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Genotype-Specific ECG-Based Risk Stratification Approaches in Patients With Long-QT Syndrome
Marina Rieder1, Paul Kreifels2, Judith Stuplich2
1Translational Cardiology, Department of Cardiology, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland.
Insights
Genotype-specific electrical parameters can differentiate symptomatic and asymptomatic congenital long-QT syndrome (LQTS) patients. Post-exercise measurements and regional electrical heterogeneity are key for risk stratification in LQT1, while QTc at rest is crucial for LQT2.
Area of Science:
- Cardiology
- Genetics
- Electrophysiology
Background:
- Congenital long-QT syndrome (LQTS) is a significant cause of sudden cardiac death (SCD) in young individuals.
- Accurate risk stratification in LQTS is challenging due to variable arrhythmic risk among individuals with the same genetic variant.
Purpose of the Study:
- To investigate the association between various electrical parameters and genotype-specific symptoms in LQTS patients.
- To evaluate the utility of resting and exercise ECG parameters, including QT interval, QT dispersion, and delta Tpeak/end, for risk stratification.
Main Methods:
- Assessed heart-rate corrected QT interval (QTc), QT dispersion, and delta Tpeak/end from 12-lead ECGs at rest and during exercise.
- Compared these electrical parameters between symptomatic and asymptomatic patients across different LQTS genotypes (LQT1 and LQT2).
Main Results:
- Resting QTc distinguished symptomatic from asymptomatic LQT2 patients, while post-exercise QTc differentiated symptomatic from asymptomatic LQT1 patients.
- Enhanced delta Tpeak/end and QT dispersion were associated with symptoms exclusively in LQT1 patients, particularly after exercise.
- Post-exercise delta Tpeak/end showed high discriminative power in LQT1, with positive values in symptomatic and negative values in asymptomatic individuals.
Conclusions:
- Different electrical parameters are crucial for distinguishing symptomatic from asymptomatic patients depending on the specific LQTS genotype.
- Genotype-specific risk stratification using electrical parameters, including post-exercise measurements and regional electrical heterogeneity, can improve LQTS risk assessment.
Background:
Congenital long-QT syndrome (LQTS) is a major cause of sudden cardiac death (SCD) in young individuals, calling for sophisticated risk assessment. Risk stratification, however, is challenging as the individual arrhythmic risk varies pronouncedly, even in individuals carrying the same variant.
Materials And Methods:
In this study, we aimed to assess the association of different electrical parameters with the genotype and the symptoms in patients with LQTS. In addition to the heart-rate corrected QT interval (QTc), markers for regional electrical heterogeneity, such as QT dispersion (QTmax-QTmin in all ECG leads) and delta Tpeak/end (Tpeak/end V5 - Tpeak/end V2), were assessed in the 12-lead ECG at rest and during exercise testing.
Results:
QTc at rest was significantly longer in symptomatic than asymptomatic patients with LQT2 (493.4 ms ± 46.5 ms vs. 419.5 ms ± 28.6 ms, p = 0.004), but surprisingly not associated with symptoms in LQT1. In contrast, post-exercise QTc (minute 4 of recovery) was significantly longer in symptomatic than asymptomatic patients with LQT1 (486.5 ms ± 7.0 ms vs. 463.3 ms ± 16.3 ms, p = 0.04), while no such difference was observed in patients with LQT2. Enhanced delta Tpeak/end and QT dispersion were only associated with symptoms in LQT1 (delta Tpeak/end 19.0 ms ± 18.1 ms vs. -4.0 ms ± 4.4 ms, p = 0.02; QT-dispersion: 54.3 ms ± 10.2 ms vs. 31.4 ms ± 10.4 ms, p = 0.01), but not in LQT2. Delta Tpeak/end was particularly discriminative after exercise, where all symptomatic patients with LQT1 had positive and all asymptomatic LQT1 patients had negative values (11.8 ± 7.9 ms vs. -7.5 ± 1.7 ms, p = 0.003).
Conclusion:
Different electrical parameters can distinguish between symptomatic and asymptomatic patients in different genetic forms of LQTS. While the classical "QTc at rest" was only associated with symptoms in LQT2, post-exercise QTc helped distinguish between symptomatic and asymptomatic patients with LQT1. Enhanced regional electrical heterogeneity was only associated with symptoms in LQT1, but not in LQT2. Our findings indicate that genotype-specific risk stratification approaches based on electrical parameters could help to optimize risk assessment in LQTS.
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