Mechanical Dysfunction in Extreme QT Prolongation

Background: Although cardiac mechanical dysfunction has not been reported in congenital long QT syndrome (LQTS), theoretically abnormal cardiac repolarization may confer a substrate for mechanical dysfunction via calcium overload during the prolonged plateau period. We report the first clinical descriptions of a patient who supports this hypothesis. Methods: Clinical, electrocardiographic, and echocardiographic evaluations were performed on a newborn presenting to Milwaukee Children's Hospital and subsequently referred to Mayo Clinic's LQTS Clinic. Mutational analysis of the 10 known LQTS-susceptibility genes was performed using denaturing high performance liquid chromatography and DNA sequencing. Results: Presenting with fetal bradycardia from 2:1 atrioventricular block, a male Caucasian infant manifested extreme QT prolongation (QT interval corrected for heart rate: 800 milliseconds), 2:1 atrioventricular conduction, and macroscopic T-wave alternans after birth. At 6 weeks of age, the infant demonstrated 20 seconds of torsades de pointes. The family history was unremarkable, screening electrocardiograms of first-degree relatives revealed normal findings, and mutational analysis of all known LQTS-susceptibility genes was negative. Echocardiographically, the infant demonstrated globally abnormal systolic and diastolic dysfunction before the onset of arrhythmias. Conclusions: This infantile presentation of QT extremis and cardiac dysfunction provides support for the hypothesis of mechanical perturbations stemming from abnormal repolarization. Future studies are needed to investigate whether or not the typical patient with congenital LQTS exhibits any evidence for mechanical dysfunction.