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We review the macroscopic and microscopic anatomy of myocardial disease associated with heart failure (HF) and sudden cardiac death (SCD) and focus on the prevention of SCD in light of its structural pathways. Compared to patients without SCD, patients with SCD exhibit 5- to 6-fold increases in the risks of ventricular arrhythmias and SCD. Epidemiologically, left ventricular hypertrophy by ECG or echocardiography acts as a potent dose-dependent SCD predictor. Dyslipidemia, a coronary disease risk factor, independently predicts echocardiographic hypertrophy. In adult SCD autopsy studies, increases in heart weight and severe coronary disease are constant findings, whereas rates of acute coronary thrombi vary remarkably. The microscopic myocardial anatomy of SCD is incompletely defined but may include prevalent changes of advanced myocardial disease, including cardiomyocyte hypertrophy, cardiomyocyte apoptosis, fibroblast hyperplasia, diffuse and focal matrix protein accumulation, and recruitment of inflammatory cells. Hypertrophied cardiomyocytes express "fetospecific" genetic programs that can account for acquired long QT physiology with risk for polymorphic ventricular arrhythmias. Structural heart disease associated with HF and high SCD risk is causally related to an up-regulation of the adrenergic renin-angiotensin-aldosterone pathway. In outcome trials, suppression of this pathway with combinations of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, and mineralocorticoid receptor blockers have achieved substantial total mortality and SCD reductions. Contrarily, trials with ion channel-active agents that are not known to reduce structural heart disease have failed to reduce these risks. Device therapy effectively prevents SCD, but whether biventricular pacing-induced remodeling decreases left ventricular mass remains uncertain.

Implantable cardioverter defibrillators (ICDs) with dual chamber and dual chamber rate responsive pacing may offer hemodynamic advantages for some ICD patients. Separate ICDs and DDDR pacemakers can result in device to device interactions, inappropriate shocks, and underdetection of ventricular fibrillation (VF). The objectives of this study were to compare the VF detection times between the Ventak AV II DR and the Ventak AV during high rate DDDR and DDD pacing and to test the safety of dynamic ventricular refractory period shortening. Patients receiving an ICD were randomized in a paired comparison to pacing at 150 beats/min (DDD pacing) or 175 beats/min (DDDR pacing) during ICD threshold testing to create a "worst case scenario" for VF detection. The VF detection rate was set to 180 beats/min, and VF was induced during high rate pacing with alternating current. The device was then allowed to detect and treat VF. The induction was repeated for each patient at each programmed setting so that all patients were tested at both programmed settings. Paired analysis was performed. Patient characteristics were a mean age of 69 +/- 11 years, 78% were men, coronary artery disease was present in 85%, and a mean left ventricular ejection fraction of 0.34 +/- 0.11. Fifty-two episodes of VF were induced in 26 patients. Despite the high pacing rate, all VF episodes were appropriately detected. The mean VF detection time was 2.4 +/- 1.0 seconds during DDD pacing and 2.9 +/- 1.9 seconds during DDDR pacing (P = NS). DDD and DDDR programming resulted in appropriate detection of all episodes of VF with similar detection times despite the "worst case scenario" tested. Delays in detection may be seen with long programmed ventricular refractory periods which shorten the VF sensing window and may be avoided with dynamic ventricular refractory period shortening.

Background Patients with implantable cardioverter–defibrillators often receive adjunctive antiarrhythmic therapy to prevent frequent shocks. We tested the efficacy and safety of sotalol, a beta-blocker with class III antiarrhythmic effects, for this purpose. Methods In a multicenter trial, patients were stratified according to left ventricular ejection fraction (≤0.30 or >0.30), randomly assigned to double-blind treatment with 160 to 320 mg of sotalol per day (151 patients) or matching placebo (151 patients), and followed for 12 months. Kaplan–Meier analyses of the time to an event were performed. Three end points were used: the delivery of a first shock for any reason or death from any cause, the first appropriate shock for a ventricular arrhythmia or death from any cause, and the first inappropriate shock for a supraventricular arrhythmia or death from any cause. Results Compliance with double-blind treatment was similar in the two groups. There were seven deaths in the placebo group and four in the sot...

Previous work had demonstrated a reduced specificity associated with head-up tilt protocols using high-dose isoproterenol in patients between 20 and 50 years of age. We evaluated the specificity of head-up tilt testing using different isoproterenol infusion doses and administration of nitroglycerin in patients aged >60 years. In addition, whether the same protocols have impact on the sensitivity of the test was also assessed. One hundred sixty subjects were included in this study. Seventy-six were volunteers randomized to either head-up tilt test with low-dose, 3- and 5-microg/min of isoproterenol (group I) or to a protocol including 0.4 mg of sublingual nitroglycerin (group II). In addition, after an upright tilt drug-free state, 58 patients with a history of syncope underwent repeat head-up tilt with increasing doses of isoproterenol infusion, followed by sublingual nitroglycerin if the test result remained negative. The remaining 33 patients were subjected to the nitroglycerin protocol after the drug-free state phase. In the control groups, the incidence of false-positive responses was 88% and 95%, respectively. In patients with syncope after a negative test result during 5 microg of isoproterenol infusion, nitroglycerin administration increased the number of positive responses from 45% to 79%. The percentage of positive tilt in patients undergoing nitroglycerin administration after the drug-free state part of the protocol was 78%. Administration of nitroglycerin was the most significant predictor of a positive upright tilt in patients with syncope. In subjects aged >60 years, head-up tilt protocols with high-dose isoproterenol infusion and nitroglycerin maintained an adequate specificity. In this subset of patients, nitroglycerin seemed to provide a better sensitivity than isoproterenol.

The Jewel 7219D was the first non-thoracotomy implantable cardioverter-defibrillator (ICD) with biphasic shock capability small enough to be placed in the prepectoral subcutaneous position. Size reduction of ICDs is desirable, but safety and efficacy of smaller devices must be demonstrated. Outcomes of patients treated with the Jewel 7219D defibrillator (n = 1,781) and with its precursor model PCD 7217B (n = 2,637) were compared. To use PCD patients (n = 2,637) as historical (n = 2,574) and concurrent controls (n = 63), statistical adjustments using the Cox proportional-hazards regression model were made. Jewel recipients (n = 1,781) treated in 106 US and 32 non-US centers exhibited similar characteristics including a mean age of 59 years, 78% men, ejection fraction of 34%, history of aborted sudden cardiac death in 41%, and coronary artery disease in 70%. Implantation was completed in 1,777 of 1,781 (99.9%) attempts and success with the first electrode configuration and polarity was 89.5%. Kaplan-Meier cumulative first-year survivals for cardiac and all-cause mortality were 98.5% and 93.3%. Complication-free first-year survival for Jewel implants in prepectoral subcutaneous (n = 582), subpectoral submuscular (n = 366), and abdominal (n = 449) positions did not differ (p >0.05). First-year survival free of pocket-related complications exceeded 98% in all locations. Adjusted cardiac and all-cause first-year mortality, and efficacy in terminating spontaneous tachyarrhythmias did not differ between the 2 device groups. In conclusion, the safety and efficacy of Jewel model 7219D in the prepectoral subcutaneous position are at least equal to either those of Jewel models implanted in different positions or to those of the previously extensively characterized PCD 7217B.

This article describes a patient who underwent right ventricular disconnection for medically refractory ventricular tachycardia associated with arrhythmogenic right ventricular dysplasia. After the operation there was no ventricular tachycardia recurrence. Two years after the operation, he received a permanent VVI pacemaker for the symptomatic second-degree AV block. Sensing function of the pacemaker was normal for the normal QRS complexes, but the tiny QRS complexes that appeared after the arrhythmia surgery were not sensed by the pacemaker and therefore caused no problem.

To study the long-term evolution, determinants, and clinical relevance of the conduction abnormalities after orthotopic heart transplantation, 87 patients, followed for a mean of 105 +/- 72 weeks, were divided into 3 groups according to the characteristics of their electrocardiograms compared with their initial electrocardiogram recorded at study entry. The first group consisted of 24 patients whose initial electrocardiogram was normal, and subsequent electrocardiograms remained normal throughout the study. The second group included 27 patients who developed electrocardiographic evidence of progressive conduction system damage. The third group comprised 36 patients whose initial electrocardiogram was abnormal and subsequent electrocardiograms remained unchanged during follow-up. Although the hemodynamic and echocardiographic evaluation of right and left ventricular function were initially similar among the 3 groups, groups 2 and 3 demonstrated a significant deterioration of left ventricular ejection fraction (62 +/- 12% to 55 +/- 16% and 62 +/- 8% to 57 +/- 14%, respectively; p < 0.05) and cardiac index (2.7 +/- 0.6 to 2.3 +/- 0.5 and 3.0 +/- 0.9 to 2.5 +/- 0.9 L/min/m2, respectively; p < 0.05) while patients in group 1 maintained their normal baseline indices. Incidence and progression of coronary artery disease, as well as frequency of rejection episodes, were comparable among the groups. Mortality was higher in the 2 groups with evidence of conduction defects. Sudden death associated with complete heart block (2 patients) or ventricular arrhythmias (3 patients) was exclusively confined to patients with evidence of progressive electrocardiogram abnormalities. We conclude that, following orthotopic heart transplantation, stable or progressive conduction system damage on the electrocardiogram is associated with left ventricular dysfunction and increased mortality. Sudden death is not uncommon among patients demonstrating worsening cardiac conduction and, in some cases, is related to the development of potentially preventable complete heart block.

During the past 10 years numerous studies on the treatment of paroxysmal atrial fibrillation (AF) by right and left atrial ablation procedures have been published. The results of studies based on follow-up periods of a few months have been repeatedly interpreted as providing evidence for curative therapy. However, insufficient focus on the variability of the natural history of paroxysmal AF, the inadequate detection of silent arrhythmic events, the eclectic post-interventional use of antiarrhythmic drugs, and the lack of appropriate control groups make the reports unconvincing. Randomized controlled trials are needed to confirm postulated long-term cure rates for AF.

Background After several days of loading, oral amiodarone, a class III antiarrhythmic, is highly effective in controlling ventricular tachyarrhythmias; however, the delay in onset of activity is not acceptable in patients with immediately life-threatening arrhythmias. Therefore, an intravenous form of therapy is advantageous. This study was designed to compare the safety and efficacy of a high and a low dose of intravenous amiodarone with bretylium, the only approved class III antiarrhythmic agent. Methods and Results A total of 302 patients with refractory, hemodynamically destabilizing ventricular tachycardia or ventricular fibrillation were enrolled in this double-blind trial at 82 medical centers in the United States. They were randomly assigned to therapy with intravenous bretylium (4.7 g) or intravenous amiodarone administered in a high dose (1.8 g) or a low dose (0.2 g). The primary analysis, arrhythmia event rate during the first 48 hours of therapy, showed comparable efficacy between the bretylium group and the high-dose (1000 mg/24 h) amiodarone group that was greater than that of the low-dose (125 mg/24 h) amiodarone group. Similar results were obtained in the secondary analyses of time to first event and the proportion of patients requiring supplemental infusions. Overall mortality in the 48-hour double-blind period was 13.6% and was not significantly different among the three treatment groups. Significantly more patients treated with bretylium had hypotension compared with the two amiodarone groups. More patients remained on the 1000-mg amiodarone regimen than on the other regimens. Conclusions Bretylium and amiodarone appear to have comparable efficacies for the treatment of highly malignant ventricular arrhythmias. Bretylium use, however, may be limited by a high incidence of hypotension.

The ability of Holter monitoring to predict clinical events during amiodarone therapy was evaluated in 83 patients with coronary artery disease and inducible monomorphic ventricular tachycardia. Sixty-four patients (77%) had significant ventricular ectopy activity (> or = 10 ventricular premature complexes [VPCs]/hour) at baseline, and 19 (23%) did not; patients were similar in age (63 and 65 years, respectively; p = 0.24) and ejection fraction (31 and 32%, respectively; p = 0.75). Over a mean of 23 +/- 17 months, there was no difference in arrhythmia recurrence (33 and 26%; p = 0.89) or sudden death (16 and 20%; p = 0.94) in patients with and without significant ectopy, respectively. In patients with significant ectopy, amiodarone decreased VPC frequency from baseline to 2 weeks, but not from 2 to 6 weeks. Forty-two patients had > 85% reduction in ectopy at 2 weeks; 20 patients did not. However, this reduction of simple VPCs did not predict a decrease in arrhythmic recurrence (29 vs 40%; p = 0.59) nor sudden death (25 vs 11%; p = 0.56) in patients with and without VPC suppression, respectively. Forty-five patients had Holter monitoring at 6 weeks. Twenty-one patients (47%) had > 95% suppression of ectopy, and 24 did not. Neither the recurrence (38 vs 38%; p = 0.54) nor sudden death (33 vs 13%; p = 0.45) rate was predicted by the degree of VPC suppression. Amiodarone is a powerful suppressant of VPCs, but Holter suppression of this ectopic activity is not predictive of clinical outcome.

Differentiation between primary and secondary (caused by acute myocardial infarction) ventricular fibrillation has important therapeutic and prognostic implications. The diagnosis of myocardial infarction is based on clinical, ECG, and creatine kinase MB isoenzyme (MBCK) activity. Enzymatic criteria might not be able to confirm the diagnosis of myocardial infarction after recent cardioversion. The routine use of electrophysiologic studies involving the induction and termination of ventricular dysrhythmias provides a setting in which enzyme release as a result of cardioversion alone can be examined. Therefore a systematic investigation of the magnitude and time course of creatine kinase (CK) and MBCK release was performed after termination of ventricular dysrhythmias in 57 patlents undergoing electrophysiologic studies. Of patients requiring external cardioversion, only 50% had an elevation in CK and MBCK activity. Elevation when present correlated with the number of shocks and cumulative energy delivered. The magnitude of MBCK release exceeded 10% of the total CK activity in 9% of observations. Pace-termination of ventricular tachycardia did not result in enzyme release. Arrhythmia characteriatics, coronary artery disease, and left ventricular function did not affect the magnitude of the time course of enzyme release. These data suggest that cardioversion with multipile shocks may result in a component of MBCK release, and thus a false positive diagnosis of primary acute myocardial infarction may be made by relying exclusively on the enzyme release pattern.

Heterotopic heart transplantation has been said to be contraindicated in patients with serious native heart arrhythmias that produce hemodynamic instability. Placement of heterotopic allografts, however, can theoretically act as a biological biventricular assist device to provide hemodynamic support during these unstable rhythms. Further, this operation might beneficially alter the hemodynamic milieu of heart failure such that the arrhythmias are ameliorated. Described is our experience with 4 patients with heart failure receiving heterotopic cardiac allografts, documenting changes in native heart arrhythmia that occurred. These cases demonstrate that heterotopic grafts can adequately sustain hemodynamics during malignant native heart dysrhythmia. We believe native heart ventricular arrhythmias are not a contraindication to heterotopic heart transplantation.

During a 9-year period 80 patients with drug-resistant sustained ventricular tachycardia underwent direct surgical ablation of arrhythmogenic myocardium. Sixty-nine were male (86%) and 11 female (14%), with 1.9 +/- 1.1 (standard deviation) ventricular tachycardia morphologies per patient. The mean number of drugs failed was 3.7 +/- 1.6 per patient. The preoperative left ventricular ejection fraction was 36.4% +/- 14.4%. Complete preoperative endocardial mapping data (greater than 4 endocardial sites in each ventricular tachycardia) were available for 60 of the 80 patients (75%) and intraoperative endocardial data in the clinical ventricular tachycardia was obtained in 37 (46.3%) of the patients. In 17 patients mapped intraoperatively by computer-assisted techniques, complete epicardial and endocardial data in the clinical ventricular tachycardia were obtained in 14 patients (82.4%). Overall, 73 of 80 (91.3%) had some mapping data available. Hospital mortality occurred in 10 patients (12.5%) at a mean interval of 13.5 days, range 0 to 62 days. Postoperatively the clinical ventricular tachycardia has not recurred in 65 of 70 surviving patients (92.9%). Nonclinical ventricular tachycardia occurred in another four patients. All nine patients with postoperative ventricular tachycardia responded to drugs. The major factors predictive of hospital mortality were prolonged cardiopulmonary bypass (greater than 150 minutes), preoperative ejection fraction less than 31%, and incomplete preoperative mapping. Hospital mortality in patients with an ejection fraction below 31% was significantly associated with a history of amiodarone usage. At 3 years of follow-up, freedom from sudden cardiac death was 95.7%, and 86.7% of patients were free of ventricular tachycardia on no antiarrhythmic drugs. These results suggest that direct ventricular tachycardia operations are an effective form of therapy for patients with sustained monomorphic ventricular tachycardia.

Summary Trials of drug treatment for prevention of sudden arrhythmic death have been disappointing, perhaps because suppressive therapy with arrhythmic agents fails to address the mechanisms leading to electrophysiological failure. We propose that preventive treatment should pay more attention to molecular mechanisms responsible for the progression of cardiac disease to electrophysiological failure. Most sudden cardiac deaths occur in people with atherogenic dyslipidaemias. Our hypothesis is that the pathogenic molecular mechanisms of dyslipidaemias contribute directly to arrhythmogenesis. Proinflammatory-prothrombotic lipid-derived mediators that may play a part in arrhythmogenesis include phospholipids and leucotrienes acting through the platelet-activating-factor and peroxisome proliferator-activated-receptor pathways. There are drugs available to test the hypothesis of dyslipidaemias-specific prevention of electrophysiological failure.

The active can defibrillator has been designed for implantation in the left prepectoral region. Whether this system can be successfully implanted on the right side is unknown. We describe six cases in which placement of the unipolar single lead defibrillation system was successfully attempted in the right prepectoral region due to impediments on the left side. The mean age of the patients was 62 +/- 12 years. Five patients had ischemic heart disease and one idiopathic dilated cardiomyopathy. The endocardial defibrillation electrode was placed in the right ventricle through the right subclavian vein and positioned at the apex in two patients and in the septal position in four patients. Defibrillation threshold testing was performed using a step-up/step-down protocol beginning at 12 J with 3-J increments or decrements. Defibrillation threshold was defined as the lowest energy of the first shock able to terminate ventricular fibrillation. The generator models used were the Medtronic 7218C in 1 patient, the Medtronic 7219C in 3 patients, and the Ventritex Cadet 115 AC in 2 patients. The mean defibrillation threshold was 15 +/- 3 J. The defibrillation thresholds were retested at 1, 3, and 6 months, and showed no significant change in five patients but decreased from 15 J to 12 J in one patient. The presence of impediments on the left side should not preclude attempts to place the unipolar active can system in the right prepectoral region.

The database of the registry for an implantable cardioverter defibrillator was analyzed to determine the efficacy and safety of antitachycardia pacing for the termination of ventricular tachycardia. In 22,339 episodes treated, termination occurred in 94% and acceleration in only 1.4%.

Table 1 Controlled Trials with Implantable Defibrillators (Ongoing Trials) Trial, ongoing (Projected size) Entry Criteria Groups Randomized Preliminary Results SCDHeFT (N ≥ 2,500) HF(NYHA Class II or III) for ≥ wk, +ACEI/ARB, EF

This chapter briefly reviews the aims and outcome of antiarrhythmic drug therapy in ICD recipients. It should be stated at the outset that very few controlled trials of antiarrhytlunic drug therapy in ICD recipients have been reported. Early ICD trials were designed to allow comparisons between patients randomized to ICD therapy or “conventional therapy”. The conventional therapy groups received heterogeneous treatments with various antiarrhytlunic drugs such as amiodarone (1, 2, 3, 4, 5, 6, 7), dl-sotalol (3, 4 7), class I antiarrhytlunics (1, 2, 3, 4 7), calcium blockers (2 3 5), and beta blockers (Table 1) (2 5 6). In most of these early trials, antiarrhythmic drug therapy in the ICD treatment groups was left to the discretion of the investigators (1-7). With the exception of the CIDS trial (4), few ICD patients received adjunctive amiodarone, dl-sotalol, or class I agents, whereas up to 70% received unspecified beta blockers in unknown dosages (Table 1). Therefore, previous ICD trials provided little specific information on adjunctive drug therapy in ICD groups. Two recent ICD trials still partly in progress, SCD-HeFT and MADIT II (8), are also not designed to assess effects of adjunctive drug therapy.

Background The prognosis of patients with sustained ventricular tachyarrhythmias varies according to clinical characteristics. We sought to identify predictors of survival in a large population of patients with documented sustained ventricular tachyarrhythmias not related to reversible or correctable causes included in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Registry. Methods and Results We analyzed the impact of 36 demographic, clinical, and discharge treatment variables on the outcome for 3559 patients. Survival status was assessed with the use of the National Death Index. Multivariate analyses were performed with the use of the Cox proportional hazards model. After a mean follow-up of 17±12 months, 631 patients died. Actuarial survival was 0.86 (95% confidence interval [Cl] 0.85 to 0.88), 0.79 (95% Cl 0.78 to 0.81), and 0.72 (95% Cl 0.70 to 0.74) at 1,2, and 3 years. Multivariate predictors of worse survival included older age, severe left ventricular dysfunction, lower systolic blood pressure, history of congestive heart failure, diabetes, smoking or atrial fibrillation, and preexistent pacemaker. The hemodynamic impact of the qualifying arrhythmia was not a predictor of outcome. Defibrillator implantation and hospital discharge while the patient was taking a β-blocker or an angiotensin-converting enzyme inhibitor were associated with better prognosis. Conclusions Despite therapeutic adbances, the mortality rates of patients with sustained ventricular tachyarrhythmias remain high. Prognosis depends on the severity of underlying heart disease, as reflected by the extent of left ventricular dysfunction and the presence of heart failure. Well-tolerated ventricular tachycardia in patients with structural heart disease does not carry a significantly better prognosis than ventricular tachyarrhythmia with more severe hemodynamic consequences.

A 23-year-old woman presented with sustained ventricular tachycardia and was found to have an endocardial mass by echocardiography and by magnetic resonance imaging. The diagnosis of cardiac endocardial tuberculoma was made, and she was treated with antituberculous therapy and an antiarrhythmic drug for one year. After a year, the mass was no longer present, and with all antiarrhythmic medications stopped, ventricular tachycardia could no longer be induced by electrophysiologic study. There has been no clinical recurrence.

This retrospective study characterized the recurring ventricular arrhythmias with an electrogram-storing defibrillator in survivors of sudden cardiac death who had no inducible sustained ventricular arrhythmias at baseline electrophysiologic testing (EPS). The study group was composed of 24 selected patients with documented ventricular fibrillation (VF) without need of revascularization or chronic antiarrhythmic therapy. The EPS protocol usually consisted of three extrastimuli at two drive cycles at two right ventricular sites. Nonischemic cardiomyopathy was the most frequent structural abnormality ( n = 11) followed by coronary artery disease ( n = 7). The mean ejection fraction was 0.37 ± 0.13. Cardiac status did not appear to change during a mean follow-up period of 16.4 ± 12.5 months, and eight (33%) patients received appropriate shocks in that time period. On the basis of intracardiac electrograms, 7 (88%) patients experienced VF and 1 (12%) patient had ventricular tachycardia as the first recurring arrhythmia. Four patients had additional recurrences and all were VF episodes. VF was usually present from the onset of the arrhythmia. In addition, 9 (38%) patients had nonsustained ventricular arrhythmias that were solely VF in 6 (67%). In conclusion, VF of sudden onset was the most frequent recurring sustained ventricular arrhythmia in this group.

Background: Programmed electrical stimulation early during amiodarone therapy has poor prognostic capabilities; and persistent inducibility has been associated with a favorable outcome in a majority of patients. These observations result from studies that differed significantly in methodology. Methods and Results: The authors prospectively enrolled 121 patients in a standardized amiodarone dosing protocol in which amiodarone was the only antiarrhythmic agent. Electrophysiologic testing was done after 2 and 6 weeks to determine noninducibility, predictive value, and the significance of drug-induced prolongation of tachycardia cycle length. The mean age of the patients in the study was 63.2 ± 11.5 years, and their ejection fraction was 32.8 ± 11.9%. Coronary artery disease was present in 103 (85%). At 2 weeks 17 patients (14%) were no longer inducible, whereas 101 patients (86%) remained inducible. Patients in these groups were similar in age and ejection fraction. During follow-up evaluation, recurrences (35% vs 24%; P =.44) and sudden death (12% vs 13.5%) were similar in the two groups. Thirty-five of 95 patients (32%) with sustained monomorphic ventricular tachycardia had more than 100 ms prolongation of their cycle length, which was hemodynamically well tolerated (partial response), but 60 did not (nonresponse). Patients with a partial response were older (66.5 vs 61.1 years; P =.02) and had longer QRS durations (143.2 vs 129.4 ms; P =.03). They also had increased recurrences (37% vs 17%; P =.01) and more sudden deaths (23% vs 8%; P =.02). At 6 weeks 11 of 76 patients studied were noninducible. They had a lower recurrence rate than those who remained inducible (8% vs 27%; P =.02) but a similar number of sudden deaths (8% vs 16%; P =.27). Thirty-two patients partially responded, and 31 patients did not respond. During follow-up examination these two groups had a similar number of recurrences (25% vs 29%; P =.76) and sudden deaths (16% vs 16%). Conclusions: Noninducibility at 2 or 6 weeks of amiodarone therapy did not identify patients at low risk of sudden death. In inducible patients, tachycardia cycle length prolongation, even when well tolerated, was not a marker for favorable outcome. Electrophysiologically guided therapy. therefore. offers little benefit over empiric amiodarone. Conclusions: Noninducibility at 2 or 6 weeks of amiodarone therapy did not identify patients at low risk of sudden death. In inducible patients, tachycardia cycle length prolongation, even when well tolerated, was not a marker for favorable outcome. Electrophysiologically guided therapy. therefore. offers little benefit over empiric amiodarone.

Background The purpose of this study was to prospectively analyze redetection problems after unsuccessful shock with different lead systems and devices. Methods and Results We prospectively analyzed detection and redetection characteristics among transvenous implantable cardioverter-defibrillators (ICDs) using standard bipolar and integrated bipolar sensing. Monophasic and biphasic ICDs were included. Subthreshold shocks were intentionally delivered, and redetection of ventricular fibrillation (VF) was assessed before discharge and at 1, 3, 6, and 12 months later. Sensing of VF resulting from antitachycardia pacing and low-energy cardioversion (≤2 J) also was analyzed. Before inclusion in the study, each patient underwent subthreshold shock testing at three different time intervals. Among the 160 ICDs with standard bipolar sensing, 530 VF inductions were analyzed. After the failed shocks, undersensing was more frequent (3% versus 20%, P P 6-mm electrode separation. After antitachycardia pacing in 1 patient and a 2-J shock in 1 patient, ventricular tachycardia turned into VF, which was undetected. Both patients used the Endotak 60 series–Cadence combination. None of the patients showing VF undersensing had sudden death at follow-up. Only 3 of the 12 patients with sensing malfunction were on antiarrhythmia drugs at the time of testing. Analysis of endocardial electrograms showed that failure to redetect VF is not associated with a uniform reduction but with a rapid and repetitive change of electrogram amplitude. Conclusions Standard bipolar sensing redetects VF more effectively than integrated bipolar sensing. Endocardial electrogram analysis provides insights into the understanding of the mechanism of undersensing, and certain lead-device combinations result in a higher occurrence of VF undersensing. The clinical relevance of this phenomenon remains unknown.

Prospective evaluations of intravenous lidocaine as therapy for sustained monomorphic ventricular tachycardia (VT) in the absence of acute myocardial infarction are lacking. Lidocaine has been promulgated as first-line therapy in patients with VT, but studies evaluating its efficacy in the electrophysiology laboratory suggest that it has poor effects in terminating or preventing induction of VT. Thus, this study sought to evaluate the clinical effectiveness of lidocaine in 3 cohorts with induced or spontaneous VT. One hundred twenty-eight patients with stable VT, occurring either spontaneously or induced at the time of electrophysiologic study either in the baseline state or at the time of pharmacologic testing, were evaluated. The response rate to lidocaine therapy as manifested by termination of VT was the primary goal of the study. Of these patients, 10 (8%) had termination of VT after lidocaine therapy. There were no significant differences in age, ejection fraction, VT cycle length, and mean dose of lidocaine between responders and 118 nonresponders. There were no serious side effects or adverse events (death, myocardial infarction, angina, or congestive heart failure). Lidocaine, although safe, is ineffective in terminating stable VT not associated with acute myocardial infarction.

To define the clinical significance of conduction defects after orthotopic heart transplantation sequential electrocardiograms (ECG) of 124 patients were analyzed during their postoperative hospital stay. The first ECG was abnormal in 90 patients (73%), with a predominance of right bundle branch block, and normal in 34 (27%). Sex, age, mean donor ischemic time, duration of aortic cross clamping and use of previous antiarrhythmic therapy were not significantly different in the 2 groups. During hospital follow-up, patients were grouped according to evolution of the initial electrocardiographic abnormalities. In group 1, 25 patients continued to have an initially normal ECG. In groups 2 and 3, 30 and 48 patients, respectively, had evidence of transient and permanent conduction defects. The 21 patients in group 4 showed progressive deterioration of conduction with either a new (9 patients) or worsening preexisting conduction defect (12 patients). The evolution of the initial ECG was strongly dependent on the duration of the donor heart ischemic time and the severity of the in-hospital cardiac rejection. Patients with persistent conduction abnormalities had a statistically longer ischemic time than either patients with normal or transient conduction defects (182 +/- 84 vs 144 +/- 68 and 130 +/- 66 minutes, p = 0.04). Although the overall percentage of patients with histologic evidence of moderate to severe rejection was similar across the groups, 66.6 and 46.1% of patients in groups 3 and 4, respectively, had multiple episodes of rejection compared with 16.6 and 0% in the remaining 2 groups (p = 0.044).(ABSTRACT TRUNCATED AT 250 WORDS)

Serial hand mapping techniques in man have identified 3 to 5 sites of epicardial breaktrough (EBT). However, transmural epicardial excitation from the widely distributed His/Purkinje system suggests a more complicated pattern may exist. Multielectrode arrays used with large mapping systems during surgery often present complicated and sometimes inconsistent activation patterns. The purpose of this work is to reconcile epicardial activation in the normal human heart with anatomical and endocardial/intramural physiological recordings using multichannel computer mapping requiring only a single beat, and rigorously defined and applied activation time detection algorithms. Eighteen subjects undergoing surgery for Wolff-Parkinson-White syndrome were recorded with a 119 site sock array during nonpreexcited sinus rhythm. None had evidence of coronary artery disease and all exhibited a normal 12-lead ECG except during periods of preexcitation or tachycardia. Each was recorded bipolarly and four also were recorded monopolarly. Recordings revealed 8.0 +/- 1.6 EBTs (range 5 to 12). Closely spaced, multiple EBTs often were observed and usually confirmed using different activation time detection algorithms. The earliest EBT always occurred over the anterior right ventricle at 14.3 +/- 6.5 msec (range -1 to 29 msec) after QRS onset. Subsequent EBTs could occur at any ventricular site with variable latencies. In contrast to previous reports describing epicardial spread of activation from a few foci, a mosaic of epicardial activation emerges. These data are consistent with endocardially initiated transmural activation of the epicardium suggested by the anatomy of the His/Purkinje system and intramural recordings.

A left subcostal surgical approach was used to implant an automatic implantable cardioverter defibrillator (AICD) in 48 patients with a history of nonfatal cardiac arrest or documented ventricular tachycardia/fibrillation. Electrophysiologic studies before surgery yielded induction of monomorphic or polymorphic ventricular tachycardia in 40 patients, whereas 8 were noninducible. Mean (± standard deviation) age was 58 ± 12 years. Mean ejection fraction was 33 ± 16%. Thirty patients (63%) had documented coronary artery disease; 14 patients (29%) had previous coronary bypass surgery. The mean intraoperative defibrillation threshold was 13.8 ± 6.6 J. In 6 patients, an adjunctive right minithoracotomy was used to position 1 patch over the right atrium and thus optimize the defibrillation threshold. Patients with prior exposure to amiodarone and previous coronary bypass surgery had higher defibrillation thresholds at implantation. Two perioperative deaths occurred. There were no infections. Long-term follow-up yielded a 1- and 5-year survival of 0.88 and 0.58, respectively, and a freedom from sudden cardiac death of 1.0 and 0.97, respectively. The nonthoracotomy, left subcostal surgical approach is safe and effective, provides adequate defibrillation thresholds in most patients, and yields long-term survival comparable to other implantation techniques.

The question is addressed whether patients with thoracotomy defibrillators and failing epicardial electrodes can be effectively treated with the implantation of prepectoral unipolar ("active can") defibrillators. Results indicate that abandoned epicardial patches in the pathway of unipolar defibrillation currents do not affect defibrillation thresholds and active can efficacy.

Objective. —To evaluate and quantitate cardiac involvement in myotonic dystrophy and assess whether the size of the trinucleotide (cytosine-thymine-guanine [CTG]) repeat expansion is a significant predictor of cardiac abnormalities. Design. —Case-control study of a large kindred with myotonic dystrophy. Patients. —Ninety-one bloodline members of the kindred underwent clinical and cardiac evaluation with electrocardiograms, echocardiography (with Doppler in the majority of cases), and genetic and neurologic evaluations. Affected individuals were age-matched to normal family members. Main Outcome Measures. —Electrocardiographic conduction abnormalities, wall motion abnormalities, mitral valve prolapse, and global parameters of systolic and diastolic function were determined by an observer blinded to all clinical data and genetic analysis. Results. —Compared with age-matched normals, patients with myotonic dystrophy (n=25) were more likely to have conduction abnormality (52% vs 9%), mitral valve prolapse (32% vs 9%), and wall motion abnormality (28% vs 0%) (all P P P =.04). Conclusions. —Cardiac involvement in myotonic dystrophy affects predominantly the conduction system and myocardial function. Alterations in myocardial relaxation and diastolic properties, in contrast to skeletal muscle myotonia, are minor. In this kindred, the number of CTG repeats was a significant predictor of cardiac dysfunction in myotonic dystrophy. ( JAMA . 1995;274:813-819)

Intraoperative mapping and cryoablation of ventricular tachycardia was achieved without ventriculotomy in seven patients, who are a subgroup of the 80 patients undergoing map-directed ablation of ventricular tachycardia over a 9-year period. There were four male and three female patients. Their mean age was 53.6 ± 24.1 years. Coronary artery disease was present in five patients, and two patients had idiopathic ventricular tachycardia. The mean preoperative ejection fraction was 42.4% ± 13.6%. The mean number of ventricular tachycardia morphologies was 1.7 (range 1 to 3). Epicardial mapping was obtained intraoperatively in all seven patients and endocardial data in five of seven patients (71.4%). There were no hospital deaths and no early or late spontaneous recurrence of clinical monomorphic ventricular tachycardia. Nonclinical monomorphic ventricular tachycardia was inducible in two patients postoperatively and both were treated with procainamide. Death occurred late after operation in two patients: One death was related to recurrent nonclinical VT at 8 months and one at 3 months was due to carcinoma of the stomach. These results suggest that the transannular approach is feasible in selected cases, especially when computerized mapping systems with endocardial balloon electrode arrays can be used.

A second-generation implantable pacemaker-cardioverter-defibrillator was evaluated in 200 patients with sustained ventricular tachycardia, ventricular fibrillation or prior cardiac arrest. The device permits demand ventricular pacing for bradyarrhythmias and for long QT interval or tachycardia suppression, uses programmable (3 to 30 J) energy shocks for conversion of ventricular tachycardia and ventricular fibrillation and is used with conventional pacing and defibrillation leads. Ventricular tachycardia/fibrillation recognition is based on the ventricular electrogram rate and requires reconfirmation before shock delivery. Two hundred patients (mean age 62 years, mean left ventricular ejection fraction 36%) were enrolled and followed up for 0 to 23 months (mean 12). Epicardial lead system implantation was performed with use of an anterolateral thoracotomy (38%), median sternotomy (26%) and subxiphoid (20%) or subcostal (16%) approach. Perioperative mortality rate was 5.5% (all nonarrhythmic deaths). Implant defibrillation threshold ranged from 3 to 30 J (mean 15), with initial programmed shock energy ranging from 3 to 30 J (mean 22). Ventricular tachycardia/fibrillation sensing threshold ranged from 0.7 to 1.8 mV (median 1) and the tachycardia detection interval from 288 to 416 ms (median 320). Reprogramming of implant variables was necessary for reliable electrographic sensing (54 patients), programmed shock therapy (61 patients) and tachycardia detection rate (63 patients). Device activation for potential shock delivery occurred in 111 patients (55.5%) with actual shock delivery after ventricular tachycardia/ fibrillation reconfirmation in 66 patients (33%). During follow-up study, there was a 1% arrhythmia mortality rate, 6.5% cardiac mortality rate and 10.5% total mortality rate. This study demonstrates that the programmable implantable pacemaker-cardioverter-defibrillator is effective in preventing arrhythmic death, yet reduces patient exposure to repeated shock therapy. Reprogramming is usually necessary during follow-up for optimal function.

OBJECTIVESThe objective of the study was to determine whether the occurrence of shocks for ventricular tachyarrhythmias during therapy with implantable cardioverter-defibrillators (ICD) is predictive of shortened survival.BACKGROUNDVentricular tachyarrhythmias eliciting shocks are often associated with depressed ventricular function, making assessment of shocks as an independent risk factor difficult.METHODSConsecutive patients (n = 421) with a mean follow-up of 756 ± 523 days were classified into those who had received no shock (n = 262) or either one of two shock types, defined as single (n = 111) or multiple shocks (n = 48) per arrhythmia episode. Endpoints were all-cause and cardiac deaths. A survival analysis using a stepwise proportional hazards model evaluated the influence of two primary variables, shock type and left ventricular ejection fraction (LVEF 35%). Covariates analyzed were age, gender, NYHA Class, coronary artery disease, myocardial infarction, coronary revascularization, defibrillation threshold and tachyarrhythmia inducibility.RESULTSThe most complete model retained LVEF (p = 0.005) and age (p = 0.023) for the comparison of any shock versus no shock (p = 0.031). The occurrence of any versus no shock, or of multiple versus single shocks significantly decreased survival at four years, and these differences persisted after adjustment for LVEF. In the LVEF subgroups

Tachyarrhythmias are common. They may occur secondary to a variety of etiologies and mechanisms. In most cases. drug therapy is effective but in some patients the arrhythmias remain symptomatic or life-threatening despite multiple drug trials. It is for these patients that electrophysiologically guided arrhythmia surgery should be considered. Effective operative therapy is available for most forms of supraventricular and ventricular arrhythmias.

Surgical treatment of sustained ventricular tachycardia due to nonischemic causes is uncommon. Nonischemic ventricular tachycardia was treated in 14 patients by map-directed surgical ablation of an arrhythmogenic site. There were 9 male and 5 female patients. The mean age was 33 +/- 13.4 years (range, 15 to 57 years). The etiology was idiopathic in 4 patients, cardiomyopathy in 3, acute myocarditis in 1, arrhythmogenic right ventricular dysplasia in 2, tumor in 1, postoperative Tetralogy of Fallot in 2, and acute bacterial endocarditis in 1. Pre- and/or intraoperative electrophysiologic mapping was achieved in 13 of 14 patients. A variety of operations were performed without death. Two late deaths have occurred, neither of them, however, from arrhythmias. After operation two patients had recurrent arrhythmias. Surgery for nonischemic ventricular tachycardia is safe and effective and should be considered early in the course of these mostly young patients.

Although successful operative treatment of atrial focal tachycardia has been reported in children, there are only isolated reports of surgical treatment of this arrhythmia in adults. In this case series of eight patients (aged 10 to 53 years) with drug-resistant right atrial focal tachycardia, results of electrophysiologic studies, surgical techniques and long-term follow-up are described. Atrial focai tachycardia was reproduced during etectrophysiologic study, and endocardial mapping localized the earliest onset of atrial activation in the right atrium in all patients. Epicardial mapping confirmed the location of atrial tachycardia foci in seven of eight patients whose tachycardia was inducible intraoperatively. Of four patients treated with epicardial cryoablation alone, two had recurrent tachycardia and required a second procedure. None have had arrhythmia recurrence, in all four patients aftar right atrial excision (two of whom had intraoperative recurrence of atrial focal tachycardia alter epicardial cryoablation alone), there has been no recurrence during a clinical follow-up period of 11 to 67 mouths (mean 30). It is concluded that in adult patients 1) electrophysiologic study with endocardial and epicardial mapping permits successful surgical treatment of atrial focal tachycardia; 2) epicardial cryoablation alone may be associated with recurrence of atrial focal tachycardia either intraoperatively or postoperatively; and 3) subtotal right atrial resection appears to be a well tolerated procedure with no long-term recurrence of atrial focal tachycardia.

High defibrillation thresholds are encountered in some patients during implantation of the automatic implantable cardioverter defibrillator (AICD). In a consecutive series of 52 patients with AICD implants, 46 had allepicardial implants by left subcostal thoracotomy, and 8 of these patients had thresholds greater than 30 J. Placement of an apicolateral large left ventricular patch and an extrapericardial large right atrial patch electrode through a limited right thoracotomy produced substantial reduction in their thresholds. Especially in patients who have had previous intrapericardial operations, this technique provides a simple solution to the problem of high thresholds.