Introduction LQTS is an inheritable condition with a suspected prevalence on 1/2000 and has a risk of sudden cardiac death due to ventricular arrhythmia if untreated. 24 hour QT analysis is a method of averaging QT measurements obtained via holter monitoring over a 24 hour period. The utility of 24 hour QT analysis to predict genotype positivity has not been widely studied.
Methods 28 probands with genetic testing results and 107 first degree relatives of genotyped LQTS patients were included in the analysis. Retrospective review of the medical charts of all patients was performed. Parameters analysed included corrected QT (QTc) interval on 12 lead ECG, 24 hour ambulatory ECG, the QTc after 4 minutes of recovery post exercise stress testing (EST), and the Schwartz score based on clinical and ECG criteria. All these parameters were then compared to the results of subsequent genetic testing.
Results 28 probands were analysed with 7 returning a positive gene test and 21 returning a negative gene test. Gene positive individuals had significantly greater QTc by resting ECG (p = 0.047), 24 hour ECG (p = 0.005) and after 4 minutes recovery post EST (p = 0.001) (independent t-test). Using standard cut offs (450 ms for males and 460 ms for females) the association between clinically positive resting ECG and positive genotype was not statistically significant (p = 0.17). Schwartz score >3.5 showed no significant difference between gene positive and gene negative groups (p = 0.33). 24 hour QTc (p = 0.029) was significantly associated with positive genotype and QTc at 4 minutes recovery post EST showed a trend toward significance (p = 0.069). Of 107 first degree relatives of LQTS cases there were 50% gene positive cases. There were statistically significant differences between gene positive and gene negative family members in QTc (p < 0.001), 24 hour QTc p < 0.001), QTc at 4 minutes recovery post EST (p = 0.001), and Schwartz score (p < 0.001). A Schwartz score of >3.5 was 98% specific for genotype positive LQTS but this test had a very low sensitivity of 29%. The most sensitive test was 24 hour QTc with a cut off of 450 ms for males and 460 ms for females with a sensitivity of 69% and specificity of 83%.
Conclusions Family screening and prevention of sudden cardiac death is central to the management of LQTS. Current individual clinical testing methods are not sufficiently sensitive to diagnose LQTS alone and must be used in combination to assess the risk of LQTS. 24 hour QT analysis is the most sensitive method of predicting positive genotype in both probands and family members of affected individuals.
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