Risk Prediction in Women With Congenital Long QT Syndrome.

Background We aimed to provide personalized risk estimates for cardiac events (CEs) and life-threatening events in women with either type 1 or type 2 long QT. Methods and Results The prognostic model was derived from the Rochester Long QT Syndrome Registry, comprising 767 women with type 1 long QT (n=404) and type 2 long QT (n=363) from age 15 through 60 years. The risk prediction model included the following variables: genotype/mutation location, QTc-specific thresholds, history of syncope, and ß-blocker therapy. A model was developed with the end point of CEs (syncope, aborted cardiac arrest, or long QT syndrome-related sudden cardiac death), and was applied with the end point of life-threatening events (aborted cardiac arrest, sudden cardiac death, or appropriate defibrillator shocks). External validation was performed with data from the Mayo Clinic Genetic Heart Rhythm Clinic (N=467; type 1 long QT [n=286] and type 2 long QT [n=181]). The cumulative follow-up duration among the 767 enrolled women was 22 243 patient-years, during which 323 patients (42%) experienced ≥1 CE. Based on genotype-phenotype data, we identified 3 risk groups with 10-year projected rates of CEs ranging from 15%, 29%, to 51%. The corresponding 10-year projected rates of life-threatening events were 2%, 5%, and 14%. C statistics for the prediction model for the 2 respective end points were 0.68 (95% CI 0.65-0.71) and 0.71 (95% CI 0.66-0.76). Corresponding C statistics for the model in the external validation Mayo Clinic cohort were 0.65 (95% CI 0.60-0.70) and 0.77 (95% CI 0.70-0.84). Conclusions This is the first risk prediction model that provides absolute risk estimates for CEs and life-threatening events in women with type 1 or type 2 long QT based on personalized genotype-phenotype data. The projected risk estimates can be used to guide female-specific management in long QT syndrome.

Left cardiac sympathetic denervation reduces skin sympathetic nerve activity in patients with long QT syndrome.

BACKGROUND: Although left cardiac sympathetic denervation (LCSD) is an effective antiarrhythmic therapy for patients with long QT syndrome (LQTS), direct evidence of reduced sympathetic activity after LCSD in humans is limited. OBJECTIVE: The purpose of this study was to assess skin sympathetic nerve activity (SKNA) in patients with LQTS undergoing LCSD. METHODS: We prospectively enrolled 17 patients with LQTS who underwent LCSD between 2017 and 2019. SKNA recordings from the left arm (L-SKNA) and chest (C-SKNA) leads were performed before and after LCSD. Mean SKNA, burst activity, and nonburst activity of L-SKNA and C-SKNA were analyzed. RESULTS: The mean patient age was 21 ± 9 years (8 men 47%). The longest baseline corrected QT value was 497 ± 55 ms at rest and 531 ± 38 ms on exercise stress testing. Five patients (29.4%) had previous LQTS-triggered cardiac events including syncope, documented torsades de pointes, and ventricular fibrillation. In the 24 hours after LCSD, mean L-SKNA decreased from 1.25 ± 0.64 to 0.85 ± 0.33 µV (P = .005) and mean C-SKNA from 1.36 ± 0.67 to 1.05 ± 0.49 µV (P = .11). The frequency of episodes of SKNA bursts recorded from the left-arm lead (2.87 ± 1.61 bursts per minute vs 1.13 ± 0.99 bursts per minute; P < .001) and mean L-SKNA during burst (1.82 ± 0.79 µV vs 1.15 ± 0.44 µV; P < .001) and nonburst (1.09 ± 0.60 µV vs 0.75 ± 0.32 µV; P = .03) periods significantly decreased after LCSD, while the frequency of episodes of SKNA bursts recorded from the chest lead (P = .57) and mean C-SKNA during burst (P = .44) and nonburst (P = .10) periods did not change significantly. No arrhythmic events were documented after 11.9 months (range 3.0-22.2 months) of follow-up. CONCLUSION: LCSD provides an inhibitory effect on cardiac sympathetic activity by suppressing burst discharge as measured by SKNA.