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Background: The benefit of novel implantable cardioverter defibrillator (ICD) programming in reducing inappropriate ICD therapy and mortality was demonstrated in Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT). However, the cause of mortality reduction remains incompletely evaluated. We aimed to identify factors associated with mortality, with focus on ICD therapy and programming in the MADIT-RIT population., Methods and Results: In MADIT-RIT, 1500 patients with a primary prophylactic indication for ICD or cardiac resynchronization therapy with defibrillator were randomized to 1 of 3 different ICD programming arms: conventional programming (ventricular tachycardia zone ≥170 beats per minute), high-rate programming (ventricular tachycardia zone ≥200 beats per minute), and delayed programming (60-second delay before therapy ≥170 beats per minute). Multivariate Cox models were used to assess the influence of time-dependent appropriate and inappropriate ICD therapy (shock and antitachycardia pacing) and randomized programming arm on all-cause mortality. During an average follow-up of 1.4±0.6 years, 71 of 1500 (5%) patients died: cardiac in 40 patients (56.3%), noncardiac in 23 patients (32.4%), and unknown in 8 patients (11.3%). Appropriate shocks (hazard ratio, 6.32; 95% confidence interval, 3.13-12.75; P<0.001) and inappropriate therapy (hazard ratio, 2.61; 95% confidence interval, 1.28-5.31; P=0.01) were significantly associated with an increased mortality risk. There was no evidence of increased mortality risk in patients who experienced appropriate antitachycardia pacing only (hazard ratio, 1.02; 95% confidence interval, 0.36-2.88; P=0.98). Randomization to conventional programming was identified as an independent predictor of death when compared with patients randomized to high-rate programming (hazard ratio, 2.0; 95% confidence interval, 1.06-3.71; P=0.03)., Conclusions: In MADIT-RIT, appropriate shocks, inappropriate ICD therapy, and randomization to conventional ICD programming were independently associated with an increased mortality risk. Appropriate antitachycardia pacing was not related to an adverse outcome., Clinical Trial Registration Url: clinicaltrials.gov Unique identifier: NCT00947310., (© 2014 American Heart Association, Inc.)

Objectives: The purpose of this multicenter study was to evaluate the safety and efficacy of a radiofrequency (RF) catheter ablation system with internal saline irrigation., Background: Catheter ablation of ventricular tachycardia (VT) associated with structural heart disease is more difficult than ablation of idiopathic VT. The larger size of responsible reentrant circuits contributes to the difficulty in achieving an adequate ablation lesion with conventional techniques. Recently, cooling of the ablation electrode by saline irrigation has been shown to increase RF lesion size., Methods: The patient population included 146 patients who participated in the Cooled RF Ablation System clinical trial and underwent an attempt at ablation of VT occurring in the presence of structural heart disease. The duration of follow-up was 243 +/- 153 days., Results: Catheter ablation was acutely successful, as defined by elimination of all mappable VTs, in 106 patients (75%). In 59 patients (41%), no VT of any type was inducible after ablation. Twelve patients (8%) experienced a major complication. After catheter ablation, 66 patients (46%) developed one or more episodes of a sustained ventricular arrhythmia., Conclusions: The results of this study demonstrate that catheter ablation of all mappable forms of sustained VT can be performed with high initial success and a moderate incidence of major complications (8%).

Background: This study evaluated the cost-effectiveness of catheter ablation therapy versus amiodarone for treating ventricular tachycardia (VT) in patients with structural heart disease. The analysis used a societal perspective for a hypothetical cohort of VT patients with implantable cardioverter-defibrillators, who were experiencing frequent shocks., Methods and Results: We calculated incremental cost-effectiveness of ablation relative to amiodarone over 5 years after treatment initiation. Event probabilities were from the Chilli randomized clinical trial (Chilli Cooled Ablation System, Cardiac Pathways Corporation, Sunnyvale, Calif), the literature, and a consensus panel. Costs were from 1998 national Medicare reimbursement schedules. Quality-of-life weights (utilities) were estimated using an established preference measurement technique. In a hypothetical cohort of 10 000 patients, 5-year costs were higher for patients undergoing ablation compared with amiodarone therapy ($21 795 versus $19 075). Ablation also produced a greater increase in quality of life (2.78 versus 2.65 quality-adjusted life-years [QALYs]). This yielded a cost-effectiveness ratio of $20 923 per QALY gained for ablation compared with amiodarone. Results were relatively insensitive to assumptions about ablation success and durability. In less severe patients with good ejection fractions who suffer their first VT episode, the incremental cost-effectiveness ratio was $6028 per QALY gained. These cost-effectiveness ratios are within the range generally thought to warrant technology adoption., Conclusions: This study demonstrates that, from a societal perspective, catheter ablation appears to be a cost-effective alternative to amiodarone for treating VT patients.

Death due to ventricular tachyarrhythmia (VT) remains an important public health problem; patients with prior myocardial infarction (MI) constitute the largest identifiable population for prophylactic interventions. Targeting of progressively higher-risk subgroups of post-MI survivors carries inevitable tradeoffs with respect to the global impact of interventions on overall mortality. Therapy with aspirin, beta blockers, and angiotensin-converting enzyme (ACE) inhibitors comprise the benchmark against which all additional interventions, including implantable defibrillators, must be measured. Initial enthusiasm for empiric amiodarone therapy has been tempered by the limited benefit demonstrated in recent randomized trials. Trials of other class III antiarrhythmic drugs, including both d,l-sotalol and d-sotalol, have also failed to demonstrate survival benefit. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) demonstrated significantly improved survival associated with defibrillators in a small subgroup of post-MI survivors with a high short-term risk of death. The ultimate number and optimal criteria for selection of patients who may benefit from prophylactic defibrillator therapy after MI will undergo continued evolution as new data from current and ongoing trials become available.

Background: Unsustained ventricular tachycardia in patients with previous myocardial infarction and left ventricular dysfunction is associated with a two-year mortality rate of about 30 percent. We studied whether prophylactic therapy with an implanted cardioverter-defibrillator, as compared with conventional medical therapy, would improve survival in this high-risk group of patients., Methods: Over the course of five years, 196 patients in New York Heart Association functional class I, II, or III with prior myocardial infarction; a left ventricular ejection fraction < or = 0.35; a documented episode of asymptomatic unsustained ventricular tachycardia; and inducible, nonsuppressible ventricular tachyarrhythmia on electrophysiologic study were randomly assigned to receive an implanted defibrillator (n = 95) or conventional medical therapy (n=101). We used a two-sided sequential design with death from any cause as the end point., Results: The base-line characteristics of the two treatment groups were similar. During an average follow-up of 27 months, there were 15 deaths in the defibrillator group (11 from cardiac causes) and 39 deaths in the conventional-therapy group (27 from cardiac causes) (hazard ratio for overall mortality, 0.46; 95 percent confidence interval, 0.26 to 0.82; P=0.009). There was no evidence that amiodarone, beta-blockers, or any other antiarrhythmic therapy had a significant influence on the observed hazard ratio., Conclusions: In patients with a prior myocardial infarction who are at high risk for ventricular tachyarrhythmia, prophylactic therapy with an implanted defibrillator leads to improved survival as compared with conventional medical therapy.

This study examines in a prospective, multicenter trial the feasibility and advantage of current-based, transthoracic defibrillation. Current-based, damped, sinusoidal waveform shocks of 18, 25, 30, 35, or 40 amperes (A) were administered beginning with 25 A for polymorphic ventricular tachycardia (VT) and ventricular fibrillation (VF) or 18 A for monomorphic VT; success rates were compared with those of energy-based shocks beginning at 200 J for VF/polymorphic VT and 100 J for VT. The current-based shocks were delivered from custom-modified defibrillators that determined impedance in advance of any shock using a "test-pulse" technique; the capacitor then charged to the exact energy necessary to deliver the operator-selected current against the impedance determined by the defibrillator. Three hundred sixty-two patients received > 1 shock for VF, polymorphic VT, or monomorphic VT: 569 current- based shocks and 420 energy-based shocks. Current-based shocks of 35/40 A achieved success rates of up to 74% for VF/polymorphic VT; 30 A shocks terminated 88% of monomorphic VT episodes. Energy-based shocks of 300 J terminated 72% of VF/polymorphic VT; 200-J shocks terminated 89% of monomorphic VT. We could not demonstrate a significant increase in the success rate of current-based shocks over energy-based shocks for patients with high transthoracic impedance; this may be due to inadequate sample size. Thus, current-based defibrillation is clinically feasible and effective. A larger study will be needed to test whether current-based defibrillation is superior to energy-based defibrillation.

The clinical significance of nonsustained ventricular tachycardia continues to undergo reevaluation as clinicians attempt to optimize screening strategies for identifying high-risk patients and to evaluate the efficacy of therapeutic interventions. The utility of ambulatory monitoring and programmed stimulation as screening tools in the patient who has suffered an infarction remains unsettled; ongoing clinical trials may help resolve these issues. New data suggest that the survival benefit associated with angiotensin-converting enzyme inhibition is unrelated to effects on spontaneous arrhythmias, similar to results previously reported for beta-blockers. Randomized clinical trials of prophylactic amiodarone in patients with congestive heart failure and nonsustained ventricular tachycardia have produced conflicting results. A strong relationship between polymorphic nonsustained ventricular tachycardia and sudden death in patients without structural heart disease or QT prolongation has been reported. The significance of nonsustained ventricular tachycardia in dilated cardiomyopathy and hypertrophic cardiomyopathy has also been reassessed.

Background: Intraoperative mapping studies suggest that an isthmus of myocardium between the mitral valve annulus and the border of inferior myocardial infarction may play a role in the genesis of ventricular tachycardia. We examined the frequency with which a slow conduction zone within the mitral isthmus was critical to the maintenance of ventricular tachycardia associated with remote inferior infarction in patients undergoing catheter ablation., Methods and Results: In 4 of 12 patients, a critical zone of slow conduction was identified within the mitral isthmus. In each of these patients, two characteristic and morphologically distinct tachycardias were induced: a left bundle (rS in V1, R in V6), left superior axis morphology and a right bundle (R in V1, QS in V6), right superior axis morphology (cycle length, 610 to 320 ms). In each patient, a zone of slow conduction, shared by both morphologies, was characterized by diastolic potentials with electrogram-QRS intervals of 85 to 161 ms (21% to 47% of tachycardia cycle length) and entrainment with concealed fusion during pacing associated with stimulus-QRS intervals of 81 to 400 ms (20% to 91% of tachycardia cycle length). In each patient, a single radiofrequency energy application at the shared site of slow conduction eliminated inducibility of both morphologies. During follow-up of 1 to 11 months, no patient had recurrent tachycardia., Conclusions: The mitral isthmus contains a critical region of slow conduction in some patients with ventricular tachycardia after inferior myocardial infarction, providing a vulnerable and anatomically localized target for catheter ablation. Characteristic tachycardia morphologies may provide clinical markers for this underlying mechanism.

Background: Oral amiodarone effectively suppresses ventricular arrhythmias; however, full activity may take days or weeks. In patients with frequent, life-threatening ventricular arrhythmias, this delay is not acceptable. Thus, in these patients, the speed and dosing accuracy of an intravenous formulation would be beneficial. The goal of this study was to demonstrate the efficacy of intravenous amiodarone in patients with refractory, recurrent hemodynamically destabilizing ventricular tachycardia or ventricular fibrillation by determining a dose response among three regimens., Methods and Results: A total of 342 patients were enrolled at 46 medical centers in the United States. Patients received one of three randomized, double-blind dose regimens delivering 125, 500, or 1000 mg during the first 24 hours. Supplemental infusions (150 mg) of intravenous amiodarone could be given to treat breakthrough ventricular arrhythmias. The key efficacy end points were the arrhythmia event rate, time to first arrhythmic event, and number of supplemental infusions administered. The event rate decreased with increasing doses: median values were 0.07, 0.04, and 0.02 events per hour for the 125-, 500-, and 1000-mg dose groups, respectively, representing a significant decrease from baseline event rates (P = .043), and approached significance in the overall test for trend (P = .067). There was a significant dose-related increase in the time to first event (trend test P = .025) and a significant dose-related decrease in the number of supplemental boluses per hour (trend test P = .043). Hypotension was the most common (26%) treatment-emergent adverse event during intravenous amiodarone therapy; there was no dose-response relationship. Seventy-eight percent of the patients survived to at least 48 hours., Conclusions: Intravenous amiodarone is effective for the treatment of recurrent, life-threatening ventricular tachyarrhythmias.

The determinants of high defibrillation energy requirements (DER) using nonepicardial lead systems (NELS) have not been well characterized. The goal of this study was to examine prospectively the influence of clinical, radiographic, echocardiographic, and procedural variables on DER during NELS placement. Data from 100 consecutive patients undergoing attempted NELS implantation were analyzed. Transvenous leads, subcutaneous patches, and monophasic shock devices from two manufacturers were used. Leads were successfully positioned for testing in 95% of patients. An adequate DER (< or = 25 J) was obtained in 73 of 95 (77%) of patients. Univariate analysis identified amiodarone therapy and left ventricular mass as predictors of high DER. With multivariate analysis, amiodarone therapy was the sole significant predictor of high DER (P = 0.002, odds ratio 5.46). The 22 patients with high NELS DER also had high epicardial DER (mean 24 +/- 9 J). The two patch epicardial DER was > 25 joules in 12 of 22 patients. Thus, adequate DER with monophasic shock waveforms can be obtained in most patients undergoing NELS testing. However, amiodarone therapy significantly increases the probability of obtaining high DER.

The prognostic significance of a de novo sustained ventricular tachyarrhythmia occurring during a dobutamine infusion is unknown. This study was performed to determine (1) the risk of recurrent ventricular arrhythmia, (2) the safety of future dobutamine infusions, and (3) the role of electrophysiologic testing. The study population consisted of 15 patients, six with coronary artery disease, and nine with idiopathic dilated cardiomyopathy. Mean ejection fraction was 17% +/- 4.1%. The arrhythmia during the infusion was ventricular tachycardia in 13 patients and ventricular fibrillation in two patients and was not associated with preceding hemodynamic instability, electrolyte abnormality, digoxin toxicity, or antiarrhythmic drug therapy. During electrophysiologic testing, 7 of 15 patients had inducible ventricular tachycardia. All patients with inducible ventricular tachycardia were treated with either antiarrhythmic drugs, defibrillators, or ablation. Over a 12.3 +/- 5.2 month follow-up period, all 15 patients received further dobutamine treatment. Seven of 15 (47%) had a recurrent sustained ventricular tachyarrhythmia. Although three of seven recurrences occurred during a dobutamine infusion, all three of these patients had hemodynamically unstable conditions and were receiving high-dose (> 10 micrograms/kg/min) therapy at the time of recurrence. The other four recurrent arrhythmias were not associated with clear precipitating factors. Ejection fraction, origin of left ventricular dysfunction, and inducibility at baseline electrophysiologic testing did not predict arrhythmia recurrence. The de novo occurrence of a sustained ventricular tachyarrhythmia during dobutamine infusion is associated with a significant risk of arrhythmia recurrence (47%), which can occur in the presence or absence of dobutamine therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

With the increasing flexibility allowed by implantable cardioverter defibrillators that use tiered therapy, it is important to match the therapy with the arrhythmia. In this article we present scatter diagram analysis, a new computationally efficient two-channel algorithm for distinguishing monomorphic ventricular tachycardia (VT) from polymorphic ventricular tachycardia and ventricular fibrillation (VF). Scatter diagram analysis plots the amplitude from one channel versus the amplitude from another channel on a graph with a 15 x 15 grid. The fraction (percentage) of the 225 grid blocks occupied by at least one sample point is then determined. We found that monomorphic VT traces nearly the same path in space and occupies a smaller percentage of the graph than a nonregular rhythm such as polymorphic VT or VF. Scatter diagram analysis was tested on 27 patients undergoing intraoperative implantable cardioverter defibrillator testing. Passages of 4.096 seconds were obtained from rate (bipolar epicardial) and morphology (patch) leads, and digitized at 125 Hz. Scatter diagram analysis distinguished 13 episodes of monomorphic VT (28.6% +/- 4.0%) from 27 episodes of polymorphic VT or VF (48.0% +/- 8.2%) with P < 0.0005. There was overlap in only one monomorphic VT episode and one polymorphic VT or VF episode.

Background: Sustained ventricular tachycardia in the absence of structural heart disease may have diverse mechanisms. Termination of the tachycardia by adenosine suggests triggered automaticity as the etiology in many of these patients. We examined the clinical characteristics, electrophysiological responses, and results of catheter ablation in this patient subgroup., Methods and Results: Intravenous adenosine terminated sustained ventricular tachycardia in seven of 14 consecutive patients without evidence of structural heart disease. In each of these patients, the tachycardia had a left bundle branch block, inferior-axis QRS configuration and occurred predominantly during stress or exertion. A morphologically similar sustained tachycardia was induced in six of seven patients during programmed ventricular stimulation, although day-to-day reproducibility was poor. Signal-averaged ECGs were normal in all patients. Imaging with 123I-metaiodobenzylguanidine did not reveal focal abnormalities in any of five patients. A discrete site of origin was identified in the free wall of the pulmonary infundibulum in all patients. Limited application of direct current shocks (two patients) or radiofrequency energy (five patients) resulted in long-term abolition of spontaneous and inducible ventricular tachycardia in all patients., Conclusions: Adenosine-sensitive ventricular tachycardia appears to arise from relatively discrete sites predominantly located in the free wall of the pulmonary infundibulum. The localized nature of this tachycardia renders it amenable to long-term cure by catheter ablation techniques.