Systolic and Diastolic Function Assessment in Fabry Disease Patients Using Speckle-Tracking Imaging and Comparison with Conventional Echocardiographic Measurements Miriam Shanks, MD, Richard B. Thompson, PhD, Ian D. Paterson, MD, Brendan Putko, BSc, Aneal Khan, MSc, MD, Alicia Chan, MD, Harald Becher, MD, PhD, and Gavin Y. Oudit, MD, PhD, Edmonton and Calgary, Alberta, Canada Background: Fabry cardiomyopathy is characterized by progressive left ventricular hypertrophy (LVH) associated with diastolic dysfunction and is the most common cause of death in Fabry disease (FD). However, LVH is not present in all subjects, particularly early in disease progression and in female patients. Direct assessment of myocardial deformation by strain and strain rate (SR) analysis may be sensitive to detect subclinical Fabry cardiomyopathy independent of the presence of LVH. Methods: Systolic (longitudinal, circumferential, and radial systolic strain and SR) and diastolic (SR during isovolumic relaxation [SR IVR ] and early diastole and strain at peak transmitral E wave) function was assessed in 16 patients with FD using two-dimensional speckle-tracking echocardiography. In addition, mean S 0 and E 0 mitral annular velocities by Doppler tissue imaging were measured. Diastolic filling indices, including E/SR IVR and E/E 0 ratios, were calculated. The patients were compared with 24 healthy age-matched and gender- matched controls. Results: All 16 patients with FD had normal left ventricular ejection fractions, and nine patients had LVH. Compared with controls, patients with FD had reduced longitudinal systolic strain (P < .001) and systolic SR (P = .007), while there were no differences in circumferential systolic strain and S 0 . Diastolic function assessment showed reduced longitudinal early diastolic SR (P = .001), SR IVR (P < .001), and E/SR IVR (P < .001), while radial and circumferential diastolic function was not affected. Of the conventional diastolic function indices, reductions were seen in E (P = .006), E 0 (P = .021), and E/E 0 ratio (P < .001). After correcting for LVH, only SR IVR (P < .001) and E/SR IVR (P = .025) remained significantly different between patients with FD and controls, with sensitivity of 94% and specificity of 92% for SR IVR of 0.235 sec 1 (area under the receiver operating characteristic curve, 0.953). Conclusions: Strain and SR analysis is useful in identifying patients with FD with reduced myocardial function, with longitudinal systolic strain and diastolic isovolumic SR being superior to the other echocardiographic measurements of myocardial contraction and relaxation and independent of LVH. (J Am Soc Echocardiogr 2013;26:1407-14.) Keywords: Echocardiography, Strain, Strain rate, Speckle-tracking, Diastolic function, Myocardial function, Fabry disease Fabry disease (FD) is an X-linked glycolipid storage disease caused by a deficiency of a-galactosidase A enzyme resulting in progressive intracellular accumulation of glycosphingolipids in different tissues. Cardiac involvement is characterized by progressive left ventricular (LV) hypertrophy (LVH), heart failure, and arrhythmias. 1-3 Im- portantly, subclinical cardiac involvement may represent the first sign of organ damage, particularly in female carriers. 4 Large screen- ing studies have shown a high incidence of late-onset FD. 5,6 Fabry cardiomyopathy is one of the most common causes of death in these patients. 7,8 Enzyme replacement therapy has proved effective in reducing glycosphingolipid accumulation in the myocardium and improving cardiac function. 9,10 Echocardiography is a standard noninvasive screening test for Fabry cardiomyopathy. Because most patients with FD have normal LV systolic function, and up to 40% From the Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute (M.S., I.D.P., B.P., H.B., G.Y.O.), the Department of Biomedical Engineering (R.B.T.), and the Department of Medical Genetics (A.C.), University of Alberta, Edmonton, Alberta, Canada; the Department of Medical Genetics and Pediatrics, University of Calgary, Calgary, Alberta, Canada (A.K.). This study received financial support from the University Hospital Foundation and Alberta Innovates-Health Solutions. Reprint requests: Gavin Y. Oudit, MD, PhD, Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, 2C2 Walter Mackenzie Health Sciences Centre, 8440-112 Street, Edmonton, AB T6G 2B7, Canada (E-mail: gavin.oudit@ualberta.ca). 0894-7317/$36.00 Copyright 2013 by the American Society of Echocardiography. http://dx.doi.org/10.1016/j.echo.2013.09.005 1407