Non-sustained microvolt level T-wave alternans in congenital long QT syndrome types 1 and 2.

BACKGROUND: Patients with long QT syndrome (LQTS) are predisposed to polymorphic ventricular tachycardia (VT) during adrenergic stimulation. Microvolt T-wave alternans (MTWA) is linked to vulnerability to VT in structural heart disease. The prevalence of non-sustained MTWA (NS-MTWA) in LQTS is unknown. METHODS: 31 LQT1, 42 LQT2, and 80 controls underwent MTWA testing during exercise. MTWA tests were classified per standardized criteria, and re-analyzed according to the modified criteria to account for NS-MTWA. RESULTS: LQT1 and LQT2 patients had a significantly higher frequency of late NS-MTWA (26% and 12%) compared to controls (0%). There was no significant difference between the groups with respect to sustained and early NS-MTWA. Late NS-MTWA was significantly associated with QTc. CONCLUSION: LQT1 and LQT2 patients had a higher prevalence of late NS-MTWA during exercise than matched controls. NS-MTWA likely reflects transient adrenergically mediated dispersion of repolarization, and could be a marker of arrhythmic risk in LQTS.

Does manual T-wave window adjustment affect microvolt T-wave alternans results in patients with structural heart disease?

INTRODUCTION: Microvolt T-wave alternans (MTWA) analysis can identify patients at low risk of sudden cardiac death who might not benefit from an implantable cardioverter-defibrillator (ICD). Current spectral methodology for performing MTWA analysis may "miss" part of the T-wave in patients with QT prolongation. The value of T-wave window adjustment in patients with structural heart disease has not been studied. METHODS: We assembled MTWA data from 5 prior prospective studies including 170 patients with reduced left ventricular ejection fraction, adjusted the T-wave window to include the entire T-wave, and reanalyzed MTWA. RESULTS: Of 170 patients, 43% required T-wave window adjustment. Only 3 of 170 patients (1.8%) had a clinically significant change in MTWA results. CONCLUSIONS: In 98.2% of patients, T-wave window adjustment did not improve the accuracy of MTWA analysis. Spectral MTWA as currently implemented remains effective for identifying patients with structural heart disease unlikely to benefit from ICD therapy.

Microvolt T-wave alternans amplifies spatial dispersion of repolarization in human subjects with ischemic cardiomyopathy.

INTRODUCTION: In experimental models, spatial dispersion of repolarization (DOR) due to discordant cellular alternans predisposes to ventricular fibrillation. To test the hypothesis that microvolt T-wave alternans (MTWA) in humans causes spatial DOR, we measured Tpeak-Tend interval (Tpe) and Tpe/QT ratio, electrocardiographic indices of spatial DOR. METHODS: Mean Tpe and Tpe/QT were compared in ischemic cardiomyopathy patients with positive and negative MTWA studies. RESULTS: MTWA was positive in 12 and negative in 24 patients. Tpe and Tpe/QT were higher in MTWA+ subjects compared to MTWA- subjects during exercise (64.5±6.8 vs. 54.9±8.7ms, p=0.001 and 0.218±0.03 vs. 0.177±0.02, p=0.001) but not at rest. CONCLUSION: Ischemic cardiomyopathy patients have increased Tpe and Tpe/QT when MTWA is induced during exercise, suggesting that MTWA causes increased spatial DOR in humans. Future studies are needed to determine if Tpe and Tpe/QT during exercise might predict increased risk of SCD alone or in combination with measurement of MTWA.

ß-blockers protect against dispersion of repolarization during exercise in congenital long-QT syndrome type 1.

INTRODUCTION: ß-Blocker therapy reduces syncope and sudden death in long-QT syndrome type 1 (LQT1), but the mechanism of protection is incompletely understood. This study tested the hypothesis that ß-blockade reduces QT prolongation and dispersion of repolarization, measured as the T peak-to-end interval (T(pe) ), during exercise and recovery in LQT1 patients. METHODS AND RESULTS: QT and T(pe) were measured in 10 LQT1 patients (33 ± 13 years) and 35 normal subjects (32 ± 12 years) during exercise tests on and off ß-blockade. In LQT1 patients, ß-blockade reduced QT (391 ± 25 milliseconds vs 375 ± 26 milliseconds, P = 0.04 during exercise; 419 ± 41 milliseconds vs 391 ± 39 milliseconds, P = 0.02 during recovery) and markedly reduced T(pe) (91 ± 26 milliseconds vs 67 ± 19 milliseconds, P = 0.03 during exercise; 103 ± 26 milliseconds vs 78 ± 11 milliseconds, P = 0.02 during recovery). In contrast, in normal subjects, ß-blockade had no effect on QT (320 ± 17 milliseconds vs 317 ± 16 milliseconds, P = 0.29 during exercise; 317 ± 13 milliseconds vs 315 ± 14 milliseconds, P = 0.15 during recovery) and mildly reduced T(pe) (69 ± 13 milliseconds vs 61 ± 11 milliseconds, P = 0.01 during exercise; 77 ± 19 milliseconds vs. 68 ± 14 milliseconds, P < 0.001 during recovery). CONCLUSION: In LQT1 patients, ß-blockers reduced QT and T(pe) during exercise and recovery, supporting the theory that ß-blocker therapy protects LQT1 patients by reducing dispersion of repolarization during exercise and recovery.