Induction Of Ventricular Fibrillation Research Articles

Chemical ablation of the left ventricular endocardium reduces ventricular fibrillation inducibility in acute ischemic canine heart.

Ventricular fibrillation remains as the major cause of death in patients with acute myocardial infarction. Effects of trans-atrial chemical ablation of the left ventricular (LV) endocardium with Lugol's solution on ventricular fibrillation inducibility and ventricular conduction were examined in canines with acute myocardial ischemia. Chemical ablation of the LV endocardium with Lugol's solution or normal saline was preformed through a left atrial appendage in 14 canines 30 min after occlusion of the left anterior coronary artery. Ventricular fibrillation threshold decreased after the coronary artery occlusion and increased after endocardial chemical ablation. There was a significant difference in the ventricular fibrillation threshold after chemical ablation between with Lugol's solution and with normal saline (25.9 ± 9.2 mA vs. 11.3 ± 2.7 mA, p < .01). QRS width significantly increased from 88 ± to 116 ± (p < .01) after the chemical ablation with Lugol's solution, and the activation map of the ventricles demonstrated a left bundle branch block ventricular conduction pattern. Histological examination of the LV endocardium showed lymphocyte infiltration for a depth of 1 mm. Chemical ablation of the LV endocardium with Lugol's solution injures endocardial conduction system and increases ventricular fibrillation threshold in the early phase of myocardial ischemia in canines. The procedure may be useful in suppressing intractable ventricular tachyarrhythmias in patients with acute myocardial ischemia.

Long-term clinical outcomes of patients with drug-induced type 1 Brugada electrocardiographic pattern: A nationwide cohort registry study

BackgroundThere are limited real-world data on the extended prognosis of patients with drug-induced type 1 Brugada electrocardiogram (ECG). ObjectiveWe assessed the clinical outcomes and predictors of life-threatening arrhythmias in patients with drug-induced type 1 Brugada ECG. MethodsThis multicenter retrospective study, conducted at 21 Italian and Swiss hospitals from July 1997 to May 2021, included consecutive patients with drug-induced type 1 ECG. The primary outcome, a composite of appropriate ICD therapies and sudden cardiac death, was assessed along with the clinical predictors of these events. ResultsA total of 606 patients (mean age 49.7 ± 14.7 years; 423 [69.8%] men) were followed for a median of 60.3 months (interquartile range 23.0–122.4 months). Nineteen patients (3.1%) experienced life-threatening arrhythmias, with a median annual event rate of 0.5% over 5 years and 0.25% over 10 years. The SCN5A mutation was the only predictor of the primary outcome (hazard ratio 4.54; P = .002), whereas a trend was observed for unexplained syncope (hazard ratio 3.85; P = .05). In patients who were asymptomatic at presentation, the median annual rate of life-threatening arrhythmias is 0.24% over 5 years and increases to 1.2% if they have inducible ventricular fibrillation during programmed ventricular stimulation. ConclusionIn patients with drug-induced type 1 Brugada ECG, the annual risk of life-threatening arrhythmias is low, with the SCN5A mutation as the only independent predictor. Unexplained syncope correlated with worse clinical outcomes. Ventricular fibrillation inducibility at programmed ventricular stimulation significantly increases the median annual rate of life-threatening arrhythmias from 0.24% to 1.2% over 5 years.

Hemodynamic Effect of Repeated Epinephrine Doses Decreases With Cardiopulmonary Resuscitation Cycle Progression.

Epinephrine is administered to increase coronary perfusion pressure during advanced life support and promote short-term survival. Recent cardiopulmonary resuscitation (CPR) guidelines recommend an epinephrine dosing interval of 3 to 5 minutes during resuscitation; however, scientific evidence supporting this recommendation is lacking. Therefore, we aimed to investigate the hemodynamic effects of repeated epinephrine doses during CPR by monitoring augmented blood pressure after its administration in a swine model of cardiac arrest. A secondary analysis of data from a published study was performed using a swine cardiac arrest model. The epinephrine dose was fixed at 1 mg, and the first dose of epinephrine was administered after no-flow and low-flow times of 2 minutes and 8 minutes, respectively, and subsequently administered every 4 minutes. Four cycles of dosing intervals were defined because a previous study was terminated 26 minutes after the induction of ventricular fibrillation. Augmented blood pressures and corresponding timelines were determined. Augmented blood pressure trends following cycles and the epinephrine effect duration were also monitored. Among the 140 CPR cycles, the augmented blood pressure after epinephrine administration was the highest during the first cycle of CPR and decreased gradually with further cycle repetitions. The epinephrine effect duration did not differ between repeated cycles. The maximum blood pressure was achieved 78 to 97 seconds after epinephrine administration. Hemodynamic augmentation with repeated epinephrine administration during CPR decreased with cycle progression. Further studies are required to develop an epinephrine administration strategy to maintain its hemodynamic effects during prolonged resuscitation.

Effect of no-flow period on the vasopressor effect of initial epinephrine administration in cardiac arrest

ObjectivesWhether a longer no-flow (NF) interval affects the magnitude of response to epinephrine in the resuscitation has not been well studied. Therefore, this study aimed to evaluate the effect of NF interval on the vasopressor effect of initial epinephrine administration in a porcine model. MethodsWe enrolled 20 pigs from two randomized porcine experimental studies using a ventricular fibrillation (VF) cardiac arrest model. The first experiment subjects were resuscitated after 4 min of NF (Short NF group), followed by three cycles (6 min) of chest compression using a mechanical cardiopulmonary resuscitation device before epinephrine administration. Second experiment subjects received 6 min of NF (Long NF group), two cycles (4 min) of chest compressions, and administration of epinephrine. Defibrillation for VF was delivered 8 and 10 min after VF induction in the Short NF and Long NF groups, respectively. The mean arterial pressure (MAP) and cerebral perfusion pressure (CePP) in the 2-min resuscitation period after epinephrine administration were compared between the study groups using the Wilcoxon rank-sum test. The mean differences in the parameters between phases were also compared. ResultsSeven pigs in the Short NF group and 13 pigs in the Long NF group were included in the analysis. All 2-min resuscitation phases from 6 to 16 min after VF induction were compared between the study groups. The Short NF group showed higher MAP and CePP in all phases (p < 0.01). Change of mean MAP after the epinephrine administration was significantly different between the study groups: mean difference (95% confidence interval) of 16.6 (15.8–17.4) mmHg in the Short NF group and 4.2 (3.9–4.5) mmHg in the Long NF group. ConclusionIn the porcine VF cardiac arrest model, 6 min of NF before resuscitation may affect the vasopressor effect of the initial epinephrine administered compared to 4 min of NF. A short NF may play a role in maximizing the effect of epinephrine in advanced cardiovascular life support.

92 The effect of repeated ventricular fibrillation inductions on defibrillation outcome in a paediatric porcine model

92 The effect of repeated ventricular fibrillation inductions on defibrillation outcome in a paediatric porcine model

Intracardiac Induced Ventricular Fibrillation for the Euthanasia of Sheep.

Euthanasia is the humane termination of an animal's life and an important consideration for scientists, veterinarians, regulators, and others contemplating investigations involving animals. Techniques for euthanasia must induce the most rapid, painless, and distress-free death possible. This study investigated the effectiveness of direct current induction of ventricular fibrillation for the euthanasia of sheep after a primary study in which artifacts or chemical contamination from injectable euthanasia agents were undesirable. Female crossbred adult sheep (Ovis aries; n = 12) under deep isoflurane general anesthesia were instrumented with electrophysiology catheters to induce ventricular fibrillation for euthanasia. Data regarding invasive arterial blood pressure, expired airway gases, limb lead electrocardiograms, and pulse oximetry were collected and assessed just prior to, immediately after, and at 5, 10, 15, and 20min after energy delivery. In all animals, a single 10-s application of 9V of direct current to the right ventricular endocardium via the electrophysiology catheter induced persistent ventricular fibrillation. Arterial blood pressure (mean ± 1 SD) immediately after fibrillation induction was 22.9±4.5mmHg, with negligible difference between systolic and diastolic pressures. The lack of differential pressure continued through the end of the monitoring period. Arterial blood pressure reached an initial nadir at 1??0.5min after fibrillation induction, peaked (40.8±11.1mmHg) due to a vasoconstrictive reflex at 3min after induction, and returned to a static uniform pressure (20.4±17.8mmHg) with mildly increased variability due to reflexive diaphragmatic contractions at 10min after induction. The use of 9V direct current for the induction of ventricular fibrillation via an electrophysiology catheter is a reliable method of euthanasia in sheep.

Development of an automatic device performing chest compression and external defibrillation: An animal-based pilot study.

Automatic chest compression devices (ACCDs) can promote high-quality cardiopulmonary resuscitation (CPR) and are widely used worldwide. Early application of automated external defibrillators (AEDs) along with high-quality CPR is crucial for favorable outcomes in patients with cardiac arrest. Here, we developed an automated CPR (A-CPR) apparatus that combines ACCD and AED and evaluated its performance in a pilot animal-based study. Eleven pigs (n = 5, A-CPR group; n = 6, ACCD CPR and AED [conventional CPR (C-CPR)] group) were enrolled in this study. After 2 min observation without any treatment following ventricular fibrillation induction, CPR with a 30:2 compression/ventilation ratio was performed for 6 min, mimicking basic life support (BLS). A-CPR or C-CPR was applied immediately after BLS, and resuscitation including chest compression and defibrillation, was performed following a voice prompt from the A-CPR device or AED. Hemodynamic parameters, including aortic pressure, right atrial pressure, coronary perfusion pressure, carotid blood flow, and end-tidal carbon dioxide, were monitored during resuscitation. Time variables, including time to start rhythm analysis, time to charge, time to defibrillate, and time to subsequent chest compression, were also measured. There were no differences in baseline characteristics, except for arterial carbon dioxide pressure (39 in A-CPR vs. 33 in C-CPR, p = 0.034), between the two groups. There were no differences in hemodynamic parameters between the groups. However, time to charge (28.9 ± 5.6 s, A-CPR group; 47.2 ± 12.4 s, C-CPR group), time to defibrillate (29.1 ± 7.2 s, A-CPR group; 50.5 ± 12.3 s, C-CPR group), and time to subsequent chest compression (32.4 ± 6.3 s, A-CPR group; 56.3 ± 10.7 s, C-CPR group) were shorter in the A-CPR group than in the C-CPR group (p = 0.015, 0.034 and 0.02 respectively). A-CPR can provide effective chest compressions and defibrillation, thereby shortening the time required for defibrillation.

Complexity analysis of electrical activity during endocardial and epicardial biventricular mapping of ventricular fibrillation.

Ventricular fibrillation (VF) is a lethal cardiac arrhythmia that is a significant cause of sudden cardiac death. Comprehensive studies of spatiotemporal characteristics of VF in situ are difficult to perform with current mapping systems and catheter technology. The goal of this study was to develop a computational approach to characterize VF using a commercially available technology in a large animal model. Prior data suggests that characterization of spatiotemporal organization of electrical activity during VF can be used to provide better mechanistic understanding and potential ablation targets to modify VF and its substrate. We therefore evaluated intracardiac electrograms during biventricular mapping of the endocardium (ENDO) and epicardium (EPI) in acute canine studies. To develop thresholds for organized and disorganized activity, a linear discriminant analysis (LDA)-based approach was performed to the known organized and disorganized activities recorded in ex vivo Langendorff-perfused rat and rabbit hearts using optical mapping experiments. Several frequency- and time-domain approaches were used as individual and paired features to identify the optimal thresholds for the LDA approach. Subsequently, VF was sequentially mapped in 4 canine hearts, using the CARTO mapping system with a multipolar mapping catheter in the ENDO left and right ventricles and EPI to capture the progression of VF at 3 discrete post-induction time intervals: VF period 1 (just after induction of VF to 15 min), VF period 2 (15 to 30 min), and VF period 3 (30 to 45 min). The developed LDA model, cycle lengths (CL), and regularity indices (RI) were applied to all recorded intracardiac electrograms to quantify the spatiotemporal organization of VF in canine hearts. We demonstrated the presence of organized activity in the EPI as VF progresses, in contrary to the ENDO, where the activity stays disorganized. The shortest CL always occurred in the ENDO, especially the RV, indicating a faster VF activity. The highest RI was found in the EPI in all hearts for all VF stages, indicating spatiotemporal consistency of RR intervals. We identified electrical organization and spatiotemporal differences throughout VF in canine hearts from induction to asystole. Notably, the RV ENDO is characterized by a high level of disorganization and faster VF frequency. In contrast, EPI has a high spatiotemporal organization of VF and consistently long RR intervals.

The electrophysiology of electrocution.

Electrocution is a death caused by an application of electrical current to the human body. Our present understanding of electrocution-as the induction of ventricular fibrillation (VF)-followed a nearly century-long path of misunderstandings and speculation primarily focused on hypotheses of asphyxia as well as central nervous system trauma. It is hard for us today to appreciate the past mystery of an unexpected sudden death usually bereft of visible trauma. Even today, a false dogma exists that direct-current shocks can cause asystole instead of VF. A lightning discharge (up to 500 megavolts) is differentiated because it can cause substantial acute and chronic neural effects leading to other cardiac arrest rhythms. The human heart is exquisitely sensitive to alternating currents, and VF can be induced with currents of one-eighth that required for mere pacing. Because of these low currents, this effect obtains only in the TQ interval, and low-power electrocution does not involve the vulnerable period. If a current is strong enough to electrocute, generally it will do so in 1-2 seconds; longer shocks do not tend to be more dangerous. Regardless of concomitant drug dosing, the electrocution cardiac arrest rhythm is still VF, suggesting that electrocution is a stand-alone cause of death; the electrical current does not potentiate the effects of the drug. The experimental and clinical data supporting VF as the mechanism for electrocution are provided.

Amiodarone does not significantly affect the success rate of ventricular fibrillation induction tests performed during or after ICD implantation. Insights from the German DEVICE registry

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): The DEVICE registries were financed by “Stiftung Institut für Herzinfarktforschung (IHF)”, with additional support by grants from Biotronik, Medtronic, and St. Jude Medical. Background Experimental data and early clinical trials suggested that amiodarone may alter the defibrillation threshold of ICD systems. However, because of its potent antiarrhythmic effect and lack of alternatives, amiodarone is frequently used for antiarrhythmic therapy in ICD or CRT-D patients, leading to the question of whether ICD testing with ventricular fibrillation induction should be repeated in these patients after starting amiodarone. Objective This study was designed to assess the impact of amiodarone therapy on the success of ventricular fibrillation induction tests in this "real life" cohort of ICD recipients of the German DEVICE registry. Methods 3,680 patients who underwent ICD implantation, revision, or upgrade in 49 centers participating in the German DEVICE Registry were enrolled 03/2007-02/2014. Results Intraoperative defibrillation testing was conducted in 2,705 patients receiving only beta-blockes as antiarrhythmic therapy and in 422 patients under betablocker plus amiodarone therapy. With regard to ineffective defibrillation tests, no difference could be described between the two groups (0.6% vs. 0.5%; p=0.77). In a similar fashion 488 patients receiving beta-blockers only and 65 patients under beta-blocker plus amiodarone therapy who were scheduled for postoperative defibrillation testing showed comparable rates of ineffective testing (14.5% vs. 15.4%; p=0.86). Conclusions Based on 3,127 intraoperative and 553 postoperative defibrillator testings, our study failed to show a significant association of amiodarone therapy and ineffective defibrillator testings in this "real life" cohort of ICD recipients of the German DEVICE registry. Our results thus underline that, apart from special situations such as right-sided implantation, HCM, extravenous ICD systems, etc., it might not be necessary to perform a DFT test after the start of an amiodarone therapy in ICD patients.

PO-04-194 PROGNOSTIC SIGNIFICANCE OF ELECTROPHYSIOLOGIC TESTING FOR VENTRICULAR ARRHYTHMIAS IN PATIENTS WITH MITRAL ANNULAR DISJUNCTION

Mitral annular disjunction (MAD), with or without mitral valve prolapse (MVP), is associated with a higher risk of ventricular arrhythmias (VA) and sudden cardiac death. The prognostic significance of VA inducibility during electrophysiological studies (EPS) in patients with MAD is unclear. To assess the prognostic significance of VA inducibility in patients with MAD undergoing EPS. We included 21 patients with MAD and no history of sustained VAs who underwent EPS for risk stratification. Patients who underwent ablation of any VA during the same procedure were excluded. EPS protocol included programmed ventricular stimulation with up to triple extrastimuli and with burst pacing from 2 ventricular sites. Post-EPS events including sustained VAs, appropriate implantable-cardioverter defibrillator (ICD) shocks, and sudden death, were assessed according to the EPS results. Mean age at the time of EPS was 46±16 years, and 15 (71.4%) patients were female. Mean MAD length was 10±4 mm. 18 (85.7%) patients had MVP (bileaflet MVP in 15 patients and posterior MVP in 3 patients). Non-sustained ventricular tachycardia (NSVT) was induced in 2 (9.5%) patients, sustained monomorphic ventricular tachycardia (VT) in 4 (19%) patients, and ventricular fibrillation (VF) in 9 (42.9%) patients, while six (28.6%) patients had no inducible VAs. 10 (47.6%) patients underwent ICD implantation due to inducible sustained VT (n=4) or VF (n=6), while 5 (23.8%) patients received an implantable loop recorder (ILR). After a median follow-up of 18.9 months, 4 (19%) patients had incident sustained VT or VF, all among patients with an ICD. These events occurred in 2 of the 4 patients with inducible VT and 2 of the 9 with inducible VF, while no events occurred in those with inducible NSVT or no inducible VAs. Inducible sustained VT or VF at EPS did not demonstrate a statistically significant association with incident sustained VAs (p=0.13). No deaths occurred in any patients in this series. More than half of patients with MAD referred for risk stratification EPS had inducible sustained VT or VF. Inducibility of VT/VF was not statistically associated with incident sustained VAs though this analysis is limited by the small sample size. Larger prospective studies are needed to clarify the role of EPS with standardized protocols in the risk stratification of patients with MAD, including investigation of the value of right and left ventricular stimulation.

PO-05-035 FASCICULAR SUBSTRATE MODIFICATION TO TREAT HUMAN VENTRICULAR FIBRILLATION: A MULTICENTER STUDY

Purkinje fibers play an important role in initiation and maintenance of ventricular fibrillation (VF). Fascicular substrate modification approaches have been suggested to treat recurrent VF in isolated case reports and small case series. To investigate the outcomes of catheter-based fascicular substrate modification to treat recurrent VF. Out of 2,212 consecutive patients with ventricular arrhythmia undergoing catheter ablation at our centers, 18 (0.81%) underwent fascicular substrate modification by targeting with short (<20 s) RF lesions in the most distal segment of the Purkinje fibers as identified with high-density mapping during sinus rhythm. Demographic, clinical, and follow-up characteristics were prospectively collected in our institutional database. A total of 18 patients (mean age: 56±3.8 years, female: 4, 22%) were included in the study. Of those, 11 (61.1%) had idiopathic VF (normal heart VF), 3 (16.7%) had non-ischemic cardiomyopathy and 4 (22.2%) had mixed cardiomyopathy. Average LVEF was 42.5%. Patients had failed ≥2 antiarrhythmic drugs pre-ablation. At baseline, all patients had inducible VF and non-inducibility of VF at the end of the procedure was achieved in 16 (88.9%) patients. In select patients, remapping revealed elimination of the targeted Purkinje potentials. At the end of the procedure, no patient demonstrated new evidence of fascicular block or bundle branch block. VF initiation and final lesion sets are shown in figure 1. There were no procedure-related complications. After a median follow-up of 24 months, 16 (88.9%) patients were arrhythmia-free on- or off-drugs; 11/11 (100%) patients with normal heart VF vs 5/7 (71.4%) with underlying cardiomyopathy (p=0.06). Catheter ablation of human VF with distal fascicular substrate modification is feasible, safe and appears highly effective with high rates of acute VF non-inducibility and long-term freedom from recurrent VF.

PO-455617-2 UNRAVELLING THE ARRHYTHMOGENIC MECHANISMS OF SHORT QT SYNDROME TYPE 3 IN AN ANIMAL MODEL OF KIR2.1M301K GAIN-OF-FUNCTION MUTATION

Short QT Syndrome Type 3 (SQTS3) is an extremely rare, highly arrhythmogenic disease caused by gain-of-function mutations in the KCNJ2 gene coding the inward rectifier potassium channel Kir2.1. We investigated arrhythmogenic mechanisms associated with the mutation Kir2.1M301K in a patient presenting an extremely abbreviated QT interval, paroxysmal atrial fibrillation, and ventricular fibrillation inducibility. To study mechanisms of life-threatening arrhythmias produced by Kir2.1M301K. We tested the hypothesis that, in addition to abolishing IK1 rectification, Kir2.1M301K produces functional defects in Kir2.1 partner proteins, predisposing patients to an arrhythmogenic phenotype. We used intravenous cardiac-specific adeno-associated virus-mediated gene transfer to generate mice expressing wild-type (WT) and M301K mutant channel. We characterized the mice using molecular and cellular biology techniques, electrocardiograms (ECGs), intracardiac stimulation and patch-clamping. We confirmed Kir2.1WT or Kir2.1M301K gene expression specifically in the mouse heart. On ECG, the corrected QT (QTc) interval of Kir2.1M301K mice was significantly shorter than Kir2.1WT mice (p<0.0001), and the QRS complex was prolonged (p<0.01). On intracardiac stimulation, 7 out of 8 Kir2.1M301K mice had inducible ventricular tachycardia/fibrillation of >500ms duration, while none of 10 Kir2.1WT mice were inducible (p=0.0009). Compared with Kir2.1WT, the current/voltage relation of Kir2.1M301K cardiomyocytes showed increased outward IK1 at voltages positive to -80 mV (p<0.0001) with no inward-going rectification. However, inward IK1 was reduced at voltages negative to -80 mV (p=0.006). Unexpectedly, Kir2.1M301K cardiomyocytes had a reduced INa density (p<0.0001) with voltage shifted activation and inactivation. Membrane fractionation and western blot analysis revealed that, while 100% of NaV1.5 channels reached the membrane in Kir2.1WT cardiomyocytes, only 77% did in Kir2.1M301K cardiomyocytes. The Kir2.1M301K mouse recapitulates the arrhythmogenic phenotype of the SQTS3 patient. Kir2.1M301K mutation produces both Kir2.1 and NaV1.5 dysfunction, confirming the reciprocal modulation of these channels in macromolecular complexes. This is the first demonstration that a KCNJ2 gain-of-function mutation modifies NaV1.5 current, thus producing severe arrhythmias by both shortening QT interval and reducing ventricular excitability.

PO-02-147 THE ANTIARRHYTHMIC EFFECTS OF MIRABEGRON IN ISOLATED RABBIT HEARTS

β-3 adrenoceptor (AR) activation opposes the effects of β-1 and β-2 AR activation and rescues the effects of excessive catecholamines. BRL37344 (beta3-AR agonist) is antiarrhythmic in canine models. Mirabegron is a β-3 agonist approved by the FDA for the treatment of overactive bladder. A previous study showed that isoproterenol activates the small conductance Ca-activated K current more in female than in male ventricles. To test the hypothesis that mirabegron reduces the proarrhythmic effects of isoproterenol more effectively in female than in male ventricles. We performed optical mapping studies in 6 male and 6 female Langendorff-perfused rabbit hearts first at baseline, then sequentially after isoproterenol (ISO, 100 nM), mirabegron (1000 nM), apamin (100 nM) administration and washout in study 1. In study 2 (5 males and 5 females), we studied at baseline, then after adding mirabegron (250 nM, 500 nM, 750 nM, and 1000 nM), followed by isoproterenol and washout. All hearts underwent 10 attempts of ventricular fibrillation (VF) induction with a ventricular burst (20 Hz for 10 s) pacing at each stage of the experiment. The number of phase singularities (PSs) was determined per episode of VF (PSs/VF). In study 1, mirabegron reduced the VF inducibility (number of VF after 10 attempts) during isoproterenol infusion by an average of -2.75 (p = 0.026). When VF was induced, the PSs/VF increased by 2.4±2.1 in males and 6.6±3.3 in females (p=0.03, Figure A). Mirabegron significantly reduced the PSs/VF in both sexes and eliminated the sex differences. Apamin given after mirabegron in the presence of isoproterenol did not further change PSs/VF (p=0.63) (Figure B). The conduction velocity (CV), estimated by the inverse of the total activation time (1/s), was 16±2.7 for all hearts at baseline and 35±10 after ISO, respectively (p=0.0006). ISO did not increase CV differentially by sex (p=0.93). Mirabegron reduced the CV by an average of 15.6 (from 34±11.4 to 18±3.9) in females, which was significantly (p=0.043) more than 5.1 (from 35±8.7 to 31±9.3) in males. Figure C shows a summary of study 2. Mirabegron significantly reduced PSs/VF at 750 nM in female (p=0.015 vs. baseline) and at 1000 nM in male (p=0.033 vs. baseline) hearts. The addition of ISO did not increase PSs/VF. During ISO infusion, mirabegron reduces the CV and the PSs/VF more in females than males during VF. These data suggest that the β3 agonist is a sex-specific antiarrhythmic agent.

The Brugada syndrome: pharmacological therapy.

Brugada syndrome is an inherited channelopathy with an increased risk of sudden cardiac death (SCD) due to ventricular arrhythmias (VA) and an increased incidence of supraventricular arrhythmias, as compared with the general population. For the prevention of SCD, the guidelines recommend the implantable cardioverter-defibrillator (ICD); however, ICD does not prevent VA. In this article, we provide a brief review of the literature on the Brugada syndrome pharmacological therapy, mainly focusing on quinidine treatment. The efficacy of quinidine therapy in the prevention of VA in Brugada syndrome has been demonstrated by several small studies in patients with ICD and recurrent shocks or in asymptomatic patients with inducible ventricular fibrillation (VF) at electrophysiological study. Quinidine has also been tested for the prophylaxis of supraventricular arrhythmias, especially atrial fibrillation/flutter, and in paediatric patients. In these studies, quinidine proved highly effective in preventing re-induction of VF and spontaneous recurrences of both ventricular and supraventricular arrhythmias. Unfortunately, this therapy is burdened by a high incidence of side effects, which may lead to drug discontinuation.

Levosimendan attenuates electrical alternans and prevents ventricular arrhythmia during therapeutic hypothermia in isolated rabbit hearts

Therapeutic hypothermia (TH) increases the susceptibility to ventricular arrhythmias (VAs) by prolonging action potential duration (APD) and facilitating arrhythmogenic spatially discordant alternans (SDA). Levosimendan, a calcium sensitizer, has been reported to shorten APD by enhancing the adenosine triphosphate (ATP)-sensitive K current. The purpose of this study was to test the hypothesis that, during TH, levosimendan shortens the already prolonged APD, attenuates SDA, and prevents VA. Langendorff-perfused isolated rabbit hearts were subjected to TH (30°C) for 15 minutes, followed by treatment with either levosimendan 0.5 μM (n = 9) or vehicle (n = 8) for an additional 30 minutes under TH. Using an optical mapping system, epicardial APD was evaluated by S1 pacing. SDA threshold was defined as the longest pacing cycle length (PCL) that induces the phenomenon of SDA. Ventricular fibrillation (VF) inducibility was evaluated by burst pacing for 30 seconds at the shortest PCL that achieved 1:1 ventricular capture. During TH, levosimendan shortened ventricular APD (PCL 400 ms; from 259 ± 8 ms to 241 ± 18 ms; P = .036) and decreased SDA threshold (from 327 ± 88 ms to 311 ± 68 ms; P = .011). VF inducibility was lowered from 39% ± 30% to 14% ± 12% with levosimendan (P = .018), whereas APD at PCL 400 ms (P = .161), SDA threshold (P = 1), and VF inducibility (P = .173) were not changed by vehicle. During TH, levosimendan could protect hearts against VA by shortening APD and decreasing SDA threshold. Enhancing ATP-sensitive K current with levosimendan might be a novel approach to preventing VA during TH.

A Model of Long-Term Ventricular Fibrillation in Isolated Rat Hearts

Ventricular fibrillation (VF) is a fatal arrhythmia with a high incidence in cardiac patients, but VF arrest under perfusion is a neglected method of intraoperative arrest in the field of cardiac surgery. With recent advances in cardiac surgery, the demand for prolonged VF studies under perfusion has increased. However, the field lacks simple, reliable, and reproducible animal models of chronic ventricular fibrillation. This protocol induces long-term VF through alternating current (AC) electrical stimulation of the epicardium. Different conditions were used to induce VF, including continuous stimulation with a low or high voltage to induce long-term VF and stimulation for 5 min with a low or high voltage to induce spontaneous long-term VF. The success rates of the different conditions, as well as the rates of myocardial injury and recovery of cardiac function, were compared. The results showed that continuous low-voltage stimulation induced long-term VF and that 5 min of low-voltage stimulation induced spontaneous long-term VF with mild myocardial injury and a high rate of recovery of cardiac function. However, the low-voltage, continuously stimulated long-term VF model had a higher success rate. High-voltage stimulation provided a higher rate of VF induction but showed a low defibrillation success rate, poor recovery of cardiac function, and severe myocardial injury. On the basis of these results, continuous low-voltage epicardial AC stimulation is recommended for its high success rate, stability, reliability, reproducibility, low impact on cardiac function, and mild myocardial injury.

Outcome and safety of intraoperative defibrillation testing during device replacement: the Simpler trial.

Intraoperative defibrillation testing (DT) during implant or replacement of implantable cardioverter-defibrillators (ICDs) has been a matter of debate for many years. This debate was put to rest by the Simple and Nordic ICD trials, and the practice of testing during new implantations has essentially been almost abandoned. Old registries demonstrated an increased incidence of significant findings in DT during replacements. The aim of the present study was to evaluate frequency of significant findings and safety of DT in subjects undergoing device replacement. A prospective observational multi-centre study included consecutive patients undergoing ICD generator replacement. The primary outcome was a failure to terminate induced ventricular fibrillation (VF) with a single shock 10 J below the maximal capacity of the device. Secondary outcomes included complications of DT. Patients were followed-up at 1- and 6-months post-procedure. A total of 92 patients were eligible, and consented to the study, of which 84 underwent DT during battery replacement. The median age was 68 years and 79.8% were males. Induction of VF was successful in 84 patients as was a successful conversion on the first attempt in all. There were no procedure-related complications. During follow up one patient had two appropriate ICD shock events. In four patients, ICD programming was changed. None suffered inappropriate shock. There was no evidence of lead malfunction. Two deaths occurred, none of which was related to arrhythmia. The present study found DT was not associated with complications in patients undergoing ICD generator replacement but produced no clinically important information.

Ventilation during continuous compressions or at 30:2 compression-to-ventilation ratio results in similar arterial oxygen and carbon dioxide levels in an experimental model of prolonged cardiac arrest

BackgroundIn refractory out-of-hospital cardiac arrest, transportation to hospital with continuous chest compressions (CCC) from a chest compression device and ventilation with 100% oxygen through an advanced airway is common practice. Despite this, many patients are hypoxic and hypercapnic on arrival, possibly related to suboptimal ventilation due to the counterpressure caused by the CCC. We hypothesized that a compression/ventilation ratio of 30:2 would provide better ventilation and gas exchange compared to asynchronous CCC during prolonged experimental cardiopulmonary resuscitation (CPR).MethodsWe randomized 30 anaesthetized domestic swine (weight approximately 50 kg) with electrically induced ventricular fibrillation to the CCC or 30:2 group and bag-valve ventilation with a fraction of inspired oxygen (FiO2) of 100%. We started CPR after a 5-min no-flow period and continued until 40 min from the induction of ventricular fibrillation. Chest compressions were performed with a Stryker Medical LUCAS® 2 mechanical chest compression device. We collected arterial blood gas samples every 5 min during the CPR, measured ventilation distribution during the CPR using electrical impedance tomography (EIT) and analysed post-mortem computed tomography (CT) scans for differences in lung aeration status.ResultsThe median (interquartile range [IQR]) partial pressure of oxygen (PaO2) at 30 min was 110 (52–117) mmHg for the 30:2 group and 70 (40–171) mmHg for the CCC group. The median (IQR) partial pressure of carbon dioxide (PaCO2) at 30 min was 70 (45–85) mmHg for the 30:2 group and 68 (42–84) mmHg for the CCC group. No statistically significant differences between the groups in PaO2 (p = 0.40), PaCO2 (p = 0.79), lactate (p = 0.37), mean arterial pressure (MAP) (p = 0.47) or EtCO2 (p = 0.19) analysed with a linear mixed model were found. We found a deteriorating trend in PaO2, EtCO2 and MAP and rising PaCO2 and lactate levels through the intervention. There were no differences between the groups in the distribution of ventilation in the EIT data or the post-mortem CT findings.ConclusionsThe 30:2 and CCC protocols resulted in similar gas exchange and lung pathology in an experimental prolonged mechanical CPR model.

PS-B02-15: LIGHT POLLUTION, OBESITY, AND HYPERTENSION- “LIFESTYLE” RISK FACTORS ASSOCIATED WITH AN INCREASED RISK OF MALIGNANT ARRHYTHMIAS. ANTIARRHYTHMIC EFFECT OF OMACOR.

Objective: Light pollution disrupts circadian rhythms that may promote obesity and hypertension, but their association with the susceptibility to malignant cardiac arrhythmias is not well known. We examined whether continuous light as well as a high sucrose diet affect rat heart gene transcripts, miRNAs, or protein expression and hence arrhythmogenesis. In parallel, the benefit of omega-3 (Omacor) supplementation was assessed. Design and method: In the first experiment, male and female spontaneously hypertensive (SHR) and normotensive Wistar (WR) rats were housed in 12 h/12 h light/dark cycles or exposed to continuous light at 300 lux for 6 weeks. In the second experiment, aged female WR rats were fed with 30% sucrose for 8 weeks. In both experiments half of the rats were supplemented with Omacor (200 mg /100 g b.w). Susceptibility to electrically-inducible ventricular fibrillation (VF) was assessed in perfused heart. Results: Rats exposed to continuous light or fed by sucrose were more vulnerable to develop VF. There was a down-regulation of myocardial connexin-43 (Cx43) along with an increased pro-inflammatory NF-kB and iNOS transcripts and decreased sarcoplasmic reticulum Ca2+ ATPase transcripts in response to continuous light. Omacor treatment increased the electrical threshold for VF induction associated with attenuation of pro-arrhythmic alterations in myocardial Cx43, NF-kB and iNOS. Sucrose fed rats exhibited suppression of Cx43 and PKC epsilon signaling, along with upregulation of myocardial PKC delta and miR-30a that is involved in fibrosis. Myocardial miR-1 expression levels involved in the regulation of Cx43 were not affected by the sucrose diet nor Omacor treatment. Antiarrhythmic effects of Omacor supplementation have been shown by attenuation of Cx43, PKC, and miR-30a myocardial abnormalities. Conclusions: Findings suggest that light pollution and sucrose diet jeopardize myocardial Cx43-mediated electrical communication, thereby increase susceptibility of the heart to malignant arrhythmias. Adverse effects were alleviated by treatment with Omacor, supporting its potential benefit and the relevance of monitoring the omega-3 index in at-risk human populations. This research was supported by VEGA 2/0002/20, 2/0158/19, APVV 21-0410, 18-0548, 19-0317, EU ITMS 26230120009