1-2-3-LQTS Risk Calculator

5-Year Risk of Life-Threatening Arrhythmic Events

Input RR and QT Intervals:

Or input QTc directly:

Genotype:

Result

Long QT Syndrome (LQTS) is an inherited cardiac channelopathy characterized by prolonged ventricular repolarization, which predisposes individuals to malignant ventricular arrhythmias, notably torsade de pointes. This condition is primarily attributed to specific genetic mutations: loss-of-function mutations in KCNQ1 (LQT1) and KCNH2 (LQT2), and gain-of-function mutations in SCN5A (LQT3). These genetic anomalies disrupt the cardiac ion channels, leading to delayed repolarization and an increased risk of life-threatening arrhythmic events.

The cornerstone of LQTS management involves lifestyle modifications, pharmacotherapy, and, in high-risk cases, device implantation. Beta-blockers, particularly non-selective agents like nadolol and propranolol, are the first-line treatment for reducing arrhythmic risk across all LQTS genotypes. These medications mitigate adrenergic stimulation, thereby decreasing the likelihood of arrhythmia onset. However, beta-blockers do not completely eliminate the risk. In LQT3 patients, where arrhythmias often occur at rest due to late sodium current augmentation, the sodium channel blocker mexiletine has demonstrated efficacy in shortening the QT interval and reducing arrhythmic events, contingent upon the specific mutation present.

For patients at elevated risk—such as those with a history of cardiac arrest, recurrent syncope despite beta-blocker therapy, or markedly prolonged QT intervals—the implantation of an implantable cardioverter-defibrillator (ICD) is recommended. ICDs provide immediate intervention during life-threatening arrhythmias, thereby preventing sudden cardiac death. The 2015 European Society of Cardiology (ESC) guidelines advocate for ICD implantation in high-risk LQTS patients, emphasizing a comprehensive risk assessment that includes genetic factors and QTc duration.

Risk Stratification and the 1-2-3-LQTS Risk Model

Accurate risk stratification is pivotal in guiding therapeutic decisions for LQTS patients. Traditional assessment methods have focused on genotype and QTc interval prolongation. In 2018, Mazzanti et al. introduced the 1-2-3-LQTS Risk model, a validated tool designed to estimate the 5-year risk of life-threatening arrhythmic events in individuals with LQT1, LQT2, and LQT3. This model was developed using a single-center longitudinal cohort and subsequently validated with an independent cohort of 1,689 patients from the International LQTS Registry in Rochester, NY, USA. The validation study reported a C-index of 0.69 (95% CI: 0.61–0.77) in the validation cohort, compared to a C-index of 0.79 (95% CI: 0.70–0.88) in the discovery cohort. A 5-year risk threshold of 5% or higher, determined by ROC curve analysis as the optimal balance for deciding on ICD implantation, yielded a number needed to treat (NNT) of nine (95% CI: 6.3–13.6).

References

Mazzanti, A., Trancuccio, A., Kukavica, D., Pagan, E., Wang, M., Mohsin, M., Peterson, D., Bagnardi, V., Zareba, W., & Priori, S. G. (2022). Independent validation and clinical implications of the risk prediction model for long QT syndrome (1-2-3-LQTS-Risk). EP Europace, 24(4), 614–619.

Priori, S. G., Blomström-Lundqvist, C., Mazzanti, A., Blom, N., Borggrefe, M., Camm, J., Elliott, P. M., Fitzsimons, D., Hatala, R., Hindricks, G., Kirchhof, P., Kjeldsen, K., Kuck, K. H., Hernandez-Madrid, A., Nikolaou, N., Norekvål, T. M., Spaulding, C., & Van Veldhuisen, D. J. (2015). 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. European Heart Journal, 36(41), 2793–2867.

Ackerman, M. J., Priori, S. G., Dubin, A. M., Kowey, P., Linker, N. J., Slotwiner, D., Triedman, J., Van Hare, G. F., & Gold, M. R. (2017). Beta-blocker therapy for long QT syndrome and catecholaminergic polymorphic ventricular tachycardia: Are all beta-blockers equivalent? Heart Rhythm, 14(1), e41–e44.

Schwartz, P. J., Crotti, L., & Insolia, R. (2012). Long-QT syndrome: From genetics to management. Circulation: Arrhythmia and Electrophysiology, 5(4), 868–877.

Wilde, A. A. M., & Amin, A. S. (2018). Clinical spectrum of SCN5A mutations: Long QT syndrome, Brugada syndrome, and cardiomyopathy. Journal of Cardiovascular Electrophysiology, 29(1), 109–120.

Mazzanti, A., Maragna, R., Vacanti, G., Monteforte, N., Bloise, R., Memmi, M., Pagan, E., & Priori, S. G. (2016). Gene-specific therapy with mexiletine reduces arrhythmic events in patients with long QT syndrome type 3. Journal of the American College of Cardiology, 67(9), 1053–1058.

Updated on 2025-01-18