Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations

BACKGROUND Patients with Long QT syndrome (LQTS) who harbor multiple mutations (i.e. >= 2 mutations in >= 1 LQTS-susceptibility gene) may experience increased risk for Life-threatening cardiac events. OBJECTIVES The present study was designed to compare the clinical course of LQTS patients with multiple mutations to those with a singe mutation. METHODS The risk for Life-threatening cardiac events (comprising aborted cardiac arrest, implantable defibrillator shock, or sudden cardiac death) from birth through age 40 years, by the presence of multiple vs. singe mutations, was assessed among 403 patients from the LQTS Registry. RESULTS Patients with multiple mutations (n=57) exhibited a Longer QTc at enrollment compared with those with a singe mutation (mean +/- SD: 506 +/- 72 vs. 480 +/- 56 msec, respectively; P=0.003) and had a higher rate of Life threatening cardiac events during follow-up (23% vs. 11%, respectively; p=0.031). Consistently, multivariate analysis demonstrated that patients with multiple mutations had a 2.3-ford (P=0.015) increased risk for Life threatening cardiac events as compared to patients with a singe mutation. The presence of multiple mutations in a singe LQTS gene was associated with a 3.2-ford increased risk for Life threatening cardiac events (P=0.010) whereas the risk associated with multiple mutation status involving > 1 LQTS gene was not significantly different from the risk associated with a singe mutation (HR 1.7, P=0.26). CONCLUSIONS LQTS patients with multiple mutations have a greater risk for Life-threatening cardiac events as compared to patients with a singe mutation.