Myocardium extending from the left atrium onto the pulmonary veins: a comparison between subjects with and without atrial fibrillation.

Rapid discharges from the myocardium extendingfrom the left atrium onto the pulmonary vein (PV) have been shown to initiate AF, and AF may be eradicated by the catheter ablation within the PV. However, if there is any difference in the distribution patterns of the myocardial sleeve onto the PV between the subjects with and without AF is to be determined. Twenty-one autopsied hearts were examined. Eleven patients previously had AF before death and another 10 patients had normal sinus rhythm as confirmed from the medical records including ECGs before death. After exposing the heart, the distance to the peripheral end of the myocardium was measured from the PV-atrial junction in each PV. Then, the PVs were sectioned and stained and the distal end of myocardium and the distribution pattern were studied. The anteroposterior diameter of the left atrium was also measured. In 74 of 84 PVs, the myocardium extended beyond the PV-atrial junction. The myocardium was localized surrounding the vascular smooth muscle layerforming a myocardial sleeve. The peripheral end of the myocardial sleeve was irregular and the maximal and minimal distances were measured in each PV. The myocardium extended most distally in the superior PVs compared to the inferior ones and the maximal distance to the peripheral end was similar between the AF and non-AF subjects (8.4 +/- 2.8 vs 8.7 +/- 4.4 mm for the left superior and 6.5 +/- 3.5 vs 5.1 +/- 3.9 mm for the right superior PV, respectively). A significant difference was found in the maximal distance in the inferior PVs: 7.3 +/- 4.6 vs 3.3 +/- 2.8 mm for the left (P < 0.05) and 5.7 +/- 2.4 vs 1.7 +/- 1.9 mm for the right inferior PV (P < 0.001) in the subjects with and without AF, respectively. The diameter of left atrium was slightly dilated in AF patients but insignificantly (4.1 +/- 0.1 vs 3.6 +/- 0.1 cm, P > 0.07). The myocytes on the PV were less uniform and surrounded by more fibrosis in patients with AF compared to those without AF. In conclusion, the myocardium extended beyond the atrium-vein junction onto the PVs. The distribution patterns of the myocardium was almost similar between subjects with and without AF, but the histology suggested variable myocytes in size and fibrosis in patients with AF.

QT interval prolongation and torsades de pointes unmasked by intracoronary acetylcholine administration.

Intracoronary acetylcholine administration, which was performed to exclude vasospasms, unmasked an abnormal QT interval prolongation and initiated torsades de pointes in a patient with normal QT interval at rest.

Inappropriate discharges by fourth generation implantable cardioverter defibrillators in patients with ventricular arrhythmias.

The study prospectively investigated the incidence, cause and efficient management of inappropriate discharge by the fourth generation implantable cardioverter-defibrillator (ICD) system in 45 patients (mean age, 57+/-16 years). During the follow-up period of 27+/-17 months, 18 patients (40%) experienced one or more inappropriate therapies: sinus and supraventricular tachycardia (15 patients) and T wave oversensing (3 patients). In the 15 patients, re-programming of the tachycardia detection interval and/or additional treatment with beta-blocking agents were effective. In the 3 patients with T wave oversensing, the arrythmia was associated with an increase in T wave amplitude, change in T wave morphology and decreased R wave amplitude, and re-programming of the sensitivity of the local electrogram or changing the number of intervals to detect ventricular tachycardia decreased the number of inappropriate discharges in all 3 patients. In conclusion, inappropriate therapies are common problems in patients treated with the fourth generation ICD system, but most of them can be resolved using the dual-chamber ICD system. However, in patients with T-wave oversensing, it is difficult to avoid inappropriate discharge completely, even if the dual-chamber ICD system is implanted.

Correlation between the effective refractory period and activation-recovery interval calculated from the intracardiac unipolar electrogram of humans with and without dl-sotalol treatment.

In experimental studies and/or human body surface mapping, the activation-recovery interval (ARI) is used as a parameter to estimate local repolarization. However, it has not been clarified whether the ARI calculated from the intracardiac unipolar electrogram of humans reasonably represents the local effective refractory period (ERP). Measurement of ARIs at multiple ventricular sites can be helpful in assessing the dispersion of ventricular refractoriness of humans, so we examined the relationship between ERP and ARI in the control state and under treatment with dl-sotalol during clinical electrophysiologic studies (EPS). Of 19 patients, an EPS was performed in the control state in 12 and during treatment with dl-sotalol in the other 7. Quadripolar electrode catheters with an interelectrode distance of 5 mm were placed at the right atrium and in the right ventricle. Using atrial pacing, the heart rate was increased incrementally by 10 beats/min, and ERP and ARI were measured for each pacing rate. The ERP at the right ventricle was measured by single extrastimulation between the first and third distal electrodes of the catheter in the right ventricle, and the ARI was calculated from the second distal unipolar electrode of the same catheter as the interval between the minimum derivative of the intrinsic deflection and the maximum derivative of the T wave. In all patients, the unipolar electrogram was stable during the entire EPS, and 83 data points in the control group and 50 in the dl-sotalol group were analyzed. At each pacing rate, the beat-to-beat difference of ARI was less than 10 ms. As the atrial pacing rate increased, the ERP and ARI were progressively shortened, and linear regression analysis revealed an excellent correlation between ERP and ARI. At the same pacing rate, the ERP and ARI in the dl-sotalol group were longer than those in the control group, but no difference was observed in the slope (close to 1.0) and in the intercept of the regression lines between ERP and ARI. In the human ventricle, the ARI calculated from the intracardiac unipolar electrogram represents the local ERP both in the control state and under treatment with dl-sotalol. The ARI can be used as a parameter of local refractoriness and used to study the distribution of refractoriness in the human ventricle.

Discrepancy between inducibility of ventricular tachycardia and activity of cardiac sarcoidosis. Requirement of defibrillator implantation for the inactive stage of cardiac sarcoidosis.

Monomorphic ventricular tachycardia (VT) developed in two patients with cardiac sarcoidosis. Before treatment with prednisolone, technetium or gallium scintigram revealed abnormal accumulation in the heart and bilateral hilar lymph nodes, but programmed electrical stimulation failed to induce VT in either case. Prednisolone was administered and the abnormal accumulation of the scintigra ms disappeared. However, VT became reproducibly inducible, and in one of the patients, transient entrainment was demonstrated in clinical VT morphology. Defibrillators were implanted in both patients. Some VTs associated with cardiac sarcoidosis are due to reentry, and inducibility of VT is not associated with the activity of cardiac sarcoidosis. Even though steroid therapy suppresses the activity of cardiac sarcoidosis, defibrillator implantation is necessary to prevent a possible arrhythmic event during the follow-up.

Cycle length-associated modulation of the regional dispersion of ventricular repolarization in a canine model of long QT syndrome.

Previous tridimensional activation mapping showed that the development of functional conduction block at the onset of torsades de pointes was regionally heterogeneous; conduction block was frequently observed in the LV and the interventricular septum (IVS) but not in the RV, in the canine anthopleurin-A (AP-A) model of long QT syndrome (LQTS). This may be related to the distribution of myocytes with M celllike electrophysiological characteristics. To better understand the regional difference of arrhythmogenicity in LQTS, the authors investigated cycle length related modulation of ventricular repolarization among three different layers: the endocardium (End), mid-myocardium (Mid), and epicardium (Epi) of the LV and RV and at two different areas: the Epi and septum (Sep) in the IVS. The LQT3 model was produced by AP-A in dogs. Using constant pacing and single premature stimulation (S1S2), the ventricular repolarization pattern was analyzed from 256 unipolar electrograms. Activation-recovery intervals (ARIs) were used to estimate local repolarization. In seven experiments, AP-A increased regional ARI dispersion to 88.1 +/- 36.0 ms in the LV, to 72.9 +/- 35.7 ms in the IVS, and to 23.0 +/- 8.7 ms in the RV at the pacing cycle length (CL) of 1,000 ms. Development of the large ARI dispersion was due to greater ARI prolongation at the Mid site in the LV and at Sep site in the IVS. As the S1S2 interval was shortened, regional ARI dispersion decreased gradually, and finally, ARI dispersion showed a reversal gradient of repolarization between the Mid and Epi sites in the LV and between the Sep and Epi sites in the IVS. Two factors contributed to create the reversal gradient of repolarization: (1) a difference in restitution kinetics at the Mid site in the LV and at the Sep site in the IVS, characterized by a larger delta ARI and slower time constant (tau), and (2) a difference in diastolic intervals at each site resulting in different input to restitution at the same CL. However, the RV showed small alteration in the transmural dispersion of repolarization in the S1S2 protocol. S2 created heterogeneous functional conduction block in the LV and IVS but not in the RV. In the LQT3 model, the arrhythmogenicity of torsades de pointes is primarily due to dispersion of repolarization in the LV and IVS because of prominent distribution of M cells. The RV seems to participate passively in reentrant excitation during torsades de pointes.

Role of alpha1-blockade in congenital long QT syndrome: investigation by exercise stress test.

Beta-blockade is widely reported to reduce the incidence of syncope in 75-80% of patients with congenital long QT syndrome (LQTS). However, despite full-dose beta-blockade, 20-25% of patients continue to have syncopal episodes and remain at high risk for sudden cardiac death. In some patients refractory to beta-blockade, the recurrence of arrhythmias is successfully prevented by left stellate ganglionectomy, and also by labetalol, a nonselective beta-blockade with alpha1-blocking action. These observations suggest that not only beta-adrenoceptors, but also alpha1-adrenoceptors, play an important pathogenic role, especially under sympathetic stimulation, in LQTS. The clinical effects of alpha1-blockade in congenital LQTS were investigated in 8 patients with familial or sporadic LQTS. Two measurements of the QT interval were taken, from the QRS onset to the T wave offset (QT) and from the QRS onset to the peak of the T wave (QTp). Using the Bruce protocol, an exercise test was performed after administration of beta-blockade alone and again after administration of alpha1-blockade. The following were compared: (1) Bazzet-corrected QT (QTc) and QTp (QTpc) intervals in the supine and standing position before exercise and in the early recovery phase after exercise; and (2) the slopes (reflecting the dynamic change in the QT interval during exercise) of the QT interval to heart rate were obtained from the linear regression during the exercise test. In the supine position before exercise, there was no change in the QTc before or after the addition of alpha1-blockade (498+/-23 vs 486+/-23 ms [NS]). However, in the upright position before exercise and in the early recovery phase after exercise, QTc was significantly shortened from 523+/-21 to 483+/-22ms (p<0.01), and from 521+/-30 to 490+/-39ms (p<0.01), respectively, by alpha1-blockade. The QTpc was unchanged in any situation. Consequently, QTc-QTpc was significantly shortened by alpha1-blockade in the upright position before exercise and in the early recovery phase after exercise (131+/-36 to 105+/-37ms (p<0.05), and 132+/-29 to 102+/-31 ms (p<0.01), respectively). The slopes of the QT interval-heart rate relation by linear regression became significantly steeper from -2.23+/-0.38 to -2.93+/-0.76 (p<0.01) with the addition of alpha1-blockade. The findings suggest that the addition of alpha1-blockade attenuated the exercise-induced prolongation of the QT interval and that the rate adaptation of the QT interval to heart rate during exercise was improved. This indicates that additional treatment with alpha1-blockade may be beneficial to prevent cardiac events in LQTS patients in whom ventricular arrhythmia is resistant to beta-blockade.

Inappropriate discharges from an intravenous implantable cardioverter defibrillator due to T-wave oversensing.

This report describes the clinical management of 2 patients with ventricular fibrillation (VF) who received inappropriate shocks from an implantable cardioverter defibrillator (ICD) due to T-wave oversensing. Cardiac sarcoidosis was confirmed as the underlying heart disease in 1 patient and idiopathic dilated cardiomyopathy in the other. Within 2 months after ICD implantation, both patients received several inappropriate shocks during sinus rhythm. Stored electrograms showed decreased R-wave amplitudes and increased T-wave amplitudes. The ICD sensed both R- and T-waves as ventricular activation, which met the rate criteria for VF treatment. Reprogramming the sensing threshold in association with administration of a drug to slow the heart rate decreased the incidence of the inappropriate shocks in both patients, but these palliative measures did not completely suppress the inappropriate shocks. To avoid T-wave oversensing, the repositioning or adding of a sensing lead is required. The potential risk of T-wave oversensing in ICD patients who have small R-wave amplitudes should be recognized.

Intravenous administration of class I antiarrhythmic drugs induced T wave alternans in a patient with Brugada syndrome.

A 71-year-old man who experienced aborted sudden death was referred to our hospital. Coronary artery disease and cerebral accident were ruled out by conventional tests. The 12-lead ECG obtained at rest showed a right bundle branch block pattern and ST segment elevation in leads V1 to V3. Double ventricular extrastimuli at coupling intervals >180 msec induced ventricular fibrillation (VF) twice during electrophysiologic study. Intravenous administration of procainamide accentuated ST segment elevation in leads V1 to V3, and visible T wave alternans was induced in leads V2 and V3 at a dose of 450 mg. Initiation of T wave alternans was not associated with changes of the cardiac cycle or development of premature beats. When procainamide infusion was discontinued, T wave alternans disappeared before the elevated ST segment returned to the control level. Pilsicainide also accentuated ST segment elevation and induced similar T wave alternans in leads V2 and V3. Class I antiarrhythmic drug-related T wave alternans has been reported rarely in Brugada syndrome, but it may represent enhanced arrhythmogenicity of VF. We need to monitor closely and study the clinical implications of T wave alternans in Brugada syndrome.

Abrupt loss of constant fusion during entrainment of ventricular tachycardia at a critical paced cycle length.

Sustained monomorphic ventricular tachycardia (VT) can be frequently entrained and interrupted with rapid pacing and the mechanism of the pacing-induced interruption is considered to be due to orthodromic block. This study focused on the incidence of VT which was interrupted at a critical cycle length and was characterized by an abrupt loss of constant fusion in the surface electrocardiogram (ECG), and the role of orthodromic block as the cause of such characteristic change and interruption of VT was analyzed. Among 45 consecutive patients with symptomatic VT, rapid pacing was performed in 43 VTs of 39 patients. The exit was mapped as the earliest site of the activation during VT and an electrode catheter was located at the site. Rapid pacing was performed at progressively shorter cycle lengths in steps of 10 msec until VT was interrupted and the timing of the orthodromic and direct capture was compared at the exit. Abrupt loss of constant fusion was observed in 25 of 39 patients (64.1%): and the loss was invariably associated with interruption of VT. When the timings of the activation of the exit were compared, which were measured from the preceding (n-1) stimulus as the time reference, the direct capture was relatively delayed compared to that of the orthodromic capture. This finding suggests that orthodromic block is the cause of the direct capture as well as the pacing-induced interruption of VT. In the remaining 13 patients (35.9%), the surface ECG showed a gradual transition into the fully paced QRS morphology. The direct capture was confirmed in the non-fused beats, but it was not necessarily associated with interruption of VT. The interval from the stimulus to the entrained electrogram at the exit showed a gradual prolongation until the exit was finally captured directly from the pacing site. The confirmation of constant fusion followed by abrupt loss in ECG can be a reliable hallmark of orthodromic block as the cause of the interruption of VT during transient entrainment at a critical paced cycle length.

Vasospastic angina accompanied by Brugada-type electrocardiographic abnormalities.

Brugada Syndrome and Vasospastic Angina. We present two patients with vasospastic angina and Brugada-type ECG abnormalities. The first patient complained of chest pain, and transient ST segment elevation was confirmed on ECG. Coronary angiogram showed no organic stenosis. The second patient had syncopal episodes following anginal chest pain, and the same symptoms were reproduced by intracoronary acetylcholine injection that induced vasospasm. In both patients, ECG at rest showed ST segment elevation in leads V1 and V2 and a right bundle branch block pattern that were accentuated by a Class I antiarrhythmic drug. Ventricular fibrillation also was induced by programmed electrical stimulation. Susceptibility to ventricular fibrillation can be modulated by the interaction of coronary vasospasm with Brugada syndrome or vice versa; therefore, it is important to study the clinical implications of the coexistence of the two diseases in such patients.

Antitachycardia burst pacing for pleomorphic reentrant ventricular tachycardias associated with non-coronary artery diseases: a morphology specific programming for ventricular tachycardias.

To study the role of antitachycardia burst pacing in patients with reentrant pleomorphic ventricular tachycardia (VT) associated with non-coronary artery diseases, the efficacy of antitachycardia pacing and appropriate antitachycardia pacing cycle length were evaluated in each pleomorphic VT morphology of seven patients. Seven patients were included in this study. Clinically documented pleomorphic VTs were reproduced in an electrophysiologic study. For each VT, rapid ventricular pacing was attempted from the apex of the right ventricle at a cycle length which was 20 ms shorter than that of VT and repeated after a decrement of the cycle length in steps of 10 ms until the VT was terminated or accelerated. All 16 VTs could be entrained by the rapid pacing, and 13 of the 16 VTs (81%) were terminated, whereas pacing-induced acceleration was observed in the other 3 VTs of the 3 patients. VT cycle length (VTCL), block cycle length (BCL) which was defined as the longest VT interrupting paced cycle length, %BCL/VTCL and entrainment zone which was defined as VTCL minus BCL, varied in each VT morphology of each patient. In two patients, antitachycardia pacing was effective in all VT morphologies and the maximum difference of the %BCL/VTCL among the pleomorphic VTs was less than 10%. Thus, antitachycardia pacing seemed to be beneficial for these patients. In the other 5 patients, a difference of more than 10% in %BCL/VTCL was observed among the pleomorphic VT morphologies and/or at least one VT morphology showed pacing-induced acceleration. Compared to the 13 terminated VTs, three accelerated VTs had a wide entrainment zone [160 +/- 44 vs 90 +/- 48 ms, p < 0.04] and small %BCL/VTCL [61 +/- 6 vs 77 +/- 11%,p<0.03]. In pleomorphic VTs associated with non-coronary artery diseases, responses to rapid pacing was not uniform; VT might be terminable or accelerated even in the same patient. We need to pay close attention when programming antitachycardia pacing in patients with pleomorphic VT.

Demonstration of transient entrainment in monomorphic sustained ventricular tachycardia associated with cardiac sarcoidosis.

A 49-year-old man was referred for further treatment of sustained monomorphic ventricular tachycardia (VT) associated with cardiac sarcoidosis. During an electrophysiologic study (EP), dl-sotalol suppressed the spontaneous VT and prevented induction of VT. However, when predonisolone treatment was started, monomorphic VT recurred frequently. To terminate the VT, a temporal pacing lead was placed at the apex of the right ventricle, and programmed electrical stimulation was attempted from the lead. During the EP study, 2 different monomorphic VTs were repetitively induced and both types were able to be terminated by rapid ventricular pacing; in one of the VT morphologies, constant and progressive fusion was obvious during the ventricular pacing. Some monomorphic VTs associated with cardiac sarcoidosis are due to reentry with an excitable gap, but the clinical efficacy of EP-guided antiarrhythmic drug treatment seems to be less certain during steroid therapy. In the present case, a defibrillator device was implanted to prevent a possible arrhythmic event.

Structure of the reentrant circuit of idiopathic left ventricular tachycardia: new insights into the role of the Purkinje network.

In idiopathic left ventricular tachycardia (ILVT), the reentrant circuit is considered to involve the Purkinje system, and the Purkinje potential (P-potential) appears to be a marker for successful ablation. However, the characteristics of the reentrant circuit in ILVT have not yet been defined. In 2 cases of ILVT, we performed detailed mapping along the left ventricular septum during VT and sinus rhythm. ILVTs were successfully ablated at the posteroapical area of the left ventricular septum where the high frequency P-potential was recorded and this portion was considered to be the exit site of the reentrant circuit. A small P-potential was also recorded at the portion proximal to the exit site, and it preceded the P-potential at the exit site. However, the local ventricular electrogram at the exit site preceded that at the proximal site during VT. Moreover, the small P-potential was orthodromically entrained by ventricular pacing from the proximal site. These findings suggest that the reentry circuit of ILVT appeared to have considerable size.

Beneficial effect of amiodarone on pacing induced terminability of reentrant ventricular tachycardia.

A 33 year-old woman was referred to our hospital for further treatment of ventricular tachycardia (VT). During treatment with amiodarone (200 mg/day), clinical VT at the cycle length of 510 ms was induced. During the VT, rapid ventricular pacing was repeated at progressively shorter cycle lengths after a decrement of 10 ms steps. The VT was entrained by the rapid pacing and reproducibly terminated at a paced cycle length of 380 ms. Four weeks after reducing the amiodarone to 100 mg/day, programmed stimulation was repeated. The VT with the same morphology but with a slightly shorter cycle length of 480 ms was again induced. However, at this time, rapid pacing from the same site could not terminate VT and transient acceleration developed at a shorter paced cycle length of 260 ms. The QT (QTc) interval, effective refractory period at the pacing site and width of the paced QRS complex were similar before and after changing the amiodarone treatment. The most characteristic change of VT in the second study was a widening of the entrainment zone, which was calculated as the difference between VT cycle length and the longest pacing cycle length which interrupts VT during the entrainment (from 130 to > 220 ms), and it may be explained by the preferential shortening of the action potential duration and/or facilitation of the depressed cell to cell conduction within the reentry circuit. Amiodarone must exert a preferential action in the reentry circuit and modulate the conduction property as well as the effective refractory period. We should pay close attention to the efficacy of antitachycardia pacing during the modification of amiodarone treatment.

Development of ventricular fibrillations with different characteristics in the local electrocardiogram: large and small amplitude of activation, and its implication for implantable cardioverter defibrillator treatment.

An implantable cardioverter defibrillator (ICD) was implanted in 2 patients with ventricular tachyarrhythmia related to old myocardial infarction, and defibrillation tests were attempted at the time of ICD implantation and at 2 or 4 weeks after the operation. Ventricular fibrillation (VF) was induced by T-wave shocks, but the amplitude of the ventricular electrogram was different in each VF. In most of the VFs with large ventricular electrograms, the local activity was appropriately detected. However, many undersensed beats were observed in other VFs that had fine ventricular electrograms and a longer time was needed before delivering the shock. The amplitude of the ventricular electrogram might be small in some cases of VF and this might result in undersensing and/or unsuccessful defibrillation. Close attention must be paid to the amplitude of ventricular activation in each VF to avoid possible difficulty in ICD therapy.

Recovery of the right atrial effective refractory period after cardioversion of chronic atrial fibrillation.

The effective refractory period was shorter in patients with than without chronic atrial fibrillation (AF). The effective refractory period was prolonged, and at 12 and 24 hours after cardioversion of AF it was the same as the subjects without AF.

Ventricular fibrillation with small amplitude of activation and its implications for implantable cardioverter defibrillator treatment.

An implantable cardioverter defibrillator (ICD) was implanted in a patient with ventricular fibrillation (VF) related to old myocardial infarction. During VF, amplitude of ventricular activation was small, and the ventricular sensitivity at 1.2 mV failed to detect several small ventricular activations. When the sensitivity was changed to 0.3 mV, both under- and oversensed beats occurred during VF, and at the ventricular sensitivity of 0.15 mV, the undersensed beats disappeared while oversensed beats markedly increased. Defibrillation test was repeated one and four weeks after the implantation, and these inappropriate beats were minimized at the ventricular sensitivity of 0.3 mV. We should pay attention to the amplitude of ventricular activation to avoid possible trouble in ICD therapy.

Mechanism of arrhythmogenicity of the short-long cardiac sequence that precedes ventricular tachyarrhythmias in the long QT syndrome.

OBJECTIVES: The purpose of this study was to investigate the electrophysiologic mechanism(s) that underlie the transition of one or more short-long (S-L) cardiac sequences to ventricular tachyarrhythmias (VTs) in the long QT syndrome. BACKGROUND: One or more S-L cardiac cycles, usually the result of a ventricular bigeminal rhythm, frequently precedes the onset of VT in patients with either normal or prolonged QT interval. Electrophysiologic mechanisms that underlie this relationship have not been fully explained. METHODS: We investigated electrophysiologic changes associated with the transition of a S-L cardiac sequence to VT in the canine anthopleurin-A model, a surrogate of LQT3. Experiments were performed on 12 mongrel puppies after administration of anthopleurin-A. Correlation of tridimensional activation and repolarization patterns was obtained from up to 384 electrograms. Activation-recovery intervals were measured from unipolar electrograms and were considered to represent local repolarization. RESULTS: We analyzed 24 different episodes of a S-L sequence that preceded VT obtained from 12 experiments. The VT followed one S-L sequence (five episodes), two to five S-L sequences (12 episodes) and more than five S-L sequences (seven episodes). The single premature ventricular beats coupled to the basic beats were consistently due to a subendocardial focal activity (SFA). There were two basic mechanisms for the development of VT after one or more S-L sequences: 1) in 10 examples of a S-L sequence due to a stable unifocal bigeminal rhythm, the occurrence of a second SFA, which arose consistently from a different site, infringed on the pattern of dispersion of repolarization (DR) of the first SFA to initiate reentrant excitation; 2) in the remaining 14 episodes of a S-L sequence, a slight lengthening (50 to 150 ms) in one or more preceding cycle lengths (CLs) resulted in alterations of the spatial pattern of DR at key sites to promote reentry. The lengthening of the preceding CL produced differentially a greater degree of prolongation of repolarization at midmyocardial and endocardial sites compared with epicardial sites with consequent increase of DR. The increased DR at key adjacent sites resulted in the development of de novo zones of functional conduction block and/or slowed conduction to create the necessary prerequisites for successful reentry. CONCLUSIONS: The occurrence of VT after one or more S-L cardiac sequences was due to well defined electrophysiologic changes with predictable consequences that promoted reentrant excitation.

Effect of atropine on QT prolongation and torsade de pointes induced by intracoronary acetylcholine in the long QT syndrome.

We recently reported a marked QT prolongation and torsade de pointes (TDP) induced by an intracoronary acetylcholine (ACh) administration in patients with long QT syndrome, but the mechanism was not determined. In the present study, the effect of atropine on the ACh-induced QT prolongation and TDP was studied in long QT syndrome. Nine patients with congenital long QT syndrome were studied. ACh at doses of 20, 50, and 100 microg were injected in a stepwise manner into the left main coronary artery, and the changes in the QT interval were measured. In 4 of the 9 patients, ACh administration at a dose of 100 microg was repeated after an intravenous atropine administration at a dose of 0.5 mg. The QT intervals were measured using 12-lead electrocardiograms, and the data were compared before and after atropine administration. The coronary angiograms were normal and coronary spasm was not induced by ACh in all patients. The intracoronary administration of ACh at a dose of 100 microg significantly prolonged the corrected QT interval (QTc), from 511 +/- 26 to 629 +/- 40 ms (p <0.05). In 5 of the 9 patients, TDP was induced and was spontaneously terminated within 10 seconds (n = 4) or required direct-current shock (n = 1). After atropine administration, intracoronary ACh at the same dose resulted in no QT prolongation, and the QTc interval remained unchanged (525 +/- 29 vs 520 +/- 21 ms before and after atropine), and no TDP was induced. These findings indicate that the muscarinic receptor is involved in ACh-induced QT prolongation and TDP, both of which were prevented by the atropine administration.