Primary myocardial dysfunction in autosomal dominant EDMD. A tissue doppler and cardiovascular magnetic resonance...

Emery-Dreifuss muscular dystrophy is a genetically heterogeneous form of muscular dystrophy. One form is inherited in an X-linked fashion and is secondary to mutations in the gene encoding the nuclear protein emerin. A more common variant is inherited in an autosomal dominant way (EDMD2) due to mutations affecting the nuclear lamina protein lamin A/C. Typical features of both conditions are relatively mild skeletal muscle weakness, but cardiac involvement develops almost invariably by adult age, including conduction defects, arrhythmias and cardiomyopathy. Thus, early detection of cardiac abnormalities may be important for planning early therapeutic intervention.

In this study, we hypothesized that early myocardial dysfunction can be detected by tissue Doppler echocardiography and CMR in unselected patients with the autosomal dominant form of Emery-Dreifuss muscular dystrophy. This would suggest that fibrosis could be implicated in the pathogenesis of cardiac dysfunction in EDMD2.

Eight consecutive patients with genetically proven EDMD2 without pacemakers were enrolled in the study and compared to eight age-matched controls. All patients and controls first underwent a comprehensive echocardiographic-Doppler examination, followed by measurement of mitral annular velocities using pulsed tissue Doppler. Color M-mode tissue images were recorded from the parasternal long axis projections to derive Myocardial Velocity Gradients (MVG). Subsequently, all subjects underwent cardiovascular magnetic resonance (CMR) imaging for function, intrinsic myocardial tissue contrast using T1 and T2 weighted spin echo (TSE) for fat deposition and extrinsic contrast (Gadolinium-DTPA late fibrosis imaging). Strain measurements, using harmonic phase imaging (HARP) tagging were also derived.

Cavity dimensions LV mass and fractional shortening were similar between patients and controls. The overall body mass index was less in patients than in controls (14.5 +/- 1.4 vs. 18.1 +/- 2.4 g/m2, p < 0.002). While systolic MVG were similar between groups, the early diastolic MVG was lower in patients than in controls (4 +/- 1.2 s-1 vs. 7.1 +/- 2.7, p < 0.02). On CMR, LA and LV, RV volumes were similar between patients and controls. CMR strain patterns, however, showed a significant reduction in inferior wall contractility in patients compared to controls (-0.06 +/- 0.02 vs -0.09 +/- 0.03, p < 0.05). No patient showed late gadolinium enhancement.

Patients with EDMD2 have abnormal left ventricular function prior to developing any cardiac symptoms. The absence of myocardial fibrosis, however, by CMR suggests that this functional abnormality may not be secondary to scarring but could precede it. Tissue Doppler echocardiography and CMR are sensitive methods of assessing the presence of myocardial dysfunction prior to the development of any cardiovascular symptoms.