926-24 Clinical and Electrophysiological Characteristics in Patients with Exercise Induced Idiopathic Multiform Ventricular Tachycardia. Differential Effects of Atrial Pacing and Isoproterenol Infusion on QTc Interval and Induction of Ventricular Arrhythmia

Idiopathic multiform ventricular tachycardia (VT) is characterized by normal QT interval at restand 3 or more distinct QRS configuration during VT, which has been distinguished from torsade de pointes in long QT syndrome. Facilitation by exercise and suppression by β-antagonist of this VT suggest that it may depend on rapid heart rate (HR) or increased sympathetic tone. To determine which factors is responsible, we performed atrial pacing (120/min) and isoproterenol (ISP) infusion (0.5 or 1.0μg to attain HR 120/min) in 6 patients (2 males/4 females, mean 15.8 years) and 10 control (4 males/6 females, mean 22.8 years). Inducibility of premature ventricular contraction (PVC) or VT, and response of QTc interval (QT/√RR) were evaluated during the procedures.controlmultiform VTp valuePVCNT inductionAtrial pacing0/71/6n.s.Isoproterenol0/86/60.001OTc (secl/2)Rest0.40±0.02 (n=10)0.40±0.03n.s.Atrial pacing0.43±0.02 (n=7)0.47±003<0.01Isoproterenol0.44±0.01 (n=8)0.50±0.05<0.001ConclusionAlthough both rapid HR and increased sympathetic tone may be responsible for this VT, contribution of the latter is predominant. Differential response of QT interval to atrial pacing and isoproterenol infusion may have a possible role for the occurrence of this VT

Sympathetic stimulation produces a greater increase in both transmural and spatial dispersion of repolarization in LQT1 than LQT2 forms of congenital long QT syndrome

AbstractOBJECTIVESThe study compared the influence of sympathetic stimulation on transmural and spatial dispersion of repolarization between LQT1 and LQT2 forms of congenital long QT syndrome (LQTS).BACKGROUNDCardiac events are more associated with sympathetic stimulation in LQT1 than in LQT2 or LQT3 syndrome. Experimental studies have suggested that the interval between Tpeak and Tend (Tp-e) in the electrocardiogram (ECG) reflects transmural dispersion of repolarization across the ventricular wall.METHODSWe recorded 87-lead body-surface ECGs before and after epinephrine infusion (0.1 μg/kg/min) in 13 LQT1, 6 LQT2, and 7 control patients. The Q-Tend (QT-e), Q-Tpeak (QT-p), and Tp-e were measured automatically from 87-lead ECGs, corrected by Bazett’s method (QTc-e, QTc-p, Tcp-e), and averaged among all 87-leads and among 24-leads, which reflect the potential from the left ventricular free wall. As an index of spatial dispersion of repolarization, the dispersion of QTc-e (QTc-eD) and QTc-p (QTc-pD) were obtained among 87-leads and among 24-leads, and were defined as the interval between the maximum and the minimum of the QTc-e and the QTc-p, respectively.RESULTSEpinephrine significantly increased the mean QTc-e but not the mean QTc-p, resulting in a significant increase in the mean Tcp-e in both LQT1 and LQT2, but not in control patients. The epinephrine-induced increases in the mean QTc-e and Tcp-e were larger in LQT1 than in LQT2, and were more pronounced when the averaged data were obtained from 24-leads than from 87-leads. Epinephrine increased the maximum QTc-e but not the minimum QTc-e, producing a significant increase in the QTc-eD in both LQT1 and LQT2 patients, but not in control patients. The increase in the QTc-eD was larger in LQT1 than in LQT2 patients.CONCLUSIONSOur data suggest that sympathetic stimulation produces a greater increase in both transmural and spatial dispersion of repolarization in LQT1 than in LQT2 syndrome, and this may explain why LQT1 patients are more sensitive to sympathetic stimulation

Effects of verapamil and propranolol on early afterdepolarizations and ventricular arrhythmias induced by epinephrine in congenital long QT syndrome

Objectives.This study used monophasic action potentials to investigate the effects of verapamil and propranolol on epinephrineinduced repolarization abnormalities in congenital long QT syndrome.Background.Early afterdepolarizations have been suggested to play a significant role in QT prolongation and ventricular arrhythmias in congenital long QT syndrome. Calcium channel blocking as well as beta-adrenergic blocking agents are reported to be effective in the management of this syndrome.Methods.Monophasic action potentials from 2 to 4 sites were recorded simultaneously in eight patients with the long QT syndrome (22 sites) and in eight control patients (23 sites) and were obtained during constant atrial pacing 1) before epinephrine infusion; 2) during epinephrine infusion (0.1 μg/kg body weight min); 3) after verapamil injection (0.1 mg/kg) during epinephrine infusion; and 4) after both propranolol (0.1 mg/kg) and verapamil injections.Results.Early afterdepolarizations were recorded in two of the eight patients (2 of 22 sites) during the control state. During epinephrine infusion, early afterdepolarizations were recorded in six patients (six sites), and ventricular premature complexes were induced in three and torsade de pointes in one. Epinephrine prolonged 90% monophasic action potential duration from 348 ± 48 (mean ± SD) to 381 ± 49 ms (22 sites, p < 0.0005) and increased the dispersion of action potential duration (difference between the longest and shortest action potential duration) from 36 ± 20 to 64 ± 34 ms (p < 0.005). Verapamil eliminated (two sites) or reduced (four sites) early afterdepolarizations and abolished ventricular premature complexes in two of the three patients as well as suppressing torsade de pointes. Verapamil shortened the action potential duration to 355 ± 28 ms (p < 0.01 vs. epinephrine) and decreased the dispersion to 44 ± 19 ms (p < 0.05 vs. epinephrine). Propranolol further eliminated (two sites) or reduced (two sites) early afterdepolarizations, abolished ventricular premature complexes in the remaining one patient and further shortened the action potential duration to 337 ± 32 ms (p = 0.09 vs. verapamil). In the control patients, none of the early afterdepolarizations, ventricular arrhythmias or marked prolongations of action potential duration were induced by epinephrine, and neither verapamil nor propranolol changed repolarization variables.Conclusions.These results indicate that both verapamil and propranolol can improve repolarization abnormalities induced by epinephrine in congenital long QT syndrome

Differential effects of beta-blockade on dispersion of repolarization in the absence and presence of sympathetic stimulation between the lqt1 and lqt2 forms of congenital long qt syndrome

AbstractObjectivesThis study compared the effects of beta-blockade on transmural and spatial dispersion of repolarization (TDR and SDR, respectively) between the LQT1 and LQT2 forms of congenital long QT syndrome (LQTS).BackgroundThe LQT1 form is more sensitive to sympathetic stimulation and more responsive to beta-blockers than either the LQT2 or LQT3 forms.MethodsEighty-seven-lead, body-surface electrocardiograms (ECGs) were recorded before and after epinephrine infusion (0.1 μg/kg body weight per min) in the absence and presence of oral propranolol (0.5–2.0 mg/kg per day) in 11 LQT1 patients and 11 LQT2 patients. The Q-Tendinterval, the Q-Tpeakinterval and the interval between Tpeakand Tend(Tp-e), representing TDR, were measured and averaged from 87-lead ECGs and corrected by Bazett’s method (corrected Q-Tendinterval [cQTe], corrected Q-Tpeakinterval [cQTp] and corrected interval between Tpeakand Tend[cTp-e]). The dispersion of cQTe(cQTe-D) was obtained among 87 leads and was defined as the interval between the maximum and minimum values of cQTe.ResultsPropranolol in the absence of epinephrine significantly prolonged the mean cQTpvalue but not the mean cQTevalue, thus decreasing the mean cTp-evalue in both LQT1 and LQT2 patients; the differences with propranolol were significantly larger in LQT1 than in LQT2 (p < 0.05). The maximum cQTe, minimum cQTeand cQTe-D were not changed with propranolol. Propranolol completely suppressed the influence of epinephrine in prolonging the mean cQTe, maximum cQTeand minimum cQTevalues, as well as increasing the mean cTp-eand cQTe-D values in both groups.ConclusionsBeta-blockade under normal sympathetic tone produces a greater decrease in TDR in the LQT1 form than in the LQT2 form, explaining the superior effectiveness of beta-blockers in LQT1 versus LQT2. Beta-blockers also suppress the influence of sympathetic stimulation in increasing TDR and SDR equally in LQT1 and LQT2 syndrome

Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome

n/

Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome Multicenter study in Japan

AbstractObjectivesWe sought to compare the arrhythmic risk and sensitivity to sympathetic stimulation of mutations located in transmembrane regions and C-terminal regions of the KCNQ1channel in the LQT1 form of congenital long QT syndrome (LQTS).BackgroundThe LQT1 syndrome is frequently manifested with variable expressivity and incomplete penetrance and is much more sensitive to sympathetic stimulation than the other forms.MethodsSixty-six LQT1 patients (27 families) with a total of 19 transmembrane mutations and 29 patients (10 families) with 8 C-terminal mutations were enrolled from five Japanese institutes.ResultsPatients with transmembrane mutations were more frequently affected based on electrocardiographic (ECG) diagnostic criteria (82% vs. 24%, p < 0.0001) and had more frequent LQTS-related cardiac events (all cardiac events: 55% vs. 21%, p = 0.002; syncope: 55% vs. 21%, p = 0.002; aborted cardiac arrest or unexpected sudden cardiac death: 15% vs. 0%, p = 0.03) than those with C-terminal mutations. Patients with transmembrane mutations had a greater risk of first cardiac events occurring at an earlier age, with a hazard ratio of 3.4 (p = 0.006) and with an 8% increase in risk per 10-ms increase in corrected Q-Tend. The baseline ECG parameters, including Q-Tend, Q-Tpeak, and Tpeak-end intervals, were significantly greater in patients with transmembrane mutations than in those with C-terminal mutations (p < 0.005). Moreover, the corrected Q-Tend and Tpeak-end were more prominently increased with exercise in patients with transmembrane mutations (p < 0.005).ConclusionsIn this multicenter Japanese population, LQT1 patients with transmembrane mutations are at higher risk of congenital LQTS-related cardiac events and have greater sensitivity to sympathetic stimulation, as compared with patients with C-terminal mutations

Epidemiology of Brugada syndrome in Japan and rest of the world

Brugada syndrome is an inherited disease that causes sudden death because of ventricular fibrillation. Its prevalence is approximately 0.15% in adults and 0.005% in children in Asia, and less than 0.02% in the West. The reason for the higher prevalence in Asia is likely ethnic-specific polymorphisms modulating the activity of the primary disease-causing mutation. In Japan, the incidence of Brugada-pattern electrocardiogram (ECG) is 14.2 per 100,000 person-years. Data from multicenter registries indicate that its frequency in men with Brugada syndrome is higher in Japanese patients (94–96%) than in Caucasian patients (72–80%). Healthy individuals with Brugada-type ECG have a favorable prognosis with an annual death rate of less than 0.5%