Substrate Ablation by Multivein, Multiballoon Coronary Venous Ethanol for Refractory Ventricular Tachycardia in Structural Heart Disease.

BACKGROUND: Ablation of ventricular tachycardia (VT) in the setting of structural heart disease often requires extensive substrate elimination that is not always achievable by endocardial radiofrequency ablation. Epicardial ablation is not always feasible. Case reports suggest that venous ethanol ablation (VEA) through a multiballoon, multivein approach can lead to effective substrate ablation, but large data sets are lacking. METHODS: VEA was performed in 44 consecutive patients with ablation-refractory VT (ischemic, n=21; sarcoid, n=3; Chagas, n=2; idiopathic, n=18). Targeted veins were selected by mapping coronary veins on the epicardial aspect of endocardial scar (identified by bipolar voltage <1.5 mV), using venography and signal recording with a 2F octapolar catheter or by guidewire unipolar signals. Epicardial mapping was performed in 15 patients. Vein segments in the epicardial aspect of VT substrates were treated with double-balloon VEA by blocking flow with 1 balloon while injecting ethanol through the lumen of the second balloon, forcing (and restricting) ethanol between balloons. Multiple balloon deployments and multiple veins were used as needed. In 22 patients, late gadolinium enhancement cardiac magnetic resonance imaged the VEA scar and its evolution. RESULTS: Median ethanol delivered was 8.75 (interquartile range, 4.5-13) mL. Injected veins included interventricular vein (6), diagonal (5), septal (12), lateral (16), posterolateral (7), and middle cardiac vein (8), covering the entire range of left ventricular locations. Multiple veins were targeted in 14 patients. Ablated areas were visualized intraprocedurally as increased echogenicity on intracardiac echocardiography and incorporated into 3-dimensional maps. After VEA, vein and epicardial ablation maps showed elimination of abnormal electrograms of the VT substrate. Intracardiac echocardiography demonstrated increased intramural echogenicity at the targeted region of the 3-dimensional maps. At 1 year of follow-up, median of 314 (interquartile range, 198-453) days of follow-up, VT recurrence occurred in 7 patients, for a success of 84.1%. CONCLUSIONS: Multiballoon, multivein intramural ablation by VEA can provide effective substrate ablation in patients with ablation-refractory VT in the setting of structural heart disease over a broad range of left ventricular locations.

Effect of Catheter Ablation With Vein of Marshall Ethanol Infusion vs Catheter Ablation Alone on Persistent Atrial Fibrillation: The VENUS Randomized Clinical Trial.

Importance: Catheter ablation of persistent atrial fibrillation (AF) has limited success. Procedural strategies beyond pulmonary vein isolation have failed to consistently improve results. The vein of Marshall contains innervation and AF triggers that can be ablated by retrograde ethanol infusion. Objective: To determine whether vein of Marshall ethanol infusion could improve ablation results in persistent AF when added to catheter ablation. Design, Setting, and Participants: The Vein of Marshall Ethanol for Untreated Persistent AF (VENUS) trial was an investigator-initiated, National Institutes of Health-funded, randomized, single-blinded trial conducted in 12 centers in the United States. Patients (N = 350) with persistent AF referred for first ablation were enrolled from October 2013 through June 2018. Follow-up concluded in June 2019. Interventions: Patients were randomly assigned to catheter ablation alone (n = 158) or catheter ablation combined with vein of Marshall ethanol infusion (n = 185) in a 1:1.15 ratio to accommodate for 15% technical vein of Marshall ethanol infusion failures. Main Outcomes and Measures: The primary outcome was freedom from AF or atrial tachycardia for longer than 30 seconds after a single procedure, without antiarrhythmic drugs, at both 6 and 12 months. Outcome assessment was blinded to randomization treatment. There were 12 secondary outcomes, including AF burden, freedom from AF after multiple procedures, perimitral block, and others. Results: Of the 343 randomized patients (mean [SD] age, 66.5 [9.7] years; 261 men), 316 (92.1%) completed the trial. Vein of Marshall ethanol was successfully delivered in 155 of 185 patients. At 6 and 12 months, the proportion of patients with freedom from AF/atrial tachycardia after a single procedure was 49.2% (91/185) in the catheter ablation combined with vein of Marshall ethanol infusion group compared with 38% (60/158) in the catheter ablation alone group (difference, 11.2% [95% CI, 0.8%-21.7%]; P = .04). Of the 12 secondary outcomes, 9 were not significantly different, but AF burden (zero burden in 78.3% vs 67.9%; difference, 10.4% [95% CI, 2.9%-17.9%]; P = .01), freedom from AF after multiple procedures (65.2% vs 53.8%; difference, 11.4% [95% CI, 0.6%-22.2%]; P = .04), and success achieving perimitral block (80.6% vs 51.3%; difference, 29.3% [95% CI, 19.3%-39.3%]; P < .001) were significantly improved in vein of Marshall-treated patients. Adverse events were similar between groups. Conclusions and Relevance: Among patients with persistent AF, addition of vein of Marshall ethanol infusion to catheter ablation, compared with catheter ablation alone, increased the likelihood of remaining free of AF or atrial tachycardia at 6 and 12 months. Further research is needed to assess longer-term efficacy. Trial Registration: ClinicalTrials.gov Identifier: NCT01898221.

Vein of Marshall ethanol infusion for persistent atrial fibrillation: VENUS and MARS clinical trial design.

BACKGROUND: Although pulmonary vein isolation (PVI) is effective in the treatment of paroxysmal atrial fibrillation (AF), its success rates in persistent AF are suboptimal. Ablation strategies to improve outcomes including additional lesions beyond PVI have not consistently shown benefit. Recurrence as perimitral flutter (PMF) is a common form of ablation failure. The vein of Marshall (VOM) contains myocardial connections and abundant sympathetic and parasympathetic innervation implicated in the genesis and maintenance of AF, and is anatomically co-localized with the mitral isthmus, the ablation target of PMF. VOM ethanol infusion is effective in targeting these arrhythmia substrates. OBJECTIVE: To test the safety and efficacy of VOM ethanol infusion when added to PVI in patients undergoing either de novo ablation of persistent AF or after a previous ablation failure. STUDY DESIGN: VENUS-AF and MARS-AF are prospective, multicenter, randomized, controlled trials. VENUS-AF will enroll patients undergoing their first catheter ablation of persistent AF. MARS-AF will enroll patients undergoing ablation after previous ablation failure(s). Patients (n = 405) will be randomized to PVI alone or in combination with VOM ethanol infusion. The primary endpoints include procedural safety and freedom from AF or atrial tachycardia (AT) of more than 30 seconds on 30-day continuous event monitors at 6 and 12 months after randomization procedure (single-procedure success), off antiarrhythmic drugs. Key secondary endpoints include AF burden, freedom from AF/AT after repeat procedures and quality of life. CONCLUSIONS: The VENUS-AF and MARS-AF will determine the safety and potential rhythm control benefit of VOM ethanol infusion when added to PVI in patients with persistent AF undergoing de novo or repeat ablation, respectively.

Stellate ganglion instrumentation for pharmacological blockade, nerve recording, and stimulation in patients with ventricular arrhythmias: Preliminary experience.

BACKGROUND: Stellate ganglion blockade (SGB) can control ventricular arrhythmias (VAs), but outcomes are unclear. Percutaneous stellate ganglion (SG) recording and stimulation in humans has not been reported. OBJECTIVE: The purpose of this study was to assess the outcomes of SGB and the feasibility of SG stimulation and recording in humans with VAs. METHODS: Two patient cohorts were included-group 1: patients undergoing SGB for drug-refractory VAs. SGB was performed by injection of liposomal bupivacaine. Incidence of VAs at 24 and 72 hours and clinical outcomes were collected; group 2: patients undergoing SG stimulation and recording during VA ablation; a 2-F octapolar catheter was placed at the SG at the C7 level. Recording (30 kHz sampling, 0.5-2 kHz filter) and stimulation (up to 80 mA output, 50 Hz, 2 ms pulse width for 20-30 seconds) was performed. RESULTS: Group 1 included 25 patients [age 59.2 ± 12.8 years; 19 (76%) men] who underwent SGB for VAs. Nineteen patients (76.0%) were free of VA up to 72 hours postprocedure. However, 15 (60.0%) had VAs recurrence for a mean of 5.47 ± 4.52 days. Group 2 included 11 patients (mean age 63 ± 12.7 years; 82.7% men). SG stimulation caused consistent increases in systolic blood pressure. We recorded unequivocal signals with temporal association with arrhythmias in 4 of 11 patients. CONCLUSION: SGB provides short-term VA control, but has no benefit in the absence of definitive VA therapies. SG recording and stimulation is feasible and may have value to elicit VA and understand neural mechanisms of VA in the electrophysiology laboratory.

Optimal conditions for high-power, short-duration radiofrequency ablation using a novel, flexible-tipped, force-sensing catheter.

Background: High-power, short-duration (HPSD) radiofrequency ablation (RFA) reduces procedure time; however, safety and efficacy thresholds vary with catheter design. Objective: The study sought to determine optimal HPSD ablation conditions with a novel flexible-tipped, contact force-sensing RFA catheter. Methods: RFA lesions were created in thigh muscle (16 swine) over a range of conditions (51-82 W, 2-40 g, 8-40 mL/min irrigation). An intracardiac study was performed (12 swine) to characterize steam pop thresholds. Lesions were created in a second intracardiac study (14 swine, n = 290 pulmonary vein isolation [PVI] lesions) with combinations of radiofrequency power, duration, and contact force. PVI was tested, animals were sacrificed, and lesions were measured. Results: The likelihood of coagulation formation in the thigh model was <20% when power was ≤79 W, when contact force was ≤40 g, when duration was ≤11 seconds, and when irrigation rates were 8 to 40 mL/min. The impact of contact force on lesion safety and efficacy was more pronounced using HPSD (60 W/8 seconds) compared with conventional ablation (30 W/45 seconds) (P = .038). During PVI, focal atrial lesions ranged in width from 4.2 to 12.5 mm and were transmural 80.8% of the time. PVI was achieved in 13 of 14 veins. Logistic regression identified that the optimal parameters for radiofrequency application were 60 to 70 W with a duration <8 seconds and <15 g contact force. Conclusions: Optimal HPSD lesions with this this flexible-tipped, force-sensing RFA catheter were created at 60 to 70 W for <8 seconds with <15 g contact force. Chronic studies are ongoing to assess radiofrequency parameter refinements and long-term lesion durability using these conditions.

Acute and Long-Term Scar Characterization of Venous Ethanol Ablation in the Left Ventricular Summit.

BACKGROUND: Venous ethanol ablation (VEA) can be effective for ventricular arrhythmias from the left ventricular summit (LVS); however, there are concerns about excessive ablation by VEA. OBJECTIVES: The purpose of this study was to delineate and quantify the location, extent, and evolution of ablated tissue after VEA as an intramural ablation technique in the LVS. METHODS: VEA was performed in 59 patients with LVS ventricular arrhythmias. Targeted intramural veins were selected by electrograms from a 2F octapolar catheter or by guide-wire unipolar signals. Median ethanol delivered was 4 mL (IQR: 4-7 mL). Ablated areas were estimated intraprocedurally as increased echogenicity on intracardiac echocardiography (ICE) and incorporated into 3-dimensional maps. In 44 patients, late gadolinium enhancement cardiac magnetic resonance (CMR) imaged VEA scar and its evolution. RESULTS: ICE-demonstrated increased intramural echogenicity (median volume of 2 mL; IQR: 1.7-4.3) at the targeted region of the 3-dimensional maps. Post-ethanol CMR showed intramural scar of 2.5 mL (IQR: 2.1-3.5 mL). Early (within 48 hours after VEA) CMR showed microvascular obstruction (MVO) in 30 of 31 patients. Follow-up CMR after a median of 51 (IQR: 41-170) days showed evolution of MVO to scar. ICE echogenicity and CMR scar volumes correlated with each other and with ethanol volume. Ventricular function and interventricular septum remained intact. CONCLUSIONS: VEA leads to intramural ablation that can be tracked intraprocedurally by ICE and creates regions of MVO that are chronically replaced by myocardial scar. VEA scar volume does not compromise septal integrity or ventricular function.

Role of the vein of Marshall in atrial fibrillation recurrences after catheter ablation: therapeutic effect of ethanol infusion.

UNLABELLED: Vein of Marshall Ethanol in Recurrent AF. INTRODUCTION: Atrial fibrillation (AF) or flutter can recur after pulmonary vein (PV) antral isolation (PVAI). The vein of Marshall (VOM) has been linked to the genesis of AF. We hypothesized that the VOM may play a role in AF recurrences and that VOM ethanol infusion may have therapeutic value in this setting. METHODS AND RESULTS: Sixty-one patients with recurrent AF or flutter after PVAI were studied. The VOM was successfully cannulated in 54; VOM and PV electrograms were recorded, and differential PV-VOM pacing was performed. VOM signals were present in all patients; however, VOM triggers of AF could not be demonstrated. VOM tachycardia was present in 1 patient. Left inferior (LIPV) and left superior (LSPV) reconnection was present in 32 and 30 patients, respectively. Differential pacing in VOM and LIPV showed VOM-mediated LIPV reconnection in 5/32 patients. In others, VOM and PV connected indirectly via left atrial tissues. Up to four 1 cc infusions of 98% ethanol were delivered in the VOM. Regardless of the reconnection pattern, ethanol infusion eliminated LIPV and LSPV reconnection in 23/32 and 13/30 patients, respectively. Ethanol terminated VOM and LIPV tachycardias in 2 patients. There were no acute procedural complications. CONCLUSIONS: VOM signals are consistently present in recurrent AF. VOM may rarely play a role in PV reconnection. However, VOM ethanol infusion can be useful in patients with recurrent AF after PVAI, assisting in achieving redisconnection of reconnected left PVs.

Neuronal stability and drift across periods of sleep: premotor activity patterns in a vocal control nucleus of adult zebra finches.

How stable are neural activity patterns compared across periods of sleep? We evaluated this question in adult zebra finches, whose premotor neurons in the nucleus robustus arcopallialis (RA) exhibit sequences of bursts during daytime singing that are characterized by precise timing relative to song syllables. Each burst has a highly regulated pattern of spikes. We assessed these spike patterns in singing that occurred before and after periods of sleep. For about half of the neurons, one or more premotor bursts had changed after sleep, an average of 20% of all bursts across all RA neurons. After sleep, modified bursts were characterized by a discrete, albeit modest, loss of spikes with compensatory increases in spike intervals, but not changes in timing relative to the syllable. Changes in burst structure followed both interrupted bouts of sleep (1.5-3 h) and full nights of sleep, implicating sleep and not circadian cycle as mediating these effects. Changes in burst structure were also observed during the day, but far less frequently. In cases where multiple bursts in the sequence changed in a single cell, the sequence position of those bursts tended to cluster together. Bursts that did not show discrete changes in structure also showed changes in spike counts, but not biased toward losses. We hypothesize that changes in burst patterns during sleep represent active sculpting of the RA network, supporting auditory feedback-mediated song maintenance.

Epiphenomenal Re-Entry and Spurious Focal Activation Detection by Atrial Fibrillation Mapping Algorithms.

OBJECTIVES: The purpose of this study was to validate the ability of mapping algorithms to detect rotational activations (RoA) and focal activations (FoA) during fibrillatory conduction (FC) and atrial fibrillation (AF) and understand their mechanistic relevance. BACKGROUND: Mapping algorithms have been proposed to detect RoA and FoA to guide AF ablation. METHODS: Rapid left atrial pacing created FC-fibrillatory electrograms-with and without AF induction in dogs (n = 17). Activation maps were constructed using Topera (Abbott, St. Paul, Minnesota) or CARTOFINDER (Biosense Webster, Irvine, California) algorithms. Mapping strategies included: panoramic noncontact mapping with a basket catheter (CARTOFINDER n = 6, Topera n = 5); and sequential contact mapping using 8-spline OctaRay catheter (Biosense Webster) (n = 6). Offline frequency and spectral analysis were also performed. Algorithm-detected RoA was manually verified. RESULTS: The right atrium (RA) consistently exhibited fibrillatory signals during FC. FC with and without AF had similar left-to-right frequency gradients. Basket maps were either uninterpretable (847 of 990 Topera, 132 of 148 Cartofinder) or had unverifiable RoA. OctaRay contact mapping showed 4% RoA (n = 30 of 679) and 63% FoA (n = 429 of 679). Verified RoA clustered at consistent sites, was more common in the RA than left atrium (odds ratio: 3.5), and colocalized with sites of frequency breakdown in the crista terminalis and RA appendage. During pacing, spurious FoA sites were identified around the atria, but not at the actual pacing sites. RoA and FoA site distribution was similar during pacing with and without induction, and during induced AF. CONCLUSIONS: Mapping algorithms were unable to detect pacing sites as true drivers of FC, and detected epiphenomenal RoA and FoA sites unrelated to AF induction or maintenance. Algorithm-detected RoA and FoA did not identify true AF drivers.

Venous anatomy of the left ventricular summit: Therapeutic implications for ethanol infusion.

BACKGROUND: Venous ethanol ablation (VEA) is effective for treatment of left ventricular (LV) summit (LVS) arrhythmias. The LVS venous anatomy is poorly understood and has inconsistent nomenclature. OBJECTIVE: The purpose of this study was to delineate the LVS venous anatomy by selective venography and 3-dimensional (3D) mapping during VEA and by venous-phase coronary computed tomographic angiography (vCTA). METHODS: We analyzed (1) LVS venograms and 3D maps of 53 patients undergoing VEA; and (2) 3D reconstructions of 52 vCTAs, tracing LVS veins. RESULTS: Angiography identified the following LVS veins: (1) LV annular branch of the great cardiac vein (GCV) (19/53); (2) septal (rightward) branches of the anterior ventricular vein (AIV) (53/53); and (3) diagonal branches of the AIV (51/53). Collateral connections between LVS veins and outflow, conus, and retroaortic veins were common. VEA was delivered to target arrhythmias in 38 of 53 septal, 6 of 53 annular, and 2 of 53 diagonal veins. vCTA identified LVS veins (range 1-5) in a similar distribution. GCV-AIV transition could either form an angle close to the left main artery bifurcation (n = 16; 88° ± 13°) or cut diagonally (n = 36; 133°±12°) (P ≤.001). Twenty-one patients had LV annular vein. In 28 patients only septal LVS veins were visualized in vCTA, in 2 patients only diagonal veins and in 22 patients both septal and diagonal veins were seen. In 39 patients the LVS veins reached the outflow tracts and their vicinity. CONCLUSION: We provide a systematic atlas and nomenclature of LVS veins related to arrhythmogenic substrates. vCTA can be useful for noninvasive evaluation of LVS veins before ethanol ablation.

Determinants of outcome impact of vein of Marshall ethanol infusion when added to catheter ablation of persistent atrial fibrillation: A secondary analysis of the VENUS randomized clinical trial.

BACKGROUND: The Vein of Marshall Ethanol for Untreated Persistent AF (VENUS) trial demonstrated that adding vein of Marshall (VOM) ethanol infusion to catheter ablation (CA) improves ablation outcomes in persistent atrial fibrillation (AF). There was significant heterogeneity in the impact of VOM ethanol infusion on rhythm control. OBJECTIVE: The purpose of this study was to assess the association between outcomes and (1) achievement of bidirectional perimitral conduction block and (2) procedural volume. METHODS: The VENUS trial randomized patients with persistent AF (N = 343) to CA combined with VOM ethanol or CA alone. The primary outcome (freedom from AF or atrial tachycardia [AT] lasting longer than 30 seconds after a single procedure) was analyzed by 2 categories: (1) successful vs no perimitral block and (2) high- (>20 patients enrolled) vs low-volume centers. RESULTS: In patients with perimitral block, the primary outcome was reached 54.3% after VOM-CA and 37% after CA alone (P = .01). Among patients without perimitral block, freedom from AF/AT was 34.0% after VOM-CA and 37.0% after CA (P = .583). In high-volume centers, the primary outcome was reached in 56.4% after VOM-CA and 40.2% after CA (P = .01). In low-volume centers, freedom from AF/AT was 30.77% after VOM-CA and 32.61% after CA (P = .84). In patients with successful perimitral block from high-volume centers, the primary outcome was reached in 59% after VOM-CA and 39.1% after CA (P = .01). Tests for interaction were significant (P = .002 for perimitral block and P = .04 for center volume). CONCLUSION: Adding VOM ethanol infusion to CA has a greater impact on outcomes when associated with perimitral block and performed in high-volume centers. Perimitral block should be part of the VOM procedure.

Double-balloon technique for retrograde venous ethanol ablation of ventricular arrhythmias in the absence of suitable intramural veins.

BACKGROUND: Venous ethanol infusion via an occlusive balloon has been used as a bailout approach to treat ablation-refractory ventricular arrhythmias (VAs). Unfavorable venous anatomy (lack of intramural veins at the targeted site or collateral vein-ethanol shunting) limits its efficacy. Blocking collateral flow with a second balloon may optimize myocardial ethanol delivery. OBJECTIVE: The purpose of this study was to validate the "double-balloon" approach to enhance ethanol delivery in cases of unfavorable venous anatomy. METHODS: Eight patients referred after failed ablations (3 left ventricular [LV] summit, 5 scar-related ventricular tachycardia) underwent endocardial mapping and additional radiofrequency ablation without VA resolution. Coronary veins were mapped using a multipolar catheter or wire, and selective venograms were obtained. The double balloon was used when (1) distal collateral branches shunted flow away from the targeted region; (2) the target vein had optimal signals only proximally; or (3) a large vein was targeted that had multiple branches for a large area of interest. RESULTS: Acute successful ethanol infusion myocardial delivery and resolution of VA was accomplished using the posterolateral LV veins (n = 2 patients, 3 procedures), lateral LV vein (n = 1), apical anterior interventricular vein (AIV; n = 1), middle cardiac vein (n = 1), and septal branches of the AIV (n = 3). At median follow-up of 313.5 days, 2 patients experienced recurrence. CONCLUSION: The double-balloon technique can enhance ethanol delivery to target isolated vein segments, block collateral flow, or target extensive areas, and can expand the utility of venous ethanol for treatment of VAs.

Intramural Venous Ethanol Infusion for Refractory Ventricular Arrhythmias: Outcomes of a Multicenter Experience.

OBJECTIVES: The aim of this study was to assess the long-term efficacy and outcomes of retrograde venous ethanol ablation in treating ventricular arrhythmias (VAs). BACKGROUND: Retrograde coronary venous ethanol ablation (RCVEA) can be effective for radiofrequency ablation (RFA)-refractory VAs, particularly those arising in the LV summit (LVS). METHODS: Patients with drug and RFA-refractory VAs were considered for RCVEA after RF failure attempts. Intramural coronary veins (tributaries of the great cardiac, anterior interventricular, lateral cardiac, posterolateral, and middle cardiac) were mapped using an angioplasty wire. Ethanol infusion was delivered in veins with appropriate signals. RESULTS: Of 63 patients (age 63 ± 14 years; 60% men) with VAs (71% extrasystole, 29% ventricular tachycardia, 76% LVS origin), RCVEA was performed in 56 patients who had suitable vein branches. These were defined as those amenable to cannulation and with intramural signals that preceded those mapped in the epicardium or endocardium and had better matching pace maps or entrainment responses. Seven patients had no suitable veins and underwent RFA. In 38 of 56 (68%) patients, the VAs were successfully terminated exclusively with ethanol infusion. In 17 of 56 (30%) patients, successful ablation was achieved using ethanol with adjunctive RFA in the vicinity of the infused vein due to acute recurrence or ethanol-induced change in VA morphology. Overall, isolated or adjuvant RCVEA was successful in 55 of 56 (98%) patients. At 1-year follow-up, 77% of patients were free of recurrent arrhythmias. Procedural complications included 2 venous dissections that led to pericardial effusions. CONCLUSIONS: RCVEA offers a significant long-term effective treatment for patients with drug and RF-refractory VAs.

Coronary vein defibrillator coil placement in patients with high defibrillation thresholds.

BACKGROUND: Elevated defibrillation threshold (DFT) occurs in 2%-6% of patients undergoing implantable cardioverter defibrillator (ICD) implantation. Adding a defibrillation coil in the coronary sinus (CS) or its branches can result in substantial reductions in the mean DFT. However, data regarding acute success and long-term stability remain lacking. We report our experience with this bailout strategy. METHODS: Patients with elevated DFT at implantation (safety margin at implantation <10 J) and those with failed ICD shocks for ventricular arrhythmias (VA) referred for high DFT underwent placement of an additional defibrillation coil in the CS. DFT testing was performed at the completion of the implantation procedure. External potentially reversible factors were excluded. High-output devices were systematically used. RESULTS: Four patients with high DFT at implantation and two with several failed shock attempts underwent placement of a defibrillation coil in the CS. Mean age was 41.8 (23-78). They presented a mean LVEF of 21% (15-30), QRS-complex duration of 109.8 milliseconds (87-168), body surface area of 1.96 m2 (1.45-2.58), and a mean R wave of 16.3 mV (8-27). Defibrillation coil implantation in the CS (final shocking configuration of right ventricle as anode and left ventricle (LV) plus can as cathode) was associated with successful DFT testing in all. Three patients had a concomitant LV lead for biventricular pacing. During a mean follow-up of 54.67 months (10-118), two patients experienced successful ICD shocks for VA (one of them also presented inappropriate shocks because of the fast conducting atrial fibrillation). CONCLUSIONS: Positioning of a defibrillation coil in the CS can result in a substantial reduction in mean DFT and associates with optimal long-term stability.

Left atrial appendage closure with the Watchman device using intracardiac vs transesophageal echocardiography: Procedural and cost considerations.

BACKGROUND: Imaging guidance for left atrial appendage (LAA) closure (LAAC) conventionally consists of transesophageal echocardiography (TEE) and fluoroscopy under general anesthesia (GA). Intracardiac echocardiography (ICE) can eliminate the need for GA, expedite procedural logistics, and reduce the patient experience to a simple venous puncture. OBJECTIVE: The purpose of this study was to define optimal ICE views and compare procedural parameters and cost of ICE vs TEE during LAAC with the Watchman device. METHODS: Optimal ICE views of the LAA for Watchman implant were delineated using Carto-Sound and 3-dimensional rendition of the LAA in 6 patients. Procedural and financial parameters of 104 consecutive patients with standard indications for LAAC undergoing Watchman implant using ICE guidance through a single transseptal puncture (n = 53 [51%]) were compared with those of TEE-guided implants (n = 51 [49%]) in 3 centers. RESULTS: Clinical characteristics were similar between the 2 groups. Total in-room, turnaround, and fluoroscopy times all were shorter using ICE (P <.05) under local anesthesia compared to the TEE group. Implant success was 100% in both groups without peri-device leaks or procedural complications. Follow-up TEE showed no significant peri-device leak in both groups. Total hospital charges for ICE with local anesthesia vs TEE were similar, as were total hospital direct and indirect costs. Professional fees were significantly lower with ICE and local anesthesia than with TEE because the charge of anesthesia staff was avoided. CONCLUSION: ICE-guided Watchman implant is safe, feasible, and comparable in cost to TEE during LAAC with a Watchman device but avoids GA and expedites procedure turnaround.

Atrioventricular ring reentry in embryonic mouse hearts.

BACKGROUND: During development, AV conduction switches from base-to-apex to apex-to-base conduction after emergence of the conduction system. We hypothesize that after this transition, the bulk of the AV ring, although no longer required for AV conduction, remains transiently able to conduct, providing a potential arrhythmia substrate. We studied AV conduction during this transition and its sensitivity to autonomic modulation. METHODS AND RESULTS: Simultaneous voltage and Ca2+ mapping with RH-237 and Rhod-2 was performed with 2 CCD cameras in embryonic mouse hearts (n = 43). Additionally, isolated calcium mapping was performed in 309 hearts with fluo-3AM. Propagation patterns in voltage and Ca2+ mapping coincided. Arrhythmias were uncommon under basal conditions, with AV block in 14 (4%) and junctional rhythms in 4 (1%). Arrhythmias increased after stimulation with isoproterenol-junctional rhythm in 9 (3%) and ventricular rhythms in 22 (6%)-although AV block decreased (3 hearts, 1%). Adding carbachol after isoproterenol caused dissociated antegrade and retrograde AV ring conduction in 30 (8.6%) of E10.5 and E11.5 hearts, occurring preferentially in the right and left sides of the ring, respectively. In 2 cases, reentry occurred circumferentially around the AV ring, perpendicular to normal propagation. Reentry persisted for multiple beats, lasting from 3 to 22 minutes. No episodes of AV ring reentry occurred in E9.5 hearts. CONCLUSIONS: AV ring reentry can occur by spatial dissociation of antegrade and retrograde conduction during combined adrenergic and muscarinic receptor stimulation. Critical maturation (> E9.5) seems to be required to sustain reentry.

Approaches to Left Atrial Appendage Closure: Device Design, Performance, and Limitations.

Up to 6.1 million people in the United States have atrial fibrillation (AF), which is associated with an increased risk of stroke. Oral anticoagulants are the mainstay of stroke prevention in AF. For decades, warfarin was the only available drug, fraught with compliance limitations, a narrow therapeutic window, and a high risk of hemorrhage. Pharmacologic developments have produced new anticoagulants that have improved the rates of stroke related to AF; however, they still confer a high risk of bleeding, making them unsuitable for some patients. Studies have shown that roughly 90% of strokes in patients with AF occur in the left atrial appendage (LAA). This understanding has prompted the development and testing of novel percutaneous strategies for LAA closure as an alternative to anticoagulation therapy. The following review examines the relative merits and shortcomings of these strategies and explores future prospects in the prevention of AF-related stroke.

The Human Left Atrial Venous Circulation as a Vascular Route for Atrial Pharmacological Therapies: Effects of Ethanol Infusion.

OBJECTIVES: This study catalogued the human venous left atrium (LA) circulation system and the ablative effects of ethanol in different branches. BACKGROUND: Vascular routes to target the LA could have significant therapeutic potential. Beyond the vein of Marshall (VOM), the fluoroscopic LA venous anatomy has not been described. METHODS: Patients undergoing ethanol infusion in the VOM as adjunctive therapy to atrial fibrillation (AF) catheter ablation were included in this study. Balloon occlusion venograms of the VOM and other LA veins were obtained in 218 patients. RESULTS: Sequentially from the coronary sinus (CS) ostium, LA veins included: 1) proximal septal vein draining the inferior septum; 2) inferior LA vein in the annular inferior LA; 3) VOM; 4) LA appendage vein; and 4) anterior LA vein. Additionally, venous sinuses not connected to the CS included roof veins and posterior wall veins, which drained into the right and left atria, respectively. Venous connections between LA veins through capillaries and with pulmonary veins were abundant. Extracardiac collateral vessels were present in 38 patients (17.4%). Ethanol infusion in LA veins led to tissue ablation in their corresponding regions. CONCLUSIONS: The atrial venous anatomy is amenable to selective cannulation. Consistent anatomical patterns are present. Targeting atrial tissues through atrial veins can be used for therapeutic purposes.

Circadian variations of stellate ganglion nerve activity in ambulatory dogs.

BACKGROUND: The presence of circadian variations in sympathetic outflow from the stellate ganglia is unclear. OBJECTIVES: The purpose of this study was to continuously record stellate ganglion nerve activity (SGNA) in ambulatory dogs. METHODS: We performed continuous 24-hour left (N = 3) or bilateral (N = 3) SGNA recordings in normal ambulatory dogs using implanted Data Sciences International transmitters. We also performed simultaneous ECG recording (n = 5) or simultaneous ECG and blood pressure recordings (n = 1). RESULTS: The total duration of continuous ambulatory recording averaged 41.5 +/- 16.6 days. Five dogs had persistent stable recording, and one dog developed hardware malfunction in week 3. SGNA was followed immediately (<1 second) by heart rate and blood pressure elevation and a reduced standard deviation of consecutive activation cycle length (SDNN) from 236 +/- 93 ms to 121 +/- 51 ms (P = 0.007). Heart rate correlated significantly with SGNA. When there was a sudden increase of SGNA, the sudden increase occurred bilaterally in 90% of the episodes. Both heart rate and SGNA showed statistically significant (P <.01) circadian variation. Nadolol (20 mg/day for 5 days) reduced average heart rate from 99 +/- 8 bpm at baseline to 88 +/- 9 bpm (N = 6, P = .001) but did not significantly alter SGNA. Immunohistochemical staining of the stellate ganglia showed tyrosine hydroxylase-positive ganglion cells and nerves at the recording site. CONCLUSION: There is a circadian variation in sympathetic outflow from canine stellate ganglia. Circadian variation of SGNA is an important cause of circadian variations of cardiac sympathetic tone.

Retrograde Coronary Venous Ethanol Infusion for Ablation of Refractory Ventricular Tachycardia.

BACKGROUND: Radiofrequency ablation (RFA) of ventricular tachycardia (VT) can fail because of inaccessibility to the VT substrate. Transarterial coronary ethanol ablation can be effective but entails arterial instrumentation risk. We hypothesized that retrograde coronary venous ethanol ablation can be an alternative bail-out approach to failed VT RFA. METHODS AND RESULTS: Out of 334 consecutive patients undergoing VT/premature ventricular contraction ablation, 7 patients underwent retrograde coronary venous ethanol ablation. Six out of 7 patients had failed RFA attempts (including epicardial in 3). Coronary venogram-guided venous mapping was performed using a 4F quadripolar catheter or an alligator-clip-connected angioplasty wire. Targeted veins included those with early presystolic potentials and pace-maps matching VT/premature ventricular contraction. An angioplasty balloon (1.5-2×6 mm) was used to deliver 1 to 4 cc of 98% ethanol into a septal branch of the anterior interventricular vein in 5 patients with left ventricular summit VT, a septal branch of the middle cardiac vein, and a posterolateral coronary vein (n=1 each). The clinical VT was successfully ablated acutely in all patients. There were no complications of retrograde coronary venous ethanol ablation, but 1 patient developed pericardial and pleural effusion attributed to pericardial instrumentation. On follow-up of 590±722 days, VT recurred in 4 out of 7 patients, 3 of whom were successfully reablated with RFA. CONCLUSIONS: Retrograde coronary venous ethanol ablation is safe and feasible as a bail-out approach to failed VT RFA, particularly those originating from the left ventricular summit.