Mode of onset of torsade de pointes in congenital long QT syndrome

Viskin, Sami; Alla, Srinivasa R.; Barron, Hal V.; Heller, Karin; Saxon, Leslie A.; Kitzis, Ilan; Hare, George F. Van; Wong, Mary J.; Lesh, Michael D.; Scheinman, Melvin M.

doi:10.1016/s0735-1097(96)00311-7

Cited by 145 publications

(77 citation statements)

References 51 publications

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“…In 1 episode, the polymorphic VT was preceded by an episode of AV 2:1 block. All 16 episodes started with an R-on-T phenomenon; in 11 of 16, we observed short-long-short episodes initiating the polymorphic VT as has been described in human patients with acquired and congenital LQTS (28). All episodes of polymorphic VT were preceded by longer periods with multiple single premature ventricular contractions or short nonsustained VTs, and 5 episodes of polymorphic VT succeeded longer periods of ventricular bigeminy.…”

Section: Figuresupporting

confidence: 69%

Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome

Brunner¹,

Peng²,

Liu³

et al. 2008

J. Clin. Invest.

145

277

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Long QT syndrome (LQTS) is a heritable disease associated with ECG QT interval prolongation, ventricular tachycardia, and sudden cardiac death in young patients. Among genotyped individuals, mutations in genes encoding repolarizing K + channels (LQT1:KCNQ1; LQT2:KCNH2) are present in approximately 90% of affected individuals. Expression of pore mutants of the human genes KCNQ1 (KvLQT1-Y315S) and KCNH2 (HERG-G628S) in the rabbit heart produced transgenic rabbits with a long QT phenotype. Prolongations of QT intervals and action potential durations were due to the elimination of I Ks and I Kr currents in cardiomyocytes. LQT2 rabbits showed a high incidence of spontaneous sudden cardiac death (>50% at 1 year) due to polymorphic ventricular tachycardia. Optical mapping revealed increased spatial dispersion of repolarization underlying the arrhythmias. Both transgenes caused downregulation of the remaining complementary I Kr and I Ks without affecting the steady state levels of the native polypeptides. Thus, the elimination of 1 repolarizing current was associated with downregulation of the reciprocal repolarizing current rather than with the compensatory upregulation observed previously in LQTS mouse models. This suggests that mutant KvLQT1 and HERG interacted with the reciprocal wild-type α subunits of rabbit ERG and KvLQT1, respectively. These results have implications for understanding the nature and heterogeneity of cardiac arrhythmias and sudden cardiac death.

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Section: Figuresupporting

confidence: 69%

Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome

Brunner¹,

Peng²,

Liu³

et al. 2008

J. Clin. Invest.

145

277

View full text Add to dashboard Cite

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“…189,201,202 The primary benefit of pacemaker therapy may be in patients with pause-dependent initiation of ventricular tachyarrhythmias 203 or those with sinus bradycardia or advanced AV block in association with the congenital long-QT syndrome, 204,205 which is most commonly associated with a sodium channelopathy. Benson et al 206 discuss sinus bradycardia due to a (sodium) channelopathy.…”

Section: Long-qt Syndromementioning

confidence: 99%

ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities

Epstein¹,

DiMarco²,

Ellenbogen³

et al. 2008

Circulation

1,243

488

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“…Previous studies have used other arbitrary cutoff values, ie, any increment, 15 a 20-ms increment, 36 or a 40-ms increment 21 over I (-2) . To study whether the choice for any particular cutoff value may confound our primary analysis, we also analyzed the proportions of pause-dependent TdP onset in LQT1 and LQT2 when cutoff values other than 50% were used to define "pause dependence" (Figure 8).…”

Section: Study Limitationsmentioning

confidence: 99%

Genotype-Specific Onset of Arrhythmias in Congenital Long-QT Syndrome

et al. 2006

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Background-The identification of the molecular-genetic substrate underlying the various forms of the congenital long-QT syndrome (LQTS) has sparked studies into possible genotype-phenotype correlations with the aim of developing genotype-tailored therapy. The onset of torsade de pointes (TdP) may differ among LQTS patients, being pause dependent in some but not all. This disparity may point to different arrhythmia mechanisms and may affect therapy strategies. We studied whether the proportion of pause-dependent TdP onset varies among LQTS genotypes. Methods and Results-We studied all LQT1 (nϭ10), LQT2 (nϭ34), and LQT3 (nϭ6) patients from 4 centers for whom ECGs of TdP onset were available and analyzed whether pauses preceded TdP onset (first available ECG per patient). Pauses preceded TdP significantly more often in LQT2 (68%) than in LQT1 (0%), and the interval immediately before TdP (pause interval) was significantly longer in LQT2 than in LQT1.

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Mode of onset of torsade de pointes in congenital long QT syndrome

Cited by 145 publications

References 51 publications

Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome

Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome

ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities

Genotype-Specific Onset of Arrhythmias in Congenital Long-QT Syndrome

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