LQTS: Difference between revisions

The LQTS may be divided into two distinct forms: congenital LQTS and acquired LQTS. These forms may however overlap when QT prolongation due to medication occurs in a patient with congenital LQTS.  

*Because the QTc can change with age, it is best to take the ECG with the longest QTc interval (without additional QT-prologing factors) for risk stratification.

Acquired LQTS is most often caused by drugs that prolong the QT interval; combined with risk factors the risk of [[Torsade de Pointes]] is likely to increase.  

The prevalence of congenital LQTS is about 1:2000-2500. More than 10 different types of congenital LQTS have been described. However, only LQTS 1-3 are relatively common.  

*Anton Jervell and Fred Lange-Nielsen from Oslo described in 1957 an congenital syndrome that was associated with QT interval prolongation, deafness and sudden death: the now called Jervell-Lange-Nielsen syndrome.  

*Andersen-Tawil syndrome was described in 1994 by Tawil et al. and was associated with potassium-sensitive periodic paralysis, ventricular ectopy and dysmorphic features (short stature, low-set ears, hypoplastic mandible, clinodactyly and scoliosis). It later appeared to be associated with a mutation in the KCNJ2 gene (LQTS type 7).

*Timothy syndrome is a LQTS syndrome (with frequently alternating T-waves) with webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycaemia, cognitive abnormalities and autism. It appeared to be caused by a single mutation in the CACNA1C gene (LQTS type 8).

Diagnosis of LQTS is established by prolongation of the QTc interval in the absence of specific conditions known to lengthen it (for example QT-prolonging drugs) and/or molecular genetic testing of genes associated with LQTS.  

The prolonged QT interval can cause torsades de pointes, which is usually self-terminating, thus potentially causing a cardiac syncopal event. In LQTS type 1, cardiac symptoms are often precipitated by exercise; especially swimming is notorious for life-threatening cardiac events. In LQTS type 2, arrhythmogenic triggers are adrenergic; especially nightly noise (such as the morning alarm clock or nightly thunderlightening) is known to cause life-threatening cardiac events. On the other hand, in LQTS type 3, QT prolongation and possibly subsequent torsade de pointes is precipitated by bradycardia.  

*The resting ECG is neither completely sensitive nor specific for the diagnosis of LQTS. The diagnostic criteria for the resting ECG are shown above in the list of diagnostic criteria by Schwartz et al. Besides a prolonged QTc, the T-wave can have different patterns among the different genotypes.

*The exercise ECG (X-ECG) commonly shows failure of the QT to shorten normally, thereby prolonging the corrected QT interval, and many individuals develop characteristic T-wave abnormalities.  

*A brisk-standing test ECG, where the QT-interval is measured after abrupt standing with subsequent heart rate acceleration. There appears to be a form of QT-stretching and QT-stunning <cite>Adler</cite> as demonstrated by Viskin et al. and Adler et al.

*Epinephrine infusion is a provocative test that might increase the sensitivity of the ECG findings. However, especially the negative predictive value is high.  

*Adenosine infusion is a test provoking transient bradycardia followed by sinus tachycardia and therefore triggers QT changes that can distinguish patients with LQTS from healthy controls<cite>adenosine</cite>

Today, 14 LQTS genes associated with LQTS have been identified. Most commonly, KCNQ1, KCNH2 and SCN5A, which are associated with LQTS type 1, type 2 and type 3 respectively, are found. Other, less frequently involved genes are displayed the table below.  

There is an important genotype-phenotype relationship on severity of the disease.<cite>Schwartz2001</cite> In genotype–phenotype studies in the Rochester LQTS registry it was shown that in both LQTS type 1 and type 2, mutation locations and the degree of ion channel dysfunction caused by the mutations are important independent risk factors influencing the clinical course of this disorder.

Gene-specific differences of the natural history of LQTS have also been demonstrated and allow genotype-based risk stratification. Indeed, QT interval duration, gender and genotype (including mutation location and degree of ion channel dysfunction) are significantly associated with the outcome, with a QTc interval >500ms, and a LQT2 or LQT3 genotype determining the worst prognosis. Gender differently modulates the outcome according to the underlying genetic defect: the LQT3 males and LQT2 females are the highest risk subgroups. Risk stratification is best done by an expert cardio-genetics cardiologist.

*Beta-blockers are the cornerstone of therapy in LQTS. Beta-blockers even reduce the risk of sudden death in patients in whom a genetic defect has been found, but no QT prolongation is visible on the ECG and also in LQTS3 patients with bradycardia-associated cardiac events <cite>congenital</cite>

*[[ICD]] implantation in combination with beta-blockers in LQTS patients with previous cardiac arrest, cardiac [[syncope]] or [[ventricular tachycardia]] while on beta-blockers. ICDs should have pacing possibilities, because arrhythmic episodes are bradycardia-associated in LQTS type 3 and since post-shock pacing is relevant in all other LQTS types.  

*Cardiac sympathetic denervation (LCSD) should be considered in the setting of beta-blocker breakthroughs, intolerance to pharmacotherapy and history of appropriate ICD therapies. Surgically, LCSD involves the resection of the lower two-third of the left stellate ganglion and the left-sided sympathetic chain at the level of T2, T3 and T4.