One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids.

Optimization of CRISPR/Cas9-mediated genome engineering has resulted in base editors that hold promise for mutation repair and disease modeling. Here, we demonstrate the application of base editors for the generation of complex tumor models in human ASC-derived organoids. First we show efficacy of cytosine and adenine base editors in modeling CTNNB1 hot-spot mutations in hepatocyte organoids. Next, we use C > T base editors to insert nonsense mutations in PTEN in endometrial organoids and demonstrate tumorigenicity even in the heterozygous state. Moreover, drug sensitivity assays on organoids harboring either PTEN or PTEN and PIK3CA mutations reveal the mechanism underlying the initial stages of endometrial tumorigenesis. To further increase the scope of base editing we combine SpCas9 and SaCas9 for simultaneous C > T and A > G editing at individual target sites. Finally, we show that base editor multiplexing allow modeling of colorectal tumorigenesis in a single step by simultaneously transfecting sgRNAs targeting five cancer genes.

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.

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.

Organoid modeling reveals the tumorigenic potential of the alveolar progenitor cell state.

Alveolar type 2 (AT2) cells, the epithelial progenitor cells of the distal lung, are known to be the prominent cell of origin for lung adenocarcinoma. The regulatory programs that control chromatin and gene expression in AT2 cells during the early stages of tumor initiation are not well understood. Here, we dissected the response of AT2 cells to Kras activation and p53 loss (KP) using combined single cell RNA and ATAC sequencing in an established tumor organoid system. Multi-omic analysis showed that KP tumor organoid cells exhibit two major cellular states: one more closely resembling AT2 cells (SPC-high) and another with loss of AT2 identity (hereafter, Hmga2-high). These cell states are characterized by unique transcription factor (TF) networks, with SPC-high states associated with TFs known to regulate AT2 cell fate during development and homeostasis, and distinct TFs associated with the Hmga2-high state. CD44 was identified as a marker of the Hmga2-high state, and was used to separate organoid cultures for functional comparison of these two cell states. Organoid assays and orthotopic transplantation studies indicated that SPC-high cells have higher tumorigenic capacity in the lung microenvironment compared to Hmga2-high cells. These findings highlight the utility of understanding chromatin regulation in the early oncogenic versions of epithelial cells, which may reveal more effective means to intervene the progression of Kras-driven lung cancer.

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.

Advanced Techniques for Ethanol Ablation of Left Ventricular Summit Region Arrhythmias.

BACKGROUND: Coronary venous ethanol ablation (VEA) can be used as a strategy to treat ventricular arrhythmias arising from the left ventricular summit, but collateral flow and technical challenges cannulating intramural veins in complex venous anatomies can limit its use. Advanced techniques for VEA can capitalize on collateral vessels between target and nontarget sites to improve success. METHODS: Of 55 patients with left ventricular summit ventricular arrhythmia, advanced techniques were used in 15 after initial left ventricular summit intramural vein mapping failed to show suitable targets for single vein, single-balloon VEA. All patients had previous radiofrequency ablation attempts. Techniques included: double-balloon for distal protection to block distal flow and target the proximal portion of a large intramural vein where best signal was proximal (n=6); balloons in 2 different left ventricular summit veins for a cross-fire multivein VEA (n=4); intramural collateral vein-to-vein cannulation to reach of targeted vein via collateral with antegrade ethanol and proximal balloon block (n=2); prolonged ethanol dwell time for vein sclerosis of large intramural vein and subsequent VEA (n=3); and intramural collateral VEA (n=1). RESULTS: Fifteen (8 females) patients (age 60.6±17.6 years) required advanced techniques. Procedure time was 210±49.9 minutes, fluoroscopy time was 25.3±14.1 minutes, and 113±17.9 cc of contrast was utilized. A median of 7 cc of ethanol was delivered (range, 4-15 cc). Intraprocedural radiofrequency ablation was delivered before ethanol in 9 out of 15 patients but failed. Ethanol achieved acute success in all 15 patients. Ethanol was used as the sole treatment in two patients. At a median follow-up of 194 days, one patient experienced recurrence. CONCLUSIONS: Advanced techniques capitalizing on venous anatomy can enable successful VEA and selective targeting of arrhythmogenic sites, by blocking distal flow, utilization of collaterals between nontarget and target veins and multivein VEA. Understanding individual anatomy is critical for VEA success.

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.

Association of acute kidney injury with outcomes in patients undergoing percutaneous left atrial appendage closure.

OBJECTIVES: Using a large nationally representative database, we aimed to examine risk factors for acute kidney injury (AKI) and its association with outcomes in patients undergoing percutaneous left atrial appendage closure (LAAC). BACKGROUND: Previous small-scale studies have reported poor outcomes with AKI following percutaneous LAAC. METHODS: We queried the Nationwide Readmission Database to identify LAAC procedures performed from 2016 to 2017. Multivariable logistic and linear regression models were used to identify risk factors for AKI and determine the association between AKI and clinical outcomes. The primary outcome of interest was in-hospital mortality. RESULTS: Of 20,703 patients who underwent LAAC during the study period, 1,097 (5.3%) had a diagnosis of AKI. Chronic kidney disease, non-elective admission, coagulopathy, weight loss, prior coronary artery disease, heart failure, diabetes mellitus, and anemia were independently associated with an increased risk of AKI after LACC. In patients undergoing LAAC, AKI was associated with an increased risk of in-hospital mortality (adjusted odds ratio [aOR], 16.01; 95% CI, 8.48-30.21), stroke/transient ischemic attack (aOR, 2.50; 95% CI, 1.69-3.70), systemic embolization (aOR, 3.78; 95% CI, 1.64-8.70), bleeding/transfusion (aOR, 1.96; 95% CI, 1.50-2.56), vascular complications (aOR, 3.53; 95% CI, 1.94-6.42), pericardial tamponade requiring intervention (aOR, 6.83; 95% CI, 4.37-10.66), index length of stay (adjusted parameter estimate, 7.46; 95% CI, 7.02-7.92), and 180-day all-cause readmissions (aOR, 1.43; 95% CI, 1.09-1.88). CONCLUSION: AKI in the setting of LAAC is uncommon but is associated with poor clinical outcomes. Further studies are needed to determine if a similar association exists for long-term outcomes.

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.

Neuromodulatory Approaches for Atrial Fibrillation Ablation.

In this review, the authors describe evolving alternative strategies for the management of AF, focusing on non-invasive and percutaneous autonomic modulation. This modulation can be achieved - among other approaches - via tragus stimulation, renal denervation, cardiac afferent denervation, alcohol injection in the vein of Marshall, baroreceptor activation therapy and endocardial ganglionated plexi ablation. Although promising, these therapies are currently under investigation but could play a role in the treatment of AF in combination with conventional pulmonary vein isolation in the near future.

Arrhythmias in COVID-19.

The coronavirus pandemic remains a major public health burden with multisystem disease manifestations. There has been an ongoing global effort to better understand the unique cardiovascular manifestations of this disease and its associated arrhythmias. In this review, we summarize the current data on incidence and outcomes of arrhythmias in the acute and convalescent period, possible pathophysiologic mechanisms, and medical management. Sinus bradycardia-reported in multiple observational studies in the acute infectious period-stands out as an unexpected inflammatory response. Atrial fibrillation has been noted as the most common pathologic arrhythmia and has been shown to be a poor prognostic marker in multiple cohorts. In the convalescent period, long-term complications such as postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia have been described.

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.

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.

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.

Device Therapy for Sudden Cardiac Death Prophylaxis After Acute Coronary Syndrome: When and Why?

Implantable cardioverter-defibrillators (ICDs) are a powerful tool in preventing sudden cardiac death due to ventricular arrhythmias in ischemic cardiomyopathy. ICD indications and timing in acute coronary syndromes are unclear. PURPOSE OF REVIEW: We reviewed several trials that delineated the indications for a cardiac defibrillator in patients with coronary artery disease. RECENT FINDINGS: The role of cardiac defibrillators in secondary prevention has been well established by AVID, CIDS, and CASH trials. AVID showed reduction in both all-cause mortality and arrhythmic death while the two smaller trials showed only improvement in arrhythmic death. Similarly, trials like MADIT, CABG Patch, MUSTT, MADIT-II, DINAMIT, and the IRIS trial have fine-tuned the indications for ICD in primary prevention of sudden cardiac death. Benefits of an ICD were most pronounced in those with reduced ejection fraction and 40 days or more since myocardial infarction or in those who were not immediately post revascularization. The recent VEST trial aimed to study wearable cardioverter-defibrillators (WCDs) in patients who did not have an indication for an implantable defibrillator. The arrhythmic deaths (1.6% vs. 2.4%) were not reduced by the WCD. Based on consistent reduction in arrhythmic death in all primary and secondary prevention trials, defibrillators are effective in carefully selected patients.

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.