Risk stratification tool in the long QT syndrome

The authors focused on the most common genetic mutations causing long-QT syndrome - potassium-channel genes KCNQ1 (LQT1 locus) and KCNH2 (LQT2 locus) and the sodium-channel gene SCN5A (LQT3 locus). They evaluated 647 patients (386 with a mutation at the LQT1 locus, 206 with a mutation at the LQT2 locus, and 55 with a mutation at the LQT3 locus) from 193 consecutively genotyped families with the long-QT syndrome. They looked at the cumulative probability of a first cardiac event, defined as the occurrence of syncope, cardiac arrest, or sudden death before the age of 40 years and before the initiation of therapy, determined according to genotype, sex, and the QT interval corrected for heart rate (QTc). They then used two clinical features - sex and QTc interval-to develop a tool to predict the risk of first cardiac event (syncope, cardiac arrest, or sudden death) before the age of 40 and before therapy. A cut-off of 500 milliseconds was used for the QTc interval because 24% of the patient population had QTc intervals above 500 milliseconds, and this was the single most important predictor of events.Priori et al found that the incidence of a first cardiac event before the age of 40 years and before the initiation of therapy was lower among patients with a mutation at the LQT1 locus (30 percent) than among those with a mutation at the LQT2 locus (46 percent) or those with a mutation at the LQT3 locus (42 percent) (PMultivariate analysis showed that the genetic locus and the QTc, but not sex, were independent predictors of risk. The QTc was an independent predictor of risk among patients with a mutation at the LQT1 locus and those with a mutation at the LQT2 locus but not among those with a mutation at the LQT3 locus, whereas sex was an independent predictor of events only among those with a mutation at the LQT3 locus. "Although an assessment of the efficacy of prophylactic therapy with beta-blockers is clearly beyond the scope of our study" the researchers note "it is reasonable to assume, on the basis of our findings, that prophylactic treatment is warranted in male and female patients with a mutation at the LQT1 locus who have a QTc of 500 milliseconds or more, male patients with a mutation at the LQT2 locus who have a QTc of 500 milliseconds or more, all female patients with a mutation at the LQT2 locus irrespective of the QTc, and all patients with a mutation at the LQT3 locus."In an accompanying editorial, Vincent describes the study by Priori et al as an important step in clarifying clinical predictors of sudden death from cardiac arrhythmia. He adds, however, that even with this important work, risk prediction is still difficult. He lists a number of cases that do not fit the risk stratification model and says these demonstrate the difficulty faced by the physician when trying to determine the appropriate therapy for a patient with long-QT syndrome.Reference...