Comparison of T-wave alternans and QT interval dispersion to predict ventricular tachyarrhythmia in patients with dilated cardiomyopathy and without antiarrhythmic drugs: a prospective study.

Microvolt T-wave alternans (TWA) and QT interval dispersion (QTD), which reflect temporal and spatial repolarization abnormalities, respectively, have been proposed as useful indices to identify patients at risk for ventricular tachyarrhythmias (VTs). The purpose of this study was to clarify which repolarization abnormality marker is more useful in predicting arrhythmic events in patients with dilated cardiomyopathy (DCM). Forty-two consecutive nonischemic DCM patients underwent the assessment of TWA and QTD. Patients undergoing antiarrhythmic pharmacotherapy, except beta-blockers and those with irregular basic rhythms, were excluded from entry. Eight patients were also excluded because of indeterminate test results. Therefore, 34 DCM patients were prospectively assessed. The end point of the study was the documentation of VT defined as > or = 5 consecutive ectopic beats during the follow-up period. TWA and QTD (> or = 65 msec) were positive in 24 (80%) and 11 (37%) of 30 patients with available follow-up data, respectively. There was no relationship between TWA and QTD. During a follow-up of 13+/-11 months, VTs occurred in 13 patients (43%). In Cox regression analysis, TWA was a significant risk stratifier (p=0.02), whereas QTD was not. The sensitivity, specificity, and positive and negative predictive values of TWA in predicting VTs were 100%, 35%, 54%, and 100%, respectively. TWA could be a useful noninvasive index to identify patients at risk for VTs in the setting of DCM. This study may suggest that temporal repolarization abnormality is associated more with arrhythmogenesis than with spatial repolarization abnormality in DCM patients.

Lack of noninvasive markers of ventricular repolarization inhomogeneity in patients with idiopathic ventricular tachyarrhythmia.

Noninvasive markers reflecting repolarization inhomogeneity have been proposed to be useful indices for identifying patients at risk of ventricular arrhythmias based on organic heart disease. In this study, we clarify whether or not repolarization inhomogeneity markers are useful in patients with idiopathic ventricular tachycardia (VT). We investigated T-wave alternans (TWA) and corrected QT-interval dispersion (QTD) in 84 consecutive patients with idiopathic VT, 90 patients with VT associated with organic heart disease (organic VT), and 87 normal individuals. VT was defined as tachycardia lasting > or =5 consecutive ventricular ectopic beats at a rate of > or =120 beats/min. TWA was positive in 20 of 84 patients (24%) with idiopathic VT, 59 of 90 patients (66%) with organic VT, and 16 of 87 normal individuals (18%). The alternans voltage was 2.6 +/- 3.1 micro V in idiopathic VT patients, 5.6 +/- 6.4 micro V in organic VT patients, and 2.9 +/- 5.7 micro V in normal individuals. QTD were 53 +/- 20 ms in idiopathic VT patients, 92 +/- 20 ms in organic VT patients, 46 +/- 18 ms in normal individuals, respectively. A positive TWA test result was seen more (P <.01) frequently, and QTD was longer (P <.01) in organic VT patients compared to normal individuals, whereas there was no difference between idiopathic VT patients and normal individuals. In addition, in patients with idiopathic VT, neither did any of these measurements differ between patients with sustained VT (lasting for > or =30 s) and those with nonsustained VT. Noninvasive markers of repolarization inhomogeneity, such as TWA and QTD, are not useful for identifying patients with idiopathic VT. Repolarization inhomogeneity may not affect to the pathogenesis of idiopathic VT.

Predicting the recurrence of ventricular tachyarrhythmias from T-wave alternans assessed on antiarrhythmic pharmacotherapy: a prospective study in patients with dilated cardiomyopathy.

BACKGROUND: Microvolt T-wave alternans (TWA) has been proposed as a useful index to identify patients at risk of ventricular tachyarrhythmias. Recent studies have demonstrated that antiarrhythmic drugs, such as amiodarone and procainamide, decrease the prevalence of TWA. In this study, we tested whether TWA in patients on antiarrhythmic pharmacotherapy significantly predicts the recurrence of ventricular tachyarrhythmias in patients with dilated cardiomyopathy. METHODS: To evaluate the ability to predict the recurrence of ventricular tachyarrhythmias, determinate TWA and left ventricular ejection fraction (LVEF) were prospectively assessed in 49 patients with ischemic or nonischemic dilated cardiomyopathy on antiarrhythmic pharmacotherapy for sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). The pharmacotherapy consisted of class I (17 patients), III (29 patients), and IV (3 patients) antiarrhythmic drugs. The study endpoint was the first recurrence of sustained VT or VF on treatment during the follow-up period. RESULTS: TWA was positive on antiarrhythmic pharmacotherapy in 30 patients (61%). During a follow-up of 13 +/- 11 months, the sustained VT or VF recurred in 21 of the 41 patients (51%) with available follow-up data. The sensitivity of TWA and LVEF for predicting recurrence of ventricular tachyarrhythmias was 76 and 38%, specificity was 60 and 70%, positive predictive value was 67 and 57%, and negative predictive value was 71 and 52%. Kaplan-Meier event-free analysis revealed that TWA was a significant risk stratifier (P = 0.02), whereas LVEF was not. CONCLUSIONS: This prospective study suggests that TWA significantly predicts the recurrence of ventricular tachyarrhythmias, even on antiarrhythmic pharmacotherapy, in patients with dilated cardiomyopathy. TWA may also be a useful marker for evaluating the efficacy of antiarrhythmic drugs for ventricular tachyarrhythmias.

Clinical usefulness of the combination of T-wave alternans and late potentials for identifying high-risk patients with moderately or severely impaired left ventricular function.

Ventricular tachyarrhythmia (VT) is an independent risk factor for an increased overall mortality in patients with impaired left ventricular (LV) function, but there is not an established noninvasive tool to detect such patients. The present study aimed to clarify the most useful noninvasive approach for identification of patients with moderately or severely impaired LV function complicated by VT. Sixty-seven patients in New York Heart Association (NYHA) classes I-III with an LV ejection fraction (LVEF) less than 40% and an LV end-diastolic dimension (LVDD) of at least 55 mm on echocardiography were enrolled. Impaired LV function was caused by either ischemic (n=30) or nonischemic dilated cardiomyopathy (n=37). T-wave alternans (TWA), QT dispersion (QTD), and late potentials (LP) on signal-averaged electrocardiography were sequentially determined without using antiarrhythmic drugs. VT was defined as more than 6 consecutive ventricular ectopic beats. The mean NYHA class was 1.9+/-0.7, mean LVEF was 31+/-8%, and mean LVDD was 65+/-10mm. A history of VT was present in 26 of the patients (39%). Univariate and multivariate logistic analysis showed that TWA and LP were closely related to VT, whereas NYHA> or =III, LVEF<30%, LVDD> or =70mm, and QTD> or =90ms were not. The combination of TWA and LP had the most significant value (p=0.0004, odds ratio=8.44) by univariate analysis, and only this combination had significant value in multivariate analysis (p=0.04). Therefore, the combination of TWA and LP could be a useful index for identifying those patients with impaired LV function who are at risk for VT.

Assessment of noninvasive markers in identifying patients at risk in the Brugada syndrome: insight into risk stratification.

OBJECTIVES: The aim of this study was to compare the use of various noninvasive markers for detecting risk of life-threatening arrhythmic events in patients with Brugada syndrome. BACKGROUND: The role of conduction disturbance in arrhythmogenesis of the syndrome is controversial, whereas it is well established that repolarization abnormalities are responsible for arrhythmias. The value of noninvasive markers reflecting conduction or repolarization abnormalities in identifying patients at risk for significant arrhythmias has not been shown. METHODS: We assessed late potentials (LP) using signal-averaged electrocardiography (ECG), microvolt T-wave alternans (TWA), and corrected QT-interval dispersion (QTD) in 44 consecutive patients who had ECGs showing a pattern of right bundle branch block and ST-segment elevation in leads V1 to V3 but structurally normal hearts. The patients were compared with 30 normal individuals. RESULTS: Eleven patients were excluded from data analysis because of an absence of ECG manifestations of Brugada syndrome at the time of the tests. A history of life-threatening events defined as syncope and aborted sudden death was present in 19 of 33 patients (58%); in 15 of the 19 patients, stimulation induced ventricular fibrillation or polymorphic ventricular tachycardia. The LP were present in 24 of 33 patients (73%); TWA were present in 5 of 31 patients (16%); and a QTD >50 ms was present in 9 of 33 patients (27%). The incidence of LP in Brugada patients was significantly (p < 0.0001) higher than in the controls, whereas incidences of TWA and QTD were not significantly different. Multivariate logistic regression analysis revealed that the presence of LP had the most significant correlation to the occurrence of life-threatening events (p = 0.006). CONCLUSIONS: Late potentials are a noninvasive risk stratifier in patients with Brugada syndrome. These results may support the idea that conduction disturbance per se is arrhythmogenic.

Atrial double potentials associated with the elimination of the electrical connection between the coronary sinus (CS) and the left atrium in two cases of Wolff-Parkinson-White syndrome with a CS-connected accessory pathway.

A curious retrograde conduction in connection with the coronary sinus (CS) musculature was observed in 2 patients. After the failed ablation procedure, the atrial electrogram during ventricular pacing presented double potentials, the first component of which was sharp and with an activation sequence that was the same before ablation (CS distal to proximal). The second component of the double potentials was dull and had a decremental property; its activation sequence was in reverse (proximal to distal). In both cases, the first component disappeared after successful ablation. These findings suggest that the first component was the CS electrogram conducted over the accessory pathway and the second component was the left atrial electrogram conducted through the inter-atrial septum. The separation of each electrogram is probably the result of a block between the accessory pathway connected to the CS musculature and the left atrium. These are unusual cases of an accessory pathway connected to the CS musculature, which separates the left atrial myocardium at the distal portion from the ostium.

Lack of an association between T-wave alternans and ST-segment depression during exercise-induced ambulatory ischemia.

It is known that T-wave alternans (TWA), which identify patients at risk for arrhythmic events, often occur during acute coronary occlusion in association with ST-segment elevation. To test the hypothesis that TWA is associated with a certain state/severity of myocardial infarction/ischemia, we assessed the association between TWA and ST-segment depression during exercise-induced ambulatory ischemia. Of 351 consecutive patients with coronary artery disease who underwent assessment of microvolt TWA by exercise, 23 patients with effort angina without a history of infarction with ST depression (> or =0.11 mV) during TWA test were selected. These patients were compared with 222 postinfarction patients consisting of 38 patients with, and 184 patients, without the ST depression, and 18 normal individuals. The incidence (9%) of determinate TWA in the patients with angina was significantly (P < .0001) lower than that (52%) in the postinfarction patients. There was no significant difference between the angina patients and the controls (6%). There was also no difference between the patients with (58%) and without the ST depression (51%) in the postinfarction patients. Moreover, no correlation existed between the TWA voltage and the ST-depression magnitude in both angina and postinfarction patients. We concluded that there is no association between TWA and ambulatory ischemia with ST depression.

Combined assessment of T-wave alternans and late potentials used to predict arrhythmic events after myocardial infarction. A prospective study.

OBJECTIVES: The aim of the present study was to determine whether the combination of two markers that reflect depolarization and repolarization abnormalities can predict future arrhythmic events after acute myocardial infarction (MI). BACKGROUND: Although various noninvasive markers have been used to predict arrhythmic events after MI, the positive predictive value of the markers remains low. METHODS: We prospectively assessed T-wave alternans (TWA) and late potentials (LP) by signal-averaged electrocardiogram (ECG) and ejection fraction (EF) in 102 patients with successful determination results after acute MI. The TWA was analyzed using the power-spectral method during supine bicycle exercise testing. No antiarrhythmic drugs were used during the follow-up period. The study end point was the documentation of ventricular arrhythmias. RESULTS: The TWA was present in 50 patients (49%), LP present in 21 patients (21%), and an EF <40% in 28 patients (27%). During a follow-up period of 13 +/- 6 months, symptomatic, sustained ventricular tachycardia or ventricular fibrillation occurred in 15 patients (15%). The event rates were significantly higher in patients with TWA, LP, or an abnormal EF. The sensitivity and the negative predictive value of TWA in predicting arrhythmic events were very high (93% and 98%, respectively), whereas its positive predictive value (28%) was lower than those for LP and EF. The highest positive predictive value (50%) was obtained when TWA and LP were combined. CONCLUSIONS: The combined assessment of TWA and LP was associated with a high positive predictive value for an arrhythmic event after acute MI. Therefore, it could be a useful index to identify patients at high risk of arrhythmic events.

A simple technique for anatomical slow pathway ablation in atrioventricular nodal reentrant tachycardia.

The slow pathway potential or the slow potential serves as a useful marker in catheter ablation of the slow pathway. However, an anatomical approach without recording of these potentials is also an effective way to cure atrioventricular nodal reentrant tachycardia (AVNRT). Moreover, the origin of these potentials is a matter of controversy. We compared 2 approaches to ascertain whether or not recording of these potentials is necessary in eliminating the slow pathway and to estimate the usefulness of the simple anatomical approach. The study population consisted of 24 patients with a conventional approach (Group P) and 19 patients with an anatomical approach (Group A). In group A, the ablation site was determined by fluoroscopy, which was the lowest one-third of the area between the His bundle electrogram recorded position and the coronary sinus orifice at the right anterior oblique view, and just in front of and above the coronary sinus orifice also posterior to the His catheter at the left anterior oblique view where the His catheter was seen tangentially. The slow pathway was successfully ablated in all patients without any complications, including more than first-degree AV block. Although there were no significant differences in total energy or number of applications between the 2 groups, the procedure time was significantly shorter in group A (p < 0.01). In conclusion, recording of the slow pathway potential or the slow potential is not always necessary for slow pathway ablation in the treatment of AVNRT. Because our anatomical approach was performed simply, effectively and safely, it is recommended for the slow pathway ablation of AVNRT.

Anatomically guided radiofrequency catheter ablation of atrial reentrant tachycardia.

Atrial reentrant tachycardia (ART) was ablated in an anatomically guided approach. Five patients with ART underwent 2 linear incisions without careful pace or activation mapping. One line was from an atrial activation site earlier than P wave onset to the nearest fixed anatomic conduction barrier, i.e., the inferior vena cava or coronary sinus ostium. The other line was made just above or closely crossed the first line vertically. Mean application time was 29 +/- 19 minutes, and the application energy was 14,001 +/- 12,322 joules. Mean follow-up after ablation was 15 +/- 10 months. Three patients underwent electrophysiologic study three months after and sustained ART was not induced. All patients were free of sustained tachycardia events without antiarrhythmic drugs during the postoperative clinical course. Although anatomically guided ablation for ART requires much time and energy, it is easily and effectively done without careful activation or pace mapping, and is indicated if ablation using activation mapping or entrainment technique fails to cure the ART.

Assessment of atrioventricular nodal electrophysiological characteristics after radiofrequency catheter ablation of the slow pathway in atrioventricular nodal reentrant tachycardia--3-month follow up.

Radiofrequency catheter ablation of the slow pathway is commonly used to treat atrioventricular (AV) nodal reentrant tachycardia. However, there has been little study of the follow-up assessment of AV nodal physiology. We compared AV nodal electrophysiological characteristics before, immediately after, and again 3 months after successful catheter ablation in 17 patients (mean age 50 +/- 16 years). Sinus cycle length, Wenckebach cycle length, A-H interval at a paced cycle length of 600 ms, effective refractory period and functional refractory period of the fast pathway were significantly changed immediately after catheter ablation, but had recovered 3 months after the procedure. There were no significant differences between the electrophysiological parameters immediately after catheter ablation and those 3 months after the procedure under the intravenous injection of atropine sulfate. We conclude that, due to changes in autonomic nervous tone, AV nodal electrophysiological characteristics are influenced immediately after catheter ablation of the slow pathway in AV nodal reentrant tachycardia.

[Electrophysiological study].

The purpose of an electrophysiological study (EPS) is to determine the mechanism of arrhythmias and to decide the means of therapy for that arrhythmia. The electrode catheters are introduced percutaneously into the atria or ventricle to record the intracardiac electrogram or to stimulate those areas by electrical current. In bradycardia, atrioventricular block and sick sinus syndrome are the good indications of EPS. To determine the indication of pacemaker implantation, recording the block site of atrioventricular block is useful, and sinus node recovery time and sinoatrial conduction time in sick sinus syndrome are important by performing an electrical stimulation to the atrial muscle. In tachyarrhythmia, if the mechanism of arrhythmia is reentry, it can be induced or terminated by electrical stimulation repeatedly. So that the drug efficacy can be defined by testing the re-inducibility after the drug therapy. If the mechanism of arrhythmia is not clear, the EPS is also performed to make the mechanism of the arrhythmia clear. In triggered activity, especially early after depolarization, the recording of monophasic action potential is useful for diagnosis. EPS can provide the ablation site clear, moreover, the indication of implantable cardioverter defibrillator has been decided by EPS. Therefore, the role of EPS has also been important in selection of non-pharmacological treatment.

Effect of radiofrequency catheter ablation of the slow pathway on the atrioventricular node.

Although the effective refractory period (ERP) of the fast pathway is reported to be shortened after radiofrequency catheter ablation of the slow pathway in atrioventricular nodal reentrant tachycardia (AVNRT), whether the atrioventricular (AV) nodal physiology maintains the same condition over the long term is controversial. To assess the AV nodal physiology after catheter ablation of the slow pathway in AVNRT, the A-H interval and ERP of the fast pathway were measured before, immediately after and 3 months after catheter ablation in 12 patients. We compared these factors in 12 patients with left concealed accessory bypass tract to clarify the mechanism of the electrophysiological change in the AV node. Both the A-H interval and ERP of the fast pathway were significantly shortened from 111 +/- 18 to 96 +/- 17 ms and 365 +/- 68 to 261 +/- 52 ms immediately after catheter ablation (p < 0.01), and recovered to 128 +/- 44 and 372 +/- 80 ms 3 months after catheter ablation. There were no significant differences in the A-H interval of the fast pathway between the period immediately after and 3 months after catheter ablation following administration of atropine sulfate (99 +/- 52). There were no significant differences in the ERP of the fast pathway between the period immediately after and 3 months after catheter ablation following administration of atropine sulfate (248 +/- 33 ms). On the contrary, there were no significant changes in the A-H interval and ERP of the AV node at these two times in patients with Wolff-Parkinson-White (WPW) syndrome. The change in characteristics of AV nodal physiology was observed only immediately after catheter ablation in AVNRT, but not in WPW syndrome. The change in electrophysiology immediately after catheter ablation was similar to that following administration of atropine sulfate in AVNRT 3 months after catheter ablation. These findings suggest that catheter ablation does not cause a permanent change in AV nodal physiology and that the location of the ablated site plays an important role in AV nodal physiology.

Cost effectiveness of radiofrequency catheter ablation versus medical treatment for paroxysmal supraventricular tachycardia in Japan.

This study evaluated the cost of performing radiofrequency catheter ablation in Japanese patients with paroxysmal supraventricular tachycardia refractory to antiarrhythmic drug therapy in comparison with the cost of continuing pharmacologic treatment. Twenty patients (mean age 44 +/- 14 years) underwent successful ablation: 15 patients with Wolff-Parkinson-White syndrome and five with atrioventricular nodal reentrant tachycardia. The mean duration of symptoms was 77 +/- 60 months. The patients had been treated with 2.6 +/- 1.7 antiarrhythmic drugs before undergoing ablation. Charges derived from hospital bills were compared with the outpatient charges for the year before ablation. The mean hospital stay for the ablation procedure was 4.3 +/- 0.5 days. The mean total charge for ablation was 982,806 yen +/- 103,195, and 5.7 +/- 0.7 times the outpatient charges in the previous year. The majority of radical cure charges were the costs of the electrode catheters used in the ablation procedure. All patients had a successful outcome and required no additional antiarrhythmic drug therapy. If medical treatment were continued without ablation, the mean total life-expectancy charges were estimated at 7,064,726 yen +/- 3,116,621, 41.0 +/- 19.2 times the outpatient charges. The total life charges of medical treatment were significantly more than the total ablation charges (p < 0.001). This study suggests that radiofrequency catheter ablation is of clinical benefit in treating paroxysmal supraventricular tachycardia, and markedly reduces the cost of definitive therapy. This strategy appears to be more economical than pharmacologic treatment.

Relation between the size of lesions and arrhythmias produced by microwave catheter ablation with a special electrode device.

The purpose of this study was to examine the effects of microwave catheter ablation of ventricular myocardium. Microwave energy with a frequency of 2450 MHz was delivered via a coaxial catheter with an electrode ball tip. Microwave energy was applied to canine isolated left ventricular endocardium in vitro and to 6 anesthetized dogs in vivo at 50 watts for 15-150 sec. Ventricular arrhythmia was not observed during ablation in any of the dogs when microwave energy was applied for less than 45 sec. When the duration of microwave ablation was greater than 45 sec, ventricular premature contractions were observed in all of the dogs. Nonsustained ventricular tachycardia developed when the duration of microwave delivery was greater than 90 sec. After the cessation of ablation, ventricular arrhythmias did not occur and ventricular programmed stimulation did not induce ventricular tachycardia in any of the dogs. Except for ventricular arrhythmia, no declines in the hemodynamic status were observed in any of the 6 dogs. The size of the ablated lesion was significantly greater as the duration of ablation was increased (p < 0.05). When ablation lasted for more than 120 sec, the coagulation layer was extended to the epicardium in all 6 dogs. The results of this study suggest that microwave ablation is feasible for the treatment of tachyarrhythmias from deep focus of ventricular myocardium with relatively small proarrhythmic effects.

[An experimental study of catheter ablation using microwave energy via coaxial electrode catheter].

The purpose of this study was to examine the efficacy, arrhythmogenicity, and the size of ablated lesions of catheter ablation with microwave energy. Microwave energy generated by a device with a frequency of 2450 MHz, was delivered via a bipolar electrode coaxial catheter with an electrode ball tip. Microwave ablation was applied (50 watts for 15-150 sec.) on the left ventricular endocardium in 6 dogs. No ventricular arrhythmia occurred during ablation in any of the dogs when microwave catheter ablation was applied for less than 45 sec. However, when the duration of microwave catheter ablation was longer than 45-60 sec, ventricular premature contractions were observed in all 6 dogs. When ablation time was set for a longer time, the dogs developed nonsustained ventricular tachycardias. Nevertheless, ventricular arrhythmias after ablation did not occur in all dogs. Ventricular programmed stimulation after ablation did not induce ventricular tachycardia in any of the dogs. When ablation time lasted more than 120 sec, the coagulation layer was extended to the epicardium in all 6 dogs. The results of this study suggest that microwave ablation is feasible for the treatment of tachyarrhythmias from a deep focus of the ventricular myocardium.