Publications by authors named "Duy T Nguyen"

76 Publications

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

Cells 2022 03 11;11(6). Epub 2022 Mar 11.

Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, FL 32611, USA.

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.
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http://dx.doi.org/10.3390/cells11060967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946834PMC
March 2022

The esophagus going steady.

J Cardiovasc Electrophysiol 2022 May 21;33(5):917-919. Epub 2022 Mar 21.

Stanford University, Stanford, California, USA.

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http://dx.doi.org/10.1111/jce.15448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018585PMC
May 2022

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

J Cardiovasc Electrophysiol 2022 Apr 15;33(4):690-695. Epub 2022 Feb 15.

Section of Cardiac Electrophysiology, Division of Cardiovascular Medicine, Stanford University, Stanford, California, USA.

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 mm vs. 34.04 ± 2.91 mm , 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.
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http://dx.doi.org/10.1111/jce.15408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9041130PMC
April 2022

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

J Interv Card Electrophysiol 2021 Sep 17. Epub 2021 Sep 17.

Section of Electrophysiology, Cardiology Division, University of Colorado, Aurora, CO, 80045, USA.

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.
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http://dx.doi.org/10.1007/s10840-021-01065-0DOI Listing
September 2021

Stent strut streamlining and thickness reduction promote endothelialization.

J R Soc Interface 2021 08 18;18(181):20210023. Epub 2021 Aug 18.

Department of Mechanical and Industrial Engineering, University of Massachusetts Amherst, Amherst, MA 01003, USA.

Stent thrombosis (ST) carries a high risk of myocardial infarction and death. Lack of endothelial coverage is an important prognostic indicator of ST after stenting. While stent strut thickness is a critical factor in ST, a mechanistic understanding of its effect is limited and the role of haemodynamics is unclear. Endothelialization was tested using a wound-healing assay and five different stent strut models ranging in height between 50 and 150 µm for circular arc (CA) and rectangular (RT) geometries and a control without struts. Under static conditions, all stent strut surfaces were completely endothelialized. Reversing pulsatile disturbed flow caused full endothelialization, except for the stent strut surfaces of the 100 and 150 µm RT geometries, while fully antegrade pulsatile undisturbed flow with a higher mean wall shear stress caused only the control and the 50 µm CA geometries to be fully endothelialized. Modest streamlining and decrease in height of the stent struts improved endothelial coverage of the peri-strut and stent strut surfaces in a haemodynamics dependent manner. This study highlights the impact of the stent strut height (thickness) and geometry (shape) on the local haemodynamics, modulating reendothelialization after stenting, an important factor in reducing the risk of stent thrombosis.
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http://dx.doi.org/10.1098/rsif.2021.0023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371379PMC
August 2021

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

Heart Rhythm O2 2021 Jun 11;2(3):271-279. Epub 2021 May 11.

University of Colorado School of Medicine, Division of Cardiology, Section of Cardiac Electrophysiologist, Aurora, Colorado.

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 ( = .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.
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http://dx.doi.org/10.1016/j.hroo.2021.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322924PMC
June 2021

Uncovering a unique path: Antidromic AVRT utilizing a left anteroseptal Mahaim-like accessory pathway.

Pacing Clin Electrophysiol 2021 01 25;44(1):185-188. Epub 2020 Aug 25.

Section of Electrophysiology, Brigham and Women's Hospital, Boston, Massachusetts.

A 40-year-old man presented to our emergency department 2 hours after onset of shortness of breath, palpitations, and presyncope secondary to an adenosine-responsive wide complex tachycardia. Electrophysiology study was diagnostic for antidromic atrioventricular (AV) reentrant tachycardia utilizing a muscular connection from the anterior interventricular vein to the left ventricle with Mahaim-like properties, successfully treated with ablation in the distal coronary sinus (CS) system. This case highlights accessory pathways (a) with unique features (i.e., Mahaim-like characteristics) and (b) involving musculature from the distal CS system, thereby limiting the value of endocardial ablation for durable treatment. Importantly, the coronary venous system is an accessible vascular network for evaluation and catheter ablation of such arrhythmias.
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http://dx.doi.org/10.1111/pace.14024DOI Listing
January 2021

Lymphatic Valves Separate Lymph Flow Into a Central Stream and a Slow-Moving Peri-Valvular Milieu.

J Biomech Eng 2020 10;142(10)

Department of Mechanical and Industrial Engineering, University of Massachusetts, N575 Life Sciences Laboratory, 240 Thatcher Way Amherst Amherst, MA 01003; Department of Biomedical Engineering, University of Massachusetts, Amherst, MA 01003.

The lymphatic system plays a pivotal role in the transport of fats, waste, and immune cells, while also serving as a metastatic route for select cancers. Using live imaging and particle tracking, we experimentally characterized the lymph flow field distal from the inguinal lymph node in the vicinity of normal bileaflet and malformed unileaflet intraluminal valves. Particle tracking experiments demonstrated that intraluminal lymphatic valves concentrate higher velocity lymph flow in the center of the vessel, while generating adjacent perivalvular recirculation zones. The recirculation zones are characterized by extended particle residence times and low wall shear stress (WSS) magnitudes in comparison to the rest of the lymphangion. A malformed unileaflet valve skewed lymph flow toward the endothelium on the vessel wall, generating a stagnation point and a much larger recirculation zone on the opposite wall. These studies define physical consequences of bileaflet and unileaflet intraluminal lymphatic valves that affect lymph transport and the generation of a heterogeneous flow field that affects the lymphatic endothelium nonuniformly. The characterized flow fields were recreated in vitro connecting different flow environments present in the lymphangion to a lymphatic endothelial cell (LEC) pro-inflammatory phenotype. Unique and detailed insight into lymphatic flow is provided, with potential applications to a variety of diseases that affect lymph transport and drug delivery.
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http://dx.doi.org/10.1115/1.4048028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477708PMC
October 2020

The New Normal.

JACC Clin Electrophysiol 2020 06;6(6):693-695

Division of Cardiology and Cardiovascular Institute, Stanford University, Stanford, California, USA.

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http://dx.doi.org/10.1016/j.jacep.2020.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244828PMC
June 2020

Patient Selection for Epicardial Ablation-Part II: The Epicardial Approach and Current Challenges Associated with Epicardial Ablation.

J Innov Card Rhythm Manag 2019 Nov 15;10(11):3906-3912. Epub 2019 Nov 15.

Section of Cardiac Electrophysiology, Division of Cardiology, University of Colorado Denver, Aurora, CO, USA.

Since their inception, percutaneous epicardial approaches have become increasingly common in clinical practice with the advent of new technology and the growth of catheter ablation for both ventricular and supraventricular arrhythmias. In addition to identifying the arrhythmogenic foci, there remain challenges to successful epicardial ablation such as the choice of energy source, optimizing irrigation during ablation, and anatomic barriers such as epicardial fat and coronary vessels. The performance of continued translational studies to understand how each of these factors contribute to lesion formation will be essential to guide future advances in the field of epicardial ablation.
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http://dx.doi.org/10.19102/icrm.2019.101105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252684PMC
November 2019

Patient Selection for Epicardial Ablation-Part I: The Role of Epicardial Ablation in Various Cardiac Disease States.

J Innov Card Rhythm Manag 2019 Nov 15;10(11):3897-3905. Epub 2019 Nov 15.

Section of Cardiac Electrophysiology, Division of Cardiology, University of Colorado Denver, Aurora, CO, USA.

Epicardial catheter ablation is most commonly performed following unsuccessful endocardial ablation. Given the frequency of epicardial substrates in certain cardiomyopathic disease states, however, a combined endocardial-epicardial approach should be considered as a primary treatment strategy. Although epicardial ablation is primarily deployed in patients with ventricular arrhythmias, the role of epicardial approaches in supraventricular tachycardias (eg, atrial fibrillation, inappropriate sinus tachycardia, and-rarely-accessory pathways) is growing, with continued advances being made.
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http://dx.doi.org/10.19102/icrm.2019.101104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252769PMC
November 2019

Patients with bicuspid aortic valves may be associated with infra-hisian conduction disease requiring pacemakers.

J Interv Card Electrophysiol 2021 Jun 26;61(1):29-35. Epub 2020 May 26.

Section of Cardiac Electrophysiology, Department of Medicine, Cardiology Division, Stanford University, 870 Quarry Road Extension, Stanford, CA, 94305, USA.

Background: Bicuspid aortic valves (BAVs) are associated with accelerated valvular dysfunction. Increasing rates of conduction system disease are seen in patients with calcific tricuspid aortic valves (TAVs). However, little is known regarding the extent of conduction disorders in BAV patients. We sought to determine the extent of infra-hisian conduction pathology among patients with BAVs undergoing EP studies.

Methods: We prospectively analyzed patients presenting to the EP laboratory from 2006 to 2017 at our institution. Thirty-three BAV patients had measured HV intervals. Each individual was matched by age and gender to two control patients. Clinical characteristics were collected and compared, and patients followed for outcomes.

Results: The BAV cohort had a mean age of 47.8 ± 17.2 years (range 19-76 years). Indications for referral to the EP lab in the BAV cohort included SVT ablation (n = 16), VT ablation (n = 10), and EP study for syncope, pre-syncope, or palpitations (n = 29). Patients with BAVs had a mean HV interval of 58.7 ms ± 18.6 ms, compared to a mean of 47.2 ms ± 9.6 ms for controls (p value = 0.0001). Over a 10-year follow-up period, 9 BAV patients (27%) went on to require permanent pacing compared to 6 patients (9%) in the control group (p value = 0.03).

Conclusion: Compared to patients with TAVs presenting for EP evaluation, individuals with BAVs have longer HV intervals and a significantly increased requirement for pacemaker therapy over long-term follow-up. Closer monitoring of progressive conduction system disease in BAV patients may be warranted.
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http://dx.doi.org/10.1007/s10840-020-00785-zDOI Listing
June 2021

Letter in reply: Continuous radiofrequency ablation in scar-based arrhythmia substrate.

J Cardiovasc Electrophysiol 2020 07 19;31(7):1892. Epub 2020 May 19.

Section of Cardiac Electrophysiology, Division of Cardiovascular Medicine, Stanford University, Stanford, California.

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http://dx.doi.org/10.1111/jce.14534DOI Listing
July 2020

Use of cell phone adapters is associated with reduction in disparities in remote monitoring of cardiac implantable electronic devices.

J Interv Card Electrophysiol 2021 Apr 12;60(3):469-475. Epub 2020 May 12.

University of Colorado, Aurora, CO, 80045, USA.

Background: Remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) is standard of care. However, it is underutilized. In July 2012, our institution began providing cell phone adapters (CPAs) to patients free of charge following CIED implantation to improve remote transmission (RT) adherence.

Methods: Patients in our institution's RM database from January 1, 2010, thru June 30, 2015, were retrospectively reviewed. There were 2157 eligible patients. Remote transmission proportion (RTP) and time to transmission (TT) were compared pre- and post-implementation of free CPA. Chi-squared analysis and Kruskal-Wallis tests were performed to compare RTP and TT.

Results: There was a significant increase in RTP (134 [18.4%] vs 99 [54.7%]; p < 0.001) and decrease in median TT in days (189[110-279] vs 58 [10-149]; p < 0.001) after CPAs were provided to patients. Caucasian patients were more likely than African Americans and Hispanics to use RM prior to CPAs (p = 0.04). After the implementation of CPAs, there was a significant increase in RTP for all racial groups (< 0.001) with no difference in RTP among racial groups (p = 0.18). The RTP for urban residents was significantly greater than non-urban residents with CPAs (p = 0.008). Patients greater than 70 years of age were significantly less likely to participate in RT before and after CPAs were provided (p = 0.03, p = 0.01, respectively).

Conclusions: CPAs significantly improve RTP and reduce median TT for all patients regardless of race, geographic residence, and age (> 70 years old to lesser extent). Broad institution of CPAs following ICD implantation could potentially reduce disparity in RTP and deserves more study.
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http://dx.doi.org/10.1007/s10840-020-00743-9DOI Listing
April 2021

Continuous ablation improves lesion maturation compared with intermittent ablation strategies.

J Cardiovasc Electrophysiol 2020 07 27;31(7):1687-1693. Epub 2020 Apr 27.

Section of Cardiac Electrophysiology, Division of Cardiovascular Medicine, Stanford University, Stanford, California.

Background: Interrupted ablation is increasingly proposed as part of high-power short-duration radiofrequency ablation (RFA) strategies and may also result from loss of contact from respiratory patterns or cardiac motion. To study the extent that ablation interruption affects lesions.

Methods: In ex vivo and in vivo experiments, lesion characteristics and tissue temperatures were compared between continuous (group 1) and interrupted (groups 2 and 3) RFA with equal total ablation duration and contact force. Extended duration ablation lesions were also characterized from 1 to 5 minutes.

Results: In the ex vivo study, continuous RFA (group 1) produced larger total lesion volumes compared with each interrupted ablation lesion group (273.8 ± 36.5 vs 205.1 ± 34.2 vs 174.3 ± 32.3 mm , all P < .001). Peak temperatures for group 1 were higher at 3 and 5 mm than groups 2 and 3. In vivo, continuous ablation resulted in larger lesions, greater lesion depths, and higher tissue temperatures. Longer ablation durations created larger lesion volumes and increased lesion depths. However, after 3 minutes of ablation, the rate of lesion volume, and depth formation decreased.

Conclusions: Continuous RFA delivery resulted in larger and deeper lesions with higher tissue temperatures compared with interrupted ablation. This study may have implications for high-power short duration ablation strategies, motivates strategies to reduce variations in ablation delivery, and provides an upper limit for ablation duration beyond which power delivery has diminishing returns.
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http://dx.doi.org/10.1111/jce.14510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534961PMC
July 2020

Ablation of Supraventricular Tachycardias From Concealed Left-Sided Nodoventricular and Nodofascicular Accessory Pathways.

Circ Arrhythm Electrophysiol 2020 05 14;13(5):e007853. Epub 2020 Apr 14.

Division of Cardiology, University of California San Francisco, San Francisco, CA (R.C.-G., M.M.S.).

Background: Nodoventricular and nodofascicular accessory pathways (AP) are uncommon connections between the atrioventricular node and the fascicles or ventricles.

Methods: Five patients with nodofascicular or nodoventricular tachycardia were studied.

Results: We identified 5 patients with concealed, left-sided nodoventricular (n=4), and nodofascicular (n=1) AP. We proved the participation of AP in tachycardia by delivering His-synchronous premature ventricular contractions that either delayed the subsequent atrial electrogram or terminated the tachycardia (n=3), and by observing an increase in VA interval coincident with left bundle branch block (n=2). The APs were not atrioventricular pathways because the septal VA interval during tachycardia was <70 ms in 3, 1 had spontaneous atrioventricular dissociation, and in 1 the atria were dissociated from the circuit with atrial overdrive pacing. Entrainment from the right ventricle showed ventricular fusion in 4 out of 5 cases. A left-sided origin of the AP was suspected after failed ablation of the right inferior extension of atrioventricular node in 3 cases and by observing a VA increase with left bundle branch block in 2 cases. The nodofascicular and 3 of the nodoventricular AP were successfully ablated from within the proximal coronary sinus (CS) guided by recorded potentials at the roof of the CS, and 1 nodoventricular AP was ablated via a transseptal approach near the CS os.

Conclusions: Left-sided nodofascicular and nodoventricular AP appear to connect the ventricles with the CS musculature in the region of the CS os. Mapping and successful ablation sites can be guided by recording potentials within or near the CS os.
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http://dx.doi.org/10.1161/CIRCEP.119.007853DOI Listing
May 2020

Direct Thrombin Inhibitors as an Alternative to Heparin During Catheter Ablation: A Multicenter Experience.

JACC Clin Electrophysiol 2020 05 26;6(5):484-490. Epub 2020 Feb 26.

Division of Cardiology, University of California San Francisco, San Francisco, California, USA. Electronic address:

Objectives: The goal of this study was to report a multicenter series of left-sided catheter ablations performed by using intravenous direct thrombin inhibitors (DTIs) as an alternative to heparin.

Background: Amidst a looming worldwide shortage of heparin, there are insufficient data to guide nonheparin-based peri-procedural anticoagulation in patients undergoing catheter ablation.

Methods: This study reviewed all catheter ablations at 6 institutions between 2006 and 2019 to assess the safety and efficacy of DTIs for left-sided radiofrequency catheter ablation of atrial fibrillation and ventricular tachycardia.

Results: In total, 53 patients (age 63.0 ± 9.3 years, 68% male, CHA₂DS₂-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category] score 2.8 ± 1.6, left ventricular ejection fraction 46 ± 15%) underwent ablation with DTIs (75% bivalirudin, 25% argatroban) due to heparin contraindication(s) (72% heparin-induced thrombocytopenia, 21% heparin allergy, 4% protamine reaction, and 4% religious reasons). The patient's usual oral anticoagulant was continued without interruption in 69%. Procedures were performed for atrial fibrillation (64%) or ventricular tachycardia/premature ventricular contractions (36%). Transseptal puncture was undertaken in 81%, and a contact force-sensing catheter was used in 70%. Vascular ultrasound was used in 71%, and femoral arterial access was gained in 36%. A bolus followed by infusion was used in all but 4 cases, and activated clotting time was monitored peri-procedurally in 72%, with 32% receiving additional boluses. Procedure duration was 216 ± 116 min, and ablation time was 51 ± 22 min. No major bleeding or embolic complications were observed. Four patients had minor self-limiting bleeding complications, including a small pericardial effusion (<1 cm), a small groin hematoma, and hematuria.

Conclusions: In this multicenter series, intravenous DTIs were safely used as an alternative to heparin for left-sided catheter ablation.
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http://dx.doi.org/10.1016/j.jacep.2019.12.003DOI Listing
May 2020

Letter in reply: Forging ahead: Update on radiofrequency ablation technology and techniques.

J Cardiovasc Electrophysiol 2020 05 6;31(5):1240. Epub 2020 Mar 6.

Division of Cardiology, Section of Electrophysiology, Stanford University, Stanford, California.

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http://dx.doi.org/10.1111/jce.14412DOI Listing
May 2020

Impact of epicardial adipose tissue and catheter ablation strategy on biophysical parameters and ablation lesion characteristics.

J Cardiovasc Electrophysiol 2020 05 18;31(5):1114-1124. Epub 2020 Feb 18.

Section of Cardiac Electrophysiology, Division of Cardiology, Stanford University, Palo Alto, California.

Background: Epicardial adipose (EA) tissue may limit effective radiofrequency ablation (RFA).

Objectives: We sought to evaluate the lesion formation of different ablation strategies on ventricular myocardium with overlying EA.

Methods: Bovine myocardium with EA was placed in a circulating saline bath in an ex vivo model. Open-irrigated (OI) RFA was performed, parallel to the myocardium, over fat at 50 W for variable RF durations, variable contact force, catheter configurations (unipolar RF vs bipolar RF), and catheter irrigants (normal saline vs half-normal saline). Ablation was also performed with a needle-tipped ablation catheter (NTAC), perpendicular to the myocardium.

Results: Increasingly thick EA attenuated lesion size regardless of ablation strategy. RF applied with longer durations and increasing CF produced larger lesion volumes and deeper lesions with ablation over EA more than 3 mm but was unable to produce measurable lesions when EA less than 3 mm. Similarly, ablation with half normal saline irrigant created slightly deeper lesions than bipolar RF and unipolar RF with normal saline as EA thickness increased, but was unable to produce measurable lesions when EA more than 3 mm. Of all ablation strategies, only NTAC produced effective lesion volumes when ablating over thick (>3 mm) EA.

Conclusions: While EA attenuates lesion depth and size, relatively larger, and deeper lesions can be achieved with longer RFA duration, higher CF, half normal saline irrigant, and, to a greater extent, by utilizing bipolar RF or NTAC, but only over thin adipose (<3 mm). Of those catheters/strategies tested, only NTAC was able to effectively deliver RF over thick (>3 mm) EA with this model.
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http://dx.doi.org/10.1111/jce.14383DOI Listing
May 2020

RADAR: A Multicenter Food and Drug Administration Investigational Device Exemption Clinical Trial of Persistent Atrial Fibrillation.

Circ Arrhythm Electrophysiol 2020 01 16;13(1):e007825. Epub 2020 Jan 16.

Helmsley Electrophysiology Center, Icahn School of Medicine at Mount Sinai, New York, NY (S.C., S.R.D., W.W., V.Y.R.).

Background: Pulmonary vein isolation is insufficient to treat all patients with persistent atrial fibrillation (AF), and effective adjunctive ablation strategies are needed. Ablation of AF drivers holds promise, but current technologies to identify drivers are limited by spatial resolution. In a single-arm, first-in-human, investigator-initiated Food and Drug Administration Investigational Device Exemption study, we used a novel system for real-time, high-resolution identification of AF drivers in persistent AF.

Methods: Patients with persistent or long-standing persistent AF underwent ablation using the RADAR (Real-Time Electrogram Analysis for Drivers of Atrial Fibrillation) system in conjunction with a standard electroanatomical mapping system. After pulmonary vein isolation, electrogram and spatial information was streamed to the RADAR system and analyzed to identify driver domains to target for ablation.

Results: Across 4 centers, 64 subjects were enrolled: 73% male, age, 64.7±9.5 years; body mass index, 31.7±6.0 kg/m; left atrium size, 54±10 mm, with persistent/long-standing persistent AF in 53 (83%)/11 (17%), prior AF ablation (re-do group) in 26 (41%). After 12.6±0.8 months follow-up, 68% remained AF-free off all antiarrhythmics; 74% remained AF-free and 66% remained AF/atrial tachycardia/atrial flutter-free on or off AADs (antiarrhythmic drugs). AF terminated with ablation in 35 patients (55%) overall and in 23/38 (61%) of de novo ablation patients. For patients with AF termination during ablation, 82% remained AF-free and 74% AF/atrial tachycardia/atrial flutter-free during follow-up on or off AADs. Patients undergoing first-time ablation generally had higher rates of freedom from AF than the re-do group.

Conclusions: This novel technology for panoramic mapping of AF drivers showed promising results in a persistent/long-standing persistent AF population. These data provide the scientific basis for a randomized trial.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03263702; IDE#G170049.
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http://dx.doi.org/10.1161/CIRCEP.119.007825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970579PMC
January 2020

Forging ahead: Update on radiofrequency ablation technology and techniques.

J Cardiovasc Electrophysiol 2020 01 18;31(1):360-369. Epub 2019 Dec 18.

Section of Electrophysiology, Division of Cardiology, Stanford University, Palo Alto, California.

Innovations in radiofrequency (RF) ablation and nonablative techniques have led to significant advances in addressing complex arrhythmogenic substrates for a variety of cardiac arrhythmias. Anatomical challenges, deep substrate, and mid-myocardial locations may pose difficulties and decrease success rates using routine methods. In this review, we provide an update on novel RF technology and techniques including (a) high-power, low-duration ablation, (b) ablation facilitated by low-ionic irrigant, and (c) bipolar ablation. In addition, we review emerging technologies including electroporation, needle catheter ablation, and ablation with the lattice catheter.
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http://dx.doi.org/10.1111/jce.14317DOI Listing
January 2020

Follow-Up After Catheter Ablation of Papillary Muscles and Valve Cusps.

JACC Clin Electrophysiol 2019 10 28;5(10):1185-1196. Epub 2019 Aug 28.

University of Colorado, Section of Cardiac Electrophysiology, Division of Cardiology, Aurora, Colorado. Electronic address:

Objectives: The goal of this study was to determine the impact of catheter ablation in the region of papillary muscles (PMs) and valvular cusps (VC) on mitral, tricuspid, or aortic valve function.

Background: Ventricular arrhythmias arising from PMs and VCs often require extensive catheter ablation. Little is known regarding the risk of valve dysfunction after radiofrequency catheter ablation of such arrhythmias.

Methods: A retrospective analysis was completed for 149 PM and VC VT/premature ventricular contraction (PVC) ablations from 2008 to 2018 at our institution. Patient and procedural details were collected for VT and PVC ablation cases involving PMs and VCs with available echocardiographic data pre-ablation and post-ablation (within 6 months). Degree of valvular regurgitation (VR) was graded from 0 (none) to 4 (severe), and significant valvular dysfunction was defined as a 2+ change in VR.

Results: Of 149 radiofrequency catheter ablation cases, there were 84 (56%) aortic valve cusp ablations, 60 (40%) left ventricular PM ablations, and 5 (3%) right ventricular PM ablations. There were no statistically significant differences between pre-ablation and post-ablation VR severity (p = 0.33). No patients had a 2+ grade change in VR severity when pre-ablation and post-ablation echocardiograms were compared. There were no significant sequelae requiring intervention in the post-ablation period. On follow-up of 36 ± 9 months, for those with a change in VR, the severity had improved to baseline or remained stable.

Conclusions: Despite often-times extensive ablation on and around valvular networks, risk of longstanding or permanent valvular dysfunction after VT/PVC ablation is rare.
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http://dx.doi.org/10.1016/j.jacep.2019.07.004DOI Listing
October 2019

Moving the needle: Tissue characterization and lesion formation during infusion-needle ablation.

Heart Rhythm 2020 03 12;17(3):406-407. Epub 2019 Oct 12.

Cardiovascular Institute and Department of Medicine, Stanford University, Stanford, California. Electronic address:

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http://dx.doi.org/10.1016/j.hrthm.2019.10.018DOI Listing
March 2020

Bipolar radiofrequency ablation creates different lesion characteristics compared to simultaneous unipolar ablation.

J Cardiovasc Electrophysiol 2019 12 13;30(12):2960-2967. Epub 2019 Oct 13.

Section of Cardiac Electrophysiology, Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts.

Introduction: Both bipolar and simultaneous radiofrequency ablation (bRFA, simRFA) have been used to treat thick midmyocardial substrate as well as during circular, multipolar ablation between shorter distances.

Objectives: We sought to evaluate the biophysical parameters of simRFA, sequential unipolar RFA (seqRFA), and bRFA.

Methods: Bovine myocardium was placed in a circulating saline bath. To simulate thick substrate conditions, two open irrigated ablation catheters were oriented across from each other, with myocardium in between. Thermocouples were placed in the center, ±2 mm, of the myocardium. Unipolar ablations were performed sequentially or simultaneously at 50 W for 60 seconds and compared to bRFA using the same settings. In addition, to simulate multipolar ablation, two open irrigated ablation catheters were oriented on the same side and perpendicular to myocardium at 1, 2, and 4 mm spacing. SimRFA were performed at 15 and 25 W for 60 seconds and compared to bRFA.

Results: For thicker tissue, simRFA produced similar lesion volume and depth compared to bRFA but with a lesion geometry similar to seqRFA. Unlike seqRFA and simRFA, bRFA had a necrotic core spanning the myocardium. Core depths, volumes, and temperatures were significantly greater for bRFA lesions compared to simRFA or seqRFA (Figure, P < .001). Similar results were consistent for bRFA and simRFA at shorter spacings.

Conclusions: BRFA has greater core lesion temperatures, corresponding to a denser and larger necrotic core, than either simRFA or seqRFA. This may have implications for considering the optimal strategy for deep midmyocardial substrates or during multipolar ablation.
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http://dx.doi.org/10.1111/jce.14213DOI Listing
December 2019

The Homeobox gene, HOXB13, Regulates a Mitotic Protein-Kinase Interaction Network in Metastatic Prostate Cancers.

Sci Rep 2019 07 4;9(1):9715. Epub 2019 Jul 4.

Department of Surgery, Washington University in St. Louis, MO, USA.

HOXB13, a homeodomain transcription factor, is linked to recurrence following radical prostatectomy. While HOXB13 regulates Androgen Receptor (AR) functions in a context dependent manner, its critical effectors in prostate cancer (PC) metastasis remain largely unknown. To identify HOXB13 transcriptional targets in metastatic PCs, we performed integrative bioinformatics analysis of differentially expressed genes (DEGs) in the proximity of the human prostate tumor-specific AR binding sites. Unsupervised Principal Component Analysis (PCA) led to a focused core HOXB13 target gene-set referred to as HOTPAM9 (HOXB13 Targets separating Primary And Metastatic PCs). HOTPAM9 comprised 7 mitotic kinase genes overexpressed in metastatic PCs, TRPM8, and the heat shock protein HSPB8, whose levels were significantly lower in metastatic PCs compared to the primary disease. The expression of a two-gene set, CIT and HSPB8 with an overall balanced accuracy of 98.8% and a threshold value of 0.2347, was sufficient to classify metastasis. HSPB8 mRNA expression was significantly increased following HOXB13 depletion in multiple metastatic CRPC models. Increased expression of HSPB8 by the microtubule inhibitor Colchicine or by exogenous means suppressed migration of mCRPC cells. Collectively, our results indicate that HOXB13 promotes metastasis of PCs by coordinated regulation of mitotic kinases and blockade of a putative tumor suppressor gene.
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http://dx.doi.org/10.1038/s41598-019-46064-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609629PMC
July 2019

Ankyrin-B dysfunction predisposes to arrhythmogenic cardiomyopathy and is amenable to therapy.

J Clin Invest 2019 07 2;129(8):3171-3184. Epub 2019 Jul 2.

Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Arrhythmogenic cardiomyopathy (ACM) is an inherited arrhythmia syndrome characterized by severe structural and electrical cardiac phenotypes, including myocardial fibrofatty replacement and sudden cardiac death. Clinical management of ACM is largely palliative, owing to an absence of therapies that target its underlying pathophysiology, which stems partially from our limited insight into the condition. Following identification of deceased ACM probands possessing ANK2 rare variants and evidence of ankyrin-B loss of function on cardiac tissue analysis, an ANK2 mouse model was found to develop dramatic structural abnormalities reflective of human ACM, including biventricular dilation, reduced ejection fraction, cardiac fibrosis, and premature death. Desmosomal structure and function appeared preserved in diseased human and murine specimens in the presence of markedly abnormal β-catenin expression and patterning, leading to identification of a previously unknown interaction between ankyrin-B and β-catenin. A pharmacological activator of the WNT/β-catenin pathway, SB-216763, successfully prevented and partially reversed the murine ACM phenotypes. Our findings introduce what we believe to be a new pathway for ACM, a role of ankyrin-B in cardiac structure and signaling, a molecular link between ankyrin-B and β-catenin, and evidence for targeted activation of the WNT/β-catenin pathway as a potential treatment for this disease.
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http://dx.doi.org/10.1172/JCI125538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668697PMC
July 2019

Electrophysiologic testing for diagnostic evaluation and risk stratification in patients with suspected cardiac sarcoidosis with preserved left and right ventricular systolic function.

J Cardiovasc Electrophysiol 2019 10 23;30(10):1939-1948. Epub 2019 Jul 23.

Division of Cardiology, Section of Cardiac Electrophysiology, University of Colorado, Aurora, Colorado.

Introduction: While cardiac sarcoidosis (CS) carries a risk of ventricular arrhythmias (VAs) and sudden cardiac death (SCD), risk stratification of patients with CS and preserved left ventricular/right ventricular (LV/RV) systolic function remains challenging. We sought to evaluate the role of electrophysiologic testing and programmed electrical stimulation of the ventricle (EPS) in patients with suspected CS with preserved ventricular function.

Methods: One hundred twenty consecutive patients with biopsy-proven extracardiac sarcoidosis and preserved LV/RV systolic function underwent EPS. All patients had either probable CS defined by an abnormal cardiac positron emission tomography or cardiac magnetic resonance imaging, or possible CS with normal advanced imaging but abnormal echocardiogram (ECG), SAECG, Holter, or clinical factors. Patients were followed for 4.5 ± 2.6 years for SCD and VAs.

Results: Seven of 120 patients (6%) had inducible ventricular tachycardia (VT) with EPS and received an implantable cardioverter defibrillator (ICD). Three patients (43%) with positive EPS later had ICD therapies for VAs. Kaplan-Meier analysis stratified by EPS demonstrated a significant difference in freedom from VAs and SCD (P = 0.009), though this finding was driven entirely by patients within the cohort with probable CS (P = 0.018, n = 69). One patient with possible CS and negative EPS had unrecognized progression of the disease and unexplained death with evidence of CS at autopsy.

Conclusions: EPS is useful in the risk stratification of patients with probable CS with preserved LV and RV function. A positive EPS was associated with VAs. While a negative EPS appeared to confer low risk, close follow-up is needed as EPS cannot predict fatal VAs related to new cardiac involvement or disease progression.
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http://dx.doi.org/10.1111/jce.14058DOI Listing
October 2019

Ambulatory Rhythm Monitoring to Detect Late High-Grade Atrioventricular Block Following Transcatheter Aortic Valve Replacement.

J Am Coll Cardiol 2019 05;73(20):2538-2547

University of Colorado School of Medicine, Division of Cardiology, Aurora, Colorado. Electronic address:

Background: High-grade atrioventricular block (H-AVB) is a well-described in-hospital complication of transcatheter aortic valve replacement (TAVR). Delayed high-grade atrioventricular block (DH-AVB) has not been systematically studied among outpatients post-TAVR, using latest-generation TAVR technology and in the early post-TAVR discharge era.

Objectives: The purpose of this study was to assess utility of ambulatory event monitoring (AEM) in identifying post-TAVR DH-AVB and associated risk factors.

Methods: Patients without pre-existing pacing device undergoing TAVR at the University of Colorado Hospital from October 2016 to March 2018, and who did not require permanent pacemaker implantation pre-discharge, were discharged with 30-day AEM to assess for DH-AVB (≥2 days post-TAVR). Clinical and follow-up data were collected and compared among those without incident H-AVB.

Results: Among 150 consecutive TAVR patients without a prior pacing device, 18 (12%) developed H-AVB necessitating permanent pacemaker <2 days post-TAVR, 1 died pre-discharge, and 13 declined AEM; 118 had 30-day AEM data. DH-AVB occurred in 12 (10% of AEM patients, 8% of total cohort) a median of 6 days (range 3 to 24 days) post-TAVR. DH-AVB versus non-AVB patients were more likely to have hypertension and right bundle branch block (RBBB). Sensitivity and specificity of RBBB in predicting DH-AVB was 27% and 94%, respectively.

Conclusions: DH-AVB is an underappreciated complication of TAVR among patients without pre-procedure pacing devices, occurring at rates similar to in-hospital, acute post-TAVR H-AVB. RBBB is a risk factor for DH-AVB but has poor sensitivity, and other predictors remain unclear. In this single-center analysis, AEM was helpful in expeditious identification and treatment of 10% of post-TAVR outpatients. Prospective study is needed to clarify incidence, risk factors, and patient selection for outpatient monitoring.
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http://dx.doi.org/10.1016/j.jacc.2019.02.068DOI Listing
May 2019

Long term follow-up after ventricular tachycardia ablation in patients with congenital heart disease.

J Cardiovasc Electrophysiol 2019 09 11;30(9):1560-1568. Epub 2019 Jun 11.

Electrophysiology Section, Division of Cardiology, University of Colorado, Aurora, Colorado.

Background: Ventricular tachycardia (VT) is frequently encountered in patients with repaired and unrepaired congenital heart disease (CHD), causing significant morbidity and sudden cardiac death. Data regarding underlying VT mechanisms and optimal ablation strategies in these patients remain limited.

Objective: To describe the electrophysiologic mechanisms, ablation strategies, and long-term outcomes in patients with CHD undergoing VT ablation.

Methods: Forty-eight patients (mean age 41.3 ± 13.3 years, 77.1% male) with CHD underwent a total of 57 VT ablation procedures at two centers from 2000 to 2017. Electrophysiologic and follow-up data were analyzed.

Results: Of the 77 different VTs induced at initial or repeat ablation, the underlying mechanism in 62 (81.0%) was due to scar-related re-entry; the remaining included four His-Purkinje system-related macrore-entry VTs and focal VTs mainly originating from the outflow tract region (8 of 11, 72.7%). VT-free survival after a single procedure was 72.9% (35 of 48) at a median follow-up of 53 months. VT-free survival after multiple procedures was 85.4% (41 of 48) at a median follow-up of 52 months. There were no major complications. Three patients died during the follow-up period from nonarrhythmic causes, including heart failure and cardiac surgery complication.

Conclusion: While scar-related re-entry is the most common VT mechanism in patients with CHD, importantly, nonscar-related VT may also be present. In experienced tertiary care centers, ablation of both scar-related and nonscar-related VT in patients with CHD is safe, feasible, and effective over long-term follow-up.
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http://dx.doi.org/10.1111/jce.13996DOI Listing
September 2019

VT arising from sub-aortic muscular outflow tract structures: In two patients with ventricular septal defects.

Pacing Clin Electrophysiol 2019 08 13;42(8):1155-1157. Epub 2019 Apr 13.

Electrophysiology Section, Division of Cardiology, University of Colorado, Denver, Colorado.

Background: Outflow tract ventricular tachycardias (OTVT) most commonly occur in the absence of structural abnormalities. We present two cases in which a structural variant in the outflow tract was critical to the OTVT.

Cases: Subaortic muscular bands were identified using intracardiac echocardiography (ICE) in each of our cases with history of VSD and VT. Mapping demonstrating their critical involvement to the tachycardia and ablation along the muscular bands rendered the ventricular tachycardias non-inducible.

Conclusion: In rare instances, a structural variant may be involved in OTVTs. The use of ICE along with electroanatomic mapping can assist in successful ablation of these ventricular tachycardias.
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http://dx.doi.org/10.1111/pace.13688DOI Listing
August 2019
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