INHERITED LONG QT SYNDROME – RECENT ADVANCES

Long QT Syndrome (LQTS) is one of the inherited arrhythmic conditions, where affected individuals may be asymptomatic or may present with syncope or sudden cardiac death. Since the original descriptions in 1957 by Jervell and Lange-Nielsen and in 1964 by Romano and Ward, our understanding of the pathophysiology of the condition and myocardial channel dysfunction has greatly increased. Molecular investigations have revealed that there are multiple sub-types, with LQT1, LQT2, and LQT 3 being the most common. Accurate measurement of the QT interval may be difficult in certain circumstances, and various formulae for correction based on heart rate have been widely used. Interpretation of the QT interval in competitive athletes may be particularly challenging. Genetic testing, where available, and cascade screening, where appropriate, have become accepted as standard practice. Risk stratification models are well established but also have limitations. There is now a strong evidence base for the use of beta-blocker therapy, with additional interventions, such as left cardiac sympathetic denervation and implantable cardiac devices, being recommended for selected high-risk individuals. Novel genetic approaches, such as siRNA technology, are being explored in cellular models. Of interest, clinical trials using drugs which have been licensed for other channelopathies, are currently underway and may result in the identification of novel therapeutic options.

AIM: Long QT Syndrome (LQTS) is one of the inherited arrhythmic conditions, where affected individuals may be asymptomatic or may present with syncope or sudden cardiac death. Since the original descriptions in 1957 by Jervell and Lange-Nielsen and in 1964 by Romano and Ward, our understanding of the pathophysiology of the condition and myocardial channel dysfunction has greatly increased.
Methodology: Molecular investigations have revealed that there are multiple sub-types, with LQT1, LQT2, and LQT 3 being the most common. Accurate measurement of the QT interval may be difficult in certain circumstances, and various formulae for correction based on heart rate have been widely used. Interpretation of the QT interval in competitive athletes may be particularly challenging.
Results: Genetic testing, where available, and cascade screening, where appropriate, have become accepted as standard practice. Risk stratification models are well established but also have limitations. There is now a strong evidence base for the use of beta-blocker therapy, with additional interventions, such as left cardiac sympathetic denervation and implantable cardiac devices, being recommended for selected high-risk individuals. Novel genetic approaches, such as siRNA technology, are being explored in cellular models.
Conclusion: Of interest, clinical trials using drugs which have been licensed for other channelopathies, are currently underway and may result in the identification of novel therapeutic options.

Professor Pascal McKeown, Queen’s University Belfast and Belfast Health & Social Care Trust, Northern Ireland.