Time- and rate-dependent alterations of the QT interval precede the onset of torsade de pointes in patients with acquired QT prolongation.

Abstract Objectives. The purpose of this study was to determine whether the QT interval dynamics that precede torsade de pointes are consistent with the initiation of this arrhythmia by early afterdepolarization-induced triggered activity. Background. Early afterdepolarization-induced triggered activity has been suggested as an electrophysiologic mechanism for torsade de pointes. Consequently, the initiation of torsade de pointes should involve time- and rate-dependent alterations of ventricular repolarization similar to those known to modulate the development of early afterdepolarizations. Methods. RR and QT intervals were measured in digitized 24-h ambulatory electrocardiographic recordings obtained from seven patients with acquired prolongation of ventricular repolarization. Each patient had one or more episodes of torsade de pointes. The relation between RR and QT intervals was determined before, during and after multiple episodes of torsade de pointes. Results. In patients with multiple episodes of ventricular arrhythmias, the onset of the arrhythmias was associated with a critical prolongation of the QT interval. In some episodes, prolongation of the QT interval was associated with sudden prolongation of the sinus cycle length, whereas in other episodes, the QT interval prolonged progressively at a constant cycle length. Conclusions. The association between a critically prolonged QT interval and the onset of ventricular arrhythmias suggests that the initial complex of torsade de pointes is an early afterdepolarization-induced triggered response. However, prolongation of the QT interval itself was not sufficient to account for the initiation of torsade de pointes, suggesting that other, as yet unidentified factors are required. (J Am Coll Cardiol 1997;30:209–17

Tpeak-Tend, Tpeak-Tend/QT ratio and Tpeak-Tend dispersion for risk stratification in Brugada Syndrome:A systematic review and meta-analysis

Background: Brugada syndrome is an ion channelopathy that predisposes affected subjects to ventricular tachycardia/fibrillation (VT/VF), potentially leading to sudden cardiac death (SCD). Tpeak-Tend intervals, (Tpeak-Tend)/QT ratio and Tpeak-Tend dispersion have been proposed for risk stratification, but their predictive values in Brugada syndrome have been challenged recently. Methods: A systematic review and meta-analysis was conducted to examine their values in predicting arrhythmic and mortality outcomes in Brugada Syndrome. PubMed and Embase databases were searched until 1 May 2018, identifying 29 and 57 studies. Results: Nine studies involving 1740 subjects (mean age 45 years old, 80% male, mean follow-up duration was 68 ± 27 months) were included. The mean Tpeak-Tend interval was 98.9 ms (95% CI: 90.5-107.2 ms) for patients with adverse events (ventricular arrhythmias or SCD) compared to 87.7 ms (95% CI: 80.5-94.9 ms) for those without such events, with a mean difference of 11.9 ms (95% CI: 3.6-20.2 ms, P = 0.005; I2 = 86%). Higher (Tpeak-Tend)/QT ratios (mean difference = 0.019, 95% CI: 0.003-0.036, P = 0.024; I2 = 74%) and Tpeak-Tend dispersion (mean difference = 7.8 ms, 95% CI: 2.1-13.4 ms, P = 0.007; I2 = 80%) were observed for the event-positive group. Conclusion: Tpeak-Tend interval, (Tpeak-Tend)/QT ratio and Tpeak-Tend dispersion were higher in high-risk than low-risk Brugada subjects, and thus offer incremental value for risk stratification

Assessment of the dynamics of atrial signals and local atrial period series during atrial fibrillation: effects of isoproterenol administration

BACKGROUND: The autonomic nervous system (ANS) plays an important role in the genesis and maintenance of atrial fibrillation (AF), but quantification of its electrophysiologic effects is extremely complex and difficult. Aim of the study was to evaluate the capability of linear and non-linear indexes to capture the fine changing dynamics of atrial signals and local atrial period (LAP) series during adrenergic activation induced by isoproterenol (a sympathomimetic drug) infusion. METHODS: Nine patients with paroxysmal or persistent AF (aged 60 ± 6) underwent electrophysiological study in which isoproterenol was administered to patients. Atrial electrograms were acquired during i) sinus rhythm (SR); ii) sinus rhythm during isoproterenol (SRISO) administration; iii) atrial fibrillation (AF) and iv) atrial fibrillation during isoproterenol (AFISO) administration. The level of organization between two electrograms was assessed by the synchronization index (S), whereas the degree of recurrence of a pattern in a signal was defined by the regularity index (R). In addition, the level of predictability (LP) and regularity of LAP series were computed. RESULTS: LAP series analysis shows a reduction of both LP and R index during isoproterenol infusion in SR and AF (R(SR )= 0.75 ± 0.07 R(SRISO )= 0.69 ± 0.10, p < 0.0001; R(AF )= 0.31 ± 0.08 R(AFISO )= 0.26 ± 0.09, p < 0.0001; LP(SR )= 99.99 ± 0.001 LP(SRISO )= 99.97 ± 0.03, p < 0.0001; LP(AF )= 69.46 ± 21.55 LP(AFISO )= 55 ± 24.75; p < 0.0001). Electrograms analysis shows R index reductions both in SR (R(SR )= 0.49 ± 0.08 R(SRISO )= 0.46 ± 0.09 p < 0.0001) and in AF (R(AF )= 0.29 ± 0.09 R(AFISO )= 0.28 ± 0.08 n.s.). CONCLUSIONS: The proposed parameters succeeded in discriminating the subtle changes due to isoproterenol infusion during both the rhythms especially when considering LAP series analysis. The reduced value of analyzed parameters after isoproterenol administration could reflect an important pro-arrhythmic influence of adrenergic activation on favoring maintenance of AF

Genotype-Phenotype Correlation in the Long-QT Syndrome

Background —The congenital long-QT syndrome (LQTS) is caused by mutations on several genes, all of which encode cardiac ion channels. The progressive understanding of the electrophysiological consequences of these mutations opens unforeseen possibilities for genotype-phenotype correlation studies. Preliminary observations suggested that the conditions ("triggers") associated with cardiac events may in large part be gene specific. Methods and Results —We identified 670 LQTS patients of known genotype (LQT1, n=371; LQT2, n=234; LQT3, n=65) who had symptoms (syncope, cardiac arrest, sudden death) and examined whether 3 specific triggers (exercise, emotion, and sleep/rest without arousal) differed according to genotype. LQT1 patients experienced the majority of their events (62%) during exercise, and only 3% occurred during rest/sleep. These percentages were almost reversed among LQT2 and LQT3 patients, who were less likely to have events during exercise (13%) and more likely to have events during rest/sleep (29% and 39%). Lethal and nonlethal events followed the same pattern. Corrected QT interval did not differ among LQT1, LQT2, and LQT3 patients (498, 497, and 506 ms, respectively). The percent of patients who were free of recurrence with β-blocker therapy was higher and the death rate was lower among LQT1 patients (81% and 4%, respectively) than among LQT2 (59% and 4%, respectively) and LQT3 (50% and 17%, respectively) patients. Conclusions —Life-threatening arrhythmias in LQTS patients tend to occur under specific circumstances in a gene-specific manner. These data allow new insights into the mechanisms that relate the electrophysiological consequences of mutations on specific genes to clinical manifestations and offer the possibility of complementing traditional therapy with gene-specific approaches