How do I assess the patient with long QT? Should I screen relatives, and how? How do I treat them?

Patients affected by the congenital long QT syndrome (LQT) are often first assessed when syncope, documented ventricular arrhythmia or aborted cardiac arrest affects them or a family member. The diagnostic cut-offs (<100%>0.46 sec (children <16>0.45 sec (adult males), and >0.47 sec (adult females), after drug induced QT prolongation has been excluded. T wave morphology should also be carefully examined, in particular for high takeoff, late onset, broad base, bifid morphology with humps, and beat-by-beat alternating polarity (T wave alternans). In several LQT variants, sinus bradycardia is an additional common feature. Holter monitoring should be performed to exclude repetitive ventricular arrhythmias of the torsade de pointes type. Family screening by 12-lead ECG of all first-degree relatives is mandatory in order to have a definite diagnosis of hereditary LQT. In Romano-Ward syndrome (1/20,000 births: autosomal dominant transmission with >90% penetrance), 50% of offspring of one affected parent are predicted to be similarly affected.

Six associated genetic loci (on chromosomes 3, 4, 7, 11, 21, 22) have been identified, of which four relate to genes that encode cardiac ion-channel proteins. Several mutations have been described for each gene. Although only 50% of all LQT affected families can be linked to one of these genes, genetic screening is 100% accurate amongst these, and can provide a definite diagnosis in phenotypically borderline cases.

Medical therapy should be promptly started in symptomatic LQT patients, and beta blockers are currently the first choice, with the occasional need for pacemaker implantation. However, recent evidence suggests that in symptomatic cases with aborted cardiac arrest, automatic implantable cardiac defibrillator (ICD) implantation, in addition to beta blocker therapy, is probably indicated. In patients who do not respond to the abovementioned measures, high cervicothoracic sympathectomy might be beneficial. Currently, there is no consensus regarding the need for therapy in asymptomatic patients, unless their phenotype is exceedingly abnormal. Gene-specific medical therapy is currently being investigated.