Patients with familial hypertrophic cardiomyopathy (FHC) are at risk for 
ventricular arrhythmias and sudden death. Regional variability in the QT 
interval [QT dispersion (QTd)] is significantly increased in humans with FHC and 
ventricular arrhythmias. A mouse model of FHC resulting from a mutation in the 
alpha-myosin heavy-chain (Arg403Gln) was used to study the electrophysiologic 
phenotype of this disease. Cardiac electrophysiology studies and surface ECGs 
were performed in FHC mice and wild-type controls to evaluate the 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 and minimum measured QT intervals. 
Male FHC mice had greater QTd than wild-type 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 wild-type mice had greater QTd than male 
wild-type mice (37.4 +/- 5.3 ms versus 23.9 +/- 1.9 ms, p = 0.005), and male FHC 
mice had greater QTd than female FHC mice (37.1 +/- 3.0 ms versus 27.2 +/- 2.0 
ms, p = 0.02). Twelve of 23 FHC mice had inducible ventricular arrhythmias, 
whereas only 2 of 32 wild-type mice were inducible (p = 0.004). Although a 
significantly increased number of FHC mice had arrhythmias compared with 
wild-type mice, QTd did not correlate with arrhythmia inducibility. The 
importance of this study is that 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 increased, they do not predict arrhythmia risk 
in FHC mice.