Marco Mercader

Use of endogenous NADH fluorescence for real-time in situ visualization of epicardial radiofrequency ablation lesions and gaps

Radiofrequency ablation (RFA) aims to produce lesions that interrupt reentrant circuits or block the spread of electrical activation from sites of abnormal activity. Today, there are limited means for real-time visualization of cardiac muscle tissue injury during RFA procedures. We hypothesized that the fluorescence of endogenous NADH could be used as a marker of cardiac muscle injury during epicardial RFA procedures. Studies were conducted in blood-free and blood-perfused hearts from healthy adult Sprague-Dawley rats and New Zealand rabbits. Radiofrequency was applied to the epicardial surface of the heart using a 4-mm standard blazer ablation catheter. A dual camera optical mapping system was used to monitor NADH fluorescence upon ultraviolet illumination of the epicardial surface and to record optical action potentials using the voltage-sensitive probe RH237. Epicardial lesions were seen as areas of low NADH fluorescence. The lesions appeared immediately after ablation and remained stable for several hours. Real-time monitoring of NADH fluorescence allowed visualization of viable tissue between the RFA lesions. Dual recordings of NADH and epicardial electrical activity linked the gaps between lesions to postablation reentries. We found that the fluorescence of endogenous NADH aids the visualization of injured epicardial tissue caused by RFA. This was true for both blood-free and blood-perfused preparations. Gaps between NADH-negative regions revealed unablated tissue, which may promote postablation reentry or provide pathways for the conduction of abnormal electrical activity.

Severe tricuspid valve stenosis secondary to pacemaker leads presenting as ascites and liver dysfunction: a complex problem requiring a multidisciplinary therapeutic approach

Tricuspid stenosis secondary to ventricular pacemaker leads is uncommon. We present a unique case of iatrogenic tricuspid stenosis secondary to fusion of the valve leaflets to transvenous implanted pacing leads. This occurred in an adult with childhood repaired Tetralogy of Fallot and high grade surgical heart block following multiple pacemaker procedures. The case was complicated by superior vena cava (SVC) and innominate vein stenosis secondary to implanted pacing leads, severe tricuspid valve (TV) stenosis, perforation of the heart by one of the implanted transvenous ventricular pacing leads, prolapse of the transvenous atrial pacing lead into the right ventricle, and unusual coronary sinus anatomy. We describe a multidisciplinary approach to management.

Seeing the Invisible: Revealing Atrial Ablation Lesions Using Hyperspectral Imaging Approach

Background Currently, there are limited means for high-resolution monitoring of tissue injury during radiofrequency ablation procedures. Objective To develop the next generation of visualization catheters that can reveal irreversible atrial muscle damage caused by ablation and identify viability gaps between the lesions. Methods Radiofrequency lesions were placed on the endocardial surfaces of excised human and bovine atria and left ventricles of blood perfused rat hearts. Tissue was illuminated with 365nm light and a series of images were acquired from individual spectral bands within 420-720nm range. By extracting spectral profiles of individual pixels and spectral unmixing, the relative contribution of ablated and unablated spectra to each pixel was then displayed. Results of spectral unmixing were compared to lesion pathology. Results RF ablation caused significant changes in the tissue autofluorescence profile. The magnitude of these spectral changes in human left atrium was relatively small (< 10% of peak fluorescence value), yet highly significant. Spectral unmixing of hyperspectral datasets enabled high spatial resolution, in-situ delineation of radiofrequency lesion boundaries without the need for exogenous markers. Lesion dimensions derived from hyperspectral imaging approach strongly correlated with histological outcomes. Presence of blood within the myocardium decreased the amplitude of the autofluorescence spectra while having minimal effect on their overall shapes. As a result, the ability of hyperspectral imaging to delineate ablation lesions in vivo was not affected. Conclusions Hyperspectral imaging greatly increases the contrast between ablated and unablated tissue enabling visualization of viability gaps at clinically relevant locations. Data supports the possibility for developing percutaneous hyperspectral catheters for high-resolution ablation guidance.

Visualization of Epicardial Cryoablation Lesions Using Endogenous Tissue Fluorescence

Background—Percutaneous cryoballoon ablation is a commonly used procedure to treat atrial fibrillation. One of the major limitations of the procedure is the inability to directly visualize tissue damage and functional gaps between the lesions. We seek to develop an approach that will enable real-time visualization of tissue necrosis during cryo- or radiofrequency ablation procedures. Methods and Results—Cryoablation of either blood-perfused or saline-perfused hearts was associated with a marked decrease in nicotinamide adenine dinucleotide (NADH) fluorescence, leading to a 60% to 70% loss of signal intensity at the lesion site. The total lesion area observed on the NADH channel exhibited a strong correlation with the area identified by triphenyl tetrazolium staining (r=0.89, P<0.001). At physiological temperatures, loss of NADH became visually apparent within 26±8 s after detachment of the cryoprobe from the epicardial surface and plateaued within minutes after which the boundaries of the lesions remained stable for several hours. The loss of electrical activity within the cryoablation site exhibited a close spatial correlation with the loss of NADH (r=0.84±0.06, P<0.001). Cryoablation led to a decrease in diffuse reflectance across the entire visible spectrum, which was in stark contrast to radiofrequency ablation that markedly increased the intensity of reflected light at the lesion sites. Conclusions—We confirmed the feasibility of using endogenous NADH fluorescence for the real-time visualization of cryoablation lesions in blood-perfused cardiac muscle preparations and revealed similarities and differences between imaging cryo- and radiofrequency ablation lesions when using ultraviolet and visible light illumination.

Newly created animal model of human postoperative junctional ectopic tachycardia.

OBJECTIVE Junctional ectopic tachycardia complicates the postoperative recovery from open heart surgery in children. The reported risk factors include younger age, prolonged cardiopulmonary bypass times, and administration of inotropic agents. Junctional ectopic tachycardia occurs early after open heart surgery, in the setting of relative postoperative sinus node dysfunction, and exhibits QRS morphology consistent with an origin from the atrioventricular node or proximal conduction system. Our goal was to develop a reproducible animal model for postoperative junctional ectopic tachycardia. METHODS Eleven pigs, aged 2 to 4 months, underwent open heart surgery after induction of general anesthesia. Electrodes were sewn to the left atrium and right ventricle. RESULTS Sinus node dysfunction was created using clamp crushing without or with radiofrequency ablation (successful in 1 of 5 pigs) or sinus node removal (successful in 4 of 4). After prolonged cardiopulmonary bypass (>120 minutes) alone and with isoproterenol infusion, no spontaneous junctional ectopic tachycardia developed. Junctional ectopic tachycardia or fascicular tachycardia could be initiated after either slow atrioventricular nodal pathway ablation and/or digoxin administration. Junctional ectopic tachycardia occurred in 8 of 9 pigs (mean ventricular rate, 171 ± 32 bpm), and fascicular tachycardia occurred in 9 of 9 pigs (mean ventricular rate, 187 ± 39 bpm). His and right bundle recordings confirmed the conduction system origin. CONCLUSIONS Experimental junctional ectopic tachycardia or fascicular tachycardia can occur in the intraoperative setting of sinus node dysfunction, prolonged cardiopulmonary bypass, and enhanced conduction system automaticity. Conduction system automaticity occurred after either physical injury (ablation or tricuspid valve stretch) or measures to augment the transient inward current of the conduction system (isoproterenol and digoxin). This animal model can serve as the basis to assess new treatments of postoperative junctional ectopic tachycardia.

Nonpharmacologic Control of Postoperative Supraventricular Arrhythmias Using AV Nodal Fat Pad Stimulation in a Young Animal Open Heart Surgical Model

Background—Supraventricular arrhythmias (junctional ectopic tachycardia [JET] and atrial tachyarrhythmias) frequently complicate recovery from open heart surgery in children and can be difficult to manage. Medical treatment of JET can result in significant morbidity. Our goal was to develop a nonpharmacological approach using autonomic stimulation of selective fat pad (FP) regions of the heart in a young canine model of open heart surgery to control 2 common postoperative supraventricular arrhythmias. Methods and Results—Eight mongrel dogs, varying in age from 5 to 8 months and weighting 22±4 kg, underwent open heart surgery replicating a nontransannular approach to tetralogy of Fallot repair. Neural stimulation of the right inferior FP was used to control the ventricular response to supraventricular arrhythmias. Right inferior FP stimulation decreased baseline AV nodal conduction without altering sinus cycle length. AV node Wenckebach cycle length prolonged from 270±33 to 352±89 ms, P=0.02. Atrial fibrillation occurred in 7 animals, simulating a rapid atrial tachyarrhythmias. FP stimulation slowed the ventricular response rate from 166±58 to 63±29 beats per minute, P<0.001. Postoperative JET occurred in 7 dogs. FP stimulation slowed the ventricular rate during postoperative JET from 148±31 to 106±32 beats per minute, P<0.001, and restored sinus rhythm in 7/7 dogs. Conclusions—Right inferior FP stimulation had a selective effect on the AV node, and slowed the ventricular rate during postoperative JET and atrial tachyarrhythmias in our young canine open heart surgery model. FP stimulation may be a useful new technique for managing children with JET and atrial tachyarrhythmias.

Mitigating the Risk of Microemboli Formation During Irrigated Radiofrequency Catheter Ablation.

Catheter ablation with open-irrigated radiofrequency catheters is an established therapy for drug-refractory atrial fibrillation.1 The catheters are commonly used because they reduce thrombus formation and steam pops.2,3 However, left atrial procedures, even with open irrigation, are associated with a higher prevalence of embolic complications (stroke, transient ischemic attack, asymptomatic cerebral embolism [ACE], and decline in cognitive function).4,5 ACE lesions can occur during left atrial ablation procedures and have been attributed to microemboli formation. They are considered the largest complication of pulmonary vein isolation procedures. Understanding the parts of the ablation procedure associated with microemboli formation will help us develop strategies to reduce stroke and ACE. See Article by Takami et al The report of ACE lesions imaged with diffusion-weighted magnetic resonance imaging after catheter ablation of atrial fibrillation led investigators to determine ways to reduce risk and improve safety of this procedure.6 Ablation with a multielectrode radiofrequency catheter was noted to increase the risk of ACE by 1.5× over irrigated catheters and cryoballoon ablation.7 In 2013, the effects of embolizing …

Chemical Ablation Of Purkinje Fibers Diminishes Spontaneous Activity In A Rat Model Of Regional Ischemia And Reperfusion

Spontaneous activity and arrhythmias associated with acute local ischemia and reperfusion were studied in isolated Langendorff-perfused hearts from healthy Sprague-Dawley rats (n=16). Epicardial fluorescence imaging of transmembrane potential and NADH were used to relate sources of electrical activity to changes in mitochondrial redox state caused by local ischemia. The left anterior descending coronary artery was cannulated and the flow of perfusate to the cannula was controlled by a high-pressure/low-flow HPLC pump. Studies were conducted using a local ischemia/reperfusion protocol that consisted of 10 min of normal flow, 20 min of regional LV ischemia, followed by 20 minutes of reduced flow reperfusion, and then 20 min of normal flow reperfusion. Control hearts (n=9) were compared with hearts in which the endocardium (containing the Purkinje fibers) was chemically ablated by applying a Lugols iodine solution to the ventricular cavities (n=7). The ablation significantly reduced spontaneous activity in each phase of the protocol. Specifically, during acute regional ischemia, spontaneous activity was reduced by 80% (p<0.005); by 70% during low-flow reperfusion (p<0.005); and by 85% during full-flow reperfusion (p<0.001). Omission of blebbistatin, an electro-mechanical uncoupling agent, did not change the diminishing effect of the ablation on spontaneous activity (n=3). Epicardial imaging showed that spontaneous ectopic beats were manifested as concentric epicardial breakthrough patterns, located near spatiotemporal gradients of NADH fluorescence. These data strongly suggest that in un-paced hearts from healthy rats that are perfused with Tyrodes solution, the main mechanism of spontaneous ectopic activity associated with either ischemia, low-flow or full-flow reperfusion is activation of local Purkinje fibers.

PCV10 RACE AND GENDER COST DIFFERENCES ASSOCIATED WITH COMORBID ATRIAL FIBRILLATION IN THE HOSPITAL

PCV8 TOTAL HEALTH CARE COSTS OF PATIENTS WITH CHRONIC NON-VALVULAR ATRIAL FIBRILLATION BEFORE AND AFTER TIA, ISCHEMIC STROKE OR MAJOR BLEED Stephenson JJ, Fernandes J, Beaulieu JF, Del Aguila MA, Hauch O, Kim J, Boccuzzi SJ Aetna Health Information Solutions, Blue Bell, PA, USA; AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA OBJECTIVES: To determine the total direct health care costs of patients newly diagnosed with chronic non-valvular atrial fibrillation (CNVAF) before diagnosis and after a transient ischemic attack (TIA), ischemic stroke (IS) or major bleed (MB). METHODS: This retrospective, observational cohort study utilized medical and pharmacy claims from a large, geographically diverse managed care organization to identify patients with ≥two atrial fibrillation (AF) claims between January 1, 2001–June 30, 2002. Continuously enrolled members with no evidence of AF (ICD-9-CM = 427.31) or warfarin claims 12 months prior to the index AF claim were followed for ≥six-months until first TIA/IS/MB (EVENT) or study end. Total direct health care costs for all patients were assessed preand post-AF index claim. For the subset of patients with an EVENT, total health care costs were also assessed preand post-EVENT (from index AF up to EVENT, and EVENT to study end). RESULTS: Of 3891 incidence CNVAF patients, 62% were male and 55% were ≥65 years. Preand post-AF total direct health care costs were

Assessing the Direct Costs of Treating Nonvalvular Atrial Fibrillation in the United States

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