943-14 Termination and Suppression of Experimental Atrial Flutter by Quinidine: Effects on Dispersion of Repolarization and Conduction

Recent studies in our canine crush-injury (CI) model of atrial flutter (AFL) suggest that elimination of dispersion of repolarization is an important antiarrhythmic effect of newer class 3 antiarrhythmic drugs. However, the effects of class 1a antiarrhythmic drugs on dispersion of repolarization and its relation to termination and suppression of AFL have not been studied. Therefore, the effects of quinidine 10) were studied in 8 dogs, using a 56-electrode plaque placed over the CI to map activation patterns during AFL and its induction and termination, and to measure effective refractory periods (ERP) at all 56 electrodes and conduction velocity (CV) parallel to the CI, before and after 0 (10mg/kg over 10 min, then 3 mg/kg/hr).ResultsInduction of AFL at baseline was due to unidirectional block below the CI. a terminated AFL in only 3 dogs, due to conduction block below the CI, occurring either abruptly or following premature eccentric activation of the reentry circuit. Sustained AFL was reinducible after a in 5 dogs, and nonsustained AFL in 3. Mean overall ERP increased 14% from 112±11msec at baseline to 128±15msec after a (p<0.001). ERP was longer below CI than above (115±10ms vs 109±10ms, p<0.001). and this difference was not eliminated by a (133±14ms vs 123±14ms, p<0.001). Overall dispersion of ERP (9.9±2.3msec) was unchanged by a (1 0.0±1.3msec, p=NS). The number of adjacent electrodes with ERP difference ≥20msec (14.4±10.4) was also not changed by a (12.5±7.9, P = NS). CV was slower below the CI than above at baseline (0.7±0.1 vs 0.9±0.1 mis,p<0.001), and this difference was unchanged by a (0.6±0.1 vs 0.8±0.1 mis,p<0.001). although CV was slowed overall(p<0.01). a prolonged AFL cycle length 57% from 123±12 to 198±37msec (p<0.01).Conclusion1) Baseline dispersion of ERP and CV is important for initiating and sustaining AFL in this model. 2) The class 1a drug quinidine is relatively ineffective in terminating and suppressing AFL in this model, because it prolongs ERP less than AFL cycle length and it does not eliminate dispersion of ERP or C

Recording sympathetic nerve activity from the skin

Sympathetic tone is important in cardiac arrhythmogenesis; however, methods to estimate sympathetic tone are either invasive or require proper sinus node function that may be abnormal in disease states. Because of the direct and extensive connections among various nerve structures, it is possible for the sympathetic nerves in the various structures to activate simultaneously. Therefore, we hypothesized that nerve activity can be recorded from the skin and it can be used to estimate the cardiac sympathetic tone. Preclinical studies in canines demonstrated that nerve activity is detectable using conventional ECG electrodes and can be used to estimate cardiac sympathetic tone. Subsequent clinical studies further supported this concept. In addition to studying the autonomic mechanisms of cardiac arrhythmia, these new methods may have broad application in studying both cardiac and non-cardiac diseases

Effects of Stepwise Denervation of the Stellate Ganglion: Novel Insights from an Acute Canine Study

Background The stellate ganglion (SG) is important for cardiac autonomic control. SG modification is an option for treating refractory ventricular tachyarrhythmias. The optimal extent of left- and right-sided SG denervation necessary for antiarrhythmic effect, however, remains to be learned. Objective The purpose of this study was to evaluate the effects of stepwise SG denervation on hemodynamic and electrophysiological parameters in dogs. Methods After sequential left and right thoracotomy in 8 healthy dogs, the SG was exposed by dissection. Two pacing wires were placed in the upper SG to deliver high-frequency stimulation. The lower SG, ansae subclaviae, and upper SG were removed in a stepwise manner. The same protocol was performed on the right side. Blood pressure (BP), heart rate, and electrophysiological parameters were recorded at baseline and after 5 minutes of stimulation. Results Systolic and diastolic BP significantly increased during stimulation of the upper left SG. The mean increase in systolic BP from baseline was 49.4 ± 26.6 mm Hg (P = .007), 25.5 ± 14.1 mm Hg after the lower SG was removed (P = .02), and 8.6 ± 3.4 mm Hg after resection of the ipsilateral ansae subclaviae (P = .048). Heart rate and other electrophysiological parameters did not change significantly. After the complete removal of the left SG, systolic BP increased by 34.0 ± 17.6 mm Hg (P = .005) after stimulation of the right SG. Conclusion Sympathetic output remains after the lower SG is removed, and sympathetic output from the right SG remains after the complete resection of the left SG and ansae subclaviae. Thus, some patients who undergo left SG denervation can still have significant sympathetic response via right SG regulation

Invasive electrophysiological testing to predict and guide permanent pacemaker implantation after transcatheter aortic valve implantation: A meta-analysis.

BACKGROUND Atrioventricular conduction abnormalities after transcatheter aortic valve implantation (TAVI) are common. The value of electrophysiological study (EPS) for risk stratification of high-grade atrioventricular block (HG-AVB) and guidance of permanent pacemaker (PPM) implantation is poorly defined. OBJECTIVE The purpose of this study was to identify EPS parameters associated with HG-AVB and determine the value of EPS-guided PPM implantation after TAVI. METHODS We performed a systematic review and meta-analysis of studies investigating the value of EPS parameters for risk stratification of TAVI-related HG-AVB and for guidance of PPM implantation among patients with equivocal PPM indications after TAVI. RESULTS Eighteen studies (1230 patients) were eligible. In 7 studies, EPS was performed only after TAVI, whereas in 11 studies EPS was performed both before and after TAVI. Overall PPM implantation rate for HG-AVB was 16%. AV conduction intervals prolonged after TAVI, with the AH and HV intervals showing the largest magnitude of changes. Pre-TAVI HV >70 ms and the absolute value of the post-TAVI HV interval were associated with subsequent HG-AVB and PPM implantation with odds ratios of 2.53 (95% confidence interval [CI] 1.11-5.81; P = .04) and 1.10 (95% CI 1.03-1.17; P = .02; per 1-ms increase), respectively. In 10 studies, PPM was also implanted due to abnormal EPS findings in patients with equivocal PPM indications post-TAVI (typically new left bundle branch block or transient HG-AVB). Among them, the rate of long-term PPM dependency was 57%. CONCLUSION Selective EPS testing may assist in the risk stratification of post-TAVI HG-AVB and in the guidance of PPM implantation, especially in patients with equivocal PPM indications post-TAVI

Characterization of skin sympathetic nerve activity in patients with cardiomyopathy and ventricular arrhythmia

Background Heightened sympathetic nerve activity is associated with occurrence of ventricular arrhythmia (VA). Objective To investigate the association of skin sympathetic nerve activity (SKNA) and VA occurrence. Methods We prospectively enrolled 65 patients with severe cardiomyopathy. Of these, 39 had recent sustained VA episodes (VA-1 group), 11 had intractable VA undergoing sedation with general anesthesia (VA-2 group), and 15 had no known history of VA (VA-Ctrl group). All patients had simultaneous SKNA and electrocardiogram recording. SKNA was assessed using an average value (aSKNA), a variable value (vSKNA), and the number of bursts of SKNA (bSKNA). Results The VA-1 group had higher aSKNA and vSKNA compared with the VA-Ctrl group (aSKNA: 1.41 ± 0.53 μV vs 0.98 ± 0.41 μV, P = .003; vSKNA: 0.52 ± 0.22 μV vs 0.30 ± 0.16 μV, P 15% reduction in aSKNA after therapy was associated with a lower subsequent VA event rate (hazard ratio, 0.222; 95% CI, 0.057–0.864; P = .03). Conclusion Patients with VA had increased SKNA as compared with control. Both SKNA and sustained VA could be suppressed by general anesthesia. The aSKNA at baseline was an independent predictor of VA recurrence

Simultaneous noninvasive recording of skin sympathetic nerve activity and electrocardiogram

BACKGROUND: Sympathetic nerve activity is important to cardiac arrhythmogenesis. OBJECTIVE: The purpose of this study was to develop a method for simultaneous noninvasive recording of skin sympathetic nerve activity (SKNA) and electrocardiogram (ECG) using conventional ECG electrodes. This method (neuECG) can be used to adequately estimate sympathetic tone. METHODS: We recorded neuECG signals from the skin of 56 human subjects. The signals were low-pass filtered to show the ECG and high-pass filtered to show nerve activity. Protocol 1 included 12 healthy volunteers who underwent cold water pressor test and Valsalva maneuver. Protocol 2 included 19 inpatients with epilepsy but without known heart diseases monitored for 24 hours. Protocol 3 included 22 patients admitted with electrical storm and monitored for 39.0 ± 28.2 hours. Protocol 4 included 3 patients who underwent bilateral stellate ganglion blockade with lidocaine injection. RESULTS: In patients without heart diseases, spontaneous nerve discharges were frequently observed at baseline and were associated with heart rate acceleration. SKNA recorded from chest leads (V1-V6) during cold water pressor test and Valsalva maneuver (protocol 1) was invariably higher than during baseline and recovery periods (P < .001). In protocol 2, the average SKNA correlated with heart rate acceleration (r = 0.73 ± 0.14, P < .05) and shortening of QT interval (P < .001). Among 146 spontaneous ventricular tachycardia episodes recorded in 9 patients of protocol 3, 106 episodes (73%) were preceded by SKNA within 30 seconds of onset. Protocol 4 showed that bilateral stellate ganglia blockade by lidocaine inhibited SKNA. CONCLUSION: SKNA is detectable using conventional ECG electrodes in humans and may be useful in estimating sympathetic tone

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701