What is the clinical evidence from this study?

Study design: Observational. Population: Long-QT Syndrome Type 1 and 2 (n=90). Intervention: LQT2 genotype vs. LQT1 genotype and unaffected family members. Primary outcome: Median TPE interval (p=<0.001).

November 4, 2002Open Access

Ambulatory Electrocardiographic Evidence of Transmural Dispersion of Repolarization in Patients With Long-QT Syndrome Type 1 and 2

Q: What are the key findings of this study?

Patients with LQT2 had a significantly greater median TPE interval (112+/-5 ms) compared to those with LQT1 (91+/-2 ms) or unaffected family members (86+/-3 ms) (P<0.001).

Key Result

Patients with LQT2 had a significantly greater median TPE interval (112+/-5 ms) compared to those with LQT1 (91+/-2 ms) or unaffected family members (86+/-3 ms) (P<0.001).

Study Design

Type

Observational (n=90)

Structured PICO

Does the TPE interval differ between patients with LQT1, LQT2, and unaffected family members, and does it relate to heart rate and symptoms?

Population

90 genotyped subjects, including 31 with LQT1, 28 with LQT2, and 31 unaffected family members, evaluated via Holter recordings.

Exposure

Measurement of T-wave peak to T-wave end (TPE) interval from Holter recordings using an automated computerized program.

Comparator

Comparison between LQT1, LQT2, and unaffected family members.

Outcome

Median TPE interval and its relationship to heart rate (RR intervals) and presence of symptoms (history of torsade de pointes).surrogate

Transmural dispersion of repolarization (measured by TPE interval) is greater in LQT2 than LQT1 patients and increases over a wider range of heart rates in LQT2, though its magnitude does not correlate with a history of torsade de pointes.

Main Result

Absolute Event Rate: 112% vs 91%

p-value: p=<0.001

Abstract

BACKGROUND: Transmural dispersion of repolarization (TDR) may be related to the genesis of torsade de pointes (TdP) in patients with the long-QT (LQT) syndrome. Experimentally, LQT2 models show increased TDR compared with LQT1, and beta-adrenergic stimulation increases TDR in both models. Clinically, LQT1 patients experience symptoms at elevated heart rates, but LQT2 patients do so at lower rates. The interval from T-wave peak to T-wave end (TPE interval) is the clinical counterpart of TDR. We explored the relationship of TPE interval to heart rate and to the presence of symptoms in patients with LQT1 and LQT2. METHODS AND RESULTS: We reviewed Holter recordings from 90 genotyped subjects, 31 with LQT1, 28 with LQT2, and 31 from unaffected family members, to record TPE intervals by use of an automated computerized program. The median TPE interval was greater in LQT2 (112+/-5 ms) than LQT1 (91+/-2 ms) or unaffected (86+/-3 ms) patients (P<0.001 for all group comparisons), and the maximal TPE values differed as well. LQT1 patients showed abrupt increases in TPE values at RR intervals from 600 to 900 ms, but LQT2 patients did so at RR intervals from 600 to 1400 ms (longest RR studied). Asymptomatic and symptomatic patients showed similar TDRs. CONCLUSIONS: TDR is greater in LQT2 than in LQT1 patients. LQT1 patients showed a capacity to increase TDR at elevated heart rates, but LQT2 patients did so at a much wider rate range. The magnitude of TDR is not related to a history of TdP.