Substrate Characterization and Outcomes of Catheter Ablation of Ventricular Arrhythmias in Patients With Mitral Annular Disjunction.

BACKGROUND: Mitral annular disjunction (MAD) has recently been recognized as an arrhythmogenic entity. Data on the electrophysiological substrate as well as the outcomes of catheter ablation of ventricular arrhythmias in patients with MAD is limited. METHODS: Forty patients with MAD (mean age 47±15 years; 70% female) underwent catheter ablation for ventricular arrhythmias. Detailed clinical, electrocardiographic, cardiac imaging, and procedural data were collected. Clinical outcomes were compared between patients who had substrate modification in the MAD area and those who did not. RESULTS: Twenty-three (57.5%) patients had ablation for premature ventricular contractions, 10 (25%) patients for sustained ventricular tachycardia, and 7 (17.5%) patients for premature ventricular contraction-triggered ventricular fibrillation. Mean end-systolic MAD length was 10.58±3.49 mm on transthoracic echocardiography. Seventeen (42.5%) patients had preprocedural cardiac magnetic resonance imaging, and 5 (29%) patients had late gadolinium enhancement. Among the 18 (45%) patients who had abnormal local electrograms (low voltage, long-duration, fractionated, isolated mid-diastolic potentials) during electroanatomical mapping, 10 (25%) patients had abnormal electrograms in the anterolateral mitral annulus and/or MAD area. Substrate modification was performed in 10 (25%) patients. Catheter ablation was acutely successful in 36 (90%) patients (elimination of premature ventricular contraction or noninducibility of ventricular tachycardia). After a median follow-up duration of 54.08 (interquartile range, 10.67-89.79) months, premature ventricular contraction burden decreased from a median of 9.75% (interquartile range, 3.25-14) before the ablation to a median of 4% (interquartile range, 1-7.75) after the ablation (P=0.03 [95% CI, 0.055-6.5]). Eight (20.5%) patients had repeat ablation for ventricular arrhythmias. Substrate modification of the MAD was associated with a trend toward lower rates of repeat ablation (0% versus 26.7%; P=0.16). CONCLUSIONS: Patients with MAD have a complex arrhythmogenic substrate, and catheter ablation is effective in reducing recurrence of ventricular arrhythmias. Substrate mapping and ablation may be considered in these patients.

Trends in Cardiovascular Implantable Electronic Device Insertion Between 1988 and 2018 in Olmsted County.

OBJECTIVES: This study sought to describe trends in cardiovascular implantable electronic device (CIED) insertion over the past 3 decades in Olmsted County. BACKGROUND: Trends in CIED insertion in the United States have not been extensively studied. METHODS: The Rochester Epidemiology Project is a medical records linkage system comprising the records of all residents of Olmsted County from 1966 to the present. CIED insertion between 1988 and 2018 was determined using International Classification of Diseases-Ninth Revision, International Classification of Diseases-10th Revision, and Current Procedural Terminology codes. Age- and sex-adjusted incidence rates, adjusted to the 2010 US White population, were calculated. Trends in incidence over time, across age groups, and between sex are estimated using Poisson regression models. RESULTS: The age- and sex-adjusted incidence of device implants for the study period were as follows: overall CIED: 82.4 (95% CI: 79.2-85.6); permanent pacemaker (PPM): 62.9 (95% CI: 60.0-65.7); implantable cardioverter-defibrillator (ICD): 14.0 (95% CI: 12.6-15.3); and cardiac resynchronization therapy (CRT): 5.6 (95% CI: 4.7-6.4) per 100,000 per year. The overall incidence of CIED insertion increased between 1988 to 1993 and 2000 to 2005 and then decreased between 2000 to 2005 and 2012 to 218 (P < 0.0001). PPM and ICD insertion incidence followed these trends, whereas the incidence of CRT insertion increased between 2000 to 2005 and 2012 to 2018. CIED insertion incidence increased with age (P < 0.0001). CIED insertion incidence was greater in men (116.3 vs 57.3 per 100,000 per year in men vs women; P < 0.0001). The overall survival of CRT recipients improved (P = 0.0044). CONCLUSIONS: The incidence values for PPM and ICD implants are decreasing, while the incidence of CRT implants is increasing. CIEDs are increasingly inserted in the elderly, men, and patients with higher comorbidities.

Sustained Improvement in Diastolic Reserve Following Percutaneous Pericardiotomy in a Porcine Model of Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction is increasing in prevalence, but few effective treatments are available. Elevated left ventricular (LV) diastolic filling pressures represent a key therapeutic target. Pericardial restraint contributes to elevated LV end-diastolic pressure, and acute studies have shown that pericardiotomy attenuates the rise in LV end-diastolic pressure with volume loading. However, whether these acute effects are sustained chronically remains unknown. METHODS: Minimally invasive pericardiotomy was performed percutaneously using a novel device in a porcine model of heart failure with preserved ejection fraction. Hemodynamics were assessed at baseline and following volume loading with pericardium intact, acutely following pericardiotomy, and then again chronically after 4 weeks. Cardiac structure was assessed by magnetic resonance imaging. RESULTS: The increase in LV end-diastolic pressure with volume loading was mitigated by 41% (95% CI, 27%-45%, P<0.0001; ΔLV end-diastolic pressure reduced from +9±3 mm Hg to +5±3 mm Hg, P=0.0003, 95% CI, -2.2 to -5.5). The effect was sustained at 4 weeks (+5±2 mm Hg, P=0.28 versus acute). There was no statistically significant effect of pericardiotomy on ventricular remodeling compared with age-matched controls. None of the animals developed hemodynamic or pathological indicators of pericardial constriction or frank systolic dysfunction. CONCLUSIONS: The acute hemodynamic benefits of pericardiotomy are sustained for at least 4 weeks in a swine model of heart failure with preserved ejection fraction, without excessive chamber remodeling, pericarditis, or clinically significant systolic dysfunction. These data support trials evaluating minimally invasive pericardiotomy as a novel treatment for heart failure with preserved ejection fraction in humans.

Long-Term Survival of Patients With Left Ventricular Noncompaction.

Background The prognosis of left ventricular noncompaction (LVNC) remains elusive despite its recognition as a clinical entity for >30 years. We sought to identify clinical and imaging characteristics and risk factors for mortality in patients with LVNC. Methods and Results 339 adults with LVNC seen between 2000 and 2016 were identified. LVNC was defined as end-systolic noncompacted to compacted myocardial ratio >2 (Jenni criteria) and end-diastolic trough of trabeculation-to-epicardium (X):peak of trabeculation-to-epicardium (Y) ratio <0.5 (Chin criteria) by echocardiography; and end-diastolic noncompacted:compacted ratio >2.3 (Petersen criteria) by magnetic resonance imaging. Median age was 47.4 years, and 46% of patients were female. Left ventricular ejection fraction <50% was present in 57% of patients and isolated apical noncompaction in 48%. During a median follow-up of 6.3 years, 59 patients died. On multivariable Cox regression analysis, age (hazard ratio [HR] 1.04; 95% CI, 1.02-1.06), left ventricular ejection fraction <50% (HR, 2.37; 95% CI, 1.17-4.80), and noncompaction extending from the apex to the mid or basal segments (HR, 2.11; 95% CI, 1.21-3.68) were associated with all-cause mortality. Compared with the expected survival for age- and sex-matched US population, patients with LVNC had reduced overall survival (P<0.001). However, patients with LVNC with preserved left ventricular ejection fraction and patients with isolated apical noncompaction had similar survival to the general population. Conclusions Overall survival is reduced in patients with LVNC compared with the expected survival of age- and sex-matched US population. However, survival rate in those with preserved left ventricular ejection fraction and isolated apical noncompaction was comparable with that of the general population.

Burden of arrhythmia in hospitalized HIV patients.

BACKGROUND: The improved life expectancy observed in patients living with human immunodeficiency virus (HIV) infection has made age-related cardiovascular complications, including arrhythmias, a growing health concern. HYPOTHESIS: We describe the temporal trends in frequency of various arrhythmias and assess impact of arrhythmias on hospitalized HIV patients using the Nationwide Inpatient Sample (NIS). METHODS: Data on HIV-related hospitalizations from 2005 to 2014 were obtained from the NIS database using International Classification of Diseases, 9th Revision (ICD-9) codes. Data was further subclassified into hospitalizations with associated arrhythmias and those without. Baseline demographics and comorbidities were determined. Outcomes including in-hospital mortality, cost of care, and length of stay were extracted. SAS 9.4 (SAS Institute Inc., Cary, NC) was utilized for analysis. A multivariable analysis was performed to identify predictors of arrhythmias among hospitalized HIV patients. RESULTS: Among 2 370 751 HIV-related hospitalizations identified, the overall frequency of any arrhythmia was 3.01%. Atrial fibrillation (AF) was the most frequent arrhythmia (2110 per 100 000). The overall frequency of arrhythmias increased over time by 108%, primarily due to a 132% increase in AF. Arrhythmias are more frequent among older males, lowest income quartile, and nonelective admissions. Patients with arrhythmias had a higher in-hospital mortality rate (9.6%). In-hospital mortality among patients with arrhythmias decreased over time by 43.8%. The cost of care and length of stay associated with arrhythmia-related hospitalizations were mostly unchanged. CONCLUSIONS: Arrhythmias are associated with significant morbidity and mortality in hospitalized HIV patients. AF is the most frequent arrhythmia in hospitalized HIV patients.

Feasibility of selective cardiac ventricular electroporation.

INTRODUCTION: The application of brief high voltage electrical pulses to tissue can lead to an irreversible or reversible electroporation effect in a cell-specific manner. In the management of ventricular arrhythmias, the ability to target different tissue types, specifically cardiac conduction tissue (His-Purkinje System) vs. cardiac myocardium would be advantageous. We hypothesize that pulsed electric fields (PEFs) can be applied safely to the beating heart through a catheter-based approach, and we tested whether the superficial Purkinje cells can be targeted with PEFs without injury to underlying myocardial tissue. METHODS: In an acute (n = 5) and chronic canine model (n = 6), detailed electroanatomical mapping of the left ventricle identified electrical signals from myocardial and overlying Purkinje tissue. Electroporation was effected via percutaneous catheter-based Intracardiac bipolar current delivery in the anesthetized animal. Repeat Intracardiac electrical mapping of the heart was performed at acute and chronic time points; followed by histological analysis to assess effects. RESULTS: PEF demonstrated an acute dose-dependent functional effect on Purkinje, with titration of pulse duration and/or voltage associated with successful acute Purkinje damage. Electrical conduction in the insulated bundle of His (n = 2) and anterior fascicle bundle (n = 2), was not affected. At 30 days repeat cardiac mapping demonstrated resilient, normal electrical conduction throughout the targeted area with no significant change in myocardial amplitude (pre 5.9 ± 1.8 mV, 30 days 5.4 ± 1.2 mV, p = 0.92). Histopathological analysis confirmed acute Purkinje fiber targeting, with chronic studies showing normal Purkinje fibers, with minimal subendocardial myocardial fibrosis. CONCLUSION: PEF provides a novel, safe method for non-thermal acute modulation of the Purkinje fibers without significant injury to the underlying myocardium. Future optimization of this energy delivery is required to optimize conditions so that selective electroporation can be utilized in humans the treatment of cardiac disease.

Venoarterial Extracorporeal Membrane Oxygenation Support for Ventricular Tachycardia Ablation: A Systematic Review.

Refractory ventricular tachycardia (VT) and electrical storm are frequently associated with hemodynamic compromise requiring mechanical support. This study sought to review the current literature on the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for hemodynamic support during VT ablation. This was a systematic review of all published literature from 2000 to 2019 evaluating patients with VT undergoing ablation with VA-ECMO support. Studies that reported mortality, safety, and efficacy outcomes in adult (>18 years) patients were included. The primary outcome was short-term mortality (intensive care unit stay, hospital stay, or ≤30 days). The literature search identified 4,802 citations during the study period, of which seven studies comprising 867 patients met the inclusion criteria. Periprocedural VA-ECMO was used in 129 (15%) patients and all were placed peripherally. Average inducible VTs were 2-3 per procedure and ablation time varied between 34 mins and 4.7 hours. Median ages were between 61 and 68 years with 93% males. Median duration of VA-ECMO varied between 140 minutes and 6 days. Short-term mortality was 15% (19 patients), with the most frequent causes being refractory VT, cardiac arrest, and acute heart failure. All-cause mortality at the longest follow-up was 25%. Major bleeding, vascular/access complications, limb ischemia, stroke, and acute kidney injury were reported with varying frequency of 1-6%. In conclusion, VA-ECMO is used infrequently for hemodynamic support for VT ablation. Further data on patient selection, procedural optimization, and clinical outcomes are needed to evaluate the efficacy of this strategy.

Injectable Flexible Subcutaneous Electrode Array Technology for Electrocardiogram Monitoring Device.

Implantable cardiac monitors have undergone considerable miniaturization. However, they continue to be associated with complications such as infection, bleeding/bruising, and device extrusion or migration. In this paper, we demonstrate the feasibility of using a small, flexible, injectable, subcutaneous microelectrode-based device to record electrocardiograms (ECGs). We describe the fabrication process and demonstrate the ease of insertion of the injectable ECG device in vivo swine model. We also demonstrate our device's high-density channel microelectrode array's ability to detect the P, R, and T waves. The amplitude of these waves showed excellent correlation with distance of the bipolar electrodes used to detect them. Given the success of our initial studies, this device has the potential to improve the safety profile of implantable cardiac monitors and simplify the implantation procedure to allow for placement in a primary care setting.

A novel percutaneous stabilizing sheath for minimal invasive epicardial echocardiography and ablation.

PURPOSE: Epicardial ablation and mapping are critical adjuncts to the electrophysiologist's approach to arrhythmias; however, ablation within the epicardial space requires the avoidance of coronary arteries (CA). We aimed to evaluate the feasibility and performance of a novel-stabilizing ablation sheath housing an intracardiac echocardiography (ICE) catheter to (1) obtain Epicardial Echocardiography (EE) images, (2) visualize CAs, and (3) enable targeted delivery of radiofrequency energy away from visualized CAs. METHODS: We designed a sheath that could enclose a regular ICE catheter. This sheath has flanges and a balloon, with three interspersed windows surrounded by an electrode. In an acute canine model (N = 6), the sheath was manipulated within the pericardial space to visualize cardiac structures and CAs. Visualization of CAs was confirmed with angiography. Ablation was then performed through the window either proximal or distal to the CA. RESULTS: The novel sheath was successfully deployed in six canines, with no acute procedural complications. Images with an excellent spatial resolution of cardiac structures were obtained including the right ventricular outflow tract; aortic, pulmonary, and mitral valves; and left atrial appendage. CAs were successfully visualized, and ablation from a sheath window either proximal or distal to the CA did not produce angiographic or histopathological evidence of CA damage despite evidence of acute injury to the adjacent ablated myocardium. CONCLUSIONS: This novel percutaneous stabilizing sheath was able to successfully obtain high-quality EE images as well as provide a non-fluoroscopic intra-procedural means to visualize CAs. Use of this sheath enabled successful delivery of energy to avoided CA damage.

Nanostim leadless pacemaker retrieval and simultaneous micra leadless pacemaker replacement: a single-center experience.

PURPOSE: The leadless pacemaker (LP) is a promising new technology in pacing therapy that avoids a generator pocket and transvenous lead-related complications. However, extraction experience with simultaneous re-implant of a leadless device remains limited. We sought to study the outcomes of Nanostim LP retrieval and simultaneous reimplantation of Micra LP. METHODS: Patients undergoing retrieval of the Nanostim LP and receiving a Micra LP implant between 2016 and 2018 at Mayo Clinic (Rochester, MN) were studied. The procedural and outcome data were collected from the electronic medical record. RESULTS: Nine patients underwent attempted Nanostim LP retrieval and 6 of these simultaneously received a Micra LP reimplant. All retrievals were considered chronic due to implant durations of > 1 year. Extraction procedures were completed with a success rate of 89% and simultaneous reimplantations were performed successfully in all cases with no major complications. Newly implanted Micra LP device function was normal at follow-up. Factors such as duration of device implant and device positioning appeared to impact ease of extraction. CONCLUSIONS: Retrieval of the Nanostim LP system and simultaneous replacement with an alternate Micra leadless device appears to be a feasible approach.

Fundamentals of Cardiac Mapping.

To characterize cardiac activity and arrhythmias, electrophysiologists can record the electrical activity of the heart in relation to its anatomy through a process called cardiac mapping (electroanatomic mapping, EAM). A solid understanding of the basic cardiac biopotentials, called electrograms, is imperative to construct and interpret the cardiac EAM correctly. There are several mapping approaches available to the electrophysiologist, each optimized for specific arrhythmia mechanisms. This article provides an overview of the fundamentals of EAM.

Comparing the incidence of ventricular arrhythmias during epicardial ablation in swine versus canine models.

BACKGROUND: Choosing the appropriate animal model for development of novel technologies requires an understanding of anatomy and physiology of these different models. There are little data about the characteristics of different animal models for the study of technologies used for epicardial ablation. We aimed to compare the incidence of ventricular arrhythmias during epicardial radiofrequency ablation between swine and canine models using novel epicardial ablation catheters. METHODS: We conducted a retrospective study using data obtained from epicardial ablation experiments performed on swine (Sus Scrofa) and canine (Canis familiaris) models. We compared the incidence of ventricular arrhythmias during ablation between swine and canine using multivariate regression analysis. Six swine and six canine animals underwent successful epicardial radiofrequency ablation. A total of 103 ablation applications were recorded. RESULTS: Ventricular arrhythmias requiring cardioversion occurred in 13.11% of radiofrequency ablation applications in swine and 9.75% in canine (relative risk: 117.6%, 95% confidence interval [CI]: 83.97-164.69, animal-based odds ratio [OR]: .55, 95% CI: .23-61.33; P = .184). When adjusting for application position, duration of ablation and power, the odds of developing potentially lethal ventricular arrhythmia in swine increased significantly compared to canine (OR: 3.60, 95% CI: 1.35-9.55; P = .010). CONCLUSIONS: The swine myocardium is more susceptible to developing ventricular arrhythmias compared to canine model during epicardial ablation. This issue should be carefully considered in future studies.

Three-Dimensional Printed Biopatches With Conductive Ink Facilitate Cardiac Conduction When Applied to Disrupted Myocardium.

BACKGROUND: Reentrant ventricular arrhythmias are a major cause of sudden death in patients with structural heart disease. Current treatments focus on electrically homogenizing regions of scar contributing to ventricular arrhythmia with ablation or altering conductive properties using antiarrhythmic drugs. The high conductivity of carbon nanotubes may allow restoration of conduction in regions where impaired electrical conduction results in functional abnormalities. We propose a new concept for arrhythmia treatment using a stretchable, flexible biopatch with conductive properties to attempt to restore conduction across regions in which activation is disrupted. METHODS: Carbon nanotube patches composed of nanofibrillated cellulose/single-walled carbon nanotube ink 3-dimensionally printed in conductive patterns onto bacterial nanocellulose were developed and evaluated for conductivity, flexibility, and mechanical properties. The patches were applied on 6 canines to epicardium before and after surgical disruption. Electroanatomic mapping was performed on normal epicardium, then repeated over surgically disrupted epicardium, and then finally with the patch applied passively. RESULTS: We developed a 3-dimensional printable carbon nanotube ink complexed on bacterial nanocellulose that was (1) expressable through 3-dimensional printer nozzles, (2) electrically conductive, (3) flexible, and (4) stretchable. Six canines underwent thoracotomy, and, during epicardial ventricular pacing, mapping was performed. We demonstrated disruption of conduction after surgical incision in all 6 canines based on activation mapping. The patch resulted in restored conduction based on mapping and assessment of conduction direction and velocities in all canines. CONCLUSIONS: We have demonstrated 3-dimensional custom-printed electrically conductive carbon nanotube patches can be surgically manipulated to improve cardiac conduction when passively applied to surgically disrupted epicardial myocardium in canines.

Pulsed electric fields for cardiac ablation and beyond: A state-of-the-art review.

Irreversible electroporation (IRE) occurs when a strong, pulsed electric field (PEF) causes permeabilization of the cell membrane, leading to cellular homeostasis disruption and cell death. IRE is a Food and Drug Administration-approved treatment of tumor ablation and has been gaining attention in cardiology as an ablation modality. Applications of PEF in cardiology are vast and include atrial fibrillation, ventricular fibrillation, septal ablation, and targeting vascular structures. PEF has appealing characteristics, including the ability to be tissue specific and its nonthermal nature. This review provides information on the biophysics and mechanisms of IRE, summarizes key studies and applications to date, and provides insight into future applications.

Real-world experience with leadless cardiac pacing.

BACKGROUND: Leadless cardiac pacing (LCP) has emerged as a new modality for permanent pacing. We sought to describe comparative outcomes between LCP and transvenous pacemakers. METHODS: Patients receiving LCP (Micra [Medtronic, Minneapolis, MN, USA] and Nanostim [St. Jude Medical/Abbott Laboratories, Chicago, IL, USA]) between 2014 and 2017 at the Mayo Clinic Heart Rhythm Enterprise practice (Rochester, MN, USA; Jacksonville, FL, USA; and Scottsdale, AZ, USA) were identified. We identified 1:1 age- and sex-matched controls receiving single-chamber transvenous ventricular pacemakers (TVP). Statistical analyses were performed with JMP 13.0.0 (SAS, Institute Cary, NC, USA). RESULTS: Ninety patients underwent LCP implantation (73 Micra and 17 Nanostim) with a median follow-up duration of 62 (interquartile range 28-169) days. Both groups had 100% successful device implant rates. There were no differences in procedure-related major (0% vs 1%) or minor complications (8% vs 3%) in the LCP versus TVP groups (P > 0.05). Excluding Nanostim patients, there was a lower rate of device-related revision or extraction in the Micra versus TVP groups (0% vs 5%, P = 0.028). Device endocarditis was more common in the TVP group (0% vs 3%, P = 0.04). Estimated longevity was greater for the LCP group (median 12.0 vs 10.0 years, P < 0.0001). An increase in severity of tricuspid valve regurgitation (TR) by ≥2 grades occurred in none of the LCP patients, and in 19% of the TVP patients (P = 0.017). CONCLUSION: There are no significant differences in procedural complications among patients receiving LCP versus TVP. The Micra group had lower rates of device-related revision/extraction compared to the TVP group. Patients with leadless pacemaker were less likely to develop endocarditis or worsening TR.