Phase I/II Trial of Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia.

BACKGROUND: Case studies have suggested the efficacy of catheter-free, electrophysiology-guided noninvasive cardiac radioablation for ventricular tachycardia (VT) using stereotactic body radiation therapy, although prospective data are lacking. METHODS: We conducted a prospective phase I/II trial of noninvasive cardiac radioablation in adults with treatment-refractory episodes of VT or cardiomyopathy related to premature ventricular contractions (PVCs). Arrhythmogenic scar regions were targeted by combining noninvasive anatomic and electric cardiac imaging with a standard stereotactic body radiation therapy workflow followed by delivery of a single fraction of 25 Gy to the target. The primary safety end point was treatment-related serious adverse events in the first 90 days. The primary efficacy end point was any reduction in VT episodes (tracked by indwelling implantable cardioverter defibrillators) or any reduction in PVC burden (as measured by a 24-hour Holter monitor) comparing the 6 months before and after treatment (with a 6-week blanking window after treatment). Health-related quality of life was assessed using the Short Form-36 questionnaire. RESULTS: Nineteen patients were enrolled (17 for VT, 2 for PVC cardiomyopathy). Median noninvasive ablation time was 15.3 minutes (range, 5.4-32.3). In the first 90 days, 2/19 patients (10.5%) developed a treatment-related serious adverse event. The median number of VT episodes was reduced from 119 (range, 4-292) to 3 (range, 0-31; P<0.001). Reduction was observed for both implantable cardioverter defibrillator shocks and antitachycardia pacing. VT episodes or PVC burden were reduced in 17/18 evaluable patients (94%). The frequency of VT episodes or PVC burden was reduced by 75% in 89% of patients. Overall survival was 89% at 6 months and 72% at 12 months. Use of dual antiarrhythmic medications decreased from 59% to 12% ( P=0.008). Quality of life improved in 5 of 9 Short Form-36 domains at 6 months. CONCLUSIONS: Noninvasive electrophysiology-guided cardiac radioablation is associated with markedly reduced ventricular arrhythmia burden with modest short-term risks, reduction in antiarrhythmic drug use, and improvement in quality of life. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02919618.

Noninvasive Cardiac Radiation for Ablation of Ventricular Tachycardia.

BACKGROUND: Recent advances have enabled noninvasive mapping of cardiac arrhythmias with electrocardiographic imaging and noninvasive delivery of precise ablative radiation with stereotactic body radiation therapy (SBRT). We combined these techniques to perform catheter-free, electrophysiology-guided, noninvasive cardiac radioablation for ventricular tachycardia. METHODS: We targeted arrhythmogenic scar regions by combining anatomical imaging with noninvasive electrocardiographic imaging during ventricular tachycardia that was induced by means of an implantable cardioverter-defibrillator (ICD). SBRT simulation, planning, and treatments were performed with the use of standard techniques. Patients were treated with a single fraction of 25 Gy while awake. Efficacy was assessed by counting episodes of ventricular tachycardia, as recorded by ICDs. Safety was assessed by means of serial cardiac and thoracic imaging. RESULTS: From April through November 2015, five patients with high-risk, refractory ventricular tachycardia underwent treatment. The mean noninvasive ablation time was 14 minutes (range, 11 to 18). During the 3 months before treatment, the patients had a combined history of 6577 episodes of ventricular tachycardia. During a 6-week postablation "blanking period" (when arrhythmias may occur owing to postablation inflammation), there were 680 episodes of ventricular tachycardia. After the 6-week blanking period, there were 4 episodes of ventricular tachycardia over the next 46 patient-months, for a reduction from baseline of 99.9%. A reduction in episodes of ventricular tachycardia occurred in all five patients. The mean left ventricular ejection fraction did not decrease with treatment. At 3 months, adjacent lung showed opacities consistent with mild inflammatory changes, which had resolved by 1 year. CONCLUSIONS: In five patients with refractory ventricular tachycardia, noninvasive treatment with electrophysiology-guided cardiac radioablation markedly reduced the burden of ventricular tachycardia. (Funded by Barnes-Jewish Hospital Foundation and others.).

Ablation using 3D maps adjusted for spatial displacement of premature ventricular complexes relative to sinus beats: Improving precision by correcting for the shift.

INTRODUCTION: Point-by-point 3-dimensional (3D) electroanatomic mapping (EAM) is used to guide catheter ablation of premature ventricular complexes (PVCs). Due to the differences in the spatial excursion of the cardiac chambers during cardiac cycles in PVCs vs sinus rhythm, the 3D location registration during PVCs is shifted relative to sinus rhythm. In this study, we describe our strategy to adjust for this displacement in real-time during PVC mapping. METHODS AND RESULTS: We report 21 patients who underwent catheter ablation of 23 unique PVCs using Carto 3. After mapping the earliest site for each PVC, we reregistered its 3D location to a sinus rhythm beat in real-time, and used this to guide ablation lesion delivery. The PVC earliest location was spatially displaced from the successful ablation lesion in sinus rhythm by average 6.7 (range 3.3-13.0) mm. Offline, we subsequently analyzed 25 unique chamber maps and 606 PVC points. For each point, we reregistered the 3D location to a preceding sinus beat. The PVC points were displaced from sinus rhythm location by average 4.4 (0.3-13.7) mm. The maximally displaced point for each chamber was 7.7 (4.7-13.7) mm. The general direction of shift during PVC was leftward and inferior relative to sinus rhythm. CONCLUSIONS: During electroanatomic mapping of PVCs using the Carto 3 system, points mapped during PVCs are spatially displaced relative to their location in sinus rhythm. Electrophysiologists should recognize this phenomenon and account for the shift to guide accurate delivery of ablation lesions.

Cardiac electrophysiological substrate underlying the ECG phenotype and electrogram abnormalities in Brugada syndrome patients.

BACKGROUND: Brugada syndrome (BrS) is a highly arrhythmogenic cardiac disorder, associated with an increased incidence of sudden death. Its arrhythmogenic substrate in the intact human heart remains ill-defined. METHODS AND RESULTS: Using noninvasive ECG imaging, we studied 25 BrS patients to characterize the electrophysiological substrate and 6 patients with right bundle-branch block for comparison. Seven healthy subjects provided control data. Abnormal substrate was observed exclusively in the right ventricular outflow tract with the following properties (in comparison with healthy controls; P<0.005): (1) ST-segment elevation and inverted T wave of unipolar electrograms (2.21±0.67 versus 0 mV); (2) delayed right ventricular outflow tract activation (82±18 versus 37±11 ms); (3) low-amplitude (0.47±0.16 versus 3.74±1.60 mV) and fractionated electrograms, suggesting slow discontinuous conduction; (4) prolonged recovery time (381±30 versus 311±34 ms) and activation-recovery intervals (318±32 versus 241±27 ms), indicating delayed repolarization; (5) steep repolarization gradients (Δrecovery time/Δx=96±28 versus 7±6 ms/cm, Δactivation-recovery interval/Δx=105±24 versus 7±5 ms/cm) at right ventricular outflow tract borders. With increased heart rate in 6 BrS patients, reduced ST-segment elevation and increased fractionation were observed. Unlike BrS, right bundle-branch block had delayed activation in the entire right ventricle, without ST-segment elevation, fractionation, or repolarization abnormalities on electrograms. CONCLUSIONS: The results indicate that both slow discontinuous conduction and steep dispersion of repolarization are present in the right ventricular outflow tract of BrS patients. ECG imaging could differentiate between BrS and right bundle-branch block.

Mechanisms of persistent atrial fibrillation and recurrences within 12 months post-ablation: Non-invasive mapping with electrocardiographic imaging.

Introduction: Catheter ablation of persistent AF has not been consistently successful in terminating AF or preventing arrhythmia recurrences. Non-invasive Electrocardiographic Imaging (ECGI) can help to understand recurrences by mapping the mechanisms of pre-ablation AF and comparing them with the patterns of recurrent arrhythmias in the same patient. Methods: Seventeen persistent AF patients underwent ECGI before their first catheter ablation. Time-domain activation maps and phase progression maps were obtained on the bi-atrial epicardium. Location of arrhythmogenic drivers were annotated on the bi-atrial anatomy. Activation and phase movies were examined to understand the wavefront dynamics during AF. Eight patients recurred within 12 months of ablation and underwent a follow-up ECGI. Driver locations and movies were compared for pre- and post-ablation AF. Results: A total of 243 focal drivers were mapped during pre-ablation AF. 62% of the drivers were mapped in the left atrium (LA). The pulmonary vein region harbored most of the drivers (43%). 35% of the drivers were mapped in the right atrium (RA). 59% (10/17) and 53% (9/17) of patients had repetitive sources in the left pulmonary veins (LPV) and left atrial appendage (LAA), and the lower half of RA, respectively. All patients had focal drivers. 29% (5/17) of patients had macro-reentry waves. 24% (4/17) of patients had rotors. Activation patterns during persistent AF varied from single macro-reentry to complex activity with multiple simultaneous wavefronts in both atria, resulting in frequent wave collisions. A total of 76 focal driver activities were mapped in 7/8 patients during recurrence. 59% of the post-ablation AF drivers were mapped in the LA. The pulmonary vein region harbored 50% of total drivers. 39% of sources were mapped in the RA. AF complexity remained similar post-ablation. 58% (44/76) of pre-ablation sources persisted during recurrence. 38% (3/8) of patients had macro-reentry and one patient had rotors. Conclusion: ECGI provides patient-specific information on mechanisms of persistent AF and recurrent arrhythmia. More than half pre-ablation sources repeated during post-ablation recurrence. This study provides direct evidence for drivers that persist days and months after the ablation procedure. Patient-tailored bi-atrial ablation is needed to successfully target persistent AF and prevent recurrence. ECGI can potentially predict recurrence and assist in choice of therapy.

Noninvasive characterization of epicardial activation in humans with diverse atrial fibrillation patterns.

BACKGROUND: Various mechanisms of atrial fibrillation (AF) have been demonstrated experimentally. Invasive methods to study these mechanisms in humans have limitations, precluding continuous mapping of both atria with sufficient resolution. In this article, we present continuous biatrial epicardial activation sequences of AF in humans using noninvasive electrocardiographic imaging (ECGI). METHODS AND RESULTS: In the testing phase, ECGI accuracy was evaluated by comparing ECGI with co-registered CARTO images during atrial pacing in 6 patients. Additionally, correlative observations from catheter mapping and ablation were compared with ECGI in 3 patients. In the study phase, ECGI maps during AF in 26 patients were analyzed for mechanisms and complexity. ECGI noninvasively imaged the low-amplitude signals of AF in a wide range of patients (97 procedural success). Spatial accuracy for determining initiation sites from pacing was 6 mm. Locations critical to maintenance of AF identified during catheter ablation were identified by ECGI; ablation near these sites restored sinus rhythm. In the study phase, the most common patterns of AF were multiple wavelets (92), with pulmonary vein (69) and non-pulmonary vein (62) focal sites. Rotor activity was seen rarely (15). AF complexity increased with longer clinical history of AF, although the degree of complexity of nonparoxysmal AF varied widely. CONCLUSIONS: ECGI offers a noninvasive way to map epicardial activation patterns of AF in a patient-specific manner. The results highlight the coexistence of a variety of mechanisms and variable complexity among patients. Overall, complexity generally increased with duration of AF.

Accurate ECG diagnosis of atrial tachyarrhythmias using quantitative analysis: a prospective diagnostic and cost-effectiveness study.

UNLABELLED: Quantitative ECG Analysis. INTRODUCTION: Optimal atrial tachyarrhythmia management is facilitated by accurate electrocardiogram interpretation, yet typical atrial flutter (AFl) may present without sawtooth F-waves or RR regularity, and atrial fibrillation (AF) may be difficult to separate from atypical AFl or rapid focal atrial tachycardia (AT). We analyzed whether improved diagnostic accuracy using a validated analysis tool significantly impacts costs and patient care. METHODS AND RESULTS: We performed a prospective, blinded, multicenter study using a novel quantitative computerized algorithm to identify atrial tachyarrhythmia mechanism from the surface ECG in patients referred for electrophysiology study (EPS). In 122 consecutive patients (age 60 ± 12 years) referred for EPS, 91 sustained atrial tachyarrhythmias were studied. ECGs were also interpreted by 9 physicians from 3 specialties for comparison and to allow healthcare system modeling. Diagnostic accuracy was compared to the diagnosis at EPS. A Markov model was used to estimate the impact of improved arrhythmia diagnosis. We found 13% of typical AFl ECGs had neither sawtooth flutter waves nor RR regularity, and were misdiagnosed by the majority of clinicians (0/6 correctly diagnosed by consensus visual interpretation) but correctly by quantitative analysis in 83% (5/6, P = 0.03). AF diagnosis was also improved through use of the algorithm (92%) versus visual interpretation (primary care: 76%, P < 0.01). Economically, we found that these improvements in diagnostic accuracy resulted in an average cost-savings of $1,303 and 0.007 quality-adjusted-life-years per patient. CONCLUSIONS: Typical AFl and AF are frequently misdiagnosed using visual criteria. Quantitative analysis improves diagnostic accuracy and results in improved healthcare costs and patient outcomes.

Left ventricular diastolic filling prior to cardiac resynchronization therapy: implications for atrioventricular delay programming.

BACKGROUND: The programmed atrioventricular delay (AVD) is an important determinant of the response in left ventricular (LV) systolic performance during cardiac resynchronization therapy (CRT). It is not well established if the optimal AVD for CRT may be influenced by the LV diastolic filling pattern. METHODS: Thirty patients were studied pre- and post-CRT at programmed AVD of 60-160 ms. Doppler measurements included the aortic and mitral velocity time integral (VTI), mitral early (E) and late diastolic filling (A) wave velocities, E- and A-wave VTI, and diastolic filling time (DFT). The optimal AVD for each of the Doppler variables was defined by the maximal improvement compared to pre-CRT. Patients were grouped by the pre-CRT mitral inflow pattern as impaired relaxation (IR, mitral E/A 1, n = 15). RESULTS: The percentage of improvement in aortic VTI was greater in the PNF/RF group (P = 0.03). Mitral E-wave velocity decreased in the PNF/RF group (P < 0 .001), E-wave VTI increased in both groups (P < 0 .05) and A-wave VTI increased in the PNF/RF group. DFT increased in both groups. The optimal AVD that maximized aortic VTI was longer than the AVD that improved DFT. CONCLUSIONS: The effects of various programmed AVD during CRT on the response in LV stroke volume and diastolic filling are influenced by the pre-CRT LV filling characteristics. AVD optimization based on maximizing DFT is shorter compared to the aortic VTI method.

The azygos defibrillator lead for elevated defibrillation thresholds: implant technique, lead stability, and patient series.

BACKGROUND: Conventional insertion of implantable cardioverter-defibrillator (ICD) includes an evaluation of the defibrillation threshold (DFT). Implanting an ancillary defibrillation lead in the azygos vein has been introduced as a therapeutic option in patients with "high" DFT. This study reports the efficacy and stability of azygos defibrillation coils implanted for elevated DFTs. METHODS: This is a retrospective review of seven consecutive patients with right and left pectoral, single- and dual-chamber, and biventricular ICDs and elevated DFTs, in whom an azygos defibrillation coil was introduced. RESULTS: Addition of an azygos defibrillator lead achieved a satisfactory safety margin during single energy defibrillation efficacy testing in four out of seven patients, with success at maximum device output in two patients. No satisfactory safety margin was achieved in the remaining patient, despite the further addition of a subcutaneous defibrillation coil. No change in lead position was observed over a mean radiographic follow-up of 8 months. No complications were noted during a mean follow-up of 14 months, including no deaths, and no ICD shocks. CONCLUSION: Implanting a defibrillation coil into the azygos vein is feasible and safe. In a majority of patients with failed defibrillation efficacy testing, adding an azygos coil achieves success on repeat testing. Therefore, this technique is one option for lowering the defibrillation threshold in patients who fail DFT testing of their ICD.

Relation of left ventricular lead placement in cardiac resynchronization therapy to left ventricular reverse remodeling and to diastolic dyssynchrony.

The effects of left ventricular (LV) lead placement for cardiac resynchronization therapy (CRT) on LV remodeling and dyssynchrony are not well defined. Sixty-one patients (age 60 +/- 11 years, 76% men) were evaluated by echocardiography before and 4 +/- 2 months after CRT and grouped by the LV lead placement (lateral, posterolateral, or anterolateral). Echocardiographic measurements included LV volumes and LV ejection fraction. Tissue Doppler imaging was used to assess for inter- and intraventricular systolic and diastolic dyssynchrony. Analysis of variance was used to determine the effect of the LV lead placement on echocardiographic variables after CRT. The LV lead was placed in a lateral cardiac vein in 33 patients (54%), posterolateral in 15 (25%), and anterior in 13 (21%). Lateral LV lead placement was associated with significantly smaller LV volumes compared with the posterolateral lead placement (p <0.01). Diastolic dyssynchrony improved significantly with lateral lead placement compared with the anterior lead location (p <0.05). Improvement in LV ejection fraction and inter- and intraventricular systolic dyssynchrony was similar among the 3 groups. In conclusion, in patients undergoing CRT, a lateral lead location resulted in greater reverse LV remodeling and improved diastolic dyssynchrony compared with other lead placement locations.

Remote controlled magnetically guided pulmonary vein isolation in canines.

BACKGROUND: Ablation of atrial fibrillation (AF) remains a challenging procedure fraught with significant risks and technical difficulties. A magnetically guided catheter system has been developed that potentially addresses many of these challenges. Fully remote controlled electrical isolation of pulmonary veins was performed in canines, facilitated by a three-dimensional computed tomogram (CT) that depicted the anatomic relationships of the pulmonary veins and the left atrium. OBJECTIVE: The purpose of this study was to evaluate the feasibility of pulmonary vein isolation with a novel remote controlled magnetically guided catheter. METHODS: CT scans were obtained in seven healthy male canines. A 7-Fr irrigated magnetic catheter was advanced transseptally to the left atrium. A magnetic guidance system was used to control the orientation of the catheter tip. A mechanical device advanced or retracted the catheter as needed. Pulmonary venography was performed and compared with the CT scan. The CT scan was used as a visual reference to set the magnetic field vectors. Radiofrequency energy was delivered through the irrigated magnetic catheter to isolate the superior pulmonary veins, as judged by elimination of pulmonary vein potentials. RESULTS: The isolation procedure was successful in all 14 pulmonary veins, and there was no evidence of stenosis at 80-100 days postprocedure. CONCLUSIONS: These results demonstrate that remote controlled catheter ablation is safe and effective for segmental pulmonary vein isolation. This technology could facilitate curative ablation of AF in humans and reduce the occupational hazards to the operator of prolonged procedures and radiation exposure.

Prospective comparison of echocardiographic atrioventricular delay optimization methods for cardiac resynchronization therapy.

BACKGROUND: Atrioventricular (AV) delay optimization can be an important determinant of the response to cardiac resynchronization therapy (CRT) in patients with medically refractory heart failure and a ventricular conduction delay. OBJECTIVES: The purpose of this study was to compare two Doppler echocardiographic methods of AV delay optimization after CRT. METHODS: Forty consecutive patients (age 59 +/- 12 years) with severe heart failure, New York Heart Association class 3.1 +/- 0.4, QRS duration 177 +/- 23 ms, and left ventricular ejection fraction 26% +/- 6% referred for CRT were studied using two-dimensional Doppler echocardiography. In each patient, the acute improvement in stroke volume with CRT in response to two methods of AV delay optimization was compared. In the first method, the AV delay that produced the largest increase in the aortic velocity time integral (VTI) derived from continuous-wave Doppler (aortic VTI method) was measured. In the second method, the AV delay that optimized the timing of mitral valve closure to occur simultaneously with the onset of left ventricular systole was calculated from pulsed Doppler mitral waveforms at a short and long AV delay interval (mitral inflow method). RESULTS: The optimized AV delay determined by the aortic VTI method resulted in an increase in aortic VTI of 19% +/- 13% compared with an increase of 12% +/- 12% by the mitral inflow method (P <.001). The optimized AV delay by the aortic VTI method was significantly longer than the optimized AV delay calculated from the mitral inflow method (119 +/- 34 ms vs 95 +/- 24 ms, P <.001). There was no correlation in the AV delay determined by the two methods (r = 0.03). CONCLUSION: AV delay optimization by Doppler echocardiography for patients with severe heart failure treated with a CRT device yields a greater systolic improvement when guided by the aortic VTI method compared with the mitral inflow method.

Radiofrequency ablation of atrioventricular nodal reentrant tachycardia using a novel magnetic guidance system compared with a conventional approach.

BACKGROUND: A novel magnetic guidance system has been developed that allows the operator to remotely navigate an electrophysiology mapping/ablation catheter to precise locations in the heart for treatment of tachyarrhythmias. To date, this new technology has not been directly compared with the conventional approach. OBJECTIVE: To compare the use of the magnetic guidance system to the conventional approach for ablation of atrioventricular nodal reentry tachycardia. METHODS: Between November 2002 and October 2004, 28 patients with atrioventricular nodal reentry tachycardia treated with the magnetic guidance system were retrospectively compared with 28 matched control patients. RESULTS: Patients treated using the magnetic guidance system had similar procedure durations and fluoroscopy times compared with the matched controls. The only statistically significant difference between the groups was a longer time between insertion of the ablation catheter and placement of the first radiofrequency lesion in the magnetic guidance system cohort (23.3 +/- 12.0 vs. 10.5 +/- 13.9, p=0.001), possibly due to the research protocol. However, there was a trend toward a shorter total time that radiofrequency energy was applied in the magnetic guidance system cohort (5.2 +/- 4.5 vs. 8.0 +/- 7.2, p=0.087). There were no major complications or recurrences after at least 3 months of follow-up among the patients treated with the magnetic guidance system. CONCLUSION: The magnetic guidance system appears to have similar, and possibly improved, clinical efficacy compared with conventional catheter navigation for the treatment of atrioventricular nodal reentrant tachycardia.

Smokers are at markedly increased risk of appropriate defibrillator shocks in a primary prevention population.

BACKGROUND: Cigarette smoking is a known risk factor for sudden cardiac death (SCD). It is unknown whether smoking status affects implantable cardioverter-defibrillator (ICD) therapy. OBJECTIVE: The primary end point was appropriate ICD therapy according to smoking status. METHODS: A total of 105 consecutive patients who underwent ICD implantation for primary prevention of SCD were retrospectively analyzed. All patients had an abnormal response to programmed ventricular stimulation performed for nonsustained ventricular tachycardia in the setting of ischemic cardiomyopathy between January 1999 and December 2003. RESULTS: Among the 105 patients, 6 (37.5%) of 16 current smokers, 14 (25.9%) of 54 former smokers, and 2 (5.7%) of 35 of never smokers received an appropriate ICD therapy (P = .02). Kaplan-Meier analysis for survival free of appropriate ICD therapy comparing never smokers with both current smokers (P = .002) and former smokers (P = .01) demonstrated statistically significant differences by log rank over a mean follow-up of 21.8 +/- 13.7 months. Cox regression analysis found that current smoking was associated with an increased risk of appropriate therapy (hazard ratio 7.36; 95% confidence interval 1.42-38.10; P = .02) as was former smoking (hazard ratio 5.42; 95% confidence interval 1.20-24.47; P = .03). There was no difference in inappropriate therapy between groups (P = .12). CONCLUSIONS: Cigarette smoking is an independent predictor of appropriate ICD therapy in a primary prevention population. While outcomes differences among current smokers, former smokers, and never smokers are demonstrable, the effect of smoking cessation on ICD therapy requires further study.

Implementation of a Screening Program for Patients at Risk for Posttraumatic Stress Disorder.

INTRODUCTION: Implantable cardioverter defibrillator (ICD) recipients who suffer from posttraumatic stress disorder (PTSD) are known to be associated with significant cardiac-specific mortality. Clinical observations suggest that PTSD is frequently undetected in ICD recipients followed up at electrophysiology (EP) outpatient clinics. Early recognition of PTSD is important to reduce the risk of serious manifestations on patient outcomes. METHODS: All ICD recipients aged 19 years or older at the Washington University School of Medicine (WASHU) EP clinic, a large urban EP clinic, were invited to participate in the project. An informed consent letter with an attached primary care: posttraumatic stress disorder (PC: PTSD) survey was offered to the participants who met the inclusion criteria. Those who completed the survey were included in the project. Individuals with positive survey result were offered a referral to mental health services. Comparisons between PTSD and non-PTSD patients were done using a two-sample t-test for continuous variables. Using Fisher's exact test, PTSD prevalence was compared to the study by Ladwig et al in which prevalence was determined as the proportion of patients with positive findings of PTSD (n = 38/147). All analyses were conducted using SAS v9.4. The proportion of patients having PTSD was determined and an exact 95% confidence interval was evaluated based on the binomial distribution. RESULTS: Using a convenience sample, 50 ICD recipients (33 males and 17 females) were enrolled. The project had a 30-day outcome period. Nine (18%) of the 50 participants had positive PC: PTSD findings and all these nine participants were referred to a mental health specialist. The current project demonstrated an 18% (9/50) PTSD prevalence rate when compared to a 26% (38/147) prevalence rate in the study by Ladwig et al (P = 0.34). Although this project did not demonstrate 20% PTSD prevalence rate, as hypothesized, the 18% PTSD prevalence rate is consistent with previous research. CONCLUSION: The prevalence of PTSD noted in the current project is consistent with previous research and validates underrecognition of PTSD in ICD patients. Offering a referral to all ICD recipients at EP clinic visits with a positive PC: PTSD screening to a mental health specialist is an important step in reducing the risk of serious manifestations on patient outcomes.

Methodology Considerations in Phase Mapping of Human Cardiac Arrhythmias.

BACKGROUND: Phase analysis of cardiac arrhythmias, particularly atrial fibrillation, has gained interest because of the ability to detect organized stable drivers (rotors) and target them for therapy. However, the lack of methodology details in publications on the topic has resulted in ongoing debate over the phase mapping technique. By comparing phase maps and activation maps, we examined advantages and limitations of phase mapping. METHODS AND RESULTS: Seven subjects were enrolled. We generated phase maps and activation maps from electrocardiographic imaging-reconstructed epicardial unipolar electrograms. For ventricular signals, phase was computed with (1) pseudoempirical mode decomposition detrending and (2) a novel Moving Average (MVG) detrending approach. For atrial fibrillation signals, MVG was modified to incorporate dynamic cycle length (DCL) changes (MVG-DCL). Phase maps were visually analyzed to study phase singularity points and rotors. Results show that phase is sensitive to cycle length choice, a limitation that was addressed by the MVG-DCL algorithm. MVG-DCL was optimal for atrial fibrillation analysis. Phase maps helped to highlight high-curvature wavefronts and rotors. However, for some activation patterns, phase generated nonrotational singularity points and false rotors. CONCLUSIONS: Phase mapping computes singularity points and visually highlights rotors. As such, it can help to provide a clearer picture of the spatiotemporal activation characteristics during atrial fibrillation. However, it is advisable to incorporate electrogram characteristics and the time-domain activation sequence in the analysis, to prevent misinterpretation and false rotor detection. Therefore, for mapping complex arrhythmias, a combined time-domain activation and phase mapping with variable cycle length seems to be the most reliable method.

Novel, magnetically guided catheter for endocardial mapping and radiofrequency catheter ablation.

BACKGROUND: Ablation of complex arrhythmias would be greatly facilitated by more precise control of ablation catheters. A feasibility study was performed in animals to evaluate a novel magnetic guidance system (MGS) that generates a magnetic field to control the movement and position of a magnetic ablation catheter. METHODS AND RESULTS: The MGS is composed of a digital biplanar fluoroscope within an array of superconducting electromagnets that surround the torso of the experimental animal and a computer control system that generates a composite magnetic field for directional catheter deflection. Magnetic catheter navigation was performed in dogs and pigs (20 to 30 kg). A 7F magnetic ablation catheter was used for intracardiac navigation and radiofrequency ablation. The performance of a standard 7F deflectable catheter was not affected by the MGS. The magnetic catheter was navigated successfully to 51 predefined targets throughout the heart in 6 animals. In 5 animals, the magnetic catheter, guided by a 3D computed tomogram, was successfully navigated to all pulmonary veins. Navigation accuracy was estimated as <1 mm displacement from the target. The magnetic catheter was used to ablate the atrioventricular node in 4 animals and to perform linear ablations across the endocardial surface underlying an epicardial multielectrode recording plaque in 4 animals. CONCLUSIONS: These results demonstrate that the MGS can navigate and stabilize an ablation catheter at endocardial targets. Linear or focal radiofrequency ablation with the magnetic catheter is not compromised by the magnetic field. This technology provides precise control of endocardial catheters.

Long-term retention of cardiac resynchronization therapy.

OBJECTIVES: The purpose of this study was to determine the frequency and causes of intermittent and permanent loss of cardiac resynchronization therapy (CRT) in patients who have undergone the successful implantation of a transvenous defibrillator that delivers CRT (CRT-D). BACKGROUND: The causes of loss of CRT have not been described. METHODS: The records of 512 patients who underwent an attempt at implantation of a transvenous CRT-D device as part of the VENTAK CHF/CONTAK CD Biventricular Pacing study were analyzed. RESULTS: Device implantation was successful in 443 of 512 (87%) of patients. Among these 443 patients, CRT was interrupted in 161 (36%) patients during a mean follow-up of 2.5 +/- 1.1 years. Reasons included the development of an atrial tachyarrhythmia (18%), loss of left ventricular capture (10%), diaphragmatic stimulation (2%), loss of right ventricular capture (2%), infection (1%), intentional discontinuation of CRT (1%), loss of right atrial sensing (1%), and ventricular oversensing (0.2%). Most patients underwent an intervention that permitted the reinstitution of CRT, such that only 20 of the 443 patients (5%) experienced the permanent loss of CRT. Using an intention-to-treat analysis, the long-term retention of CRT was 83% during the course of 2.5 years. CONCLUSIONS: Cardiac resynchronization therapy is interrupted in more than one-third of patients after the successful implantation of a CRT-D device. However, CRT can be reinstituted in most patients and has a high long-term retention rate. Because patients with slower heart rates were more likely to develop atrial tachyarrhythmias, a dual-chamber rate-modulated pacing mode (DDDR) may reduce interruptions of CRT.

Magnetic guidance system for cardiac electrophysiology: a prospective trial of safety and efficacy in humans.

OBJECTIVES: We evaluated in humans the safety and efficacy of a novel magnetic guidance system (MGS) for electrophysiological mapping, pacing, and ablation. BACKGROUND: Catheter ablation of atrial fibrillation and other complex arrhythmias requires precise catheter manipulation and stabilization. We have shown in animals that the MGS can precisely manipulate a mapping catheter within the heart with an external magnetic field rather than manual catheter control. METHODS: Thirty-one adults referred for diagnostic electrophysiology studies were enrolled in a prospective trial of the MGS. The magnetic catheter was navigated to preselected sites in the right atrium (RA) and right ventricle (RV) in the first 20 patients. Electrograms were recorded at each target site, and pacing thresholds were measured. In a subset of five patients, RA and RV electrograms and stimulation thresholds were recorded with both a standard ablation catheter and the magnetic catheter. Eleven additional patients were recruited for supraventricular tachycardia (SVT) mapping, and seven of these underwent ablation. RESULTS: Navigation was successful in 200 of 202 predetermined right-sided navigation targets and 13 of 13 targets in the left atria. Pacing thresholds and electrogram amplitudes in the RA and RV were not significantly different between the standard and magnetic catheters. The SVT mapping with the magnetic catheter was successful in 13 patients, including 4 with left-sided accessory pathways. The MGS was used for successful ablation of SVT in seven of seven patients. There were no procedural complications. CONCLUSIONS: These results demonstrate that the MGS can be used for intracardiac mapping, pacing, and ablation safely and effectively.

Implantable cardioverter-defibrillator therapy improves long-term survival in patients with unexplained syncope, cardiomyopathy, and a negative electrophysiologic study.

OBJECTIVES: The purpose of this study was to evaluate the long-term outcomes of patients with unexplained syncope, ischemic or nonischemic cardiomyopathy, and a negative electrophysiologic study (EPS). BACKGROUND: EPS is frequently performed to evaluate syncope in patients with left ventricular dysfunction. Limited long-term data evaluating all-cause mortality in patients with no inducible arrhythmia or examining the potential benefits from implantable cardioverter-defibrillator (ICD) therapy are available. METHODS: We evaluated 102 consecutive patients with unexplained syncope, cardiomyopathy, and a negative EPS from September 1996 to December 2000. A blinded matched case-control analysis utilized 51 of these patients (19 treated with an ICD and 32 matched controls treated with conventional therapy). We compared primary endpoint of death and documented cardiac arrest of patients treated with ICD therapy to matched controls. RESULTS: Baseline characteristics were similar between groups. There were 14 primary events among the study population during a follow-up period of 44.3 +/- 20 months: 2 in the ICD group and 12 in the conventional therapy group. The hazard ratio for the risk of event in the ICD group compared with the conventional therapy group was 0.18 (95% confidence interval, 0.04-0.85; P = .04). Other comorbid conditions, including age, sex, ischemic etiology of heart failure, ejection fraction, and antiarrhythmic use, did not predict outcome. Appropriate ICD shocks occurred in 26% of patients at 2 years. CONCLUSIONS: This study suggests that empiric ICD therapy improves long-term outcomes in patients with unexplained syncope, ischemic or nonischemic cardiomyopathy, and negative EPS.