ECG Device for LQTS Screening in Newborns, Phase II

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DESCRIPTION (provided by applicant): The congenital long QT syndrome (LQTS) is thought to occur in 1 in 2,000 infants and cause 10-15% of deaths from SIDS (sudden infant death syndrome). Electrocardiograms (ECGs) can detect LQTS before fatal cardiac events happen. In our Phase I STTR project, we successfully developed and tested an ECG device designed for LQTS screening in newborns. This device, now called QTScreen, was produced exactly as specified in our Phase I proposal. Both Specific Aims in Phase I were completed and all milestones were reached on schedule. In this Phase II proposal, our goal is to demonstrate the effectiveness of the QTScreen for LQTS screening in newborns in the U.S., so that the QTScreen can become a commercialized product and service. To achieve our goal, we propose a clinical trial to validate the QTScreen device for LQTS screening, assess strategies for newborn screening, and define the epidemiology of LQTS in the Southern California -- and thus the potential market. In Aim 1, we will perfect the QTScreen for use in a large clinical trial. The refinements will enhance QTScreen function and make it more user-friendly. The design will comply with FDA standards and allow scalable production. In Aim 2, we will show the effectiveness of QTScreen for LQTS screening in newborns in Southern California. We will conduct a clinical trial on 4,000 babies. Results will establish the prevalence of LQTS in Southern California, and validate QTScreen as a newborn screening tool. In Aim 3, we will identify strategies to understand and minimize false positive screens. False positive results cause unneeded parental anxiety and raise costs due to expensive genetic testing. Our strategies to minimize false positive results are to: (1) identify the optimal QTc threshold for rescreening and gene testing; and (2) identify common single nucleotide variants that affect QT intervals in newborns, apart from LQTS mutations. Expected outcomes of Phase II are a validated QTScreen device for newborn screening, a marketable product ready for FDA filing, and valuable data on LQTS occurrence in the U.S. With Phase II results, we will seek investments and apply for an NHLBI Phase IIB Small Market Award. In Phase IIB, we will propose a multi-center trial for nationwide newborn LQTS screening in the U.S. and cost effectiveness analyses.