyopathy of Anderson-Fabry disease: a randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa. Heart 2:153–158
Kampmann C, Wiethoff CM, Martin C et al (2002) Electrocardiographic signs of hypertrophy in fabry disease-associated hypertrophic cardiomyopathy. Acta Paediatr Suppl 439:21–27
Linhart A, Lubanda JC, Palecek T et al (2001) Cardiac manifestations in Fabry disease. J Inherit Metab Dis 75–83; discussion 65.
Mehta J, Tuna N, Moller JH, Desnick RJ (1977) Electrocardiographic and vectorcardiographic abnormalities in Fabry’s disease. Am Hear J 6:699–705
Mehta A, Clarke JT, Giugliani R et al (2009) Natural course of Fabry disease: changing pattern of causes of death in FOS - Fabry Outcome Survey. J Med Genet 8:548–552
Moon JC, Sachdev B, Elkington AG et al (2003) Gadolinium enhanced cardiovascular magnetic resonance in Anderson-Fabry disease. Evidence for a disease specific abnormality of the myocardial interstitium. Eur Heart J 23:2151–2155
Moon JC, Sheppard M, Reed E, Lee P, Elliott PM, Pennell DJ (2006) The histological basis of late gadolinium enhancement cardiovascular magnetic resonance in a patient with Anderson-Fabry disease. J Cardiovasc Magn Reson 3:479–482
Namdar M, Kampmann C, Steffel J et al (2010) PQ interval in patients with Fabry disease. Am J Cardiol 5:753–756
Namdar M, Steffel J, Vidovic M et al (2011) Electrocardiographic changes in early recognition of Fabry disease. Heart 6:485–490
Niemann M, Breunig F, Beer M et al (2010) The right ventricle in Fabry disease: natural history and impact of enzyme replacement therapy. Heart 23:1915–1919
Niemann M, Herrmann S, Hu K et al (2011) Differences in Fabry cardiomyopathy between female and male patients: consequences for diagnostic assessment. JACC Cardiovasc Imaging 6:592–601
Roudebush CP, Foerster JM, Bing OH (1973) The abbreviated PR interval of Fabry’s disease. N Engl J Med 7:357–358
Schiffmann R, Kopp JB, Austin HA 3rd et al (2001) Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA 21:2743–2749
Shah JS, Hughes DA, Sachdev B et al (2005) Prevalence and clinical significance of cardiac arrhythmia in Anderson-Fabry disease. Am J Cardiol 6:842–846
Waldek S, Patel MR, Banikazemi M, Lemay R, Lee P (2009) Life expectancy and cause of death in males and females with Fabry disease: findings from the Fabry Registry. Genet Med Off J Am Coll Med Genet 11:790–796
Weidemann F, Breunig F, Beer M et al (2003) Improvement of cardiac function during enzyme replacement therapy in patients with Fabry disease: a prospective strain rate imaging study. Circulation 11:1299–1301
Weidemann F, Breunig F, Beer M et al (2005) The variation of morphological and functional cardiac manifestation in Fabry disease: potential implications for the time course of the disease. Eur Heart J 12:1221–1227
Weidemann F, Niemann M, Breunig F et al (2009) Long-term effects of enzyme replacement therapy on fabry cardiomyopathy: evidence for a better outcome with early treatment. Circulation 4:524–529
Whybra C, Miebach E, Mengel E et al (2009) A 4-year study of the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa in 36 women with Fabry disease. Genet Med 6:441–449
Xia Y, Liang Y, Kongstad O, Holm M, Olsson B, Yuan S (2005) Tpeak-Tend interval as an index of global dispersion of ventricular repolarization: evaluations using monophasic action potential mapping of the epi- and endocardium in swine. J Interv Card Electrophysiol 2:79–87
Competing interest
Dr Wanner is a member of the European Advisory Board of the Fabry Registry sponsored by Genzyme Corp and has received travel assistance, speaking fees and research support. Drs Niemann, Weidemann and Breunig have received speaking fees from Genzyme Corp. The other authors report no conflicts.
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Communicated by: Robin Lachmann
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Niemann, M., Hartmann, T., Namdar, M. et al. Cross-sectional baseline analysis of electrocardiography in a large cohort of patients with untreated Fabry disease. J Inherit Metab Dis 36, 873–879 (2013). https://doi.org/10.1007/s10545-012-9540-8
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DOI: https://doi.org/10.1007/s10545-012-9540-8