Hi, my name is Jeremy Moore at the UCLA Medical Center in Los Angeles, California. It is known that newborns and infants affected by a particularly severe form of congenital long QT syndrome, characterized by 2 to 1 AV block, or TORSAD, are at elevated risk for sudden cardiac death. We conducted a study to follow the clinical course of fetuses and newborns affected by the severe form of congenital long QT syndrome. This was a retrospective collaboration involving 25 international centers, spanning a 30-year period. Importantly, only fetuses and newborns that were genotype positive for long QT type 1, type 2, or type 3 were included. The two major outcomes of interest were age at first cardiac event and age at death or heart transplantation following discharge from the newborn hospitalization. We identified 84 fetuses and newborns with the severe form of congenital long QT syndrome. The most common genetic diagnosis was long QT type 3, followed by long QT type 2, and least commonly long QT type 1. In the fetal period, two fetuses died, both confirmed to have long QT type 3 by cord blood or direct tissue sampling. There were 82 live newborns delivered at a median age of 37 weeks gestation. One long QT type 3 patient died from arrhythmia-related cardiomyopathy before hospital discharge. 81 patients were discharged to home at a median of three weeks of life and were followed for over five years in the outpatient setting and were therefore eligible for the primary outcome analysis. The primary endpoint of time to first cardiac event occurred most commonly for long QT type 3, and in the multivariate model, only long QT type 3 predicted cardiac events with a p-value of less than 0.001. The second major endpoint of death or heart transplantation during follow-up was also most common for long QT type 3, also with a p-value of less than 0.001. Importantly, during outpatient follow-up, four of the patients with long QT type 3 died despite a combination of antiarrhythmic drugs, ICD placement, and cardiac sympathetic denervation. Conversely, for the three patients in the study that received heart transplantation, all were alive at last follow-up. Finally, long QT type 3 patients were most likely to undergo invasive interventions such as cardiac sympathetic denervation and ICD placement and experience adverse developmental and neurologic outcomes. To summarize, this large multicenter study examined the clinical outcomes of genotype-positive long QT syndrome fetuses and newborns and assessed the prenatal, postnatal inpatient, and postnatal outpatient courses. We found that patients with long QT type 3 were most likely to undergo invasive interventions and were most likely to experience comorbidities related to their diagnosis. Most importantly, long QT type 3 patients were also most likely to suffer major cardiac events with the poorest transplant-free survival as compared to the other long QT genotypes. These findings may be relevant to family counseling in the pre- and postnatal period and for therapeutic decision-making prior to hospital discharge. It is also suggested that early heart transplantation for long QT type 3 patients with severe ventricular arrhythmia be considered on an individualized basis. Thank you.

UCLA Medical Center

clinical outcomes

congenital long QT syndrome

genetic diagnosis

cardiac events