What is the role of gene-specific therapy for the treatment of long QT syndrome (LQTS)?

Updated: Nov 29, 2017
  • Author: Ali A Sovari, MD, FACP, FACC; Chief Editor: Mikhael F El-Chami, MD  more...
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Answer

Gene-specific therapy is an area under investigation in the treatment of long QT syndrome (LQTS). For example, because LQT3 is associated with gain-of-function mutations in sodium channels, antiarrhythmic agents with sodium channel blocking properties have been suggested as gene-specific therapy for patients with LQTS3. Nevertheless, this area is complex and requires further investigations and studies.

For example, Ruan and colleagues found that mexiletine, a sodium channel blocker, can facilitate F1473 mutant protein trafficking, resulting in a net effect of a further increase in the sodium current and a worsening of QT prolongation in a subset of patients with LQTS3 who have this specific mutation. [34]

In a retrospective cohort study of 34 LQT3 patients, Mazzanti et al found evidence that mexiletine is an effective therapy. The median duration of oral mexiletine therapy was 36 months. Mexiletine significantly shortened QTc, reduced the percentage of patients with arrhythmic events, reduced the mean number of arrhythmic events per patient, and reduced the annual rate of arrhythmic events. [33]

Trigger-specific risk stratification and therapy have been suggested by some studies. For example, Kim and colleagues showed that certain types of mutations in LQT2 are associated with certain triggering events (exercise triggers vs arousal triggers vs nonarousal/nonexercise triggers) and that patients with exercise-related triggering events respond to the treatment with beta-blockers. [35]


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