Asirvatham, Samuel J.

AbstractIntroductionAutonomic modulation has been used as a therapy to control recurrent ventricular arrhythmia (VA). This study was to explore stellate ganglion block (SGB) effect on cardiac electrophysiologic properties and evaluate the long‐term outcome of cardiac sympathetic denervation (CSD) for patients with recurrent VA and structural heart disease (SHD).Materials and MethodsPatients who had recurrent VA due to SHD were enrolled prospectively. Electrophysiologic study and ventricular tachycardia (VT) induction were performed before and after left and right SGB. VA burden and long‐term outcomes were assessed for a separate patient group who underwent left or bilateral CSD for drug‐refractory VA due to SHD.ResultsElectrophysiologic study of nine patients showed that baseline mean (SD) corrected sinus node recovery time (cSNRT) increased from 320.4 (73.3) ms to 402.9 (114.2) ms after left and 482.4 (95.7) ms after bilateral SGB (P = .03). SGB did not significantly change P‐R, QRS, and Q‐T intervals and ventricular effective refractory period, nor did the inducibility of VA. Nineteen patients underwent left (n = 14) or bilateral (n = 5) CSD. CSD reduced VA burden and appropriate ICD therapies from a median (interquartile range) of 2.5 (0.4‐11.6) episodes weekly to 0.1 (0.0‐2.4) episodes weekly at 6‐month follow‐up (P = .002). Three‐year freedom from orthotopic heart transplant (OHT) and death was 52.6%. New York Heart Association functional class III/IV and VT rate less than 160 beats per minute were predictors of recurrent VA, OHT, and death.ConclusionSGB increased cSNRT without changing heart rate. CSD was more beneficial for patients with mild‐to‐moderate heart failure and faster VA.

Background: The treatment of heart failure with reduced ejection fraction has been the subject of numerous randomized controlled trials involving medications and cardiac implantable electronic device therapies. As newer effective pharmacological therapies suggest significant reductions in all-cause mortality, the role of additional device therapy in heart failure with reduced ejection fraction deserves further scrutiny. Methods: A systematic review and network meta-analysis on the effect of medication and device therapies in heart failure with reduced ejection fraction on all-cause mortality was performed. Randomized controlled trials published between January 1980 and July 2017 were identified using Medline, EMBASE, and Cochrane Controlled Register of Trials databases. Pcnetmeta package in R was used to calculate treatment arm–based estimated rates, rate ratios, and probability ranks with 95% credible intervals. Results: Combination therapy of ACE (angiotensin-converting enzyme) inhibitors or ARBs (angiotensin receptor blockers) with β-blockers (BBs) alone or in addition to implantable cardiac defibrillators or cardiac resynchronization therapy with defibrillators demonstrated a significant reduction of all-cause mortality when compared with placebo. By probability rank, implantable cardiac defibrillator+ACE inhibitor or ARB+BB+mineralocorticoid receptor antagonist, implantable cardiac defibrillator+ACE inhibitor or ARB+BB, and angiotensin receptor-neprilysin inhibitor+BB+mineralocorticoid receptor antagonist combination therapies have the highest probability of being ranked the best treatment. There was no significant difference in the rate of mortality when comparing angiotensin receptor-neprilysin inhibitor+BB+mineralocorticoid receptor antagonist to implantable cardiac defibrillator+optimal pharmacological combination therapy. Conclusions: BB and renin-angiotensin system blockers alone or in combination with defibrillator device therapy have robust evidence for a reduction in mortality compared with placebo. The comparative efficacy of pharmacological therapy with angiotensin receptor-neprilysin inhibitors and device therapy deserves further investigation.

Abstract 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.

AbstractIntroductionIt is unknown if ANO‐1 is expressed in the heart, though the presence of a calcium‐activated chloride current has been proposed to mediate some cardiac dysrhythmias. Furthermore, a specific cell type termed telocytes, morphologically mimicking Cajal cells which use ANO‐1 to modulate their pacemaker activity in the gut, have been described in the heart. We therefore sought to determine whether this channel is expressed in the canine heart.MethodsMyocardium was sampled from the ventricles of five canines. Sections were labeled with anti‐Kit and anti‐ANO‐1 antibodies. Slides were reviewed by four investigators looking at cell morphology, distribution, and co‐localization. Identification of telocytes was based on criteria including morphology, Kit positivity (+), and ANO‐1 positivity (+).ResultsClusters of cells meeting criteria for telocytes were seen in the epicardium, sub‐epicardium, and mid‐myocardium. A small subset of cells that were morphologically similar to myocytes was ANO‐1 (+) but Kit (−). In total, three different cell classes were found: (i) Kit (+), ANO‐1 (+) cells with the appearance of telocytes; (ii) Kit (+), ANO‐1 (−) cells; and (iii) Kit (−), ANO‐1 (+) cells with the morphologic appearance of cardiac myocytes.ConclusionsTelocytes are present in the canine ventricle and express ANO‐1. These data merit further study to elucidate the functional expression of these channels in the heart and whether they may be targets for cardiac arrhythmias.

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.

AbstractBackgroundLeadless cardiac pacing (LCP) has emerged as a new modality for permanent pacing. We sought to describe comparative outcomes between LCP and transvenous pacemakers.MethodsPatients 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).ResultsNinety 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).ConclusionThere 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.