Therapy From a Novel Substernal Lead: The ASD2 Study.

OBJECTIVES: The ASD2 (Acute Extravascular Defibrillation, Pacing, and Electrogram) study evaluated the ability to adequately sense, pace, and defibrillate patients with a novel implantable cardioverter-defibrillator (ICD) lead implanted in the substernal space. BACKGROUND: Subcutaneous ICDs are an alternative to a transvenous defibrillator system when transvenous implantation is not possible or desired. An alternative extravascular system placing a lead under the sternum has the potential to reduce defibrillation energy and the ability to deliver pacing therapies. METHODS: An investigational lead was inserted into the substernal space via a minimally invasive subxiphoid access, and a cutaneous defibrillation patch or subcutaneous active can emulator was placed on the left mid-axillary line. Pacing thresholds and extracardiac stimulation were evaluated. Up to 2 episodes of ventricular fibrillation were induced to test defibrillation efficacy. RESULTS: The substernal lead was implanted in 79 patients, with a median implantation time of 12.0 ± 9.0 min. Ventricular pacing was successful in at least 1 vector in 76 of 78 patients (97.4%), and 72 of 78 (92.3%) patients had capture in ≥1 vector with no extracardiac stimulation. A 30-J shock successfully terminated 104 of 128 episodes (81.3%) of ventricular fibrillation in 69 patients. There were 7 adverse events in 6 patients causally (n = 5) or possibly (n = 2) related to the ASD2 procedure. CONCLUSIONS: The ASD2 study demonstrated the ability to pace, sense, and defibrillate using a lead designed specifically for the substernal space.

A multicenter study of shock pathways for subcutaneous implantable defibrillators.

INTRODUCTION: A purely subcutaneous implantable cardioverter defibrillator (ICD) requires higher energy but may be an effective alternative to transvenous ICDs to deliver lifesaving therapies. OBJECTIVE: To identify combinations of anteroposterior subcutaneous shock pathways and waveforms with defibrillation efficacy comparable to transvenous ICDs. METHODS: Defibrillation testing was performed in 141 patients temporarily implanted with an active can emulator and subcutaneous coil electrodes. The patients were subdivided into 5 groups within 2 study phases. In all groups, a posterior electrode was positioned with its tip close to the spine. In the first study phase, 2 different can locations were evaluated: (1) an inframammary pocket (IM-1-750), or (2) a conventional infraclavicular pocket (IC-1-750). In both cases, a 70 J biphasic shock was used (peak voltage 750 V; 270 µF capacitance). In the second phase, configuration IC-1-750 was enhanced by the addition of a second (parasternal) subcutaneous electrode (IC-2-750). Furthermore, the effects of a different 70 J shock waveform (1,000 V, 160 µF) were evaluated for configurations IM-1-750 and IC-2-750 (becoming IM-1-1000 and IC-2-1000). RESULTS: The proportion of patients satisfying a defibrillation safety margin test of 2 consecutive successes at ≤50 J was 74%, 11%, and 44%, respectively, for the IM-1-750, IC-1-750, and IC-2-750 configurations, and 93% and 86% for the IM-1-1000 and IC-2-1000 configurations. CONCLUSIONS: Defibrillation efficacy comparable to that of a transvenous system was achieved with an anteroposterior subcutaneous ICD configuration, with 160 µF capacitance, 1,000 V, and 70 J output. An infraclavicular pocket location becomes feasible if a parasternal subcutaneous coil is added.

Differences in effects of electrical therapy type for ventricular arrhythmias on mortality in implantable cardioverter-defibrillator patients.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) shocks have been associated with an increased risk of death. It is unknown whether this is due to the ventricular arrhythmia (VA) or shocks and whether antitachycardia pacing (ATP) termination can reduce this risk. OBJECTIVE: The purpose of this study was to determine whether mortality in ICD patients is influenced by the type of therapy (shocks of ATP) delivered. METHODS: Cox models evaluated effects of baseline characteristics, ventricular tachycardia (VT; <188 bpm), fast VT (FVT; 188-250 bpm), ventricular fibrillation (VF; >250 bpm), and therapy type (shocks or ATP) on mortality among 2135 patients in four trials of ATP to reduce shocks. RESULTS: Over 10.8 +/- 3.3 months, 24.3% patients received appropriate shocks (50.6%) or ATP only (49.4%), and 6.6% died. Mortality predictors were age (hazard ratio 1.07, 95% confidence interval 1.04-1.08, P <.0001), New York Heart Association class III/IV (3.50 [2.27-5.41]; P <.0001), coronary disease (3.08 [1.31-7.25]; P = .01), and cumulative VA (VT + FVT + VF) episodes shocked (1.20 [1.13, 1.29]; P <.0001). Beta-blockers (0.65, 0.46-0.92; P <.0001) and remote myocardial infarction (0.53, [0.38-0.76] P = .0004) predicted reduced risk. Since 92% of VT and all VF received a single therapy type (ATP and shocks, respectively), the effect of therapy on episode risk could not be established. For FVT (32% shocked, 68% ATP), episode and therapy effects could be uncoupled; ATP-terminated FVT did not increase episode mortality risk, whereas shocked FVT increased risk by 32%. Survival rates were highest among patients with no VA (93.8%) of ATP-only (94.7%) and lowest for shocked patients (88.4%). Monthly episode rates were 80% higher among shocked versus ATP-only patients. CONCLUSIONS: Shocked VA episodes are associated with increased mortality risk. Shocked patients have substantially higher VA episode burden and poorer survival compared with ATP-only-treated patients.

Acute defibrillation performance of a novel, non-transvenous shock pathway in adult ICD indicated patients.

OBJECTIVES: The purpose of this study was to evaluate the efficacy of a totally subcutaneous, anteroposterior defibrillation shock pathway using a long time-constant shock waveform that emulates a proposed device having approximately twice the capacitance and thus twice the available energy of traditional transvenous devices. BACKGROUND: A non-transvenous defibrillation system potentially offers advantages over a transvenous system including simplification of the implant procedure and reduction of the impact of device complications by eliminating the need to place a lead within the heart. Previous non-transvenous defibrillation efficacy studies have been reported using anterolateral and anterior-anterior shock vectors. An external anteroposterior shock vector has demonstrated superior efficacy compared to anterolateral shock vectors but a prospective study on an anteroposterior shock vector with implanted electrodes has not been previously reported. METHODS: The non-transvenous shock vector consisted of an anterior low pectorally-placed active can emulator electrode and a posterior subcutaneous coil electrode. The shock waveform was a biphasic with 50% tilt per phase and a time constant of decay of 12 ms. Defibrillation efficacy was characterized using a step-down defibrillation threshold protocol (35 J, 25 J, 15 J). RESULTS: A total of 33 patients with standard ICD indications were enrolled in the study with 32 fully completing the protocol. The patient population was 69% male, with a mean age of 59 +/- 12 years. Mean ejection fraction was 27 +/- 12%. Of the 32 patients tested, 26 patients (81%) were successfully defibrillated at 35 J or less, 18 patients were defibrillated at 25 J or less and 9 patients were successfully defibrillated at 15 J. CONCLUSIONS: Defibrillation using a long time-constant waveform delivered through an anteroposterior non-transvenous pathway including a pectoral active can emulator electrode and a posterior subcutaneous coil electrode is feasible with over 80% of patients defibrillated successfully using 35 J or less.

Optimizing implantable cardioverter-defibrillator treatment of rapid ventricular tachycardia: antitachycardia pacing therapy during charging.

BACKGROUND: Previous studies in implantable cardioverter-defibrillator (ICD) patients demonstrated the efficacy and safety of antitachycardia pacing (ATP) for rapid ventricular tachycardias (VT). To prevent shock delay in case of ATP failure, a new feature (ATP during charging) was developed to deliver ATP for rapid VT while charging for shock. OBJECTIVE: The purpose of this study was to determine the efficacy and safety of this new feature. METHODS: In a prospective, nonrandomized trial, patients with standard ICD indication received an EnTrust ICD. VT and ventricular fibrillation (VF) episodes were reviewed for appropriate detection, ATP success, rhythm acceleration, and related symptoms. RESULTS: In 421 implanted patients, 116 VF episodes occurred in 37 patients. Eighty-four (72%) episodes received ATP during or before charging. ATP prevented a shock in 58 (69%) of 84 episodes in 15 patients. ATP stopped significantly more monomorphic (77%) than polymorphic VTs (44%, P = .05). Five (6%) episodes accelerated after ATP but were terminated by the backup shock(s). No symptoms were related to ATP during charging. In four patients, 38 charges were saved by delivering ATP before charging. Of 98 induced VF episodes, 28% were successfully terminated by ATP versus 69% for spontaneous episodes (P <.01). CONCLUSION: Most VTs detected in the VF zone can be painlessly terminated by ATP delivered during charging, with a low risk of acceleration or symptoms. ATP before charging allows delivery of two ATP attempts before shock in the same time that would otherwise be required to deliver only one ATP plus a shock. It also offers potential battery energy savings.

The dilemma of ICD implant testing.

Ventricular fibrillation (VF) has been induced at implantable cardioverter defibrillator (ICD) implant to ensure reliable sensing, detection, and defibrillation. Despite its risks, the value was self-evident for early ICDs: failure of defibrillation was common, recipients had a high risk of ventricular tachycardia (VT) or VF, and the only therapy for rapid VT or VF was a shock. Today, failure of defibrillation is rare, the risk of VT/VF is lower in some recipients, antitachycardia pacing is applied for fast VT, and vulnerability testing permits assessment of defibrillation efficacy without inducing VF in most patients. This review reappraises ICD implant testing. At implant, defibrillation success is influenced by both predictable and unpredictable factors, including those related to the patient, ICD system, drugs, and complications. For left pectoral implants of high-output ICDs, the probability of passing a 10 J safety margin is approximately 95%, the probability that a maximum output shock will defibrillate is approximately 99%, and the incidence of system revision based on testing is < or = 5%. Bayes' Theorem predicts that implant testing identifies < or = 50% of patients at high risk for unsuccessful defibrillation. Most patients who fail implant criteria have false negative tests and may undergo unnecessary revision of their ICD systems. The first-shock success rate for spontaneous VT/VF ranges from 83% to 93%, lower than that for induced VF. Thus, shocks for spontaneous VT/VF fail for reasons that are not evaluated at implant. Whether system revision based on implant testing improves this success rate is unknown. The risks of implant testing include those related to VF and those related to shocks alone. The former may be due to circulatory arrest alone or the combination of circulatory arrest and shocks. Vulnerability testing reduces risks related to VF, but not those related to shocks. Mortality from implant testing probably is 0.1-0.2%. Overall, VF should be induced to assess sensing in approximately 5% of ICD recipients. Defibrillation or vulnerability testing is indicated in 20-40% of recipients who can be identified as having a higher-than-usual probability of an inadequate defibrillation safety margin based on patient-specific factors. However, implant testing is too risky in approximately 5% of recipients and may not be worth the risks in 10-30%. In 25-50% of ICD recipients, testing cannot be identified as either critical or contraindicated.

QRS duration does not predict occurrence of ventricular tachyarrhythmias in patients with implanted cardioverter-defibrillators.

OBJECTIVES: The aim of this study was to determine whether QRS duration (QRSd) correlates with occurrence of ventricular arrhythmia in patients with coronary disease (CAD) receiving implantable cardioverter-defibrillators (ICDs). BACKGROUND: A QRSd measured on a standard electrocardiograph (ECG) correlates with total mortality risk in CAD patients at high risk for sudden death; however, the relationship between QRSd and risk of ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]) is unclear. METHODS: PainFREE Rx II was a randomized trial, comparing efficacy of antitachycardia pacing versus shock therapy for VT/VF in patients receiving ICDs. We retrospectively correlated the QRSd and specific ECG conduction abnormalities on the 12-lead ECG at study entry with occurrence of VT/VF in 431 patients with CAD enrolled in the trial. RESULTS: The QRSd was < or =120 ms in 291 of 431 (68%) patients. Left bundle branch block (LBBB) was present in 65 patients, right bundle branch block (RBBB) in 48 patients, and nonspecific intraventricular conduction delay (IVCD) was present in 124 patients. Over 12 months' follow-up, VT/VF occurred in 95 (22%) patients (22% of patients with QRSd < or =120 ms vs. 23% of patients with QRSd >120 ms, p = NS). Patients with LBBB were less likely to experience at least one VT/VF episode than patients with QRSd <120 ms. Patients with RBBB and nonspecific IVCD did not differ from patients with narrow QRS complexes with regard to occurrence of tachycardias. CONCLUSIONS: The QRSd and ECG conduction abnormalities are not useful to predict ICD benefit in patients having the characteristics of our study population. The utility of QRSd to predict VT/VF events in patients with CAD requires further prospective evaluation.

Appropriate and inappropriate ventricular therapies, quality of life, and mortality among primary and secondary prevention implantable cardioverter defibrillator patients: results from the Pacing Fast VT REduces Shock ThErapies (PainFREE Rx II) trial.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) reduce mortality in primary and secondary prevention. Quality of life, mortality, appropriate therapies for specific ventricular rhythms, and inappropriate therapies for supraventricular tachycardia (SVT) were compared among 582 patients (primary prevention=248; secondary prevention=334) in PainFREE Rx II, a 634-patient prospective, randomized study of antitachycardia pacing or shocks for fast ventricular tachycardia (FVT). METHODS AND RESULTS: ICDs were programmed identically with 3 zones (ventricular tachycardia [VT] <188 bpm; FVT=188 to 250 bpm; ventricular fibrillation [VF] >250 bpm) but randomized to antitachycardia pacing or shock as initial therapy for FVT. All treated episodes with electrograms were adjudicated. Primary prevention patients had lower ejection fractions and more coronary artery disease. beta-Blocker use, antiarrhythmic drug use, and follow-up duration were similar. Over 11+/-3 months, 1563 treated episodes were classified as VT (n=740), FVT (n=350), VF (n=77), and SVT (n=396). The distribution of VT, FVT, and VF was not different between primary and secondary prevention patients (respectively, VT 52% versus 54%, FVT 35% versus 35%, and VF 14% versus 10%). More secondary prevention patients had appropriate therapies (26% versus 18%, P=0.02), but among these patients, the median number of episodes per patient was similar. Inappropriate therapies occurred in 15% of both groups and accounted for similar proportions of all detected and treated episodes (46% in primary prevention patients versus 34% in secondary prevention patients, P=0.09). Quality of life improved modestly in both groups, and mortality was similar. CONCLUSIONS: Primary prevention patients are slightly less likely to have appropriate therapies than secondary prevention patients, but episode density is similar among patients with appropriate therapies. SVT resulted in more than one third of therapies in both groups, but quality of life and mortality were similar.

Prospective randomized multicenter trial of empirical antitachycardia pacing versus shocks for spontaneous rapid ventricular tachycardia in patients with implantable cardioverter-defibrillators: Pacing Fast Ventricular Tachycardia Reduces Shock Therapies (PainFREE Rx II) trial results.

BACKGROUND: Successful antitachycardia pacing (ATP) terminates ventricular tachycardia (VT) up to 250 bpm without the need for painful shocks in implantable cardioverter-defibrillator (ICD) patients. Fast VT (FVT) >200 bpm is often treated by shock because of safety concerns, however. This prospective, randomized, multicenter trial compares the safety and utility of empirical ATP with shocks for FVT in a broad ICD population. METHODS AND RESULTS: We randomized 634 ICD patients to 2 arms-standardized empirical ATP (n=313) or shock (n=321)-for initial therapy of spontaneous FVT. ICDs were programmed to detect FVT when 18 of 24 intervals were 188 to 250 bpm and 0 of the last 8 intervals were >250 bpm. Initial FVT therapy was ATP (8 pulses, 88% of FVT cycle length) or shock at 10 J above the defibrillation threshold. Syncope and arrhythmic symptoms were collected through patient diaries and interviews. In 11+/-3 months of follow-up, 431 episodes of FVT occurred in 98 patients, representing 32% of ventricular tachyarrhythmias and 76% of those that would be detected as ventricular fibrillation and shocked with traditional ICD programming. ATP was effective in 229 of 284 episodes in the ATP arm (81%, 72% adjusted). Acceleration, episode duration, syncope, and sudden death were similar between arms. Quality of life, measured with the SF-36, improved in patients with FVT in both arms but more so in the ATP arm. CONCLUSIONS: Compared with shocks, empirical ATP for FVT is highly effective, is equally safe, and improves quality of life. ATP may be the preferred FVT therapy in most ICD patients.

Incidence and characteristics of type-2 breaks in response to antitachycardia pacing therapy in implantable cardioverter defibrillator patients.

INTRODUCTION: Antitachycardia pacing (ATP) effectively treats monomorphic ventricular tachycardia (VT). The VT may cease immediately upon ATP completion (type-1 break), or it may persist or change to another tachyarrhythmia for one or more beats before termination (type-2 break). We investigated the prevalence and characteristics of type-2 breaks in ICD patients. METHODS AND RESULTS: We analyzed VT episodes with stored electrograms that had at least one ATP therapy delivered in PainFREE Rx trial, a multicenter trial with 220 coronary artery disease patients. Further subanalysis was performed by classifying the VT as slow or fast based on the cycle length (CL); slow VT: CL >320 ms, fast VT: 240 < or =CL < or =320 ms. To assess the effect of ATP on VT, comparison was performed of pre-ATP and post-ATP CL variability, average CL, and morphology. A total of 514 episodes (264 slow VT and 250 fast VT) were analyzed. The burst ATP terminated 457 (89%; 239 slow VT and 218 fast VT) of 514 episodes. Forty five (10%) episodes in 18 (32%) patients had type-2 breaks. The mean number of beats during type-2 breaks was 5.4 +/- 3.1 (median 4). The mean time for episode termination measured from the end of ATP to return of first sinus/paced beat was 2.9 +/- 1.2 seconds (median 2.6). The VT CL variability increased by 150% after ATP delivery. The ATP affected either VT CL or morphology, or both of 36 (80%) type-2 breaks (9% accelerated, 47% decelerated, 22% changed in morphology only). Among the 9 (20%) episodes that remained unchanged in morphology and CL, four episodes (9%) were unaffected by ATP. CONCLUSION: Approximately 10% of VT episodes that were successfully terminated with burst ATP therapy had type-2 breaks. Type-2 breaks are associated with an increase in CL variability. Approximately 9% of all type-2 episodes may be spontaneously terminating nonsustained VT given that ATP did not affect these episodes in any way.

Prospective randomized comparison of 65%/65% versus 42%/42% tilt biphasic waveform on defibrillation thresholds in humans.

BACKGROUND: The waveform tilt of biphasic shocks yielding the lowest defibrillation threshold (DFT) is not well defined. Some evidence indicates that tilts less than 65% may improve DFTs. METHODS: In 57 patients undergoing ICD implantation, DFTs were determined with truncated exponential biphasic waveform tilts at 65%/65% and at 42%/42%. An external defibrillator with custom software was used for testing. The effective capacitance of the defibrillator was 132-microF for both waveforms. DFTs were determined using a binary search method starting with 12 Joules (J). Patients were randomly assigned to initial testing with either one of the two tilts. Thirty patients (Group 1) were tested with a two electrode (active can to RV coil, or SVC coil to RV coil) and 27 patients (Group 2) were tested with a three electrode system (subcutaneous patch or active can + SVC coil to RV coil). RESULTS: Groups 1 and 2 did not differ in age, ejection fraction or antiarrhythmic medications. Group 1 delivered energy DFTs were 10.1 +/- 5.5 J with the 65%/65% tilt and 10.1 +/- 5.9 J for the 42%/42% tilt (p = 0.92). In group 2 the average DFT for the 65%/65% tilt was 8.4 +/- 5.7 J and for the 42%/42% tilt was 8.1 +/- 5.3 J (p = 0.70). There were no significant differences in DFTs for either group. The system impedance for Group 1 was 64 +/- 12 ohms and for Group 2 was 39 +/- 6 ohms (p < 0.0001). CONCLUSIONS: We found no differences in DFTs between 65%/65% tilt and 42%/42% tilt using either 2- or 3-electrode defibrillation systems. Further research is needed to optimize waveforms in order to minimize DFTs, which will result in smaller ICDs and/or greater safety margins for defibrillation.