Subepicardial dysfunction leads to global left ventricular systolic impairment in patients with limb girdle muscular dystrophy 2I

Abstract

AimThe mechanisms of cardiac dysfunction in limb girdle muscular dystrophy 2I (LGMD2I) are unclear. This study assessed deficits in cardiac morphology, function, and metabolism quantitatively in patients with a confirmed genetic diagnosis of the homozygous c.826C . A FKRP (fukutin-related protein) mutation, using a comprehensive magnetic resonance (MR) examination. Methods and resultsTen patients (7 male and 3 female) and 10 matched control subjects were recruited prospectively. Cardiac morphology by cine imaging, cardiac torsion and strain by MR tagging, and cardiac energetics by phosphorus-31 MR spectroscopy were measured. LGMD2I subjects were found to have a significant reduction in peak cardiac torsion (3.9 + 1.38 vs. 6.4 + 1.58, P ¼ 0.04), and in the ratio of torsion to endocardial strain (0.31 + 0.05 vs. 0.51 + 0.14, P ¼ 0.03), compared with control subjects. The impairment in torsion correlated strongly with reduction in EF (r ¼ 0.93, P , 0.001). Peak circumferential and longitudinal strains were preserved in the patients, however [LGMD2I, 16.4 + 3.2% vs. 18.3 + 3.5%, non-significant (NS); and LGMD2I, 17.0 + 3.0% vs. 18.4 + 3.5%, NS]. Cardiac cine analysis demonstrated reduced EF (47 + 7% vs, 58 + 4%, P ¼ 0.02) and stroke volume (61 + 11 mL vs. 81 + 13 mL, P ¼ 0.04), though no evidence of LV hypertrophy was found. The ratio of phosphocreatine to ATP (PCr/ATP) was reduced in the LGMD2I subjects compared with controls (1.50 + 0.24 vs. 1.94 + 0.12, P ¼ 0.0001). ConclusionsThe loss of torsion with preservation of circumferential and longitudinal strain in LGMD2I is a unique finding and suggests subepicardial dysfunction with abnormal transmission of force across the cardiac wall.--

Global FKRP Registry: observations in more than 300 patients with Limb Girdle Muscular Dystrophy R9

“…It is recognized that LGMDR9 may sometimes follow the presentation of DMD. Therefore, the care standards for DMD 21,22 should be followed, which include monitoring heart and lung function to enable intervention before significant deterioration occurs, as is the same with the congenital muscular dystrophies 23,24 …”

Left ventricular functional, structural and energetic effects of normal aging: Comparison with hypertension

“…Details of cardiac cine imaging and our algorithm for contour selection and calculating LV mass and systolic and diastolic parameters have been previously published [9] (S1 Appendix). The following hemodynamic parameters were derived: effective arterial elastance, a measure of afterload (Ea = end-systolic pressure (= systolic blood pressure x 0.9) / stroke volume normalised to body surface area), and end-systolic elastance, a measure of left ventricular systolic performance (Ees = end-systolic pressure / end-systolic volume normalised to body surface area [10].…”

“…Two tagged short axis images were obtained at the same session as previously described [2,14] (S1 Appendix). The Cardiac Image Modelling package (University of Auckland) was used to analyse the tagging data by aligning a mesh on the tags between the endo- and epicardial contours, and is described in detail elsewhere [9]. The epicardial torsion between the two short axis planes (taken as the circumferential-longitudinal shear angle defined on the epicardial surface) was calculated (Fig 1).…”

Effect of Physical Activity on Age-Related Changes in Cardiac Function and Performance in Women

“…Short axis slices of 10-mm thickness were prescribed as previously detailed. 37 The Cardiac Image Modelling package (University of Auckland) was used to analyze the tagging data by aligning a mesh on the tags between the endo-and epicardial contours. Circumferential strain was calculated throughout the cardiac cycle and is quoted for both the whole myocardial wall and the endocardial third of the wall thickness at midventricle.…”

“…The cardiac torsion was calculated for each cardiac phase. 37 In the healthy heart, torsion occurs such that there is homogeneity of fiber shortening across the myocardial wall 6 and indicates the dominance of epicardial fibers over endocardial fibers as a consequence of greater radius. The relationship between torsion and strain can be approximated by a ratio of the peak torsion and the peak circumferential strain in the endocardial third of the myocardium, the torsion:shortening ratio.…”