Frequency Of Ventricular Fibrillation Research Articles

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.

AMplitude spectral area of ventricular fibrillation and amiOdarone Study in patients with out-of-hospital cArdIaC arrest. The MOSAIC study.

Antiarrhythmic drugs are recommended for out of hospital cardiac arrest (OHCA) with shock-refractory ventricular fibrillation (VF). Amplitude Spectral Area (AMSA) of VF is a quantitative waveform measure that describes the amplitude-weighted mean frequency of VF, it correlates with intramyocardial adenosine triphosphate (ATP) concentration, it is a predictor of shock efficacy and an emerging indicator to guide defibrillation and resuscitation efforts. How AMSA might be influenced by amiodarone administration is unknown. In this international multicentre observational study, all OHCAs receiving at least one shock were included. AMSA values were calculated by retrospectively analysing the pre-shock ECG interval of 2 s. Multivariable models were run and a propensity score based on the probability of receiving amiodarone was created to compare two randomly matched samples. 2,077 shocks were included: 1,407 in the amiodarone group and 670 in the non-amiodarone group. AMSA values were lower in the amiodarone group [8.8 (6-12.7) mV·Hz vs. 9.8 (6-14) mV·Hz, p = 0.035]. In two randomly matched propensity score-based groups of 261 shocks, AMSA was lower in the amiodarone group [8.2 (5.8-13.5) mV·Hz vs. 9.6 (5.6-11.6), p = 0.042]. AMSA was a predictor of shock success in both groups but the predictive power was lower in the amiodarone group [Area Under the Curve (AUC) non-amiodarone group 0.812, 95%CI: 0.78-0.841 vs. AUC amiodarone group 0.706, 95%CI: 0.68-0.73; p < 0.001]. Amiodarone administration was independently associated with the probability of recording lower values of AMSA. In patients who have received amiodarone during cardiac arrest the predictive value of AMSA for shock success is significantly lower, but still statistically significant.

Ventricular Fibrillation in Acute Coronary Syndrome with Elevated ST Segment: Incidence and Predictive Factors.

Background: Ventricular fibrillation is the principal cause of sudden cardiac death; in acute coronary syndrome (ACS) with elevated ST segment, its incidence and predictive factors, have been the subject of several international studies; however, its epidemiological data is lacking in Algeria. Aims: The main objective of our study is the determination of the frequency of ventricular fibrillation in acute coronary syndrome with elevated ST segment, the secondary objective was the analysis of predictive factors of this arrhythmia, and related mortality. Methods and materials: In this prospective study, conducted in the cardiology department of Hussein Dey hospital (Algiers-Algeria), 467 patients with acute coronary syndrome with elevated ST segment (87 women and 380 men) were enrolled between 28 February 2014 and 16 July 2015. The average age is 60 ± 13 years; at admission, a Holter recorder was attached for continuous ECG monitoring during 48 hours Kruskal’s ANNOVA or H tests were used for comparison of quantitative variables, χ2 test or Fisher’s exact test, were used for qualitative variables, all tests were performed with 1st species risk of 5%. Results: The frequency of ventricular fibrillation is 5.8% (27 patients), CI 95%: [3.7%-7.9%], multivariate analysis identified the following independent predictors: low diastolic blood pressure: high ST segment elevation, large diastolic left and right ventricular diameters. The risk of mortality expressed by Hazard Ration (HR) is 12.9 (CI 95%: [4.9-34], p &lt; 0.001), the predictors of mortality are right ventricular failure and failure of thrombolysis. Conclusion: Ventricular fibrillation is the principal cause of sudden cardiac death, during acute coronary syndrome with elevated ST segment, its predictive factors according to our study are: low diastolic blood pressure: high ST segment elevation, large diastolic left and right ventricular diameters, its occurrence increases the risk of hospital mortality, this high risk is partly explained by the therapeutic strategy.

Effects of Preoperative Statin on the Frequency of Ventricular Fibrillation and C-Reactive Protein Level in Patients Undergoing Isolated Coronary Artery Bypass Grafting.

To investigate the effects of statin use in preoperative period on the development of ventricular fibrillation (VF) following the removal of aortic cross-clamp (ACC) and on the levels of inflammation biomarker C-reactive protein (CRP) in patients who undergo elective isolated coronary artery bypass grafting (CABG). Observational study. Department of Cardiovascular Surgery, Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey, between May 2019 and January 2020. A total of 104 patients, who underwent elective isolated CABG with cardiopulmonary bypass, were included in this prospective study. Fifty patients, who received statin treatment for at least 16 weeks in preoperative period, were identified as Group S; and 54 patients, who did not receive statin treatment, were identified as Group N. The frequency of VF and defibrillation counter shock (DCS) requirement and postoperative CRP levels were compared in groups after ACC removal. VF development and related DCS counts were lower at significant levels in Group S compared to Group N (p <0.001 for both). Although no statistically significant differences were detected between the median preoperative CRP levels of the groups; median CRP levels, which were measured in postoperative 2nd and 7th days, were found to be significantly lower in Group S (p <0.001 for both). Preoperative statin use significantly reduced VF development after the removal of ACC, and decreased postoperative CRP levels. Key Words: Coronary artery bypass grafting, Statins, Pleiotropic effect, Ventricular fibrillation, C-reactive protein.

Atrial natriuretic peptide accelerates onset and dynamics of ventricular fibrillation during hypokalemia in isolated rabbit hearts

BackgroundAtrial natriuretic peptide (ANP), which is released by the heart in response to acute cardiac stretch, possesses cardiac electrophysiological properties that include modulation of ion channel function and repolarization. However, data regarding whether ANP can directly modulate electrical instability or arrhythmias are largely lacking. ObjectiveThis study sought to determine whether ANP modifies onset or electrophysiological characteristics of ventricular fibrillation (VF) induced by severe hypokalemia in an isolated heart model. MethodsLangendorff-perfused rabbit hearts in the absence and presence of 10 nM ANP (n = 9 in each group) were subjected to a low potassium (K+) perfusate (1.2 mM K+). Left ventricular (LV) epicardial monophasic action potential (MAP) and pressure were monitored continuously. Incidence and time to onset of VF and dominant frequency during VF determined by spectral analysis were evaluated. ResultsANP did not alter ventricular repolarization (MAP duration) or LV pressure during perfusion with physiologic, K+-containing solution. Within the first 30 s after low K+ perfusion, ANP accelerated the onset of beat-to-beat repolarization alternans (100% vs. 33% in ANP-treated vs. non-treated hearts, p < 0.01). During low K+ perfusion, the incidence of VF did not differ between ANP-treated and non-treated hearts (8 of 9 [89%] in each group). However, VF occurred sooner (3.75 ± 0.33 vs. 5.78 ± 0.70 min, P < 0.05) and immediately after VF onset, peak dominant frequency was higher (24.1 ± 7.3 vs. 14.2 ± 2.3 Hz, P = 0.01) in ANP-treated than in non-treated hearts. ConclusionsANP accelerates initiation of VF and increases maximum dominant frequency during VF in isolated hearts subjected to severe hypokalemia.

Abstract 127: The Effect of Cutoff Frequency Range on Amplitude Spectrum Area Performance in Predicting Defibrillation Outcome

Introduction: Both clinical and experimental studies have demonstrated that ventricular fibrillation (VF) waveform-based amplitude spectrum area (AMSA) predicts defibrillation outcome with high sensitivity and specificity. A commonly used cutoff frequency range for calculation of AMSA is 4-48 Hz, but the median VF frequency in patients is less than 7 Hz. In the present study, we investigated whether the AMSA performance in predicting defibrillation outcome may be affected by different cutoff frequency ranges. Hypothesis: A selected cutoff frequency range would affect AMSA performance in predicting defibrillation outcome in patients. Methods: A total of 450 segments (179-defibrillation success and 271-defibrillation failure) of VF waveforms from patients with out-of-hospital cardiac arrest were analyzed. Each 4.096-s segment prior to defibrillation was acquired with a sampling rate of 250 Hz. Using MATLAB (MathWorks, Natck, MA), the AMSA of each segment of VF waveform was calculated with five cutoff frequency ranges (Shown in Figure 1). Sensitivity and specificity were calculated when defibrillation success rate was 50% which was estimated by a logistic regression curve. Area under the receiver operating characteristic curve (AUC) was used to evaluate AMSA performance within different cutoff frequency ranges. Results: AMSA threshold was decreased from 20.5 to 6.5 mV·Hz when the cutoff frequency range was changed from 3-48 Hz to 3-10 Hz (Figure 1). Sensitivity of AMSA in 3-10 Hz was increased by 81.3% compared with that of AMSA in 3-48 Hz. Specificity of AMSA in 3-10 Hz was decreased by 8.1% compared with that of AMSA in 3-48 Hz. The corresponding AUC was increased from 0.724 (3-48 Hz) to 0.768 (3-10 Hz). Conclusions: A cutoff frequency range of 3-10 Hz significantly increases the sensitivity of AMSA for predicting defibrillation success in patients with cardiac arrest with a slight decrease in specificity.

The Selective Late Sodium Current Inhibitor Eleclazine, Unlike Amiodarone, Does Not Alter Defibrillation Threshold or Dominant Frequency of Ventricular Fibrillation.

We examined the effects of the selective late INa inhibitor eleclazine on the 50% probability of successful defibrillation (DFT50) before and after administration of amiodarone to determine its suitability for use in patients with implantable cardioverter defibrillators (ICDs). In 20 anesthetized pigs, transvenous active-fixation cardiac defibrillation leads were fluoroscopically positioned into right ventricular apex through jugular vein. ICDs were implanted subcutaneously. Dominant frequency of ventricular fibrillation was analyzed by fast Fourier transform. The measurements were made before drug administration (control), and at 40 minutes after vehicle, eleclazine (2 mg/kg, i.v., bolus over 15 minutes), or subsequent/single amiodarone administration (10 mg/kg, i.v., bolus over 10 minutes). Eleclazine did not alter DFT50, dominant frequency, heart rate, or mean arterial pressure (MAP). Subsequent amiodarone increased DFT50 (P = 0.006), decreased dominant frequency (P = 0.022), and reduced heart rate (P = 0.031) with no change in MAP. Amiodarone alone increased DFT50 (P = 0.005; NS compared to following eleclazine) and decreased dominant frequency (P = 0.003; NS compared to following eleclazine). Selective late INa inhibition with eleclazine does not alter DFT50 or dominant frequency of ventricular fibrillation when administered alone or in combination with amiodarone. Accordingly, eleclazine would not be anticipated to affect the margin of defibrillation safety in patients with ICDs.

L-Type Calcium Channels Do Not Play a Critical Role in Chest Blow Induced Ventricular Fibrillation: Commotio Cordis.

Background. In a commotio cordis swine model, ventricular fibrillation (VF) can be induced by a ball blow to the chest believed secondary to activation of mechanosensitive ion channels. The purpose of the current study is to evaluate whether stretch induced activation of the L-type calcium channel may cause intracellular calcium overload and underlie the VF in commotio cordis. Method and Results. Anesthetized juvenile swine received 6 chest wall strikes with a 17.9 m/s lacrosse ball timed to the vulnerable period for VF induction. Animals were randomized to IV verapamil (n = 6) or placebo (n = 6). There was no difference in the observed frequency of VF between verapamil (19/26: 73%) and placebo (20/36: 56%) treated animals (p = 0.16). There was also no significant difference in the combined endpoint of VF or nonsustained VF (21/26: 81% in verapamil versus 24/36: 67% in controls, p = 0.22). Conclusions. In this experimental model of commotio cordis, verapamil did not prevent VF induction. Thus, in commotio cordis it is unlikely that stretch activation of the L-type calcium channel with resultant intracellular calcium overload plays a prominent role.

Electrocardiographic characteristics of ventricular fibrillation in patients with a wearable cardioverter defibrillator

Introduction: Surface electrocardiographic (ECG) changes in ventricular fibrillation (VF) waveform characteristics at its onset in patients experiencing cardiac arrest have not been quantified. The amplitude spectral area (AMSA) method was developed to analyze surface ECG VF amplitude and frequency characteristics and contains information related to VF rotor stability and myocardial viability. We aimed to characterize changes in AMSA at the onset of VF to gain insight into myocardial dynamics in patients with a wearable cardioverter defibrillator (WCD).

Is hands-on defibrillation safe when using insulating gloves? A clinical trial

Introduction: Surface electrocardiographic (ECG) changes in ventricular fibrillation (VF) waveform characteristics at its onset in patients experiencing cardiac arrest have not been quantified. The amplitude spectral area (AMSA)methodwas developed to analyze surface ECG VF amplitude and frequency characteristics and contains information related to VF rotor stability and myocardial viability. We aimed to characterize changes in AMSA at the onset of VF to gain insight into myocardial dynamics in patients with a wearable cardioverter defibrillator (WCD). Methods: Out of 30 patients randomly identified from a manufacturer-maintained registry, 25 patients (14 Male, 11 Female, Age=62±14 yr) were included. Remaining patients experienced either sustained monomorphic ventricular tachycardia or hadmotion artifact, precludingAMSAanalysis. Using theWCDECG, AMSA was calculated as the summed product of frequency and square root of power at that frequency from 2 to 48Hz with a continuous sliding 2.1 s Tukey window. The median time to shock for the WCD is 45 s. AMSA was calculated every 0.5 s and averaged every 1 s for up to 45 s after VF initiation. Results are presented as mean± standard error. Results: At onset of VF, AMSA was 33.6±3.3mVHz which decreased progressively to 23.4±2.2mVHz (p<0.01) after 45 sec of untreated VF (Fig. 1).

Vagal control of cardiac electrical activity and wall motion during ventricular fibrillation in large animals

Vagal inputs control pacemaking and conduction systems in the heart. Anatomical evidence suggests a direct ventricular action, but functional evidence that separates direct and indirect (via the conduction system) vagal actions is less well established. We studied vagus nerve stimulation (VNS) during sinus rhythm and ventricular fibrillation (VF) in pigs and sheep to determine: 1) the range of unilateral and bilateral actions (inotropic and chronotropic) and 2) whether VNS alters left ventricular motion and/or electrical activity during VF, a model of abnormal electrical conduction of the left ventricle that excludes sinus and atrioventricular nodal function. Adult pigs (N=8) and sheep (N=10) were anesthetized with urethane and mechanically ventilated. VNS was performed in animals at 1, 2, 5, 10, 20, 50, and 100Hz for 20s. VF was induced with direct current to the ventricles or occlusion of the left anterior descending coronary artery. In 4 pigs and 3 sheep, left ventricular wall motion was assessed from endocardial excursion in epicardial echocardiography. In sheep and pigs, the best frequency among those tested for VNS during sinus rhythm to produce sustained electrical and mechanical ventricular standstill was 50Hz for unilateral or bilateral stimulation. When applied during VF, bilateral VNS increased the variability of the dominant VF frequency, indicating a direct impact on the excitability of ventricular myocytes, and decreased endocardial excursion by more than 50% during VF. We conclude that the vagus nerve directly modulates left ventricular function independently from its effects on the conduction system.

Regional ion channel gene expression heterogeneity and ventricular fibrillation dynamics in human hearts.

RationaleStructural differences between ventricular regions may not be the sole determinant of local ventricular fibrillation (VF) dynamics and molecular remodeling may play a role.ObjectivesTo define regional ion channel expression in myopathic hearts compared to normal hearts, and correlate expression to regional VF dynamics.Methods and ResultsHigh throughput real-time RT-PCR was used to quantify the expression patterns of 84 ion-channel, calcium cycling, connexin and related gene transcripts from sites in the LV, septum, and RV in 8 patients undergoing transplantation. An additional eight non-diseased donor human hearts served as controls. To relate local ion channel expression change to VF dynamics localized VF mapping was performed on the explanted myopathic hearts right adjacent to sampled regions. Compared to non-diseased ventricles, significant differences (p<0.05) were identified in the expression of 23 genes in the myopathic LV and 32 genes in the myopathic RV. Within the myopathic hearts significant regional (LV vs septum vs RV) expression differences were observed for 13 subunits: Nav1.1, Cx43, Ca3.1, Cavα2δ2, Cavβ2, HCN2, Na/K ATPase-1, CASQ1, CASQ2, RYR2, Kir2.3, Kir3.4, SUR2 (p<0.05). In a subset of genes we demonstrated differences in protein expression between control and myopathic hearts, which were concordant with the mRNA expression profiles for these genes. Variability in the expression of Cx43, hERG, Na+/K+ ATPase ß1 and Kir2.1 correlated to variability in local VF dynamics (p<0.001). To better understand the contribution of multiple ion channel changes on VF frequency, simulations of a human myocyte model were conducted. These simulations demonstrated the complex nature by which VF dynamics are regulated when multi-channel changes are occurring simultaneously, compared to known linear relationships.ConclusionsIon channel expression profile in myopathic human hearts is significantly altered compared to normal hearts. Multi-channel ion changes influence VF dynamic in a complex manner not predicted by known single channel linear relationships.

Median Frequencies of Prolonged Ventricular Fibrillation treated by V-A ECMO Correspond to a Return of Spontaneous Circulation Rate

The aim of our study was to analyze, in a pig model of prolonged ventricular fibrillation (VF) treated by veno-arterial extracorporeal membrane oxygenation (ECMO), the time dependent changes of VF wavelet frequency obtained from intracardial signals and its relations to return of spontaneous circulation (ROSC). 11 female pigs (50.3 ± 3.4 kg) under general anesthesia had undergone 15 min of VF with ECMO flow of 5 to 10 ml/kg per min simulating "untreated" VF followed by continued VF with full ECMO flow of 100 ml/kg per min. The median frequency (MF) of VF from right ventricular apex, coronary perfusion pressure, myocardial oxygen metabolism and resuscitability were determined. Median (interquartile range) of MF of fibrillatory wavelets in minute 15 of low ECMO flow [9.7 Hz (8.3; 10.1)] was not significantly changed in comparison to minute 1 [10.5 Hz (9.8; 12.4)], p = 0.12. Five minutes after full ECMO initiation MF increased [11.6 Hz (10.6; 13.5)], p = 0.04 (compared to minute 15 of VF) and did not deteriorate during the rest of ECMO treatment. Out of all subjects, three animals did not reach ROSC. Those subjects demonstrated deeper decrease of MF at the VF minute 15 as compared to others [-2.4 Hz (-2.5; -2.3) vs. -0.6 Hz (-1.6; -0.1)] and continuously significantly higher increase in MF on full ECMO support [4.3 Hz (2.9; 5.6) vs. 1.1 Hz (0.6; 1.6)] with p = 0.05 for both observations, respectively. The veno-arterial ECMO reperfusion influences MF of VF wavelet obtained from right ventricular apex. The course of changes in wavelet frequency corresponds to a presence of later ROSC.

Effect of chronic exercise and ATP-sensitive potassium channel blockade on the spectral characteristics evolution of ventricular fibrillation in acute regional ischemia

Purpose: It has been proposed that chronic exercise produces a KATP channel blockade in ischemic myocardium. We have also reported that channel blockade and training exert very similar effects on energy required to defibrillate. In fact it is postulated that one mechanism by which exercise exerts an antiarrhythmic effect, is by blocking KATP channel. We have analyzed the evolution of spectrum characteristics of ventricular fibrillation (VF), in normoxic conditions and after acute myocardial ischemia, in isolated hearts from trained rabbits, and in hearts submitted to KATP channel blockade. Our hypothesis is that the spectrum characteristics of VF evolve similarly in trained hearts and in hearts undergoing KATP channel blockade. Material and method: 12 NZW rabbits were submitted to a six-week endurance exercise training program, and 14 rabbits (glibenclamide group) and 17 rabbits (control group) were not trained. After exercise program, rabbits were anaesthetized (ketamine, 10 mg/kg i.v.), euthanized and the hearts excised, isolated and perfused in a Langendorff system. A pacing electrode and a plaque with 256 recording electrodes were positioned on the left ventricle. The blockade of KATP channels was performed by glibenclamide (10 μM). VF was induced at increasing frequencies. Five minutes after VF triggering, the circumflex coronary artery was occluded. Dominant frequency (DF) of VF was determined by a spectral analysis. Determinations were analyzed 5min after the onset of VF and 60 and 180 s after coronary occlusion. An ANOVA test (two factors) repeated on one factor was used to comparisons. Differences were significant when p<0.05. Results: See Table. View this table: Dominant frequency of VF Conclusions: Unlike what occurs with other parameters, the effect of training on the evolution of VF characteristics in the ischemic myocardium does not appear to be mediated by the blockade of KATP channel.

Dominant frequency of ventricular fibrillation can be one of predictive values to discriminate high risk patients with Brugada syndrome

Purpose: Recent European and Japanese studies showed the induction of ventricular fibrillation (VF) during electrophysiological stimulation test (EPS) could not predict the sudden cardiac death in patients with Brugada syndrome (BrS). However, some recent studies indicated that the shortness of effective refractory period (ERP) or the mode of induction of VF might be good predictive value. Those indicated the exist of inherent electrical substrates in high risk patients with BrS. We accessed VF cycle length as the dominant frequency (DF) obtained by a fast Fourier transformation (FFT) analysis. Methods: The induced VF recorded from RV apex (RVA) and RV outflow tract (RVOT) was performed with a 4096 point-FFT analysis in 28 patients (all male, 51±14 years old) with BrS. DF was obtained by Fast Fourier transform from 4-s data (phase) and sequentially every 2 s before cardioversion. The average of DF from intracardiac electrograms were compared between the symptomatic group (n=15) and the asymptomatic group (n=13). EPS was performed during isoproterenol (ISP) and after propranolol (PRO) in selected patients. Results: The DF had a weak negative correlation to ERP. The relationship of DF between RVA and RVOT had a very good correlation in all phases. The DF significantly increased from phase 1 to 6 (p<0.003; 5.72±0.36 Hz to 6.19±0.49 Hz). The DFs were significantly higher in symptomatic group than in asymptomatic group (p=0.012). ISP significantly (p<0.05) shorten ERP of RV and prevented induction of VF in 20 of 25 patients (80%). During ISP, 5 patients experienced induction of VF. ISP significantly influenced DF transition compared with the control state. DF gradually increased but was unchanged after the middle phase. PRO induced VF in 5 (83.3%) of 6 patients who tested negative during ISP. DF after PRO was higher than that in the corresponding phase in the control state. ISP suppressed the induction of VF and the increase of DF with time. PRO aggravated VF and accelerated DF. Those pharmacological results were not inconsistent with the previous reports. Conclusions: Those data suggested that the DF of VF in patients with BrS was related to the ERP of RV and/or the maintenance of VF as an electrophysiological substrate of high risk patients. Higher DF of VF can be one of predictive values to discriminate the high risk Brugada patients.

Different Ventricular Fibrillation (VF) Dynamics in Long QT Syndrome Type 1 vs. 2 in a Transgenic Rabbit Model

Long QT syndrome (LQTS) is a congenital disease characterized by APD prolongation and associated with sudden cardiac death. LQT1 and LQT2, the most common types of LQTS, lack delayed rectifying potassium currents, IKs and IKr, respectively. We hypothesize that the differential kinetic properties of IKs and IKr can influence vulnerability to ventricular fibrillation (VF) through genotype-specific enhancement of VF maintenance. We investigated VF dynamics in transgenic rabbit models of LQT1, LQT2, and littermate controls (LMC) with optical mapping (n=6). VF frequency (VFF) analysis showed wave propagation to be slowest in LQT2 in line with APD gradient in groups (LQT2=7.06Hz, LQT1=11.72Hz, LMC=12.14Hz). Despite low frequency in LQT2, complexity of VFs was comparable to LMC. Further pattern analysis revealed that LQT2 exhibited higher incidence of wave breaks per wave while LQT1 shows even lower than LMC (LQT2=0.374 vs. LQT1=0.234, LMC=0.320). These results highlight role of IKr vs. IKs in VF maintenance, suggesting that VFs in LQT1 and 2 are maintained by different mechanisms such as wave breaks and re-initiation of reentry vs. triggered activity.View Large Image | View Hi-Res Image | Download PowerPoint Slide

Abstract 97: The Overlap in Frequency Spans of Ventricular Fibrillation and Chest Compression in Cardiac Arrest Patients

Background In treating sudden cardiac arrest (SCA) patients, automatic external defibrillators automatically analyze the ECG rhythm to determine if defibrillation is necessary. Currently, this analysis must be done during hands-off period because the electrical artifact induced by chest compression (CC) makes the analysis unreliable. It is desired to analyze the ECG rhythm during CPR to minimize the hands-off period, and hence, improve CPR success. Simple filtering of CC artifact would work only if there is no significant overlap between frequency spans of CC and ventricular fibrillation (VF); otherwise, it would distort the ECG. Objective To investigate the overlap between CC and VF frequency spans. Methods ECG recordings from 170 SCA adult patients with VF rhythm were used. These cases were a subset of a larger database collected for a clinical study in 6 ambulances in 3 European regions using Laerdal HeartStart 4000 defibrillators. The defibrillator had an extra chest pad with an accelerometer and a pressure sensor to record the CC signal. The VF and CC frequency spans were calculated by frequency-domain analysis of the signals. Results The figure below demonstrates the frequency spans of VF and CC in patients with VF rhythm going under CPR. The plots are normalized and also include the higher harmonics. A significant overlap is observed at the range of 80 to 140 compressions-per-minute. Conclusion The significant overlap in frequency spans of VF and CC makes it challenging to filter the CC artifact without removing parts of VF information and hence distorting the ECG signal. Therefore, techniques for analyzing ECG during CPR should be smarter than merely filtering the CC artifact.

Modifications of mechanoelectric feedback induced by 2,3‐butanedione monoxime and Blebbistatin in Langendorff‐perfused rabbit hearts

Myocardial stretching is an arrhythmogenic factor. Optical techniques and mechanical uncouplers are used to study the mechanoelectric feedback. The aim of this study is to determine whether the mechanical uncouplers 2,3-butanedione monoxime and Blebbistatin hinder or modify the electrophysiological effects of acute mechanical stretch. The ventricular fibrillation (VF) modifications induced by acute mechanical stretch were studied in 27 Langendorff-perfused rabbit hearts using epicardial multiple electrodes and mapping techniques under control conditions (n=9) and during the perfusion of 2,3-butanedione monoxime (15mM) (n=9) or Blebbistatin (10μm) (n=9). In the control series, myocardial stretch increased the complexity of the activation maps and the dominant frequency (DF) of VF from 13.1±2.0Hz to 19.1±3.1Hz (P<0.001, 46% increment). At baseline, the activation maps showed less complexity in both the 2,3-butanedione monoxime and Blebbistatin series, and the DF was lower in the 2,3-butanedione monoxime series (11.4±1.2Hz; P<0.05). The accelerating effect of mechanical stretch was abolished under 2,3-butanedione monoxime (maximum DF=11.7±2.4Hz, 5% increment, ns vs baseline, P<0.0001 vs. control series) and reduced under Blebbistatin (maximum DF = 12.9 ± 0.7 Hz, 8% increment, P<0.01 vs. baseline, P<0.0001 vs. control series). The variations in complexity of the activation maps under stretch were not significant in the 2,3-butanedione monoxime series and were significantly attenuated under Blebbistatin. The accelerating effect and increased complexity of myocardial activation during VF induced by acute mechanical stretch are abolished under the action of 2,3-butanedione monoxime and reduced under the action of Blebbistatin.

Effects of isoproterenol and propranolol on the inducibility and frequency of ventricular fibrillation in patients with Brugada syndrome

Isoproterenol (ISP), a beta-adrenergic agonist, suppresses arrhythmic storm in patients with sporadic Brugada syndrome (BS). However, the influence of ISP and the beta-adrenergic antagonist propranolol (PRO) on the inducibility and frequency of ventricular fibrillation (VF) in BS patients remains unclear. Twenty-seven BS patients with induced VF>10s in a control state were enrolled. Electrophysiological stimulation (EPS) testing was performed during ISP and after PRO in selected patients. The inducibility and frequency of VF were compared. Dominant frequency (DF) was obtained by Fast Fourier transform from 4-s data (phase) and sequentially every 2s up to phase 5. ISP prevented induction of VF in 20 of 25 patients (80%). During ISP, 5 patients experienced induction of VF. ISP significantly influenced DF transition compared with the control state. DF gradually increased but was unchanged after the middle phase. PRO had no effect on incidence of induced VF in 5 patients; increased PRO induced VF in 5 (83.3%) of 6 patients who tested negative during ISP. After PRO, 10 patients experienced induction of VF. Thus, PRO significantly influenced DF transition. DF after PRO was higher than that in the corresponding phase in the control state. ISP suppressed induction of VF and the increase of DF with time. PRO aggravated VF and accelerated DF.

Evaluation of Arrhythmia Scoring Systems and Exercise-Induced Cardioprotection

Exercise is protective against ventricular arrhythmias induced by ischemia (I), the condition of inadequate blood flow, and reperfusion (R), the reestablishment of blood flow. This protection is observed clinically and scientifically by decreased incidence in ECG abnormalities. Numerous scoring systems exist for the quantification of ventricular arrhythmia severity. On the basis of preventricular contractions, ventricular tachycardia, and ventricular fibrillation frequency, these scoring systems are intended to provide more robust ECG outcome indicators than individual arrhythmia variables. Scoring systems vary primarily on continuous versus discontinuous treatment of the data, which should be considered when matching these arrhythmia metrics to scientific applications. The aim of this investigation was to evaluate seven ECG scoring systems in the assessment of ventricular arrhythmia severity after IR in male Sprague-Dawley rats. Animals remained sedentary or exercised (3 d of treadmill exercise for 60 min) before surgically induced IR. A subset of sedentary animals served as sham, undergoing surgical procedure without IR. ECGs were evaluated under blinded conditions by three trained individuals. Single arrhythmia data and the parametric score were analyzed by one-way ANOVA, whereas the Kruskal-Wallis was used to compare group means for all nonparametric scoring systems between groups. IR produced a significant arrhythmic response in exercised and sedentary rats as determined by all arrhythmia scoring systems. Four arrhythmia metrics resulted in significant differences between exercised and sedentary treatments (P < 0.001), whereas three metrics did not. Continuous versus discontinuous treatment of the data may account for variation in scoring system outcomes. These data confirm that exercise protects against IR-induced arrhythmias, and care must be taken when selecting an arrhythmia scoring system for ECG evaluation.