Right Ventricular Involvement in Patients with Fabry’s Disease and the Effect of Enzyme Replacement Therapy

Zusammenfassung

Ziel: Laut Echokardiografie betrifft der Morbus Fabry nicht nur den linken Ventrikel (LV), sondern auch den rechten Ventrikel (RV). Bis heute ist die Auswirkung der Enzymersatztherapie (ERT) auf den rechten Ventrikel mittels MRT noch nicht untersucht worden. Material und Methoden: In dieser prospektiven Studie wurden vierzehn Patienten mit genetisch gesichertem Morbus Fabry vor und nach 13 ± 1 Monaten ERT mittels 1,5 T MRT-Gerät untersucht. Alle Patienten wurden mittels Herz-MRT untersucht und die rechts- und linksventrikuläre Morphologie und die Funktionsparameter wurden ausgewertet. Ergebnisse: Der Ausgangswert für die RV Masse betrug 31 ± 6 g/m², enddiastolisches Volumen (EDV) 88 ± 13 ml/m², endsystolisches Volumen (ESV) 39 ± 9 ml/m², Schlagvolumen (SV) 49 ± 7 ml/m² und die Ejektionsfraktion (EF) 56 ± 5 %. Die rechtsventrikuläre Masse und das EDV verringerten sich signifikant nach 13 ± 1 Monaten Therapie (Masse 27 ± 7 g/m², p < 0,05, EDV 76 ± 24 ml/m², p < 0,05) ohne signifikante Veränderung des ESV (33 ± 13 ml/m²), SV (43 ± 12 ml/m²) und der EF (57 ± 7 %). Die LV Masse (102 ± 26 g/m² vs. 94 ± 27 g/m², p < 0,05), das EDV (76 ± 13 ml/m² vs. 66 ± 22 ml/m², p < 0,05) und ESV (29 ± 9 ml/m² vs. 23 ± 9 ml/m², p < 0,05) verringerten sich signifikant, während sich die EF (64 ± 7 % vs. 66 ± 5 %, p < 0,05) signifikant erhöhte. Schlussfolgerung: Neben dem bekannten Einfluss der ERT auf den linken Ventrikel verbessert die ERT die rechtsventrikuläre Masse und das EDV.

Abstract

Purpose: According to echocardiography reports, Fabry cardiomyopathy not only affects the left ventricle (LV) but also the right ventricle (RV). Until now no MRI studies about the effect of enzyme replacement therapy (ERT) on the RV are available. We evaluated the effect of ERT on the RV. Materials and Methods: In this prospective trial 14 patients with genetically proven Fabry’s disease were examined using a 1.5 T MR scanner before ERT and after 13 ± 1 months of ERT. All patients underwent cardiac MR imaging and the RV/LV cardiac morphology and function were analyzed. Results: At baseline examination the values were as follows: RV mass 31 ± 6 g/m², end-diastolic volume (EDV) 88 ± 13 ml/m², end-systolic volume (ESV) 39 ± 9 ml/m², stroke volume (SV) 49 ± 7 ml/m² and ejection fraction (EF) 56 ± 5 %. The RV mass and EDV decreased significantly after 13 ± 1 months on ERT (mass 27 ± 7 g/m², p < 0.05, EDV 76 ± 24 ml/m², p < 0.05), with no significant change of ESV (33 ± 13 ml/m²), SV (43 ± 12 ml/m²) and EF (57 ± 7 %). The LV mass (102 ± 26 g/m² vs. 94 ± 27 g/m², p < 0.05), EDV (76 ± 13 ml/m² vs. 66 ± 22 ml/m², p < 0.05) and ESV (29 ± 9 ml/m² vs. 23 ± 9 ml/m², p < 0.05) decreased significantly while the EF (64 ± 7 % vs. 66 ± 5 %; p < 0.05) increased significantly. Conclusion: Besides the known beneficial effect on the LV, ERT improves RV mass and EDV.

Key words

cardiac - MR imaging - metabolic Disorders

References

• 1 Uchino M, Uyama E, Kawano H et al. A histochemical and electron microscopic study of skeletal and cardiac muscle from a Fabry disease patient and carrier.  Acta Neuropathol. 1995;  90 334-338
• 2 Elleder M. Sequelae of storage in Fabry disease – pathology and comparison with other lysosomal storage diseases.  Acta Paediatr Suppl. 2003;  92 46-53 ; discussion 45
• 3 Kampmann C, Wiethoff C M, Perrot A et al. The heart in Anderson Fabry disease.  Z Kardiol. 2002;  91 786-795
• 4 Linhart A, Lubanda J C, Palecek T et al. Cardiac manifestations in Fabry disease. Review.  J Inherit Metab Dis. 2001;  24 75-83 ; discussion 65
• 5 Kampmann C, Baehner F A, Whybra C et al. The right ventricle in Fabry disease.  Acta Paediatr Suppl. 2005;  94 15-18 ; discussion 9 – 10
• 6 Palecek T, Dostalova G, Kuchynka P et al. Right ventricular involvement in Fabry disease.  J Am Soc Echocardiogr. 2008;  21 1265-1268
• 7 Niemann M, Breunig F, Beer M et al. The right ventricle in Fabry disease: natural history and impact of enzyme replacement therapy.  Heart. 2010;  96 1915-1919
• 8 Zehender M, Kasper W, Kauder E et al. Right ventricular infarction as an independent predictor of prognosis after acute inferior myocardial infarction.  N Engl J Med. 1993;  328 981-988
• 9 Engler R, Ray R, Higgins C B. Clinical assessment and follow up of functional capacity in patients with chronic congestive cardiomyopathy.  Am J Cardiol. 1982;  49 1832-1837
• 10 Baker B J, Wilen M M, Boyd C M et al. Relation of right ventricular ejection fraction to exercise capacity of patients with chronic left ventricular failure.  Am J Cardiol. 1984;  54 596-599
• 11 Di Salvo T G, Mathier M, Semigran M J et al. Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure.  J Am Coll Cardiol. 1995;  25 1143-1153
• 12 Beer M, Wagner D, Myers J et al. Effects of exercise training on myocardial energy metabolism and ventricular function assessed by quantitative phosphorus-31 magnetic resonance spectroscopy and magnetic resonance imaging in dilated cardiomyopathy.  J Am Coll Cardiol. 2008;  51 1883-1891
• 13 Kraemer N, Balzer J C, Schoth F et al. Vorhoftumoren in der kardialen MRT.  Fortschr Röntgenstr. 2009;  181 1038-1049
• 14 Eicher W, Kau T, Scarpatetti M et al. Bildgebung eines aorto-linksventrikulären Tunnels bei infektiöser Endokarditis mittels Dual-Source-Multidetektor-CT-Angiografie.  Fortschr Röntgenstr. 2009;  181 1084-1086
• 15 Wüst W, Zunker C, May M et al. Abgrenzbarkeit des interventrikulären Septums mit einem 20 % Kontrastmittelspülbolus in der CT-Koronarangiografie: Ein Vergleich von 64-Schicht- und Dual-Source-CT.  Fortschr Röntgenstr. 2009;  181 324-331
• 16 Grothues F, Moon J C, Bellenger N G et al. Interstudy reproducibility of right ventricular volumes, function, and mass with cardiovascular magnetic resonance.  Am Heart J. 2004;  147 218-23
• 17 Grothues F, Smith G C, Moon J CC et al. Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure or left ventricular hypertrophy.  Am J Cardiol. 2002;  90 29-34
• 18 Nassenstein K, Waltering K, Hollenhorst M et al. Kardiale MRT zur Quantifizierung der mikrovaskulären Obstruktion beim akuten Myokardinfarkt.  Fortschr Röntgenstr. 2009;  181 669-674
• 19 Nassenstein K, Bruder O, Breuckmann F et al. Prevalence, pattern, and functional impact of late gadolinium enhancement in left ventricular hypertrophy due to aortic valve stenosis.  Fortschr Röntgenstr. 2009;  181 472-476
• 20 Bansmann P M, Sénégas J, Muellerleile K et al. Assessment of left ventricular function parameters with a new three-dimensional shape model.  Fortschr Röntgenstr. 2009;  181 161-168
• 21 Nassenstein K, Breuckmann F, Huger M et al. Detection of myocardial fibrosis in systemic sclerosis by contrast-enhanced magnetic resonance imaging.  Fortschr Röntgenstr. 2008;  180 1054-1060
• 22 Kjaergaard J, Petersen C L, Kjaer A et al. Evaluation of right ventricular volume and function by 2D and 3D echocardiography compared to MRI.  Eur J Echocardiogr. 2006;  7 430-438
• 23 Fujimoto S, Mizuno R, Nakagawa Y et al. Estimation of the right ventricular volume and ejection fraction by transthoracic three-dimensional echocardiography: a validation study using magnetic resonance imaging.  Int J Card Imaging. 1998;  14 385-390
• 24 Katz J, Whang J, Boxt L M et al. Estimation of right ventricular mass in normal subjects and in patients with primary pulmonary hypertension by nuclear magnetic resonance imaging.  J Am Coll Cardiol. 1993;  21 1475-1481
• 25 Petersen S E, Hudsmith L E, Robson M D et al. Sex-specific characteristics of cardiac function, geometry, and mass in young adult elite athletes.  J Magn Reson Imaging. 2006;  24 297-303
• 26 Ortiz A, Oliveira J P, Wanner C et al. Recommendations and guidelines for the diagnosis and treatment of Fabry nephropathy in adults.  Nat Clin Pract Nephrol. 2008;  4 327-336
• 27 Lang R M, Bierig M, Devereux R B et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology.  J Am Soc Echocardiogr. 2005;  18 1440e63
• 28 Shors S M, Fung C W, François C J et al. Accurate quantification of right ventricular mass at MR imaging by using cine true fast imaging with steady-state precession: study in dogs.  Radiology. 2004;  230 383-388
• 29 Barbier C E, Johansson L, Lind L et al. The exactness of left ventricular segmentation in cine magnetic resonance imaging and its impact on systolic function values.  Acta Radiol. 2007;  48 285-291
• 30 Cerqueira M D, Weissman N J, Dilsizian V et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association.  Int J Cardiovasc Imaging. 2002;  18 539-542
• 31 Patel M R, Cecchi F, Cizmarik M et al. Cardiovascular events in patients with fabry disease natural history data from the fabry registry.  J Am Coll Cardiol. 2011;  57 1093-1099
• 32 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
• 33 Eng C M, Guffon N, Wilcox W R et al. Safety and efficacy of recombinant human alpha-galactosidase A-replacement-therapy in Fabry’s disease.  N Engl J Med. 2001b;  345 9-16
• 34 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
• 35 Imbriaco M, Pisani A, Spinelli L et al. Effects of enzyme-replacement therapy in patients with Anderson-Fabry disease: a prospective long-term cardiac magnetic resonance imaging study.  Heart. 2009;  95 1103-1107
• 36 Moon J C, Sachdev B, Elkington A G et al. 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
• 37 Tamborini G, Brusoni D, Torres Molina J E et al. Feasibility of a new generationthree-dimensional echocardiography for right ventricular volumetric and functional measurements.  Am J Cardiol. 2008;  102 499-505
• 38 Puchalski M D, Williams R V, Askovich B et al. Assessment of right ventricular size and function: echo versus magnetic resonance imaging.  Congenit Heart Dis. 2007;  2 27-31
• 39 Lorenz C H, Walker E S, Morgan V L et al. Normal human right and left ventricular mass, systolic function, and gender differences by cine magnetic resonance imaging.  J Cardiovasc Magn Reson. 1999;  1 7-21
• 40 Sandstede J, Lipke C, Beer M et al. Age- and gender-specific differences in left and right ventricular cardiac function and mass determined by cine magnetic resonance imaging.  Eur Radiol. 2000;  10 438-442
• 41 Winter M M, Bernink F J, Groenink M et al. Evaluating the systemic right ventricle by CMR: the importance of consistent and reproducible delineation of the cavity.  J Cardiovasc Magn Reson. 2008;  10 40
• 42 Alfakih K, Plein S, Bloomer T et al. Comparison of right ventricular volume measurements between axial and short axis orientation using steady-state free precession magnetic resonance imaging.  J Magn Reson Imaging. 2003;  18 25-32
• 43 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