The AF-FICIENT magnetic resonance imaging and endoscopy safety substudy: A visually guided radiofrequency balloon ablation catheter for pulmonary vein isolation.

BACKGROUND: Early experience with a novel multielectrode saline-irrigated radiofrequency balloon (RFB) catheter with an integrated camera system found that it was safe and effective in performing single-shot pulmonary vein isolation (PVI) for atrial fibrillation. OBJECTIVE: The purpose of this study was to further assess potential treatment risks by looking for subclinical events. METHODS: The study was performed at 2 sites. Patients underwent PVI by RFB. A control group underwent conventional point-by-point radiofrequency ablation. Stroke scale questionnaire and brain magnetic resonance imaging (MRI) were performed before and after the ablation procedure, and esophageal endoscopy was performed after the procedure in RFB patients only. RESULTS: We enrolled 27 patients in the RFB group and 15 patients in the control group. The RFB and control groups were well matched [predominantly male: 62% vs 53%; CHA2DS2-VASc score: 1.9 ± 1.3 vs 1.5 ± 1.6; mean age 60 years in both groups]. All patients underwent successful ablation and completed study assessments. Clinically silent, new MRI diffusion weighted imaging cerebral lesions were observed in 8 patients (30%) in the RFB group and 1 patient (7%) in the control group, and 11 susceptibility weighted imaging lesions in the RFB group and 1 in the control group. Endoscopy showed a minor thermal injury in 1 patient in the RFB group. CONCLUSION: An increased rate of clinically silent cerebral events was seen in the RFB group. A low rate of esophageal thermal injury was observed.

A Novel Visually Guided Radiofrequency Balloon Ablation Catheter for Pulmonary Vein Isolation: One-Year Outcomes of the Multicenter AF-FICIENT I Trial.

[Figure: see text].

Automated rhythm-based control of radiofrequency ablation close to the atrioventricular node: Preclinical, animal, and first-in-human testing.

BACKGROUND: The risk of heart block during radiofrequency ablation of atrioventricular (AV) nodal reentrant tachycardia and septal accessory pathways is minimized by rapidly ceasing ablation in response to markers of risk, such as atrioventricular dissociation, fast junctional rhythm, PR interval prolongation, or 2 consecutive atrial or ventricular depolarizations. Currently this is done manually. OBJECTIVES: The objectives of this study were to build and test a control system able to monitor cardiac rhythm and automatically terminate ablation energy when required. METHODS: The device was built from off-shelf componentry. Preclinical testing involved real-time input of electrogram/electrocardiogram data from 209 ablation procedures (20 patients) over slow (n = 19) and fast (n = 1) AV nodal pathways. The device response speed was compared with the human response speed. The device's ability to prevent heart block was tested in 5 sheep. First-in-human testing was then performed in 12 patients undergoing AV nodal reentrant tachycardia ablation. RESULTS: Risk conditions necessitating shutoff of ablation (200 total; 111 preclinical and 89 first-in-human) were detected by the device with 100% sensitivity and 94% specificity, automatically terminating ablation while still allowing successful ablation in all patients. Device shutoff of ablation was always faster than human response (median difference 1.24 seconds). In each of 5 sheep, 40 consecutive attempts to cause heart block by ablating over the His bundle were unsuccessful because of automatic shutoff in response to rhythm change. CONCLUSION: Automated shutoff of ablation close to the AV node in response to markers of the risk of heart block is feasible with high accuracy as well as faster response than human response. The system may improve the safety of ablation near the AV node by preventing heart block.

First-in-Human Chronic Implant Experience of the Substernal Extravascular Implantable Cardioverter-Defibrillator.

OBJECTIVES: The aim of this study was to evaluate the safety and performance of an extravascular (EV) implantable cardioverter-defibrillator (ICD). BACKGROUND: Limitations of existing transvenous and subcutaneous ICD systems include lead reliability and morbidity issues associated with ICD lead implantation in the vasculature or lack of pacing therapies (e.g., antitachycardia pacing) in subcutaneous systems. The EV defibrillator uses a novel substernal lead placement to address these limitations. METHODS: This was a prospective, nonrandomized, chronic pilot study conducted at 4 centers in Australia and New Zealand. Participants were 21 patients referred for ICD implantation. Patients received EV ICD systems. Data collection included major systemic and procedural adverse events, defibrillation testing at implantation, and sensing and pacing thresholds. RESULTS: Among 20 patients who underwent successful implantation, the median defibrillation threshold was 15 J, and 90% passed defibrillation testing with a ≥10-J safety margin. Mean R-wave amplitude was 3.4 ± 2.0 mV, mean ventricular fibrillation amplitude was 2.8 ± 1.7 mV, and pacing was successful in 95% at ≤10 V. There were no intraprocedural complications. Two patients have undergone elective chronic system removal since hospital discharge. In the 15 patients presently implanted, the systems are stable in long-term follow-up. CONCLUSIONS: This first-in-human evaluation of an EV ICD demonstrated the feasibility of substernal lead placement, defibrillation, and pacing with a chronically implanted system. There were no acute major complications, and pacing, defibrillation, and sensing performance at implantation were successful in most patients. (Extravascular ICD Pilot Study [EV ICD]; NCT03608670).

Two major earthquakes in Christchurch were not associated with increased ventricular arrhythmias: Analysis of implanted defibrillator diagnostics.

AIM: Christchurch, New Zealand, experienced two major earthquakes on 4th September 2010 and 22nd February 2011. Previous studies have demonstrated that earthquakes are associated with sudden cardiac deaths. Whilst myocardial ischemia would contribute to this, ventricular arrhythmia triggered by stress has also been suggested. We aim to study the impact of the two earthquakes on ventricular arrhythmia events. METHODS: We conducted a retrospective review of all patients resident in the earthquake zone with implantable defibrillators. Ventricular arrhythmia requiring therapy and non-sustained events were recorded from the period of 30 days before thru 30 days after the two earthquakes. Weekly event rates were calculated and compared using log rank analysis. Results are expressed as mean (range), significance was determined at the <0.05 level. RESULTS: For the 211 patients who were exposed to the 2010 earthquake, there was no difference in the proportion of patients free of therapy, either Shock or ATP (0.943 before and 0.933 after the earthquake, p = 0.85, ns). Similarly, there was no significant increase in events requiring therapy in the 236 patients exposed to the 2011 earthquake (0.957 before and 0.961 after the earthquake, p = 0.80, ns). We identified one patient who required multiple therapy for ventricular tachycardia immediately following both earthquakes. CONCLUSION: The two Christchurch earthquakes were not associated with an increase in the event rate of either sustained or non-sustained ventricular arrhythmias in our patients. We identified only a single patient who had arrhythmic storms immediately following the earthquakes.

High-Resolution Infrared Thermography of Esophageal Temperature During Radiofrequency Ablation of Atrial Fibrillation.

BACKGROUND: Catheter ablation for atrial fibrillation has potential to cause esophageal thermal injury. Esophageal temperature monitoring during ablation is commonly used; however, it has not eliminated thermal injuries, possibly because conventional sensors have poor spatial sampling and response characteristics. To enhance understanding of temperature dynamics that may underlie esophageal injury, we tested a high-resolution, intrabody, infrared thermography catheter to continuously image esophageal temperatures during ablation. METHODS AND RESULTS: Atrial fibrillation ablation patients were instrumented with a flexible, 9F infrared temperature catheter inserted nasally (n=8) or orally (n=8) into the esophagus adjacent to the left atrium. Ablation was performed while the infrared catheter continuously recorded surface temperatures from 7680 points per second circumferentially over a 6-cm length of esophagus. Physicians were blinded to temperature data. Endoscopy was performed within 24 hours to document esophageal injury. Thermal imaging showed that most patients (10/16) experienced ≥1 events where peak esophageal temperature was >40°C. Three patients experienced temperatures >50°C; and 1 experienced >60°C. Analysis of temperature data for each subject's maximum thermal event revealed high gradients (2.3±1.4°C/mm) and rates of change (1.5±1.3°C/s) with an average length of esophageal involvement of 11.0±5.4 mm. Endoscopy identified 3 distinct thermal lesions, all in patients with temperatures >50°C; all resolved within 2 weeks. CONCLUSIONS: Infrared thermography provided dynamic, high-resolution mapping of esophageal temperatures during cardiac ablation. Esophageal thermal injury occurred with temperatures >50°C and was associated with large spatiotemporal gradients. Additional studies are warranted to determine the relationships between thermal parameters and esophageal injury.

Thoracic impedance measures tissue characteristics in the vicinity of the electrodes, not intervening lung water: implications for heart failure monitoring.

The rationale for intrathoracic impedance (Z) detection of worsening heart failure (HF) presupposes that changes in Z reflect changes in pulmonary congestion, but is confounded by poor specificity in clinical trials. We therefore tested the hypothesis that Z is primarily affected by tissue/water content in proximity to electrodes rather than by lung water distribution between electrodes through the use of a new computational model for deriving the near-field impedance contributions from the various electrodes. Six sheep were implanted with a left atrial pressure (LAP) monitor and a cardiac resynchronization therapy device which measured Z from six vectors comprising of five electrodes. The vector-based Z was modelled as the summation of the near-field impedances of the two electrodes forming the vector. During volume expansion an acute increase in LAP resulted in simultaneous reductions in the near-field impedances of the intra-cardiac electrodes, while the subcutaneous electrode showed several hours of lag (all p<0.001). In contrast, during the simulated formation of device-pocket edema (induced by fluid injection) the near-field impedance of the subcutaneous electrode had an instantaneous response, while the intra-cardiac electrodes had a minimal inconsistent response. This study suggests that the primary contribution to the vector based Z is from the tissue/water in proximity to the individual electrodes. This novel finding may help explain the limited utility of Z for detecting worsening HF.

Electrophysiology assessment and radiofrequency ablation of arrhythmias in adult patients with congenital heart defects: the Christchurch experience.

INTRODUCTION: Adults with congenital heart disease (CHD) frequently have cardiac arrhythmias, many of which are best treated with radiofrequency ablation (RFA). We present our experience in this group. METHODS: Retrospective chart based review of diagnosis, arrhythmia type, results of cardiac electrophysiological assessment, and procedural and long-term clinical success of radiofrequency ablation. RESULTS: Forty-five patients were identified with CHD and arrhythmias undergoing RFA; including surgically repaired atrial septal defects (21), Ebstein's anomaly (12), repaired transposition of the great arteries (3), repaired Tetralogy of Fallot (4), repaired ventricular septal defect (3), repaired coarctation (1) and unrepaired anomalous pulmonary venous anatomy (1). Arrhythmias were atrial flutter (24), atrial fibrillation (1), atrial tachycardia (3), atrioventricular nodal re-entrant tachycardia (5), and atrioventricular re-entrant tachycardia (12). Procedural success was ultimately obtained in 36 patients, with 6 having unsuccessful ablation and 3 an undetermined result. Twelve patients required a repeat procedure. One patient required a third procedure and had insertion of permanent pacemaker and atrioventricular nodal ablation. With follow-up (range 2-264 months) 31 patients (69%) remained in sinus rhythm, 9 have developed atrial fibrillation, 3 are in atrial flutter or atrial tachycardia, 1 patient reports ongoing palpitations with no documented arrhythmia and 1 patient has died. Procedural complications were major venous access bleeding (2), transient heart block during slow pathway ablation with late complete heart block (1). CONCLUSIONS: The majority of arrhythmias in adult patients with congenital heart defects can be successfully treated with radiofrequency ablation at a relatively low risk.

Effects of AV delay and VV delay on left atrial pressure and waveform in ambulant heart failure patients: insights into CRT optimization.

BACKGROUND: We hypothesized that left atrial pressure (LAP) obtained by a permanent implantable sensor is sensitive to changes in cardiac resynchronization therapy (CRT) settings and could guide CRT optimization to improve the response rate. We investigated the effect of CRT optimization on LAP and its waveform parameters in ambulant heart failure (HF) patients. METHODS: CRT optimization was performed in eight ambulant HF patients, using echocardiography as reference. LAP waveform was acquired at each of eight atrioventricular (AV) intervals and five inter-ventricular (VV) intervals. Selected waveform parameters were also evaluated for their sensitivity to CRT changes and agreement with echocardiography-guided optimal settings. RESULTS: Optimal AV and VV intervals varied considerably between patients. All patients exhibited significant changes in waveform morphology with AV optimization. Optimal AV delay determined from echocardiography ranged between 140 ms and 225 ms. Mean LAP tended to be lower at optimal setting 14 ± 3 mmHg compared to shorter (<100 ms) or longer (>160 ms) AV settings (P = 0.16). There were clear trends to smaller peak a-wave (P = 0.11) and gentler positive a-slope (P = 0.15) and positive v-slope (P = 0.09) with longer AV delays. Mean LAP and negative v-wave slope correlated well with echo-guided optimal setting, r = 0.91 (P = 0.001) and 0.79 (P = 0.03), respectively. No significant effects on LAP or waveform were seen during VV optimization. CONCLUSIONS: LAP and its waveform changes considerably with AV optimization. There is good agreement between echo-guided optimal setting and LAP. LAP could provide an objective guide to CRT optimization. (Clinical Trial Registry information: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00632372).

Comparative pathology of an implantable left atrial pressure sensor.

A left atrial pressure (LAP) monitoring system was developed for guiding the management of patients with heart failure. The LAP sensor is implanted into the left atrium via transseptal catheterization and affixed to the interatrial septum by nitinol anchors. The long-term safety of permanent implantation of the LAP sensor in patients was evaluated based on the comparative pathology in animals. Tissue specimens of the LAP sensor from 7 patients, 49 canines, and 14 ovine were examined for thrombosis and tissue overgrowth. Implant duration ranged from 22 to 1,686 days. Gross examination showed minimal-to-moderate tissue overgrowth with no evidence of migration, erosion, or perforation. There was no excessive host-to-device reaction or active thrombogenesis in any of the subjects that followed the antithrombotic therapy protocol. Micro-computed tomography scanning confirmed the structural integrity of the device. Low vacuum scanning electron microscopy and histology showed neoendocardial tissue overgrowth with no inflammation or fibrin. The pathology of both animal models was found to closely approximate the pathology in humans and favorably supports the long-term safety of the device.

Geographic, ethnic and socioeconomic factors influencing access to implantable cardioverter defibrillators (ICDs) in New Zealand.

BACKGROUND: We examined equity of access to implanted cardioverter defibrillators (ICDs) in New Zealand in 2010 by district health board (DHB), ethnicity and socioeconomic status. METHODS: All new ICD recipients in 2010 were examined according to home district health board, ethnicity according to the national health database, and socioeconomic status using the NZDep index. RESULTS: During 2010, 352 new ICDs were implanted nationwide, giving an overall implantation rate of 80.6/million. However, implant rates varied significantly across the 20 DHBs with the highest implant rate observed in Tairawhiti at 192.3/million, and the lowest at 22/million in the Nelson region. There was also significant variation in implant rate by ethnicity, with Maori ethnicity at an implant rate of 114/million, European patients at 83/million, Pacific Island patients at 47/million and Asian patients an implant rate of 32/million. There was no significant difference in number of implants by socioeconomic decile. CONCLUSIONS: The variance in implantation rate by district health board and by ethnicity suggests that access to ICD therapy is not equitable in New Zealand. Investigation into causes of inequity of access is required.

Pulmonary vein ablation for atrial fibrillation: the Christchurch, New Zealand experience.

AIMS: To report the long-term results following percutaneous pulmonary vein ablation (PVA) for atrial fibrillation (AF) at Christchurch Hospital. METHODS: A retrospective observational audit review of outcomes. The sample population included all patients identified as having undergone percutaneous radiofrequency ablation of multiple pulmonary veins at Christchurch Hospital, from the first procedure performed on 29 September 2001 until 15 December 2009. RESULTS: A total of 187 patients underwent pulmonary vein ablation. The patient population was predominantly younger (mean age 51) and male (83%) with no important comorbidity. Following a single procedure only, the chance of remaining free of AF at 12 months was 0.74 for patients with paroxysmal AF (PAF) and 0.60 for patients with persistent AF (PsAF). 52 patients (28%) underwent a repeat procedure within 12 months of their index ablation owing to early recurrence of AF. 5-year survival free of clinical AF when analysed following these early repeat procedures, if required, was 0.74 and 0.56 for PAF and PsAF patients respectively. Complications occurred following 6% of procedures and were serious in 2.5%. New atrial flutter developed in 6% of patients. CONCLUSIONS: PVA is an effective treatment for AF, with better outcomes in patients with paroxysmal atrial fibrillation. However, as it carries a significant risk, we recommend that its application be reserved for patients with highly symptomatic, medication-refractory disease.

Prediction of cardiac rhythm 1 year following cardioversion for atrial fibrillation.

BACKGROUND: There is little recent information regarding outcome and its determinants following cardioversion (CV) for atrial fibrillation (AF) or flutter. This study aims to help improve prediction of cardiac rhythm outcome following CV for AF. METHODS: Cardiac rhythm at 6 weeks and 12 months was documented following elective (EC; n=496) or immediate (IC; n=52) cardioversion for AF or atrial flutter in a single referral centre. RESULTS: 65 and 58% of IC patients remained in sinus rhythm (SR) 6 weeks and 1 year after CV (respectively) compared with 43% and 30% in EC patients (P<0.001). Independent positive predictors of SR 6 weeks after cardioversion included amiodarone therapy (OR 2.04 [1.28-3.33], P<0.01) and atrial flutter (OR 1.85 [1.09-3.13], P<0.05). Negative predictors included the need for >1 shock to achieve SR (OR 1.61 [1.12-2.37], P=0.011) and arrhythmia duration, (OR 0.96 [0.95-0.97], P<0.001). At 1 year, amiodarone, duration of arrhythmia and the need for >1 shock remained independent predictors of rhythm. CONCLUSIONS: The number of shocks required to achieve SR is a newly demonstrated independent predictor of rhythm outcome after elective CV.

Serial Doppler echocardiography and tissue Doppler imaging in the detection of elevated directly measured left atrial pressure in ambulant subjects with chronic heart failure.

OBJECTIVES: This study sought to determine the accuracy of Doppler echocardiography and tissue Doppler imaging (TDI) measurements in detecting elevated left atrial pressure (LAP) in ambulant subjects with chronic heart failure using directly measured LAP as the reference. BACKGROUND: Echocardiographic indexes including the ratio of transmitral to annular early diastolic velocities (E/e') may identify raised invasively measured left ventricular filling pressures when tested in cross-sectional studies in some populations. The accuracy of these indexes when measured sequentially remains untested. We determined the accuracy of Doppler echocardiography and TDI measurements in detecting elevated directly measured LAP in ambulant subjects with stable chronic heart failure. METHODS: Fifteen patients with New York Heart Association functional class II to III heart failure and a permanently implanted direct LAP monitoring device underwent serial echocardiography. Simultaneous resting mean LAP, Doppler mitral inflow, mitral annular TDI, and pulmonary venous inflow velocities were obtained on each occasion. Receiver-operator characteristic curve analysis was used to compare the accuracy of the Doppler variables to detect an elevated device LAP ≥15 and ≥20 mm Hg. RESULTS: The patients (13 men, mean age: 71 years, mean left ventricular ejection fraction: 32 ± 12%) underwent 60 simultaneous echocardiographic studies and LAP measurements with a median of 4 (1 to 7) studies per patient. Mean LAP was 16.9 (range 5 to 39 mm Hg) at echocardiography (n = 60). E/e' had the greatest accuracy for detection of LAP ≥15 mm Hg with an area beneath the receiver-operator characteristic curve >0.9. In comparison, area under the curve for mitral E velocity and mitral E/A were 0.77 and 0.76, respectively (p < 0.008 vs. E/e' medial and average). CONCLUSIONS: Single and serial measurements of mitral inflow and mitral annular TDI velocities (E/e') can reliably detect raised directly measured LAP in ambulant subjects with compensated chronic heart failure. (Hemodynamically Guided Home Self-Therapy in Severe Heart Failure Patients [HOMEOSTASIS]; NCT00547729).

An unmet need for implantable cardioverter-defibrillators in New Zealand.

AIMS: This study examined the prior history of all patients presenting to the regional ambulance service with community cardiac arrest to determine what proportion of these patients had prior indications for implanted cardioverter-defibrillator (ICD) therapy. METHODS AND RESULTS: We reviewed the medical history of all adult patients presenting to our regional ambulance service with cardiac arrest between 1 June 2007 and 31 May 2008 (n= 144). Patients were classified as either not having an ICD indication, having a possible ICD indication, or having an ICD indication by two electrophysiologists. Eighty-seven patients (60%) had no pre-existing indication for an ICD. Twenty-two patients (15%) had a possible indication for an ICD but required further investigation to confirm this. This group consisted of 6 patients (4%) with previously documented left ventricular ejection fraction <35%, but without a measurement in the last 12 months, 14 patients (10%) with heart failure (n= 10) or syncope (n= 4) without appropriate investigations, and 2 patients with an ICD indication but with co-morbidities that required further investigation. Thirty-five patients (24%) had a documented indication for an ICD. In 11 (8%) there was no evidence of a contraindication, in 3 (2%) alternative therapy was judged more appropriate, and in 21 (15%) contraindications to ICD implantation were also present. Addition of the 11 patients with an ICD indication and the 6 patients with a documented indication requiring updated measurement, 17 patients (12%) had a prior documented ICD indication but had not been referred for this therapy. CONCLUSIONS: Our observation that 12% of sudden cardiac arrest patients had prior indications for an ICD demonstrates that there is an unmet need for ICDs in New Zealand.

Direct left atrial pressure monitoring in severe heart failure: long-term sensor performance.

We report the stability, accuracy, and development history of a new left atrial pressure (LAP) sensing system in ambulatory heart failure (HF) patients. A total of 84 patients with advanced HF underwent percutaneous transseptal implantation of the pressure sensor. Quarterly noninvasive calibration by modified Valsalva maneuver was achieved in all patients, and 96.5% of calibration sessions were successful with a reproducibility of 1.2 mmHg. Absolute sensor drift was maximal after 3 months at 4.7 mmHg (95% CI, 3.2-6.2 mmHg) and remained stable through 48 months. LAP was highly correlated with simultaneous pulmonary wedge pressure at 3 and 12 months (r = 0.98, average difference of 0.8 ± 4.0 mmHg). Freedom from device failure was 95% (n = 37) at 2 years and 88% (n = 12) at 4 years. Causes of failure were identified and mitigated with 100% freedom from device failure and less severe anomalies in the last 41 consecutive patients (p = 0.005). Accurate and reliable LAP measurement using a chronic implanted monitoring system is safe and feasible in patients with advanced heart failure.

Monitoring of heart failure: comparison of left atrial pressure with intrathoracic impedance and natriuretic peptide measurements in an experimental model of ovine heart failure.

Monitoring of HF (heart failure) with intracardiac pressure, intrathoracic impedance and/or natriuretic peptide levels has been advocated. We aimed to investigate possible differences in the response patterns of each of these monitoring modalities during HF decompensation that may have an impact on the potential for early therapeutic intervention. Six sheep were implanted with a LAP (left atrial pressure) sensor and a CRT-D (cardiac resynchronization therapy defibrillator) capable of monitoring impedance along six lead configuration vectors. An estimate of ALAP (LAP from admittance) was determined by linear regression. HF was induced by rapid ventricular pacing at 180 and 220 bpm (beats/min) for a week each, followed by a third week with daily pacing suspensions for increasing durations (1-5 h). Incremental pacing induced progressively severe HF reflected in increases in LAP (5.9 ± 0.4 to 24.5 ± 1.6 mmHg) and plasma atrial (20 ± 3 to 197 ± 36 pmol/l) and B-type natriuretic peptide (3.7 ± 0.7 to 32.7 ± 5.4 pmol/l) (all P<0.001) levels. All impedance vectors decreased in proportion to HF severity (all P<0.001), with the LVring (left ventricular)-case vector correlating best with LAP (r2=0.63, P<0.001). Natriuretic peptides closely paralleled rapid acute changes in LAP during alterations in pacing (P<0.001), whereas impedance changes were delayed relative to LAP. ALAP exhibited good agreement with LAP. In summary, impedance measured with an LV lead correlates significantly with changes in LAP, but exhibits a delayed response to acute alterations. Natriuretic peptides respond rapidly to acute LAP changes. Direct LAP, impedance and natriuretic peptide measurements all show promise as early indicators of worsening HF. ALAP provides an estimate of LAP that may be clinically useful.

An entirely subcutaneous implantable cardioverter-defibrillator.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) prevent sudden death from cardiac causes in selected patients but require the use of transvenous lead systems. To eliminate the need for venous access, we designed and tested an entirely subcutaneous ICD system. METHODS: First, we conducted two short-term clinical trials to identify a suitable device configuration and assess energy requirements. We evaluated four subcutaneous ICD configurations in 78 patients who were candidates for ICD implantation and subsequently tested the best configuration in 49 additional patients to determine the subcutaneous defibrillation threshold in comparison with that of the standard transvenous ICD. Then we evaluated the long-term use of subcutaneous ICDs in a pilot study, involving 6 patients, which was followed by a trial involving 55 patients. RESULTS: The best device configuration consisted of a parasternal electrode and a left lateral thoracic pulse generator. This configuration was as effective as a transvenous ICD for terminating induced ventricular fibrillation, albeit with a significantly higher mean (+/-SD) energy requirement (36.6+/-19.8 J vs. 11.1+/-8.5 J). Among patients who received a permanent subcutaneous ICD, ventricular fibrillation was successfully detected in 100% of 137 induced episodes. Induced ventricular fibrillation was converted twice in 58 of 59 patients (98%) with the delivery of 65-J shocks in two consecutive tests. Clinically significant adverse events included two pocket infections and four lead revisions. After a mean of 10+/-1 months, the device had successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia. CONCLUSIONS: In small, nonrandomized studies, an entirely subcutaneous ICD consistently detected and converted ventricular fibrillation induced during electrophysiological testing. The device also successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia. (ClinicalTrials.gov numbers, NCT00399217 and NCT00853645.)