Abstract 2006: Risk of Aborted Cardiac Arrest or Sudden Cardiac Death in Subjects With Genotype-Confirmed Long-QT Syndrome and Normal-Range QTc
Background: Current data regarding the clinical course and risk factors for life-threatening events in subjects with genotype-confirmed long-QT syndrome (LQTS) who do not exhibit prolongation of the corrected QT interval (QTc) are limited.
Methods: We assessed the risk for aborted cardiac arrest (ACA) and sudden cardiac death (SCD) from birth through age 40 years among 3,681 genotyped patients from the International LQTS Registry, categorized as genotype-negative (n=1750), genotype-positive/phenotype-positive LQTS (QTc >440 msec [n=1445]; Group A), and genotype-positive/phenotype-negative LQTS (QTc ≤440 msec [n=486]; Group B).
Results: Group A and Group B LQTS subjects exhibited an 8.0-fold (p<0.001) and a 2.4-fold (p=0.001) increased risk for ACA/SCD, respectively, as compared with genotype-negative subjects. In multivariate analysis, the location-type of mutation (categorized as transmembrane-missense mutations vs. [nontransmembrane or nonmissense mutations]) was the only independent predictor of life-threatening events among genotype-positive/phenotype-negative Group B LQTS subjects (HR =5.7; p=0.006 [Figure⇓]). Clinical factors (QTc duration [>500 msec: HR=2.96; p<0.001] and gender [female >13 years: HR=1.95; p=0.002]) but not location-type of mutation identified ACA/SCD risk in the phenotype-positive/genotype-positive Group A LQTS subjects.
Conclusions: Genotype-confirmed LQTS subjects with normal range QTc duration make up about 25% of the at-risk LQTS patients, and mutation characteristics identify increased risk for ACA/SCD in this overall low-risk group of LQTS subjects.