Amino Terminal Acetylation of HOXB13 Regulates the DNA Damage Response in Prostate Cancer.

Advanced localized prostate cancers (PC) recur despite chemotherapy, radiotherapy and/or androgen deprivation therapy. We recently reported HOXB13 lysine (K)13 acetylation as a gain-of-function modification that regulates interaction with the SWI/SNF chromatin remodeling complex and is critical for anti-androgen resistance. However, whether acetylated HOXB13 promotes PC cell survival following treatment with genotoxic agents is not known. Herein, we show that K13-acetylated HOXB13 is induced rapidly in PC cells in response to DNA damage induced by irradiation (IR). It colocalizes with the histone variant γH2AX at sites of double strand breaks (DSBs). Treatment of PCs with the Androgen Receptor (AR) antagonist Enzalutamide (ENZ) did not suppress DNA-damage-induced HOXB13 acetylation. In contrast, HOXB13 depletion or loss of acetylation overcame resistance of PC cells to ENZ and synergized with IR. HOXB13K13A mutants show diminished replication fork progression, impaired G2/M arrest with significant cell death following DNA damage. Mechanistically, we found that amino terminus regulates HOXB13 nuclear puncta formation that is essential for proper DNA damage response. Therefore, targeting HOXB13 acetylation with CBP/p300 inhibitors in combination with DNA damaging therapy may be an effective strategy to overcome anti-androgen resistance of PCs.

Adult-to-adult right lobe graft living donor liver transplantation for acute-on-chronic liver failure: a single-centre retrospective study in Vietnam.

Introduction: Acute-on-chronic liver failure (ACLF) has a high mortality rate, and liver transplantation is considered a definite treatment for patients with this condition. This study aims to evaluate the outcomes of living donor liver transplantation (LDLT) in ACLF patients in a single centre in a lower middle-income country, Vietnam. Materials and methods: This was a retrospective study at the 108 Military Central Hospital (Hanoi, Vietnam), enroling 51 patients diagnosed with ACLF based on Asian Pacific Association for the Study of the Liver (APASL) criteria who underwent LDLT with a right lobe graft from December 2019 to December 2022. The authors utilize the model for end-stage liver disease (MELD) and APASL ACLF Research Consortium (AARC) scores to evaluate and stratify the severity of ACLF. Results: The average age of all patients was 47.27±13.61, with 88.24% being male. The average BMI was 22.78±2.61. The most common underlying liver disease was chronic viral hepatitis B (88.2%). The average MELD score of the patients was 34.90±5.61, with 33.3% having MELD score greater than or equal to 40. In terms of ACLF severity, five patients (9.8%) had grade I ACLF, 35 patients (68.6%) had grade II ACLF, and 11 patients (21.6%) had grade III ACLF. The average AARC score was 9.43±1.68. The duration of treatment in the ICU was 8.59±7.27 days, and the length of hospital stay was 28.02±13.45 days. The most common post-transplant complication was biliary complication (19.61%). Death occurred in 7 patients (13.7%). The survival rates at 6 months, 1 year, and 3 years were 84%, 81.7%, and 81.7%, respectively. Conclusion: Living donor liver transplantation for ACLF patients is safe and has a high post-transplant survival rate. Multidisciplinary care before, during, and after surgery, and the decision to do a liver transplant early, is essential in saving the lives of ACLF patients.

Bioconjugated liquid-like solid enhances characterization of solid tumor - chimeric antigen receptor T cell interactions.

Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable success as an immunotherapy for hematological malignancies, and its potential for treating solid tumors is an active area of research. However, limited trafficking and mobility of T cells within the tumor microenvironment (TME) present challenges for CAR T cell therapy in solid tumors. To gain a better understanding of CAR T cell function in solid tumors, we subjected CD70-specific CAR T cells to a challenge by evaluating their immune trafficking and infiltration through a confined 3D microchannel network in a bio-conjugated liquid-like solid (LLS) medium. Our results demonstrated successful CAR T cell migration and anti-tumor activity against CD70-expressing glioblastoma and osteosarcoma tumors. Through comprehensive analysis of cytokines and chemokines, combined with in situ imaging, we elucidated that immune recruitment occurred via chemotaxis, and the effector-to-target ratio plays an important role in overall antitumor function. Furthermore, through single-cell collection and transcriptomic profiling, we identified differential gene expression among the immune subpopulations. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach. STATEMENT OF SIGNIFICANCE: The use of specialized immune cells named CAR T cells to combat cancers has demonstrated remarkable success against blood cancers. However, this success is not replicated in solid tumors, such as brain or bone cancers, mainly due to the physical barriers of these solid tumors. Currently, preclinical technologies do not allow for reliable evaluation of tumor-immune cell interactions. To better study these specialized CAR T cells, we have developed an innovative in vitro three-dimensional model that promises to dissect the interactions between tumors and CAR T cells at the single-cell level. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach.

Facilitated Myocardial Ablation Using Heat-Sensitive Liposomes Containing Doxorubicin: A Proof-of-Concept Preclinical Study.

The authors sought to evaluate a method for improving radiofrequency (RF) lesion durability using doxorubicin encased in heat-sensitive liposomes (HSL-dox). Using a porcine model, RF ablations were performed in the right atrium after systemic infusion of either HSL-dox or saline control given immediately before mapping and ablation. Lesion geometry was measured with voltage mapping immediately postablation and after 2 weeks of survival. After 2 weeks, lesions demonstrated less regression in scar area in HSL-dox-exposed animals compared with control animals. We demonstrate improved RF lesion durability in animals treated with HSL-dox, and the cardiotoxic effect was more pronounced after RF applications with higher power and longer duration.

Three-Dimensional Bioconjugated Liquid-Like Solid (LLS) Enhance Characterization of Solid Tumor - Chimeric Antigen Receptor T cell interactions.

Cancer immunotherapy offers lifesaving treatments for cancers, but the lack of reliable preclinical models that could enable the mechanistic studies of tumor-immune interactions hampers the identification of new therapeutic strategies. We hypothesized 3D confined microchannels, formed by interstitial space between bio-conjugated liquid-like solids (LLS), enable CAR T dynamic locomotion within an immunosuppressive TME to carry out anti-tumor function. Murine CD70-specific CAR T cells cocultured with the CD70-expressing glioblastoma and osteosarcoma demonstrated efficient trafficking, infiltration, and killing of cancer cells. The anti-tumor activity was clearly captured via longterm in situ imaging and supported by upregulation of cytokines and chemokines including IFNg, CXCL9, CXCL10, CCL2, CCL3, and CCL4. Interestingly, target cancer cells, upon an immune attack, initiated an "immune escape" response by frantically invading the surrounding microenvironment. This phenomenon however was not observed for the wild-type tumor samples which remained intact and produced no relevant cytokine response. Single cells collection and transcriptomic profiling of CAR T cells at regions of interest revealed feasibility of identifying differential gene expression amongst the immune subpopulations. Complimentary 3D in vitro platforms are necessary to uncover cancer immune biology mechanisms, as emphasized by the significant roles of the TME and its heterogeneity.

mRNA challenge predicts brain cancer immunogenicity and response to checkpoint inhibitors.

To prospectively determine whether brain tumors will respond to immune checkpoint inhibitors (ICIs), we developed a novel mRNA vaccine as a viral mimic to elucidate cytokine release from brain cancer cells in vitro. Our results indicate that cytokine signatures following mRNA challenge differ substantially from ICI responsive versus non-responsive murine tumors. These findings allow for creation of a diagnostic assay to quickly assess brain tumor immunogenicity, allowing for informed treatment with ICI or lack thereof in poorly immunogenic settings.

Ambient circulation surrounding an ablation catheter tip affects ablation lesion characteristics.

INTRODUCTION: The association between ambient circulating environments (CEs) and ablation lesions has been largely underexplored. METHODS: Viable bovine myocardium was placed in a saline bath in an ex vivo endocardial model. Radiofrequency (RF) ablation was performed using three different ablation catheters: 3.5 mm open irrigated (OI), 4, and 8 mm. Variable flow rates of surrounding bath fluids were applied to simulate standard flow, high flow, and no flow. For in vivo epicardial ablation, 24 rats underwent a single OI ablation and performed with circulating saline (30 ml/min; n = 12), versus those immersed in saline without circulation (n = 12). RESULTS: High flow reduced ablation lesion volumes for all three catheters. In no-flow endocardial CE, both 4 mm and OI catheters produced smaller lesions compared with standard flow. However, the 8 mm catheter produced the largest lesions in a no-flow CE. Ablation performed in an in vivo model with CE resulted in smaller lesions compared with ablation performed in a no-flow environment. No statistically significant differences in steam pops were found among the groups. CONCLUSION: A higher endocardial CE flow can decrease RF effectiveness. Cardiac tissue subjected to no endocardial CE flow may also limit RF for 4 mm catheters, but not for OI catheters; these findings may have implications for RF ablation safety and efficacy, especially in the epicardial space without circulating fluid or in the endocardium under varying flow conditions.

Evaluating temperature gradients across the posterior left atrium with radiofrequency ablation.

INTRODUCTION: Esophageal injury is a well-known complication associated with catheter ablation. Though novel methods to mitigate esophageal injury have been developed, few studies have evaluated temperature gradients with catheter ablation across the posterior wall of the left atrium, interstitium, and esophagus. METHODS: To investigate temperature gradients across the tissue, we developed a porcine heart-esophageal model to perform ex vivo catheter ablation on the posterior wall of the left atrium (LA), with juxtaposed interstitial tissue and esophagus. Circulating saline (5 L/min) was used to mimic blood flow along the LA and alteration of ionic content to modulate impedance. Thermistors along the region of interest were used to analyze temperature gradients. Varying time and power, radiofrequency (RF) ablation lesions were applied with an externally irrigated ablation catheter. Ablation strategies were divided into standard approaches (SAs, 10-15 g, 25-35 W, 30 s) or high-power short duration (HPSD, 10-15 g, 40-50 W, 10 s). Temperature gradients, time to the maximum measured temperature, and the relationship between measured temperature as a function of distance from the site of ablation was analyzed. RESULTS: In total, five experiments were conducted each utilizing new porcine posterior LA wall-esophageal specimens for RF ablation (n = 60 lesions each for SA and HPSD). For both SA and HPSD, maximum temperature rise from baseline was markedly higher at the anterior wall (AW) of the esophagus compared to the esophageal lumen (SA: 4.29°C vs. 0.41°C, p < .0001 and HPSD: 3.13°C vs. 0.28°C, p < .0001). Across ablation strategies, the average temperature rise at the AW of the esophagus was significantly higher with SA relative to HPSD ablation (4.29°C vs. 3.13°C, p = .01). From the start of ablation, the average time to reach a maximum temperature as measured at the AW of the esophagus with SA was 36.49 ± 12.12 s, compared to 16.57 ± 4.54 s with HPSD ablation, p < .0001. Fit to a linear scale, a 0.37°C drop in temperature was seen for every 1 cm increase in distance from the site of ablation and thermistor location at the AW of the esophagus. CONCLUSION: Both SA and HPSD ablation strategies resulted in markedly higher temperatures measured at the AW of the esophagus compared to the esophageal lumen, raising concern about the value of clinical intraluminal temperature monitoring. The temperature rise at the AW was lower with HPSD. A significant time delay was seen to reach the maximum measured temperature and a modest increase in distance between the site of ablation and thermistor location impacted the accuracy of monitored temperatures.

Glucose dissociates DDX21 dimers to regulate mRNA splicing and tissue differentiation.

Glucose is a universal bioenergy source; however, its role in controlling protein interactions is unappreciated, as are its actions during differentiation-associated intracellular glucose elevation. Azido-glucose click chemistry identified glucose binding to a variety of RNA binding proteins (RBPs), including the DDX21 RNA helicase, which was found to be essential for epidermal differentiation. Glucose bound the ATP-binding domain of DDX21, altering protein conformation, inhibiting helicase activity, and dissociating DDX21 dimers. Glucose elevation during differentiation was associated with DDX21 re-localization from the nucleolus to the nucleoplasm where DDX21 assembled into larger protein complexes containing RNA splicing factors. DDX21 localized to specific SCUGSDGC motif in mRNA introns in a glucose-dependent manner and promoted the splicing of key pro-differentiation genes, including GRHL3, KLF4, OVOL1, and RBPJ. These findings uncover a biochemical mechanism of action for glucose in modulating the dimerization and function of an RNA helicase essential for tissue differentiation.

Needle-Tipped Catheter Ablation of Papillary Muscle Results in Deeper and Larger Ablation Lesions.

Ventricular tachycardia associated with papillary muscle (PM) is often refractory to standard radiofrequency ablation (RFA). The needle-tipped ablation catheter (NT-AC) has been used to treat deep intramyocardial substrates, but its use for PM has not been characterized. Using an ex vivo experimental platform, both 3 mm and 6 mm NT-AC created larger ablation lesion volumes and depths than open-irrigated ablation catheter did (OI-AC; e.g., 57.12 ± 9.70mm3 and 2.42 ± 0.22 mm, respectively; p < 0.01 for all comparisons). Longer NT-AC extension (6 mm) resulted in greater ablation lesion volumes and maximum depths (e.g., 333.14 ± 29.13mm3 and 6.46 ± 0.29 mm, respectively, compared to the shorter 3 mm NT-AC extension, 143.33 ± 12.77mm3, and 4.46 ± 0.14 mm; both p < 0.001). There were no steam pops. In conclusion, for PM ablation, the NT-AC was able to achieve ablation lesions that were larger and deeper than with conventional OI-AC. Ablation of PM may be another application for needle-tip ablation. Further studies are warranted to establish long-term safety and efficacy in human studies.

Catheter Ablation for Atrial Fibrillation in Adult Congenital Heart Disease: An International Multicenter Registry Study.

BACKGROUND: Data on atrial fibrillation (AF) ablation and outcomes are limited in patients with congenital heart disease (CHD). We aimed to investigate the characteristics of patients with CHD presenting for AF ablation and their outcomes. METHODS: A multicenter, retrospective analysis was performed of patients with CHD undergoing AF ablation between 2004 and 2020 at 13 participating centers. The severity of CHD was classified using 2014 Pediatric and Congenital Electrophysiology Society/Heart Rhythm Society guidelines. Clinical data were collected. One-year complete procedural success was defined as freedom from atrial tachycardia or AF in the absence of antiarrhythmic drugs or including previously failed antiarrhythmic drugs (partial success). RESULTS: Of 240 patients, 127 (53.4%) had persistent AF, 62.5% were male, and mean age was 55.2±13.3 years. CHD complexity categories included 147 (61.3%) simple, 68 (28.3%) intermediate, and 25 (10.4%) severe. The most common CHD type was atrial septal defect (n=78). More complex CHD conditions included transposition of the great arteries (n=14), anomalous pulmonary veins (n=13), tetralogy of Fallot (n=8), cor triatriatum (n=7), single ventricle physiology (n=2), among others. The majority (71.3%) of patients had trialed at least one antiarrhythmic drug. Forty-six patients (22.1%) had reduced systemic ventricular ejection fraction <50%, and mean left atrial diameter was 44.1±8.2 mm. Pulmonary vein isolation was performed in 227 patients (94.6%); additional ablation included left atrial linear ablations (40%), complex fractionated atrial electrogram (19.2%), and cavotricuspid isthmus ablation (40.8%). One-year complete and partial success rates were 45.0% and 20.5%, respectively, with no significant difference in the rate of complete success between complexity groups. Overall, 38 patients (15.8%) required more than one ablation procedure. There were 3 (1.3%) major and 13 (5.4%) minor procedural complications. CONCLUSIONS: AF ablation in CHD was safe and resulted in AF control in a majority of patients, regardless of complexity. Future work should address the most appropriate ablation targets in this challenging population.

Proper Orthogonal Decomposition Analysis Reveals Cell Migration Directionality During Wound Healing.

A proper orthogonal decomposition (POD) order reduction method was implemented to reduce the full high dimensional dynamical system associated with a wound healing cell migration assay to a low-dimensional approximation that identified the prevailing cell trajectories. The POD analysis generated POD modes that were representative of the prevalent cell trajectories. The shapes of the POD modes depended on the location of the cells with respect to the wound and exposure to disturbed (DF) or undisturbed (UF) fluid flow where the net flow was in the antegrade direction with a retrograde component or fully antegrade, respectively. For DF and UF, the POD modes of the downstream cells identified trajectories that moved upstream against the flow, while upstream POD modes exhibited sideways cell migrations. In the absence of flow, no major shape differences were observed in the POD modes on either side of the wound. The POD modes also served to reconstruct the cell migration of individual cells. With as few as three modes, the predominant cell migration trajectories were reconstructed, while the level of accuracy increased with the inclusion of more POD modes. The POD order reduction method successfully identified the predominant cell migratory trajectories under static and varying pulsatile fluid flow conditions serving as a first step in the development of artificial intelligence models of cell migration in disease and development.

Acetylated HOXB13 Regulated Super Enhancer Genes Define Therapeutic Vulnerabilities of Castration-Resistant Prostate Cancer.

PURPOSE: Androgen receptor (AR) antagonism is exacerbated by HOXB13 in castration-resistant prostate cancers (CRPC). However, it is unclear when and how HOXB13 primes CRPCs for AR antagonism. By mass-spectrometry analysis of CRPC extract, we uncovered a novel lysine 13 (K13) acetylation in HOXB13 mediated by CBP/p300. To determine whether acetylated K13-HOXB13 is a clinical biomarker of CRPC development, we characterized its role in prostate cancer biology. EXPERIMENTAL DESIGN: We identified tumor-specific acK13-HOXB13 signal enriched super enhancer (SE)-regulated targets. We analyzed the effect of loss of HOXB13K13-acetylation on chromatin binding, SE proximal target gene expression, self-renewal, enzalutamide sensitivity, and CRPC tumor growth by employing isogenic parental and HOXB13K13A mutants. Finally, using primary human prostate organoids, we evaluated whether inhibiting an acK13-HOXB13 target, ACK1, with a selective inhibitor (R)-9b is superior to AR antagonists in inhibiting CRPC growth. RESULTS: acK13-HOXB13 promotes increased expression of lineage (AR, HOXB13), prostate cancer diagnostic (FOLH1), CRPC-promoting (ACK1), and angiogenesis (VEGFA, Angiopoietins) genes early in prostate cancer development by establishing tumor-specific SEs. acK13-HOXB13 recruitment to key SE-regulated targets is insensitive to enzalutamide. ACK1 expression is significantly reduced in the loss of function HOXB13K13A mutant CRPCs. Consequently, HOXB13K13A mutants display reduced self-renewal, increased sensitivity to enzalutamide, and impaired xenograft tumor growth. Primary human prostate tumor organoids expressing HOXB13 are significantly resistant to AR antagonists but sensitive to (R)-9b. CONCLUSIONS: In summary, acetylated HOXB13 is a biomarker of clinically significant prostate cancer. Importantly, PSMA-targeting agents and (R)-9b could be new therapeutic modalities to target HOXB13-ACK1 axis regulated prostate cancers.

CAR T Cell Locomotion in Solid Tumor Microenvironment.

The promising outcomes of chimeric antigen receptor (CAR) T cell therapy in hematologic malignancies potentiates its capability in the fight against many cancers. Nevertheless, this immunotherapy modality needs significant improvements for the treatment of solid tumors. Researchers have incrementally identified limitations and constantly pursued better CAR designs. However, even if CAR T cells are armed with optimal killer functions, they must overcome and survive suppressive barriers imposed by the tumor microenvironment (TME). In this review, we will discuss in detail the important role of TME in CAR T cell trafficking and how the intrinsic barriers contribute to an immunosuppressive phenotype and cancer progression. It is of critical importance that preclinical models can closely recapitulate the in vivo TME to better predict CAR T activity. Animal models have contributed immensely to our understanding of human diseases, but the intensive care for the animals and unreliable representation of human biology suggest in vivo models cannot be the sole approach to CAR T cell therapy. On the other hand, in vitro models for CAR T cytotoxic assessment offer valuable insights to mechanistic studies at the single cell level, but they often lack in vivo complexities, inter-individual heterogeneity, or physiologically relevant spatial dimension. Understanding the advantages and limitations of preclinical models and their applications would enable more reliable prediction of better clinical outcomes.

3D In Vitro Platform for Cell and Explant Culture in Liquid-like Solids.

Existing 3D cell models and technologies have offered tools to elevate cell culture to a more physiologically relevant dimension. One mechanism to maintain cells cultured in 3D is by means of perfusion. However, existing perfusion technologies for cell culture require complex electronic components, intricate tubing networks, or specific laboratory protocols for each application. We have developed a cell culture platform that simply employs a pump-free suction device to enable controlled perfusion of cell culture media through a bed of granular microgels and removal of cell-secreted metabolic waste. We demonstrated the versatile application of the platform by culturing single cells and keeping tissue microexplants viable for an extended period. The human cardiomyocyte AC16 cell line cultured in our platform revealed rapid cellular spheroid formation after 48 h and ~90% viability by day 7. Notably, we were able to culture gut microexplants for more than 2 weeks as demonstrated by immunofluorescent viability assay and prolonged contractility.

Perpendicular catheter orientation during papillary muscle ablation results in larger, deeper lesions.

INTRODUCTION: Ablation of papillary muscles (PMs) for refractory ventricular arrhythmias can often be challenging. The catheter approach and orientation during ablation may affect optimal radiofrequency (RF) delivery. Yet, no previous study investigated the association between catheter orientation and PM lesion size. We evaluated ablation lesion characteristics with various catheter orientations relative to the PM tissue during open irrigated ablation, using a standardized, experimental setting. METHODS: Viable bovine PM was positioned on a load cell in a circulating saline bath. RF ablation was performed over PM tissue at 50 W, with the open irrigated catheter positioned either perpendicular or parallel to the PM surface. Applied force was 10 g. Ablation lesions were sectioned and underwent quantitative morphometric analysis. RESULTS: A catheter position oriented directly perpendicular to the PM tissue resulted in the largest ablation lesion volumes and depths compared with ablation with the catheter parallel to PM tissue (75.26 ± 8.40 mm3 vs. 34.04 ± 2.91 mm3 , p < .001) and (3.33 ± 0.18 mm vs. 2.24 ± 0.10 mm, p < .001), respectively. There were no significant differences in initial impedance, peak voltage, peak current, or overall decrease in impedance among groups. Parallel catheter orientation resulted in higher peak temperature (41.33 ± 0.28°C vs. 40.28 ± 0.24°C, p = .003), yet, there were no steam pops in either group. CONCLUSION: For PM ablation, catheter orientation perpendicular to the PM tissue achieves more effective and larger ablation lesions, with greater lesion depth. This may have implications for the chosen ventricular access approach, the type of catheter used, consideration for remote navigation, and steerable sheaths.

Opportunities and challenges in heart rhythm research: Rationale and development of an electrophysiology collaboratory.

There are many challenges in the current landscape of electrophysiology (EP) clinical and translational research, including increasing costs and complexity, competing demands, regulatory requirements, and challenges with study implementation. This review seeks to broadly discuss the state of EP research, including challenges and opportunities. Included here are results from a Heart Rhythm Society (HRS) Research Committee member survey detailing HRS members' perspectives regarding both barriers to clinical and translational research and opportunities to address these challenges. We also provide stakeholder perspectives on barriers and opportunities for future EP research, including input from representatives of the U.S. Food and Drug Administration, industry, and research funding institutions that participated in a Research Collaboratory Summit convened by HRS. This review further summarizes the experiences of the heart failure and heart valve communities and how they have approached similar challenges in their own fields. We then explore potential solutions, including various models of research ecosystems designed to identify research challenges and to coordinate ways to address them in a collaborative fashion in order to optimize innovation, increase efficiency of evidence generation, and advance the development of new therapeutic products. The objectives of the proposed collaborative cardiac EP research community are to encourage and support scientific discourse, research efficiency, and evidence generation by exploring collaborative and equitable solutions in which stakeholders within the EP community can interact to address knowledge gaps, innovate, and advance new therapies.

Increased incidence of cavotricuspid isthmus atrial flutter following slow pathway ablation.

PURPOSE: The incidence of atrial flutter following radiofrequency ablation of supraventricular tachycardias is poorly understood. Ablation of atrioventricular nodal reentry tachycardia may place patients at risk of flutter because ablation of the slow pathway is in close proximity to the cavotricuspid isthmus. This study aims to evaluate the risk of atrial flutter following ablation of atrioventricular nodal reentry tachycardia relative to ablation of other supraventricular tachycardias. METHODS: A single-center retrospective analysis was completed for all supraventricular tachycardia ablations performed between July 2006 and July 2016. Patient and procedural details were collected for 544 patients who underwent atrioventricular nodal reentry tachycardia ablation (n = 342), atrioventricular reentry tachycardia ablation (n = 125), or atrial tachycardia ablation (n = 60). Follow-up for flutter after ablation of their incident arrhythmia was assessed. RESULTS: Patients who underwent atrioventricular nodal reentry tachycardia ablation were more likely to develop CTI-dependent flutter than patients who underwent ablation of other supraventricular tachycardias (4.97% vs. 0%; p = 0.002). Compared with patients who did not develop flutter, patients who developed flutter after atrioventricular nodal reentry tachycardia ablation were more likely to have undergone ablation of atypical atrioventricular nodal reentry tachycardia (11.8% vs. 2.15%; p = 0.016). CONCLUSIONS: We identified an association between atrioventricular nodal reentry tachycardia ablation and development of CTI-dependent atrial flutter. This finding may have implications for the management and follow-up after atrioventricular nodal reentry tachycardia ablation.

Open surgical ablation of ventricular tachycardia: Utility and feasibility of contemporary mapping and ablation tools.

BACKGROUND: Ventricular tachycardia (VT) catheter ablation success may be limited when transcutaneous epicardial access is contraindicated. Surgical ablation (SurgAbl) is an option, but ablation guidance is limited without simultaneously acquired electrophysiological data. OBJECTIVE: We describe our SurgAbl experience utilizing contemporary electroanatomic mapping (EAM) among patients with refractory VT storm. METHODS: Consecutive patients with recurrent VT despite antiarrhythmic drugs (AADs) and prior ablation, for whom percutaneous epicardial access was contraindicated, underwent open SurgAbl using intraoperative EAM guidance. RESULTS: Eight patients were included, among whom mean age was 63 ± 5 years, all were male, mean left ventricular ejection fraction was 39% ± 12%, and 2 (25%) had ischemic cardiomyopathy. Reasons for surgical epicardial access included dense adhesions owing to prior cardiac surgery, hemopericardium, or pericarditis (n = 6); or planned left ventricular assist device (LVAD) implantation at time of SurgAbl (n = 2). Cryoablation guided by real-time EAM was performed in all. Goals of clinical VT noninducibility or core isolation were achieved in 100%. VT burden was significantly reduced, from median 15 to 0 events in the month pre- and post-SurgAbl (P = .01). One patient underwent orthotopic heart transplantation for recurrent VT storm 2 weeks post-SurgAbl. Over mean follow-up of 3.4 ± 1.7 years, VT storm-free survival was achieved in 6 (75%); all continued AADs, although at lower dose. CONCLUSION: Surgical mapping and ablation of refractory VT with use of contemporary EAM is feasible and effective, particularly among patients with contraindication to percutaneous epicardial access or with another indication for cardiac surgery.