Young patients may experience LTE from WPW syndrome without prior symptoms or markers of high-risk on EPS.

Background: Left ventricular non-compaction (LVNC) may manifest an undulating phenotype ranging from dilated to hypertrophic appearance. It is unknown whether tissue Doppler (TD) velocities can predict adverse clinical outcomes including death and need for transplantation in children with LVNC. Methods and results: 56 children (median age 4.5 years, median follow-up 26 months) with LVNC evaluated at one hospital from January 1999 to May 2004 were compared with 56 age/sex-matched controls. Children with LVNC had significantly decreased early diastolic TD velocities (Ea) at the lateral mitral (11.0 vs 17.0 cm/s) and septal (8.9 vs 11.0 cm/s) annuli compared with normal controls (p,0.001 for each comparison). Using receiver operator characteristic curves, the lateral mitral Ea velocity proved the most sensitive and specific predictor for meeting the primary end point (PEP) at 1 year after diagnosis (area under the curve = 0.888, SE = 0.048, 95% CI 0.775 to 0.956). A lateral mitral Ea cut-off velocity of 7.8 cm/s had a sensitivity of 87% and a specificity of 79% for the PEP. Freedom from death or transplantation was 85% at 1 year and 77% at 2 years. Conclusions: TD velocities are significantly reduced in patients with LVNC compared with normal controls. Reduced lateral mitral Ea velocity helps predict children with LVNC who are at risk of adverse clinical outcomes including death and need for cardiac transplantation.

Background The rapid expansion of genetic testing has led to increased utilization of clinical whole exome sequencing (WES). Clinicians and genetic researchers are being faced with assessing risk of disease vulnerability from incidentally identified genetic variants which is typified by variants found in genes associated with sudden death-predisposing CPVT. We sought to determine whether incidentally identified variants in genes associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) from WES clinical testing represent disease-associated biomarkers. Methods and Results CPVT-associated genes RYR2 and CASQ2 variants were identified in one of the world’s largest collections of clinical WES referral tests (N = 6517, Baylor Miraca Genetics Laboratories) and compared to a control cohort of ostensibly healthy individuals (N = 60,706) and a case cohort of CPVT cases (N = 155). Within the WES cohort, the rate of rare variants in CPVT-associated genes was 8.8% compared to 6.0% among controls and 60.0% among cases. There was a predominance of variants of undetermined significance (VUS, 97.7%). Following protein topology mapping, WES variants colocalized more frequently to residues with variants found in controls compared to cases. Retrospective clinical evaluation of individuals referred to our institution with WES-positive variants demonstrated no evidence of clinical CPVT in individuals with a low pre-test clinical suspicion for CPVT. Conclusions The prevalence of incidentally CPVT-associated variants is ~9% among WES tests. VUSs in CPVT-associated genes in WES genetic testing, in the absence of clinical suspicion for CPVT, are unlikely to represent markers of CPVT pathogenicity.