A Prospective Randomized Trial of Apixaban Dosing During Atrial Fibrillation Ablation: The AEIOU Trial.

OBJECTIVES: This study sought to determine whether uninterrupted apixaban would have similar rates of bleeding and thromboembolic events as does minimally interrupted apixaban at the time of atrial fibrillation (AF) ablation and to compare those results with rates in historical patients treated with uninterrupted warfarin. BACKGROUND: The safety, efficacy, and optimal dosing regimen for apixaban at the time of AF ablation are uncertain. METHODS: This prospective, multicenter clinical trial enrolled 306 patients undergoing catheter ablation for nonvalvular AF and randomized 300 to uninterrupted versus minimally interrupted (holding 1 dose) periprocedural apixaban. A retrospective cohort of patients treated with uninterrupted warfarin at the same centers was matched to the apixaban-treated subjects for comparison. Endpoints included clinically significant bleeding, major bleeding, and nonhemorrhagic stroke or systemic embolism (SE) from the time of ablation through 30 days. RESULTS: There were no stroke or SE events. Clinically significant bleeding occurred in 11.3% of 150 evaluable patients on uninterrupted apixaban and 9.7% of 145 evaluable patients on interrupted apixaban (risk difference: 1.7% [95% confidence interval: -5.5% to 8.8%]; p = NS). Rates of major bleeding were 1.3% with uninterrupted apixaban, and 2.1% with interrupted (risk difference: -0.7%; p = NS). The rates of clinically significant and major bleeding were similar for all apixaban patients combined (10.5% and 1.7%), compared with the matched warfarin group (9.8% and 1.4%). CONCLUSIONS: Both uninterrupted and minimally interrupted apixaban at the time of AF ablation were associated with a very low rate of thromboembolic events, and rates of both major (<2%) and clinically significant bleeding were similar to uninterrupted warfarin. (Apixaban Evaluation of Interrupted Or Uninterrupted Anticoagulation for Ablation of Atrial Fibrillation [AEIOU]; NCT02608099).

Atrial tachycardia initiating atrial fibrillation successfully ablated in the non-coronary cusp of the aorta.

A 60-year-old woman was referred for catheter ablation of atrial fibrillation (AF). Atrial flutter and atrial tachycardia (AT) also had been clinically documented. During the electrophysiological study, the clinical AT was induced by burst atrial pacing during isoproterenol infusion and exhibited negative P waves in the inferior leads, positive P waves in leads I, aVL, and aVR, and biphasic P waves in lead V1. The AT repeatedly and spontaneously accelerated to initiate AF by causing fibrillatory conduction in the atria. Successful catheter ablation of the AT was achieved in the non-coronary cusp of the aorta (NCC) where the local atrio-ventricular electrogram amplitude ratio was >1 during both the AT and sinus rhythm. The tailored approach targeting the NCC AT alone without left atrial ablation completely eliminated the AF. In catheter ablation of AF in a patient with a co-existing clinical AT, it may be recommended to examine the clinical AT first. If the clinical AT initiates the AF and local atrial activations in the His bundle region precede the P wave onset during AT, mapping in the NCC should be considered prior to left atrial catheterization.

Successful transseptal catheter ablation of premature ventricular contractions arising from the mitral annulus: a case with a pure annular origin.

A 74-year-old man with symptomatic premature ventricular contractions (PVCs) with a right bundle branch block and right inferior axis QRS morphology underwent electrophysiologic testing. During the PVCs, coronary sinus mapping revealed ventricular prepotentials with the earliest activation in the distal great cardiac vein (GCV) where the local ventricular electrograms were smaller in amplitude than the atrial electrograms. The transaortic approach could not reach the earliest activation site within the GCV, but the transseptal catheter ablation successfully eliminated the PVCs on the mitral valve. With catheter ablation of ventricular arrhythmias with pure mitral annular origins, a transseptal approach may be necessary.

Transmural recording of shock potential gradient fields, early postshock activations, and refibrillation episodes associated with external defibrillation of long-duration ventricular fibrillation in swine.

BACKGROUND: Knowledge of the shock potential gradient (nablaV) and postshock activation is limited to internal defibrillation of short-duration ventricular fibrillation (SDVF). OBJECTIVE: The purpose of this study was to determine these variables after external defibrillation of long-duration VF (LDVF). METHODS: In six pigs, 115-20 plunge needles with three to six electrodes each were inserted to record throughout both ventricles. After the chest was closed, the biphasic defibrillation threshold (DFT) was determined after 20 seconds of SDVF with external defibrillation pads. After 7 minutes of LDVF, defibrillation shocks that were less than or equal to the SDVF DFT strength were given. RESULTS: For DFT shocks (1632 +/- 429 V), the maximum minus minimum ventricular voltage (160 +/- 100 V) was 9.8% of the shock voltage. Maximum cardiac nablaV (28.7 +/- 17 V/cm) was 4.7 +/- 2.0 times the minimum nablaV (6.2 +/- 3.5 V/cm). Although LDVF did not increase the DFT in five of the six pigs, it significantly lengthened the time to earliest postshock activation following defibrillation (1.6 +/- 2.2 seconds for SDVF and 4.9 +/- 4.3 seconds for LDVF). After LDVF, 1.3 +/- 0.8 episodes of spontaneous refibrillation occurred per animal, but there was no refibrillation after SDVF. CONCLUSION: Compared with previous studies of internal defibrillation, during external defibrillation much less of the shock voltage appears across the heart and the shock field is much more even; however, the minimum nablaV is similar. Compared with external defibrillation of SDVF, the biphasic external DFT for LDVF is not increased; however, time to earliest postshock activation triples. Refibrillation is common after LDVF but not after SDVF in these normal hearts, indicating that LDVF by itself can cause refibrillation without requiring preexisting heart disease.

The transmural activation sequence in porcine and canine left ventricle is markedly different during long-duration ventricular fibrillation.

BACKGROUND: Humans are more similar in transmural Purkinje and cardiac ion channel distributions to dogs than pigs. The Purkinje network in pigs is transmural but confined to the endocardium in dogs. Little is known about intramural activation during long-duration ventricular fibrillation (LDVF) given these differences. We tested the hypothesis that the transmural activation sequence is similar in sinus rhythm (SR) and LDVF in dogs as well as pigs, but different between species. METHODS AND RESULTS: In six pigs and seven dogs, 50-60 plunge needles (six electrodes, 2-mm spacing) were placed throughout the left ventricle. Unipolar recordings were made for >10 minutes of LDVF. SR and LDVF activation times were grouped into waves by linking activations along each needle. Origin (earliest activation) and propagation direction were determined for each wave. The mean wave origin was significantly more endocardial in dogs than pigs for SR and 1 through 10 minutes of LDVF. Predominant propagation direction in LDVF and SR was endocardial to epicardial in dogs, but the opposite or equal in both directions in pigs. Fastest activation rate was epicardial in pigs, but endocardial in dogs with an increasing endocardial-to-epicardial activation rate gradient as LDVF progressed in dogs but not pigs. CONCLUSIONS: The transmural activation sequence in SR and LDVF is markedly different between pigs and dogs. These differences may be related to differences in Purkinje fiber and ion channel distributions and suggest that dogs are a better model for investigating activation sequences during LDVF, given the similarities with humans.

Transmural and endocardial Purkinje activation in pigs before local myocardial activation after defibrillation shocks.

BACKGROUND: Earliest recorded postshock myocardial activations in pigs originate in the subepicardium of the apex and lateral free wall of the left ventricle (LV) 30-90 ms after the shock. OBJECTIVE: The purpose of this study was to determine whether the Purkinje system is a candidate for the source of postshock activations by performing endocardial and transmural postshock activation mapping. METHODS: In five pigs, 32 plunge needles with 12 electrodes (1-mm spacing) were inserted into the LV apex and lateral free wall. Up to 70 plunge needles with six electrodes (2-mm spacing) were spread throughout the remainder of the LV, while 9-12 plunge needles with four electrodes (2-mm spacing) were inserted into the right ventricle. A basket catheter with 32 bipolar recording sites was inserted into the LV. Defibrillation-threshold (DFT)-level shocks were delivered during 10 episodes of electrically induced ventricular fibrillation. Electrograms of postshock activation cycles were analyzed for Purkinje and myocardial activations. RESULTS: Purkinje activations were recorded before local myocardial activation in 9% of basket electrograms and in 15% of plunge needles during the first postshock activation cycle. Purkinje activations were identified during the first and subsequent several postshock activation cycles in at least one basket and one needle electrogram in 96% and 98% of defibrillation episodes, respectively. CONCLUSIONS: The Purkinje system is active during the early postshock activation cycles after DFT-level shocks. Further studies are required to determine whether activation initiates in the Purkinje system or whether it is activated by the myocardium or by Purkinje-myocardial junctional cells.

Guidelines for plunge needle recording for effective detection of purkinje activation.

Direct recording of Purkinje fiber activity may lead to a better understanding of the role of the specialized conduction system in pathological cardiac conditions. Two studies were conducted in pigs to determine guidelines for effective plunge needle recording techniques. In the first experiment, Purkinje fiber activations were recorded at 16 KHz with 3 bipolar electrodes (2 mm spacing) on epoxy plunge needles, and were later lowpass filtered and downsampled to determine the rate required for effective identification of Purkinje activation. Purkinje spikes were identifiable at sampling rates of 4 KHz and greater, but were not easily distinguished at sampling rates of 2 KHz or less. In the second experiment, 4 plunge needles with 15 electrodes (1 mm spacing) were inserted 8 times into different locations around the left ventricle. Unipolar (15 per needle) and bipolar (14 per needle) signals were recorded simultaneously at a sampling rate of 8 KHz. Purkinje activations were identified in 13/32 plunge needle sites. Of the 13 sites with identified Purkinje activations, 10 were within 2 mm of the endocardium. Bipolar recordings demonstrated Purkinje potentials that were 13% of the amplitude of the following myocardial activation, while unipolar recordings from the same electrodes recorded Purkinje potentials that were only 5% of the amplitude of the following myocardial activations. Three guidelines were developed for effective Purkinje fiber recording: 1) use a minimum sampling rate of 4 KHz., 2) record near the endocardium, and 3) use bipolar rather than unipolar recording electrodes.

Printed circuit board electrodes for transmural cardiac mapping.

Plunge needle recording techniques have provided valuable insights into transmural activation in cardiac tissue. Construction of plunge needles has been a costly and time intensive endeavor. Plunge needles constructed with standard printed circuit board (PCB) technology and methods are outlined. PCB plunge needles are less expensive in terms of raw materials and time required for construction than hypodermic stock or epoxy plunge needles. Tested PCB plunge needles recorded signals comparable to signals recorded by other plunge needles. PCB plunge needles provide an economical and rapid alternative to previously published techniques for plunge needle design.

Artificial neural network modeling of stress single-photon emission computed tomographic imaging for detecting extensive coronary artery disease.

Single-photon emission computed tomographic imaging is a useful, noninvasive method to detect coronary artery disease (CAD). We tested the hypothesis that artificial neural network modeling could predict CAD extent better than visual interpretation; 109 patients who underwent stress single-photon emission computed tomography and coronary angiography were selected. Twenty patients who had a <5% probability of CAD were also selected for calculation of normalcy rate. A model was trained for each vessel. Stress images were decreased to 25 points by pixel averaging the polar map. The model output was 1 for vessel stenosis >60% and 0 otherwise. Model sensitivities were 92% (55 of 60) for left anterior descending artery versus 62% (37 of 60) for visual interpretation (p = 0.0002), 69% (20 of 29) for left circumflex artery versus 55% for visual interpretation (p = 0.30), and 94% (45 of 48) for right coronary artery versus 78% for visual interpretation (p = 0.024). Model specificities and normalcy rates were 78% and 85% for the left anterior descending artery, 93% and 100% for the left circumflex artery, and 85% and 90% for the right circumflex artery, respectively. Single-vessel CAD was predicted in 27 of 28 patients (96%) by modeling versus 23 of 28 patients (82%) by visual interpretation (p = 0.11). Multivessel CAD was correctly predicted in 30 of 46 patients (65%) by modeling versus 16 of 46 patients (35%) by visual interpretation (p = 0.004). Thus, artificial neural network models can predict CAD from stress single-photon emission computed tomographic images when using separate models for the 3 major epicardial vessels. Because of their high sensitivity and specificity in detecting extensive CAD, these models have great promise as an aid to correctly identify patients at high risk for CAD.