Severity of congenital Long QT Syndrome disease onset and risk of depression, anxiety, and mortality: a nationwide study
Authors: Kroell J , Jensen H.K , Jespersen C , Kanters J.K , Hansen M.S , Christiansen M , Westergaard L.M , Fosboel E.L , Roerth R , Torp-Pedersen C , Koeber L , Bundgaard H , Tfelt-Hansen J , Weeke P.E 
Published: November 2020

Abstract

Introduction
The congenital Long QT Syndrome (cLQTS) is associated with an increased risk of sudden cardiac death (SCD). Thus, cLQTS patients are susceptible to develop depression or anxiety, both of which have been associated with poor outcomes including risk of mortality.

Aim
We examined if a cLQTS diagnosis and the severity of cLQTS disease onset was associated with an increased risk of depression, anxiety, and all-cause mortality compared with a matched control population.

Methods
Using Danish nationwide registries and inherited cardiac disease clinics, we identified all patients with known cLQTS (1994–2016) who were ≥18 years at the time of diagnosis. The disease onset for cLQTS was identified as asymptomatic, ventricular tachycardia [VT]/ syncope, aborted SCD [aSCD], or unknown (i.e. no available information). After cLQTS diagnosis, we determined the risk of depression (i.e. depression diagnosis or prescription of antidepressants), anxiety (i.e. anxiety diagnosis or prescription of anxiolytics), and mortality using multivariable Cox proportional hazards regression. Patients were followed for three years. An age and gender matched control population was identified (matching 1:4). Competing risk analysis with death as competing risk was used to generate cumulative incidence plots.

Results
Overall, 428 cLQTS patients were identified of which 107/428 (25%) developed depression or anxiety after being diagnosed with cLQTS compared with 285/1712 (16.6%) from the control population (p&lt;0.001). The severity of disease onset was identified for 229/428 (55%) cLQTS patients; 104 (24%) were asymptomatic, 89 (21%) had VT/ syncope, and 36 (8.4%) had aSCD. A graded relationship between the severity of cLQTS disease onset and risk of depression or anxiety was identified (Figure 1). In multivariable models, patients with aSCD as disease onset had a higher risk of developing depression or anxiety compared with asymptomatic cLQTS patients (HR=2.34, CI: 1.03–5.32). Furthermore, previous depression (HR=6.38, CI: 4.80–8.48) and anxiety (HR=4.20, CI: 3.15–5.59) was found as associated risk factors. However, no risk was associated with concurrent treatment with beta-blockers (HR=1.23, CI: 0.90–1.69). During follow-up, 8 cLQTS patients died of which 4 had developed depression or anxiety (50%). No significant association between all-cause mortality and depression or anxiety was found, although numbers were low (P=0.22).

Conclusion
The prevalence of depression and anxiety was high among cLQTS patients after diagnosis. Moreover, a graded relationship between severity of disease onset and risk of depression or anxiety was identified. These findings highlight a need for increased awareness following a cLQTS diagnosis in order to reduce the risk of adverse outcomes.
Cumulative incidence curve

Funding Acknowledgement
Type of funding source: Public hospital(s). Main funding source(s): Fund of Rigshospitalet