Katsuro Shimomura

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.

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.

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.

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.

Relation between the widening of the fragmented atrial activity zone and atrial fibrillation

Fragmented electrical activity is often recorded by a local atrial electrogram in response to atrial extrastimuli. To assess the relation between fragmented activity and the spontaneous occurrence of atrial fibrillation or flutter (AFF), the fragmented activity zone was measured in 57 patients. The electrograms of the high right atrium, low right atrium and left atrium (through the coronary sinus) were recorded simultaneously during high right atrial stimulation. The fragmented activity zone was defined as the S1-S2 interval (S1 = stimulus of a basic beat, S2 = stimulus of a premature beat) during which a significant fragmented activity was recorded by a high right atrial electrogram after S2. Fifteen patients had neither sinoatrial disease nor atrial arrhythmias (Group I, controls), 16 had sick sinus syndrome (SSS) with a history of paroxysmal AFF (Group II), 14 had SSS without a history of paroxysmal AFF (Group III), and 12 had idiopathic paroxysmal AFF (Group IV). The fragmented activity zone was significantly wider in Group II (112 +/- 26 ms [mean +/- standard deviation], p less than 0.001), Group III (77 +/- 38 ms, p less than 0.001) and Group IV (86 +/- 19 ms, p less than 0.001) than in Group I (31 +/- 25 ms). Patients in Group II had a wider fragmented activity zone than those in Group III (p less than 0.01). Thus, the widening of the fragmented atrial activity zone is characteristic of AFF and may be a good index of a tendency to develop spontaneous AFF.

Long-term outcome of verapamil-sensitive sustained left ventricular tachycardia in patients without structural heart disease

OBJECTIVES This study attempted to determine the long-term outcome of verapamil-sensitive sustained left ventricular tachycardia in patients without apparent structural heart disease. BACKGROUND Several types of idiopathic ventricular tachycardia have been reported, and their clinical, electrophysiologic and electropharmacologic characteristics are different. It is possible that the prognosis of each type of ventricular tachycardia might also be different. METHODS We studied mortality and morbidity in 37 consecutive patients (27 male, 10 female; mean [+/- SD] age 33 +/- 14 years) with verapamil-sensitive sustained left ventricular tachycardia who had no apparent structural heart disease. Patients were followed up for 1 to 13 years (mean 5.8). Verapamil repeatedly terminated ventricular tachycardia in all patients. Ventricular tachycardia originated from the inferior and inferoseptal regions of the left ventricle in 33 patients and the superior and superioseptal regions in 4. Severity of ventricular tachycardia was classified according to the extent to which symptoms limited daily activities. Ventricular tachycardia was mild (minimal limitation) in 14 patients, moderate (some limitation) in 17 and severe (severe limitation) in 6. RESULTS Fourteen patients with mild ventricular tachycardia were followed up without any drug therapy, and the ventricular tachycardia remained mild in all patients. Antiarrhythmic therapy was initiated empirically in the 23 patients with moderate and severe ventricular tachycardia (verapamil in 20, propranolol in 2, digoxin in 1). Moderate ventricular tachycardia became mild ventricular tachycardia after drug therapy in all patients, but the six patients with severe ventricular tachycardia showed no improvement. The six patients with severe ventricular tachycardia had nonpharmacologic therapy (cryosurgery in one, catheter ablation in four, antitachycardia pacing device in one). During the follow-up period, all patients remained alive except for one who died suddenly after implantation of an antitachycardia pacing device. CONCLUSIONS 1) The long-term prognosis of verapamil-sensitive sustained left ventricular tachycardia in patients without apparent structural heart disease is good. 2) Verapamil is the drug of choice for alleviating symptoms, but nonpharmacologic therapy is necessary in some patients.

Usefulness of Electron-Beam Computed Tomography in Arrhythmogenic Right Ventricular Dysplasia Relationship to Electrophysiological Abnormalities and Left Ventricular Involvement

BACKGROUND Electron-beam computed tomography (CT) may be useful for detecting myocardial fat infiltration and diagnosing arrhythmogenic right ventricular dysplasia (ARVD). There are several characteristic electron-beam CT findings of ARVD. However, the incidence, their relation to electrophysiological abnormalities, and the usefulness of electron-beam CT for evaluating left ventricular involvement are unknown. This study aimed to clarify these issues. METHODS AND RESULTS Electron-beam CT was performed in 14 patients with ARVD (ARVD group), 16 age- and sex-matched patients with right ventricular enlargement and/or dysfunction without ARVD (RV enlargement group), and 13 control subjects (control group). The incidences of abnormal electron-beam CT findings in the three groups were examined. Furthermore, we examined the endocardial fat-infiltrated areas detected by electron-beam CT (CT-A) and electrophysiologically abnormal areas detected in the mapping electrophysiology study (EPS-A) and compared the relationship between them in the ARVD group. (1) The frequencies of abundant epicardial adipose tissue, low-attenuation trabeculations, scalloping of the right ventricular free wall, and intramyocardial fat deposits were 86%, 71%, 79%, and 50%, respectively, in the ARVD group, whereas these findings were not observed in the RV enlargement and control groups. (2) Three ARVD patients (21%) had adipose tissue involvement of the left ventricle. (3) The relationship between CT-A and EPS-A was as follows: CT-A > EPS-A, 71%; CT-A = EPS-A, 14%; and EPS-A only, 14%. CONCLUSIONS Characteristic electron-beam CT findings are frequently observed only in patients with ARVD. Electron-beam CT is useful for evaluating for left ventricular involvement and can estimate EPS-A.

The role of initial minimum potentials on body surface maps in predicting the site of accessory pathways in patients with Wolff-Parkinson-White syndrome.

Forty-one patients (23 men and 18 women, ages 20 to 66 years) with Wolff-Parkinson-White syndrome were studied with isopotential body surface maps during sinus rhythm to find the most reliable index for predicting the sites of single accessory pathways. The sites predicted by surface maps were compared with those confirmed by multicatheter electrophysiologic study or in the course of surgical operation. Location of the initial minimum by a time criterion, 40 msec after onset of the QRS complex, was not reliable enough for prediction in patients with the small delta wave on their electrocardiograms, because ventricular activation via the normal conduction pathway significantly influenced the location of the minimum. Location of the minimum by an amplitude criterion, -0.15 mV or slightly deeper, was influenced minimally by fusion of ventricular activation, the patients body size, or age and corresponded well to the site of the accessory pathway in 36 of 41 patients. Those minima appeared on circumscribed areas of the map in accordance with the anatomic subdivisions of the atrioventricular ring. Thus location of the minimum by the amplitude criterion was an excellent index for predicting the site of the accessory pathway, regardless of the degree of ventricular fusion. These amplitude-based map features suggest that nonstandard electrocardiograms recorded from selected positions on the body surface can be used as accurate predictors of the sites of accessory pathways.

Effect of ventricular hypertrophy on conduction velocity of activation front in the ventricular myocardium

To study the effect of ventricular hypertrophy on conduction velocity of the activation front noninvasively, transmural conduction indexes were obtained from findings of echocardiography and body surface potential mapping performed in 40 patients with right bundle branch block uncomplicated by the left anterior fascicular block. Because in these patients, left ventricular activation proceeds radially without being modified by right ventricular activation, the index was obtained by dividing ventricular septal thickness measured from the echocardiogram by transmural conduction time, which was taken as the time interval from the onset of the QRS complex to the time when the left ventricular epicardial breakthrough minimum appeared on the potential map. The indexes, ranging from 11 to 45 cm/s, has a good positive linear correlation with the septal thickness (Y = 2.37X - 1.33, correlation coefficient [r] = 0.83) and were abnormally small in some failed hearts. Further, both the mean ventricular activation times in lead V5 and the mean value for total duration of left ventricular activation did not differ significantly in patients with and without left ventricular hypertrophy. These findings suggest that conduction velocity was increased in the hypertrophied ventricle and decreased in the failed hearts. Because there were no significant differences in the mean serum sodium and potassium concentrations in the patients with and without left ventricular hypertrophy, it is concluded that hypertrophy itself most likely caused greater conduction velocity. Enlarged cells and multiple intercalated discs abundant in hypertrophied ventricle would have facilitated intercellular current flow and, hence, conduction velocity and impaired cellular connection in the failed heart would have reduced them. Thus, the transmural conduction index is suggested to be an important aid in interpreting electrocardiograms as well as in estimating the pathologic state of the heart.

Diagnostic Value of Plasma Levels of Brain Natriuretic Peptide in Arrhythmogenic Right Ventricular Dysplasia

BACKGROUND Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by local or diffuse wall motion abnormalities in the right ventricle (RV), associated with recurrent ventricular tachycardia (VT) of RV origin. Brain natriuretic peptide (BNP) was first isolated from a porcine brain extract. In humans, BNP is expressed predominantly in the ventricles of failing hearts, and its expression has been observed primarily in myocytes in the interstitial fibrous area in dilated cardiomyopathy. We hypothesized that BNP is increasingly secreted from the residual myocytes within the atrophic tissue in patients with ARVD. METHODS AND RESULTS Plasma BNP levels were measured in 17 patients with ARVD, 12 patients with idiopathic RV outflow tract tachycardia (RVOT), and 120 control subjects. We performed cardiac catheterization, RV endomyocardial biopsy, electron- beam CT, and biventricular endomyocardial mapping in the ARVD patients. There was a significant increase in plasma BNP levels in the ARVD patients compared with the RVOT patients and control subjects (61.4+/-59.6 pg/mL versus 8.3+/-5. 5 pg/mL and 9.3+/-5.8 pg/mL; P<0.0001, respectively). The plasma BNP levels had no correlation with any of the hemodynamic data, but they had a significant correlation with the RV ejection fraction (r=-0. 588, P=0.025) and with the fractionated-area scores (r=0.705, P=0. 005). Light microscopic immunohistochemistry showed strong BNP immunoreactivity in residual myocytes with fibrofatty replacement. CONCLUSIONS These results suggest that plasma BNP levels were not increased in RVOT patients but were increased in ARVD patients, and that the increased BNP levels indicate the severity of both the RV dysfunction and the arrhythmogenic substrate.