Congenital long QT syndrome - can a 12-lead Holter ECG improve diagnosis?

Background

Long QT syndrome (LQTS) is a congenital disorder associated with risk of sudden cardiac death (SCD) due to ventricular arrhythmia. This syndrome is diagnosed based on a prolonged corrected QT (QTc) interval on the resting ECG, if the Schwartz criteria are met, or after confirmation of a pathogenic variant carrier. However, this syndrome is characterized by reduced penetrance and variable QT prolongation over time, resulting in a normal QTc on the resting ECG in 25% of carriers of the pathogenic mutation. Furthermore, developing a genetic test result for the presence of a pathogenic variant usually requires several weeks. Therefore, an easily accessible tool is needed to facilitate diagnosis. The importance of 24-hour Holter ECG recording in the diagnosis and prognosis of LQTS has not yet been established.

Purpose

The aim of this study is to test the hypothesis that parameters obtained from 24-hour Holter ECG recordings can facilitate the diagnosis of LQTS.

Methods

24-hour 12-lead Holter monitoring was performed in two subgroups of patients:

1. the study group - 18 patients with genetically confirmed long QT syndrome and

2. the control group - 17 healthy individuals matched for age and gender.

The Reynolds Advanced QTc Analysis software was used for beat-to-beat QTc interval assessment. The analysis was performed for sinus rhythm <120/min. The following parameters were evaluated: minimum, maximum and mean QTc, percentage of QTc>480ms in LQTS patients and percentage of QTc>460ms in healthy individuals. The Holter test result was considered diagnostic if at least 20% of the beats or at least 20,000 QRS complexes could be reliably assessed. All the LQTS patients were treated with beta-blokers. No one in the control group received any QT affecting drug.

Results

The mean age of study participants was 39 (22- 49) years and 65.7% of them were females. The mean percentage of analyzed QTc intervals in patients with LQTS was 44.5 (28 – 74) compared to 94 (89 – 97) in the control group (p=0,002). The minimum QTc interval in LQTS ranged from 359 to 468ms (mean 367ms) and in healthy individuals from 326 to 352ms (mean 343ms), (p=0,001). The maximum QTc interval was 520–596 ms in the LQTS group and 464–492 ms in the control group (p<0,001). The mean QTc interval was 435–468 ms (mean 451 ms) in the LQTS group and 384–404 ms (mean 397 ms) in the healthy group (p<0.001). The percentage of QTc >480ms in LQTS was 2 – 14% (mean 5%). In the control group, the percentage of QTc > 460 ms was not greater than 1%.

Conclusions

· Holter ECG monitoring may be a valuable diagnostic tool in patients with LQTS, despite limitations related to the challenging assessment of QTc caused by significant ST-T segment variability.

· The minimum, mean and maximum QTc in 12-lead Holter recording was significantly higher in LQTs group.

· QTc>500ms does not occur in people who are not carriers of pathogenic mutations.