QT dispersion in alpha-myosin heavy-chain familial hypertrophic cardiomyopathy mice

Patients with familial hypertrophic cardiomyopathy (FHC) are at risk for ve ntricular arrhythmias and sudden death. Regional variability in the QT inte rval [QT dispersion (QTd)] is significantly increased in humans with FHC an d ventricular arrhythmias. A mouse model of FHC resulting from a mutation i n the alpha-myosin heavy-chain (Arg403Gln) was used to study the electrophy siologic phenotype of this disease. Cardiac electrophysiology studies and s urface ECGs were performed in FHC mice and wild-type controls to evaluate t he feasibility and significance of QTd measurements in predicting the risk for ventricular arrhythmias. Atrial and ventricular pacing electrodes were placed by either a transvenous or epicardial approach. Standard pacing and extrastimulus protocols were followed. The QT interval was measured in six surface ECG leads. QTd was defined as the difference between the maximum an d minimum measured QT intervals. Male FHC mice had greater QTd than wild-ty pe controls (37.1 +/- 3.0 ms versus 23.9 +/- 1.9 ms, p = 0.001). There was also a significant gender difference in QTd within each genotype; female wi ld-type mice had greater QTd than male wild-type mice (37.4 +/- 5.3 ms vers us 23.9 +/- 1.9 ms, p = 0.005), and male FHC mice had greater QTd than fema le FHC mice (37.1 +/- 3.0 ms versus 27.2 +/- 2.0 ms, p = 0.02). Twelve of 2 3 FHC mice had inducible ventricular arrhythmias, whereas only 2 of 32 wild -type mice were inducible (p = 0.004). Although a significantly increased n umber of FHC mice had arrhythmias compared with wild-type mice, QTd did not correlate with arrhythmia inducibility. The importance of this study is th at it validates the mouse model for further investigation of arrhythmogenic risk and gender differences in the electrophysiologic phenotype in FHC. It also suggests that although gender- and genotype-specific QTd values are i ncreased, they do not predict arrhythmia risk in FHC mice.