Inducible Ventricular Tachyarrhythmias Research Articles

Comparison of event rates and survival in patients with unexplained syncope without documented ventricular tachyarrhythmias versus patients with documented sustained ventricular tachyarrhythmias both treated with implantable cardioverter-defibrillators

Patients with unexplained syncope and inducible ventricular tachyarrhythmias during electrophysiologic testing have an increased cardiac mortality rate. We compared event rates and survival of 178 patients with unexplained syncope and no documented ventricular arrhythmias (syncope group) versus 568 patients with documented sustained ventricular tachycardia (VT) or fibrillation (VF) (VT/VF group) treated, as part of a lead (Ventritex TVL) investigation, with similar implantable cardioverter-defibrillators (ICDs) capable of extensive data storage. The 2 groups shared similar clinical characteristics. The mean follow-up was 11 months for the syncope group and 14 months for the VT/VF group. The mean time from device implantation to first appropriate therapy was similar in the 2 groups (109 ± 140 vs 93 ± 131 days, p = 0.40). Actuarial probability of appropriate ICD therapy was 49% and 55% at 1 and 2 years, respectively, in syncope group and 49% and 58% in VT/VF group (p = 0.57). Recurrent syncope was associated with ventricular tachyarrhythmias in 85% and 92% of the syncope group and VT/VF group, respectively (p = 0.54). At 2 years, actuarial survival was 91% in the syncope group and 93% in VT/VF group (p = 0.85). We conclude that patients treated with ICD with unexplained syncope and induced VT/VF have an equally high incidence of appropriate ICD therapy and low mortality compared with similar patients with documented VT/VF. These findings, plus the high association between recurrent syncope and ventricular arrhythmias, indicate that VT/VF are likely etiologies in selected patients with unexplained syncope and support ICD therapy in such cases.

Influence of CYP3A Metabolizer Status on the Pharmacokinetics and Pharmacodynamics of Amiodarone

The present work was designed to determine whether the individual differences in pharmacokinetics and pharmacodynamics of amiodarone and its N-desethyl metabolite are related to cytochrome CYP3A metabolizer status. 12 cardiac patients with inducible ventricular tachyarrhythmias during the baseline electrophysiologic study were enrolled in this study. Urinary 24-hour excretion of 6 beta-hydroxycortisol (6 beta-OHC and the ratio of 6 beta-hydroxycortisol to urinary free cortisol (6 beta-OHC/UFC) were measured before the first amiodarone administration. Trough plasma concentrations of amiodarone and N-desethylamiodarone (N-DEA) were measured after 79 +/- 11 days (2nd period) and after 182 +/- 25 days (3rd period). Electrophysiologic effects of amiodarone therapy were established with serial electrophysiologic studies in 9 of these patients at the baseline and after 79 +/- 11 days (during the second period). Both the 6 beta-OHC excretion and 6 beta-OHC/UFC ratio varied approximately 6-fold between the patients. We found significant inverse correlation between the 6 beta-OHC excretion and the trough plasma concentrations of amiodarone at the time of the 3rd period (rs = -0.58, p < 0.05). Similarly, there was correlation between the 24-hour urinary 6 beta-OHC excretion and trough plasma concentrations of amiodarone during the 3rd period (rs = -0.64, p < 0.025). We were unable to detect any association between CYP3A activity and amiodarone pharmacodynamics. This study points toward important information value of CYP3A metabolizer status in the context of therapeutic drug monitoring of amiodarone.

Implantable defibrillator event rates in patients with unexplained syncope and inducible sustained ventricular tachyarrhythmias: A comparison with patients known to have sustained ventricular tachycardia

OBJECTIVESTo assess the clinical significance of inducible ventricular tachyarrhythmias among patients with unexplained syncope.BACKGROUNDInduction of sustained ventricular arrhythmias at electrophysiology study in patients with unexplained syncope and structural heart disease is usually assigned diagnostic significance. However, the true frequency of subsequent spontaneous ventricular tachyarrhythmias in the absence of antiarrhythmic medications is unknown.METHODSIn a retrospective case-control study, the incidence of implantable cardiac defibrillator (ICD) therapies for sustained ventricular arrhythmias among patients with unexplained syncope or near syncope (syncope group, n = 22) was compared with that of a control group of patients (n = 32) with clinically documented sustained ventricular tachycardia (VT). Sustained ventricular arrhythmias were inducible in both groups and neither group received antiarrhythmic medications. All ICDs had stored electrograms or RR intervals. Clinical variables were similar between groups except that congestive cardiac failure was more common in the syncope group.RESULTSKaplan-Meier analysis of the time to first appropriate ICD therapy for syncope and control groups produced overlapping curves (p = 0.9), with 57 ± 11% and 50 ± 9%, respectively, receiving ICD therapy by one year. In both groups, the induced arrhythmia was significantly faster than spontaneous arrhythmias, but the cycle lengths of induced and spontaneous arrhythmias were positively correlated (R = 0.6, p < 0.0001). During follow-up, three cardiac transplantations and seven deaths occurred in the syncope group, and two transplantations and five deaths occurred in the control group (36-month survival without transplant 52 ± 11% and 83 ± 7%, respectively, p = 0.03).CONCLUSIONSIn patients with unexplained syncope, structural heart disease and inducible sustained ventricular arrhythmias, spontaneous sustained ventricular arrhythmias occur commonly and at a similar rate to patients with documented sustained VT. Thus, electrophysiologic testing in unexplained syncope can identify those at risk of potentially life-threatening tachyarrhythmias, and aggressive treatment of these patients is warranted.

T-wave alternans in microwave frequency as a new indicator of disordered ventricular repolarization: pathophysiology, methodology, clinical results

Primary prevention of sudden cardiac death is hampered by the inability to accurately identify high risk patients. Various noninvasive methods such as determination of left ventricular function or heart rate variability as well as invasive electrophysiologic testing are currently used for risk stratification. Noninvasive measurement of microvolt T wave alternans (TWA) is a promising new method to assess repolarization abnormalities; in experimental studies, TWA was associated with an increased incidence of ventricular tachyarrhythmias. Since the occurrence of TWA is heart rate-dependent, it is measured either during atrial pacing or during exercise stress testing. The first clinical validation of the method was performed in patients undergoing invasive EP testing to assess prediction of inducibility of ventricular tachyarrhythmias. A first prospective validation of the noninvasive method was performed in patients surviving out-of-hospital cardiac arrest fitted with an ICD. Further studies have shown a good concordance between invasive and noninvasive TWA determination. The occurrence of TWA in this population was of predictive value with respect to arrhythmia recurrence. Recently published data confirm the value of TWA assessment with respect to identification of patients with congestive heart failure at high risk of malignant ventricular tachyarrhythmias. The use of this method in post myocardial infarction risk stratification is currently under prospective evaluation.

Evolution, mechanisms, and classification of antiarrhythmic drugs: focus on class III actions

Since the use of cinchona bark to treat heart palpitations in the 1700s, antiarrhythmic drug therapy has developed with the discovery of new compounds and the identification of ionic, cellular, and tissue mechanisms of action. Classifications have been developed that organize the large amount of information available about antiarrhythmic drugs around groups of compounds with common mechanisms of action. Despite important and well-recognized limitations, antiarrhythmic drug classification is still widely used. In particularly broad use is the system developed by Singh and Vaughan Williams in the early 1970s and subsequently modified by Singh and Hauswirth and by Harrison. This classification divides drug actions into class I for sodium-channel blockade (with subclasses IA, IB and IC), class II for adrenergic antagonism, class III for action-potential prolongation, and class IV for calcium-channel blockade. The development of class I drugs was curtailed when studies showed that potent sodium-channel blockers (particularly IC agents) can increase mortality in patients with active coronary artery disease. The emphasis in drug development shifted to class III agents, but their use has been limited by the risk of ventricular tachyarrhythmia induction associated with QT prolongation. Current research focuses on the development of new class III drugs that may have improved safety by virtue of greater selectivity of action at faster rates (like those of arrhythmia) or for atrial tissue. Alternative approaches include the modification of existing molecules (like amiodarone) to maintain positive properties while removing undesirable ones, and treatments that target development of the arrhythmia substrate instead of the final electrical product.

Relationships among electrophysiological findings and clinical status, heart function, and extent of DNA mutation in myotonic dystrophy.

Impulse-conduction abnormalities and arrhythmias are common in myotonic dystrophy (MD). This study was performed to determine whether a correlation exists between electrophysiological (EP) testing data and clinical status, heart function, or size of the DNA abnormality (cytosine-thymine-guanine sequence repeat). Eighty-three MD patients underwent invasive EP studies prompted primarily by the presence of asymptomatic conduction abnormalities. AV conduction disturbances were common and mainly distal (HV interval, 66.2+/-14 ms). AV conduction observed from the surface ECG was generally concordant with endocardial measurements. However, 11 of 20 patients with normal surface ECGs had abnormal subhisian conduction. Atrial arrhythmias were inducible in 41% of cases and correlated with prolongation of the AH interval (P=0.02) and a shorter atrial refractory period (P=0.04). Induction of ventricular arrhythmias (18%) correlated strongly with age (P=0. 0003). After adjustment for age, the extent of DNA mutation correlated with the Walton score (P=0.0018) but not with conduction abnormalities or induction of arrhythmias. Prolongation of the HV interval is the most common conduction abnormality in MD and can be reliably recognized only by invasive EP testing. It raises the issue of prophylactic pacing to limit the incidence of sudden death in MD. Atrial and ventricular arrhythmias are often inducible, although their predictive value remains to be determined. Young age emerged as the most powerful predictor of inducible ventricular tachyarrhythmias. Conversely, we found no relationship between ECG or EP abnormalities recorded during invasive testing and the DNA mutation size or severity of peripheral muscle involvement.

Beta blockers: evidence versus wishful thinking

Catecholamines and ischemia play an important role in the induction of ventricular tachyarrhythmias. Beta blockers antagonize the effect of catecholamines and have anti-ischemic properties. Several controlled studies performed in the early 1980s in patients after myocardial infarction have shown that β-blocker therapy clearly decreases sudden and nonsudden cardiac death. Despite the lack of recent randomized trials, data from uncontrolled studies suggest that the beneficial effect of β blockers is still present in the thrombolytic era. Thus, it is incomprehensible that today in the United States and in most parts of Europe, <40% of post-myocardial infarction patients are treated with β blockers. Even in patients with documented sustained ventricular tachycardias (VTs) or ventricular fibrillation (VF), clinical studies indicate that β blockers improve survival. Thus, even in the thrombolytic era, β blockers should be used as a basic therapy in patients who are at risk of sudden cardiac death.

The utility of quantitative body surface isoarea mapping for predicting ventricular tachyarrhythmias.

Noninvasive techniques, such as the signal averaged ECG, have been used to assess risk of ventricular tachyarrhythmias (VT). However, these methods produce false positive and negative results. The purpose of this study was to develop body surface map algorithms which would enhance prediction of susceptibility to VT. Fifty-three patients referred for programmed electrical stimulation were enrolled in this study. All patients underwent signal averaged ECG, body surface map, programmed electrical stimulation. Group I patients had no sustained inducible VT and group II patients had either inducible sustained VT at electrophysiology study or previously documented spontaneous, sustained VT. For body surface map analysis, the difference between extrema on isoarea maps was calculated and defined as the gradient range. An abnormal body surface map was defined as a QRST gradient range < or = 109 mv.ms. The mean QRST gradient range in group II was significantly < that in group I (P < 0.05). By logistic regression analysis, the presence of coronary artery disease, a QRST gradient range < or = 109 mv.ms, an EF < 40% and a signal averaged ECG QRS duration > 114 ms predicted VT. The sensitivity, specificity, positive and negative predictive values for predicting VT susceptibility of an algorithm which combines the signal averaged ECG QRS duration and the QRST gradients were 0.93, 0.76, 0.79, and 0.91, respectively, while those for the signal averaged ECG alone were 0.52, 0.69, 0.63, and 0.59 for VT susceptibility. A combined body surface map-signal averaged ECG algorithm was more sensitive in detecting susceptibility to VT than the signal averaged ECG alone.

Navigation in the mega-trials waters: reflections on the multicenter automatic defibrillator implantation trial and the antiarrhythmics versus implantable defibrillators study

Today, cardiology seems to be driven by mega-trials and meta-analyses. Guidelines published by scientific and professional cardiovascular societies, such as the American Heart Association, the American College of Cardiology, and the European Society of Cardiology, follow the rules of evidence-based medicine. Such evidence is not always sufficiently conclusive to practice clinically helpful medicine. Sometimes, relatively small trials, such as the Multicenter Automatic Defibrillator Implantation Trial and the Antiarrhythmics Versus Implantable Defibrillators study, may be taken as guides for current clinical decisions and as inspiration for future investigations. Large mega-trials with a great lack of homogeneity among the recruited patients are less important for clinically helpful medicine than studies enrolling well-defined, high-risk patients. It is probably important to acknowledge that the best possible treatment for many patients with ventricular tachyarrhythmias remains obscure. Among these situations are the following: (1) sustained ventricular tachycardia (VT) in patients without coronary artery disease; (2) sustained, nonsyncopal VT in patients with coronary artery disease and left ventricular dysfunction; (3) post myocardial infarction survivors with an ejection fraction ≤35%, frequent/complex ventricular arrhythmias, depressed heart rate variability, and inducible sustained ventricular tachyarrhythmias during electrophysiologic study. Many studies are being conducted to add light where uncertainty exists, but probably only a few will contribute to the practice of clinically helpful medicine, although some will be used to produce meta-analysis to sustain evidence-based medicine.

Prospective comparison of intravenous quinidine and intravenous procainamide in patients undergoing electrophysiologic testing

Background Intravenous procainamide hydrochloride is frequently used in the acute care setting and during electrophysiologic testing, but intravenous quinidine gluconate is rarely used because of concerns about its safety. This study prospectively compares the hemodynamic and electrophysiologic effects of these agents in patients undergoing electrophysiologic testing. Methods and Results Sixty-five consecutive patients with inducible ventricular tachyarrhythmias were prospectively treated with either intravenous quinidine gluconate or intravenous procainamide hydrochloride in an alternating unblinded fashion. The hemodynamic and electrophysiologic effects of these two drugs were compared. Seven (22%) patients assigned to intravenous quinidine gluconate and eight (24%) patients assigned to intravenous procainamide hydrochloride were rendered noninducible for ventricular tachyarrhythmias. Four (13%) patients assigned to intravenous quinidine gluconate were unable to complete the infusion compared with none ( p = 0.05) assigned to intravenous procainamide hydrochloride. Otherwise, the overall hemodynamic and electrophysiologic effects of the two drugs were similar. Conclusions Intravenous quinidine gluconate is a reasonable alternative to intravenous procainamide hydrochloride in patients requiring a parenteral type IA antiarrhythmic agent. (Am Heart J 1998;136:49-56.)

Lack of benefit of very short basic drive train cycle length or repetition of extrastimulus coupling intervals for induction of ventricular tachycardia.

There are considerable variations of uncertain importance in basic drive train cycle lengths and degree of repetition of extrastimuli used in programmed ventricular stimulation protocols in different laboratories. We compare prospectively three different stimulation protocols to examine the influence of a short basic drive train cycle length and repetition of extrastimuli on induction of ventricular tachycardia. Thirty consecutive patients who had documented ventricular tachycardia or fibrillation based on underlying coronary artery disease underwent programmed ventricular stimulation with each of the three study protocols. Protocol A used a basic drive train cycle length of 400 msec with each extrastimulus coupling interval delivered only once. Protocol B used the same basic drive train cycle length, but with each extrastimulus coupling interval repeated three times before decrementing. Protocol C used 300 msec as the cycle length of basic drive trains without repetition of extrastimuli. Sixty-three percent, 67%, and 63% of the study patients had ventricular tachycardia inducible with protocols A, B, and C, respectively (P = NS). Ventricular fibrillation was induced in 23% of the 30 patients in all three protocols. There were no significant differences in the mean cycle lengths of induced ventricular tachycardia, the number of extrastimuli used, and the coupling interval of the last extrastimulus inducing ventricular tachycardia among the three protocols. This study showed no clinical benefit for repetition of extrastimuli that have failed to induce a ventricular tachyarrhythmia during programmed ventricular stimulation. A short basic cycle length of 300 msec was not superior to 400 msec for induction of ventricular tachyarrhythmias. We recommend the use of basic cycle length 400 msec with delivery of each extrastimulus interval only once as the initial protocol for programmed ventricular stimulation.

Discordant prolongation of the refractory period and repolarization time by a class III agent, E4031, in the healing phase of myocardial infarction.

Susceptibility to reentrant tachyarrhythmias and the antiarrhythmic efficacy of class III agents are related more to the duration of the refractory period (ERP) than to the repolarization time (RT). We measured both ERP and RT in a canine model of healing myocardial infarction, and evaluated the effect of a class III agent (E4031) on these parameters and on the inducibility of ventricular tachyarrhythmias. ERP and RT on the unipolar electrogram were measured at several cycle lengths in the normal (NZ) and infarct zones (IZ), respectively, in 10 canine myocardial infarction models and extrastimulation was used to induce ventricular arrhythmias. Measurements were repeated after E4031 administration. At baseline, both ERP and RT were significantly longer in IZ than in NZ with ERP/RT ratio also higher in IZ. This ratio tended to increase at longer cycle lengths. E4031 increased ERP and RT both in NZ and IZ at all cycle lengths, but increased the ERP/RT ratio predominantly in IZ. E4031 prevented induction of sustained VT or VF, which was inducible in 3 out of 10 dogs at baseline, although it facilitated induction of VF in 1 dog with no baseline arrhythmia. By increasing the ERP/RT ratio, class III drugs may shorten the relative refractory period in IZ at the expense of a greater ERP difference created between NZ and IZ.

Pacientes con cardiopatía estructural, síncope de etiología desconocida y arritmias ventriculares inducibles tratados con desfibrilador implantable

This study evaluates the hypothesis that in patients with syncope of unknown origin and heart anomalies, inducible ventricular arrhythmias are specific arrhythmias and therefore should be treated as such. Although syncope is a frequent clinical entity, the evaluation and treatment of patients with syncope without a clear etiology still remains undefined. Many patients with syncope of undetermined origin undergo invasive electrophysiologic evaluation. Abnormalities of the sinus node, prolongation of conduction times or inducible arrhythmias found during these evaluations are usually assumed to be the cause of syncope, and are consequently treated. However, whether tachyarrhythmias are truly the cause of syncope, and whether treatment of these tachyarrhythmias can prevent recurrent syncope and arrhythmic death, is unknown. An electrophysiological study was performed on 160 patients with structural heart disease and syncope of unknown origin. In 23 out of the 160 patients (16%), programmed electrical stimulation induced sustained ventricular arrhythmias. In 18 out of the 23 patients an automatic defibrillator was implanted and they form the study group. In these 18 patients, programmed ventricular stimulation induced sustained monomorphic ventricular tachycardia in 12, sustained polymorphic ventricular tachycardia in 2 and ventricular fibrillation in 4. During a mean follow-up of 14 months, 9 patients received 81 appropriate therapies from the device (53 because of ventricular tachycardia and 23 because of ventricular fibrillation). The probability of appropriate therapy was 100% at 1 year follow-up. There were no episodes of sudden death and 1 patient died of congestive heart failure. In patients with syncope of undetermined origin, heart disease and inducible ventricular tachyarrhythmias treated with a implantable cardioverter defibrillator, there is a high incidence of appropriate therapies. Our results support the practice of using implantable cardioverter defibrillators in patients with syncope of unknown origin, heart disease and inducible ventricular arrhythmias.

Heart Rate Variability and Dispersion of QT Interval in Patients With Vulnerability to Ventricular Tachycardia and Ventricular Fibrillation After Previous Myocardial Infarction

Objectives. This study was designed to compare QT dispersion measured from the standard 12-lead electrocardiogram and 24-h heart rate variability in patients with vulnerability to either ventricular tachycardia or ventricular fibrillation after a previous myocardial infarction.Background. Increased QT interval dispersion and reduced heart rate variability have been shown to be associated with vulnerability to ventricular tachyarrhythmias, but the data have mainly been pooled from patients with presentation of stable ventricular tachycardia and ventricular fibrillation.Methods. QT dispersion and time domain and two-dimensional vector analysis of heart rate variability were studied in 30 survivors of ventricular fibrillation with a previous myocardial infarction and with inducible unstable ventricular tachyarrhythmia by programmed electrical stimulation and in 30 postinfarction patients with clinical and inducible stable monomorphic sustained ventricular tachycardia. Both of these patient groups were matched, with respect to age, gender and left ventricular ejection fraction, with an equal number of postinfarction control patients without a history of arrhythmic events or inducible ventricular tachyarrhythmia and arrhythmia-free survival during a follow-up period of 2 years. Forty-five age-matched healthy subjects served as normal control subjects.Results. Standard deviation of all sinus intervals and long-term continuous RR interval variability analyzed from Poincaré plots were reduced in patients with vulnerability to ventricular fibrillation (p < 0.001 for both), but not in patients with ventricular tachycardia (p = NS for both), compared with postinfarction control subjects. Corrected QT (QTc) dispersion was significantly broader both in patients with ventricular fibrillation (p < 0.001) and in those with ventricular tachycardia (p < 0.05) than in matched postinfarction control subjects. Heart rate variability performed better than QTc dispersion in predicting vulnerability to ventricular fibrillation.Conclusions. Increased QT dispersion is associated with vulnerability to both ventricular tachycardia and ventricular fibrillation. Low heart rate variability is specifically related to susceptibility to ventricular fibrillation but not to stable monomorphic ventricular tachycardia, suggesting that the autonomic nervous system modifies the presentation of life-threatening ventricular arrhythmias.

A simple electrocardiographic algorithm for detecting ventricular tachycardia.

The purpose of this study was to determine whether a simple ECG algorithm could be developed for predicting susceptibility to ventricular tachyarrhythmias (VT) as defined by sustained spontaneous or inducible VT. Two different QT dispersion algorithms were determined by the difference between the longest and shortest QT interval measured in three orthogonal leads (I, aVF, V1; QTD3), and at least 11 of 12 leads (QTD12) from the 12-lead ECG. These QT dispersion algorithms were investigated (with and without the QRS duration from the 12-lead ECG) and compared to the signal-averaged ECG (SAECG) in order to determine their sensitivity and specificity for detecting VT. Only patients who underwent SAECG and were referred for programmed electrical stimulation were included in this study. A positive SAECG was defined by filtered QRS duration > 114 ms, and/or low amplitude signal duration > 38 ms, and/or root mean square voltage in the last 40 ms of < 20 microV. Sixty patients were enrolled in this study with a mean age of 63 +/- 2 years. Fifty-five percent of the patients had coronary artery disease. A simple ECG algorithm consisting of the sum of QTD3 plus the QRS duration had a sensitivity and specificity of 90% and 63%, respectively, wheras the SAECG had a sensitivity and specificity of 60% and 63%, respectively (P = 0.022). We conclude that a simple ECG algorithm is more sensitive than the SAECG for predicting VT. This algorithm combines two easily measured variables obtained from the 12-lead ECG, and can easily be performed without expensive computer equipment.

Effect of β-adrenergic stimulation on the QRS duration of the signal-averaged electrocardiogram

Am Heart J 1997;134:395-8.

Safety of transvenous atrial defibrillation: studies in the canine sterile pericarditis model.

It is recognized that a ventricular vulnerability period exists during which atrial shock delivery may induce a ventricular tachyarrhythmia. This study was designed to define the zone in which the ventricles are vulnerable to induction of ventricular tachyarrhythmia during delivery of atrial shocks in the sterile pericarditis canine model of atrial fibrillation. Two days after creation of sterile pericarditis, 24 dogs underwent either a four-part or five-part ventricular vulnerability protocol during which atrial shocks were delivered between transvenous catheters, one in the distal coronary sinus and one in the right atrial appendage. The protocol included part 1, shocks during induced atrial fibrillation; parts 2 through 4, shocks delivered synchronously with the last ventricular beat of one of the following three ventricular pacing protocols: constant ventricular rates (S1S1), short-long-short cycles (S1S2S3-V), and ventricular premature beats (S1); and part 5, shocks delivered synchronously with the last R wave resulting from an atrially paced short-long-short cycle (S1S2S3-A). Ventricular tachyarrhythmia was induced 122 times: 2 of 665 shocks in two dogs in part 1, 29 of 786 shocks in nine dogs in part 2, 67 of 734 shocks in 15 dogs in part 3, 24 of 919 shocks in five dogs in part 4, and none in part 5. All ventricular proarrhythmia resulted from shocks delivered during the T wave of a preceding ventricular beat. No episodes of ventricular tachyarrhythmia were induced by atrial shocks synchronized to R waves with the previous RR at intervals above the QT+60 ms interval (absolute interval >320 ms), with one exception, at the QT+100 ms interval (absolute interval 360 ms). With transvenous electrode catheters used to deliver atrial shocks, life-threatening ventricular rhythms were induced but were limited to a specific zone defined by the QT interval.

High Incidence of Appropriate Implantable Cardioverter-Defibrillator Therapy in Patients With Syncope of Unknown Etiology and Inducible Ventricular Arrhythmias

Objectives. This study evaluates the hypothesis that in patients with syncope of unknown origin, inducible ventricular arrhythmias are specific arrhythmias and therefore should be appropriately treated.Background. Although syncope is a common clinical entity, the evaluation and treatment of patients with syncope without a clear etiology are not well defined. Many patients with syncope of undetermined origin undergo invasive electrophysiologic evaluation. Abnormalities of the sinus node, prolongation of conduction times or inducible arrhythmias found at these evaluations are usually assumed to be the cause of syncope and are therefore treated. However, whether tachyarrhythmias are truly the cause of syncope, and whether treatment of these tachyarrhythmias can prevent recurrent syncope and arrhythmic death, is unknown.Methods. This study included 50 consecutive patients with syncope of undetermined origin, ventricular tachyarrhythmias at electrophysiologic evaluation and treatment with an implantable cardioverter-defibrillator.Results. Ventricular stimulation led to sustained monomorphic ventricular tachycardia in 36 patients, nonsustained ventricular tachycardia in 5 and ventricular fibrillation in 9. Over a 23 ± 15-month (mean ± SD) follow-up period, 18 patients received appropriate implantable cardioverter-defibrillator shock. Actuarial probability of appropriate therapy was 22% at 1 year and 50% at 3 years. Recurrent syncope was seen in five patients, three of whom had appropriate defibrillator detections at the time of syncope. Four patients died (sudden death in one, congestive heart failure in two).Conclusions. In patients with syncope of undetermined origin and inducible ventricular tachyarrhythmias, appropriate implantable cardioverter-defibrillator therapy is common at follow-up. Sudden cardiac death is uncommon. This low incidence of sudden cardiac death and high incidence of appropriate defibrillator therapy support the current practice of using implantable cardioverter-defibrillators in patients with syncope of unknown origin and inducible ventricular arrhythmias.(J Am Coll Cardiol 1997;29:370–5)

Programmed stimulation of the ventricles--back to the future.

In the inaugural issue of this journal appeared two articles describing programmed electrical stimulation of the ventricles. Fisher et al. evaluated a new method for induction of ventricular tachycardia, in “Ultrarapid Train Stimulation versus Conventional Programmed Electrical Stimulation for Induction of Ventricular Arrhythmias in Patients with Coronary Artery Disease”[1]. Wyse et al. describe the effects of a conventional programmed stimulation protocol on QT dispersion, in “Divergence of Endocardial QT Interval Components during Programmed Electrical Stimulation Including Observations during Induction of Sustained Ventricular Tachyarrhythmias”[2]. The publication of these articles, 25 years after Wellens ~rst described programmed stimulation of the ventricles in humans [3], offers an opportunity to re_ect on the status of programmed electrical stimulation in clinical electrophysiology, its utility and limitations. In order to interpret appropriately the signi~cance of these two studies, it may be useful to consider how we use programmed ventricular stimulation in practice. While programmed stimulation was initially applied to elucidate the mechanisms responsible for monomorphic sustained ventricular tachycardia, and to aid in its diagnosis [3], later investigators applied the technique to patients who had experienced syncope or survived cardiac arrest (without documentation of the initiating arrhythmia), for similar reasons that it had been utilized in patients with spontaneous sustained ventricular tachycardia [4,5]. It has been used more recently in patients who have never experienced any symptomatic arrhythmia, in order to assess their risk for sudden cardiac death [6]. Further complicating these matters, is the fact that the technique has been applied to patients with the above arrhythmias occurring in association with a variety of anatomic substrates, including coronary artery disease, cardiomyopathies, etc. Why are these factors important? It is very likely that not only are the mechanisms responsible for ventricular tachyarrhythmias dependent on the type of associated heart disease, but even within the subset of patients with coronary artery disease for example, the characteristics of tachycardias are dependent in many respects on the clinical presentation [7]. There is also evidence that within the group of patients with coronary artery disease, the site of previous myocardial infarction can in_uence the arrhythmia substrate [8,9]. In this light, I would like to review brie_y the highlights of the studies by Fisher and Wyse. Fisher and his colleagues extended their earlier studies of the termination of ventricular tachycardia by ultrarapid stimulation trains, to the potential of this technique for initiation of ventricular tachycardia [10]. By coupling ultrarapid trains (at cycle lengths of 10, 20, or 30 msec) of progressively increasing duration to a standard “drive” of seven or eight beats, they were able to deliver 1, 2, or 3 extrastimuli with the greatest possible degree of prematurity relatively quickly. Their results show a high degree of concordance for inducible ventricular tachyarrhythmias between their standard stimulation protocol, and the ultrarapid train protocol, but the train protocol reached one of the predetermined endpoints in signi~cantly less time (5.25 versus 16.1 minutes). Unfortunately, the reproducibility of tachycardia induction was evaluated in only 3 patients. Wyse and his colleagues examined the effect of programmed ventricular stimulation on the difference between the endocardial QT intervals of the last extrastimulus, recorded at the right ventricular apex and out_ow tract. By using unique and original recording technology, the investigators were able to achieve very high ~delity measures of local QT intervals. The duration of the initial portion of the QT interval bore a linear relationship to the prematurity of the extrastimulus in the control group of patients without structural heart disease. As expected, this interval shortened as the extrastimulus prematurity increased. Of interest, the terminal portions of the QT interval did not exhibit the expected rate adaptation, but rather remained constant or increased with increasing extrastimulus prematurity. In contrast, the experimental patient group, consisting of patients with prior myocardial infarction undergoing electrophysiologic studies for evaluation of spontaneous ventricular tachyarrhythmias, showed a blunting of the adaptation of the initial and total QT interval to extrastimulus prematurity. The terminal component of the QT interval in the study patients behaved in a manner similar to that of the control group. The control patients showed minimal “dispersion” of the QT intervals that displayed a _at relationship to extrastimulus prematurity. The QT “dispersion” of patients with ventricular arrhythmias Journal of Interventional Cardiac Electrophysiology 1997;1:281–285 © Kluwer Academic Publishers. Boston. Printed in U.S.A.

ATRIAL DEFIBRILLATION: New Frontiers

External electrical atrial defibrillation was developed in the early 1960s. Direct current electrical external shocks convert atrial fibrillation to sinus rhythm in the majority of patients. Although much has been learned about the mechanisms of the arrhythmia and those responsible for successful external direct current atrial defibrillation, the technique has remained essentially unchanged since it was first described by Lown and colleagues. Animal and human studies have shown that atrial defibrillation can be terminated by shocks delivered by way of internal electrode catheters. The technique is most effective when biphasic waveform shocks are delivered by way of large surface area electrodes in the right atrium and the coronary sinus. Synchronization of shocks to R waves greater than 500 msec after the previous beat prevents induction of ventricular tachyarrhythmias. Therefore, internal atrial defibrillation provides an effective and safe method for restoring sinus rhythm in patients who fail external direct current cardioversion. The success of the implantable cardioverter-defibrillator and the encouraging safety and efficacy data from studies of internal atrial defibrillation have generated considerable interest in developing an implantable atrial defibrillator. The efficacy of low-energy shocks to terminate the arrhythmia suggests that such a device might be tolerated by patients. Data about the pathogenesis of atrial fibrillation suggest that rapid detection and immediate termination of atrial fibrillation theoretically might prevent recurrence of the arrhythmia. These data support the development of an implantable atrial defibrillator and the initiation of clinical trials to determine its utility.