Naohiko Aihara

Idiopathic sustained left ventricular tachycardia: clinical and electrophysiologic characteristics.

Electrophysiologic studies were performed in 16 patients 11 to 45 years old (mean 33 years) with idiopathic sustained (lasting more than 5 min) ventricular tachycardia (VT) originating from the left ventricle. Endocardial mapping during VT showed that the earliest site of activation was at the apical inferior portion of the left ventricle in 14 patients whose QRS morphology during VT showed a right bundle branch block pattern and left-axis deviation, but at the apical anterosuperior portion of the left ventricle in two patients whose QRS morphology during VT showed a right bundle branch block and right-axis deviation. Single programmed ventricular stimulation induced VT in 13 patients, and rapid ventricular pacing induced VT in the remaining three patients. Rapid ventricular pacing terminated VT in all patients. The relationship between the coupling interval and the echo interval was inverse in all eight patients with a wide VT inducible zone. Entrainment was recognized in three of six patients. The initiation of VT by constant pacing depended on the number of pacing beats but not the duration of pacing in all four patients tested. Intravenous verapamil terminated the VT in 13 of 14 patients. Long-term oral verapamil was also effective in all five patients who required long-term oral therapy for their symptoms associated with VT. In conclusion (1) idiopathic left ventricular tachycardia has unique electrocardiographic, electrophysiologic, and electropharmacological properties, (2) the electrophysiologic characteristics suggest that the mechanism is reentry, and (3) verapamil is effective in both the short- and long-term treatment of VT.

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

OBJECTIVES This study was designed to test the hypothesis that epinephrine infusion may be a provocative test able to unmask nonpenetrant KCNQ1 mutation carriers. BACKGROUND The LQT1 form of congenital long QT syndrome is associated with high vulnerability to sympathetic stimulation and appears with incomplete penetrance. METHODS The 12-lead electrocardiographic parameters before and after epinephrine infusion were compared among 19 mutation carriers with a baseline corrected QT interval (QTc) of > or =460 ms (Group I), 15 mutation carriers with a QTc of <460 ms (Group II), 12 nonmutation carriers (Group III), and 15 controls (Group IV). RESULTS The mean corrected Q-Tend (QTce), Q-Tpeak (QTcp), and Tpeak-end (Tcp-e) intervals among 12-leads before epinephrine were significantly larger in Group I than in the other three groups. Epinephrine (0.1 microg/kg/min) increased significantly the mean QTce, QTcp, Tcp-e, and the dispersion of QTcp in Groups I and II, but not in Groups III and IV. The sensitivity and specificity of QTce measurements to identify mutation carriers were 59% (20/34) and 100% (27/27), respectively, before epinephrine, and the sensitivity was substantially improved to 91% (31/34) without the expense of specificity (100%, 27/27) after epinephrine. The mean QTce, QTcp, and Tcp-e before and after epinephrine were significantly larger in 15 symptomatic than in 19 asymptomatic mutation carriers in Groups I and II, and the prolongation of the mean QTce with epinephrine was significantly larger in symptomatic patients. CONCLUSIONS Epinephrine challenge is a powerful test to establish electrocardiographic diagnosis in silent LQT1 mutation carriers, thus allowing implementation of prophylactic measures aimed at reducing sudden cardiac death.

Long-Term Prognosis of Probands With Brugada-Pattern ST-Elevation in Leads V1–V3

Background—The prognosis of patients with saddleback or noncoved type (non–type 1) ST-elevation in Brugada syndrome is unknown. The purpose of this study was to clarify the long-term prognosis of probands with non–type 1 ECG and those with coved (type 1) Brugada-pattern ECG. Methods and Results—A total of 330 (123 symptomatic, 207 asymptomatic) probands with a coved or saddleback ST-elevation ≥1 mm in leads V1–V3 were divided into 2 ECG groups—type 1 (245 probands) and non–type 1 (85 probands)—and were prospectively followed for 48.7±15.0 months. The absence of type 1 ECG was confirmed by drug provocation test and multiple recordings. The ratio of individuals with a family history of sudden cardiac death (14%) was lower than previous studies. Clinical profiles and outcomes were not notably different between the 2 groups (annual arrhythmic event rate of probands with ventricular fibrillation; type 1: 10.2%, non–type 1: 10.6%, probands with syncope; type 1: 0.6%, non–type 1: 1.2%, and asymptomatic probands; type 1: 0.5%, non–type 1: 0%). Family history of sudden cardiac death at age <45 years and coexistence of inferolateral early repolarization with Brugada-pattern ECG were independent predictors of fatal arrhythmic events (hazard ratio, 3.28; 95% confidence interval, 1.42 to 7.60; P=0.005; hazard ratio, 2.66; 95% confidence interval, 1.06 to 6.71; P=0.03, respectively, by multivariate analysis), although spontaneous type 1 ECG and ventricular fibrillation inducibility by electrophysiological study were not reliable parameters. Conclusions—The long-term prognosis of probands in non–type 1 group was similar to that of type 1 group. Family history of sudden cardiac death and the presence of early repolarization were predictors of poor outcome in this study, which included only probands with Brugada-pattern ST-elevation.

Long-term Prognosis of Probands with Brugada-pattern ST Elevation in V1-V3 Leads

Background—The prognosis of patients with saddleback or noncoved type (non–type 1) ST-elevation in Brugada syndrome is unknown. The purpose of this study was to clarify the long-term prognosis of probands with non–type 1 ECG and those with coved (type 1) Brugada-pattern ECG. Methods and Results—A total of 330 (123 symptomatic, 207 asymptomatic) probands with a coved or saddleback ST-elevation ≥1 mm in leads V1–V3 were divided into 2 ECG groups—type 1 (245 probands) and non–type 1 (85 probands)—and were prospectively followed for 48.7±15.0 months. The absence of type 1 ECG was confirmed by drug provocation test and multiple recordings. The ratio of individuals with a family history of sudden cardiac death (14%) was lower than previous studies. Clinical profiles and outcomes were not notably different between the 2 groups (annual arrhythmic event rate of probands with ventricular fibrillation; type 1: 10.2%, non–type 1: 10.6%, probands with syncope; type 1: 0.6%, non–type 1: 1.2%, and asymptomatic probands; type 1: 0.5%, non–type 1: 0%). Family history of sudden cardiac death at age <45 years and coexistence of inferolateral early repolarization with Brugada-pattern ECG were independent predictors of fatal arrhythmic events (hazard ratio, 3.28; 95% confidence interval, 1.42 to 7.60; P=0.005; hazard ratio, 2.66; 95% confidence interval, 1.06 to 6.71; P=0.03, respectively, by multivariate analysis), although spontaneous type 1 ECG and ventricular fibrillation inducibility by electrophysiological study were not reliable parameters. Conclusions—The long-term prognosis of probands in non–type 1 group was similar to that of type 1 group. Family history of sudden cardiac death and the presence of early repolarization were predictors of poor outcome in this study, which included only probands with Brugada-pattern ST-elevation.

Dynamic changes of 12-lead electrocardiograms in a patient with Brugada syndrome.

Dynamic ECG Changes in Brugada Syndrome. We present a patient with Brugada syndrome in whom 12‐lead ECXis were recorded just before and after an episode of ventricular fibrillation (VF). A progressive elevation of both the RS‐T segment and J waves just preceding and following the VF, and a close relationship between the amplitude of the RS‐T segment and the preceding R‐R intervals during atrial fibrillation, were documented. These findings support the hypothesis that RS‐T elevation and a subsequent VF are related to a transient outward current‐mediated spike‐and‐dome morphology of the epicardial action potential.

Early afterdepolarizations induced by isoproterenol in patients with congenital long QT syndrome.

Background Several recent experimental and clinical studies have shown that early afterde-polarizations (EADs) are important in the genesis of QTU prolongation and ventricular tachyarrhythmias (VTs) in patients with long QT syndrome. On the other hand, sympathetic stimulation is well known to contribute to the genesis of QTU prolongation and VTs in patients with congenital long QT syndrome. The present study was performed to examine the influence of isoproterenol on the genesis of EADs and on the action potential durations and QTU intervals in patients with congenital long QT syndrome. Methods and Results We recorded monophasic action potentials (MAPs) with a contact electrode during right atrial pacing at a constant cycle length of 500 msec before and after continuous isoproterenol infusion (1 μg/min). MAPs were obtained from the right and left ventricular endocardium in six patients with congenital long QT syndrome (LQT group, 18 recording sites) and in eight control patients (control group, 19 recording sites). Although no EADs were recorded from either group during the control state, MAP duration at 90% repolarization (MAPD90) was significantly longer in the LQT group (n = 18) than in the control group (n = 19) (275 ± 36 versus 231 ± 22 msec;p < 0.0005). Isoproterenol induced EADs in four of the six LQT patients (five of 18 recording sites) but not in the eight control patients (zero of 19 recording sites). The appearance of EADs in the LQT group was associated with an increased amplitude of the late component of the TU complex, and the corrected QT (QTj) interval was prolonged by isoproterenol from 543 ± 53 to 600 ± 30 msec12 (n = 6; p < 0.05). Isoproterenol also prolonged the MAPD90 from 275 ± 36 to 304 ± 50 msec in the LQT group (n = 18; p< 0.005), whereas it shortened the MAPD90 from 231 ± 22 to 224 ± 25 msec in the control group (n = 19; p< 0.05). Moreover, isoproterenol increased the dispersion of MAPD90 (difference between the longest MAPD90 and the shortest MAPD90 in each patient) from 30 ± 5 to 62 ± 35 msec in the LQT group (n = 6; p=0.08), whereas it did not change the dispersion of MAPD90 in the control group (n = 8; 25 ± 14 versus 27 ± 14 msec). Conclusions. These results suggest that patients with congenital long QT syndrome have primary repolarization abnormalities and that EADs induced by isoproterenol play an important role in the exaggeration of these repolarization abnormalities.

The electrophysiologic mechanism of ST-segment elevation in Brugada syndrome.

OBJECTIVES We sought to demonstrate the electrophysiologic (EP) mechanism of the ST-T change in Brugada syndrome. BACKGROUND Brugada syndrome is characterized by various electrocardiographic manifestations (e.g., right bundle branch block, ST-segment elevation, and terminal T-wave inversion in the right precordial leads) and sudden cardiac death caused by ventricular fibrillation. Direct evidence in support of the EP mechanism underlying this intriguing syndrome has been lacking. METHODS Monophasic action potentials (MAPs) were obtained from three patients with the coved-type ST-segment elevation (Brugada patients) and five control patients using the contact electrode method. Epicardial MAPs were recorded during open-chest surgery in all patients. RESULTS A spike-and-dome configuration was documented from epicardial sites of the right ventricular (RV) outflow tract in all Brugada patients but not in control patients. Monophasic action potential recordings from the endocardium with special focus on the RV outflow tract could not demonstrate any morphological abnormalities in three Brugada patients. CONCLUSIONS The presence of a deeply notched action potential in the RV epicardium, but not in endocardium, would be expected to induce a transmural current that would contribute to elevation of the ST-segment in the right precordial leads. The spike-and-dome configuration may also prolong the epicardial action potential, thus contributing to a rapid reversal of the transmural gradients and inscription of an inverted T-wave.

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 epinephrine-induced 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 microgram/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 after depolarizations, 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.

Electrophysiologic characteristics andimplications of induced ventricular fibrillationin symptomatic patients with brugada syndrome

OBJECTIVES: The study examined the electrocardiographic and electrophysiologic characteristics in relation to programmed ventricular stimulation (PVS)-induced ventricular fibrillation (VF), as well as the implications of PVS-induced VF on the recurrence of cardiac events in symptomatic Brugada syndrome. BACKGROUND: Brugada syndrome is characterized by ST-segment elevation in the right precordial leads (V(1)-V(3)) and an episode of VF. METHODS: Thirty-four symptomatic patients with Brugada syndrome (33 men and 1 woman; 44 +/- 12 years old) were classified into two groups according to the inducibility of VF with PVS: 22 patients with induced VF requiring direct cardioversion for termination (Induced VF group) and 12 patients without induced VF (Noninduced VF group). RESULTS: The induced VF group showed a longer QRS duration, a higher incidence of right bundle branch block and late potentials detected on the signal-averaged electrocardiogram, longer His-ventricular intervals and a longer conduction time from the RVOT to the left ventricle at extrastimulation than those in the non-induced VF group. However, there was no significant difference in the recurrence of cardiac events (VF documented by an implantable cardioverter-defibrillator and sudden cardiac death) between the two groups (8 [36%] of 22 patients vs. 7 [58%] of 12 patients) during long-term follow-up (range 1 to 149 months; mean 38). CONCLUSIONS: Our data suggest that induction of VF by PVS depends on the severity of depolarization abnormalities but does not predict the recurrence of cardiac events in symptomatic Brugada syndrome, indicating that both depolarization and repolarization abnormalities are important in the development of VF.

Bradycardia-induced abnormal QT prolongation in patients with complete atrioventricular block with torsades de pointes

Fourteen patients with complete atrioventricular block with or without torsades de pointes (TdP) were included in this study. They were divided into 2 groups, 6 patients with TdP (TdP[+] group) and 8 patients without TdP (TdP[-] group). The patients were evaluated at 2 different periods, before (acute period) and after (chronic period) pacemaker implantation. In the acute period, the QRS and heart rate during the escape rhythm were not significantly different between the 2 groups; however, the QT and QTc intervals were significantly longer in the TdP(+) group than in the TdP(-) group: 753 +/- 57.5 vs 635 +/- 78.4 ms (p less than 0.01) and 585 +/- 44.8 vs 476 +/- 58.3 ms (p less than 0.01). In the chronic period (greater than 2 months after pacemaker implantation), we changed the pacemaker rate from 90 or 100 beats/min to 50 beats/min and examined the QT interval changes in relation to the heart rate. The QT interval in the TdP(+) group was significantly prolonged compared with the TdP(-) group when the pacing rate was decreased less than or equal to 60 beats/min: 551 +/- 40 vs 503 +/- 36 ms at 60 beats/min (p less than 0.05), and 700 +/- 46 vs 529 +/- 43 ms at 50 beats/min (p less than 0.001). Patients with complete atrioventricular block with TdP had a bradycardia-sensitive repolarization abnormality and this characteristic remained after pacemaker implantation. The critical heart rate that induced abnormal QT prolongation in the TdP(+) group was less than or equal to 60 beats/min.