Spontaneous Ventricular Fibrillation Research Articles

Genetically engineered SCN5A mutant pig hearts exhibit conduction defects and arrhythmias.

SCN5A encodes the α subunit of the major cardiac sodium channel Na(V)1.5. Mutations in SCN5A are associated with conduction disease and ventricular fibrillation (VF); however, the mechanisms that link loss of sodium channel function to arrhythmic instability remain unresolved. Here, we generated a large-animal model of a human cardiac sodium channelopathy in pigs, which have cardiac structure and function similar to humans, to better define the arrhythmic substrate. We introduced a nonsense mutation originally identified in a child with Brugada syndrome into the orthologous position (E558X) in the pig SCN5A gene. SCN5A(E558X/+) pigs exhibited conduction abnormalities in the absence of cardiac structural defects. Sudden cardiac death was not observed in young pigs; however, Langendorff-perfused SCN5A(E558X/+) hearts had an increased propensity for pacing-induced or spontaneous VF initiated by short-coupled ventricular premature beats. Optical mapping during VF showed that activity often began as an organized focal source or broad wavefront on the right ventricular (RV) free wall. Together, the results from this study demonstrate that the SCN5A(E558X/+) pig model accurately phenocopies many aspects of human cardiac sodium channelopathy, including conduction slowing and increased susceptibility to ventricular arrhythmias.

Detection of T-wave beat-by-beat variations prior to ventricular arrhythmias onset in ICD-stored intracardiac electrograms: the Endocardial T-Wave Alternans Study (ETWAS).

The aim of the Endocardial T-Wave Alternans Study was to prospectively assess the presence of T-wave alternans (TWA) or beat-to-beat repolarization changes on implantable cardioverter-defibrillator (ICD)-stored electrograms (EGMs) immediately preceding the onset of spontaneous ventricular tachycardia (VT) or fibrillation (VF). Thirty-seven VT/VF episodes were compared to 116 baseline reference EGMs from the same 57 patients. A Bayesian model was used to estimate the T-wave waveform in each cardiac beat and a set of 10 parameters was selected to segment each detected T wave. Beat-by-beat differences in each T-wave parameter were computed using the absolute value of the difference between each beat and the following one. Fisher criterion was used for determining the most discriminant T-wave parameters, then top-M ranked parameters yielding a normalized cumulative Fisher score > 95% were selected, and analysis was applied on these selected parameters. Simulated TWA EGMs were used to validate the algorithm. In the simulation study, TWA was detectable even in the case of the smallest simulated alternans of 25 μV. In 13 of the 37 episodes (35%) occurring in nine of 16 patients, significant larger beat-to-beat variations before arrhythmia onset were detected compared to their respective references (median one positive episode per patient). Parameters including the T-wave apex amplitude seem the more discriminant parameters. Detection of beat-by-beat repolarization variations in ICD-stored EGMs is feasible in a significant subset of cases and may be used for predicting the onset of ventricular arrhythmias.

Which number of morphological types of ventricular premature beats predicts poor prognosis in subjects with various cardiomyopathies without obstructed coronary arteries?

Conduction abnormalities within the QRS complex manifest as fragmented QRS waves, which appear as multiple spikes within the QRS wave complex. Fragmented QRS waves are important markers for spontaneous ventricular fibrillation in Brugada syndrome and predict the occurrence of high risk syncope [1]. Ventricular premature beats (VPBs) of long duration (≥160 ms) with fragmented QRS waves are simple and reliable 12-lead electrocardiographic (ECG) markers for a dilated and globally hypokinetic left ventricle (LV) in a nonspecifically-diseased heart, while a VPB with smooth contour or narrow notching with short duration (b160 ms) reflects a normal-sized heart with normal or near-normal systolic function despite the presence of underlying disease [2]. Various morphologies of VPBs are observed in cardiomyopathy subjects especially in subjects with hypertrophic cardiomyopathy (HCM), but their significance is unknown. In this study, we evaluated the significance of the numbers of morphological types of VPBs and VPBs with fragmented QRS waves (fragmented VPBs) on 12-lead Holter ECG in various cardiomyopathy subjects without obstructed coronary arteries as diagnosed by multislice computed tomography (CT). Thiswas a retrospective analysis of 64 consecutive subjects (46males, mean age 61 ± 14 years) who satisfied the definitions of cardiomyopathies published in Circulation 2006 [3] and did not have any obstructed coronary arteries on CT. Final clinical diagnosis (N= 64) were represented in Table 1. Percentage of HCM was 75%. Patients' characteristics were represented inTable2. Theyunderwent cardiacmultisliceCTand12lead Holter ECG within 12 months of each other from July 2007 to April 2012. Exclusioncriteriawas as follows: coronaryarterystenosis (N50%)on CT and previous myocardial infarction. Subjects were followed for a median of 50 months for occurrence of major adverse cardiovascular events (MACE). MACE included cardiovascular death, critical ventricular arrhythmia and hospitalization due to heart failure. Critical ventricular arrhythmias included subjects with appropriate implantable cardioverter defibrillator therapy such as appropriate discharge of implantable cardioverter defibrillator and anti-tachycardia pacing for ventricular tachycardia and performance of radiofrequency catheter ablation of ventricular arrhythmia. A fragmented VPB was defined as a VPB with one or more notches in the R or S waves on a routine 12-lead Holter ECG [4,5] (Fig. 1). Obvious complete right or left bundle branch block-shaped VPBs were excluded from fragmented VPBs in this analysis. The numbers of morphological types of all VPBs and fragmented VPBs were counted automatically, but were manually revised by experienced technologists. Thereafter, an experienced cardiologist blinded to the CT findings confirmed the results of the printed results. Retrospective ECG gated CT scans were performed on all subjects to evaluate coronary arteries, myocardium and cardiac function [6–9] depending upon the ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/ SCMR 2010 appropriate use criteria for cardiac CT [10]. The total numbers of morphological types of all VPBs and fragmented VPBs were 10.1 ± 21.6 and 2.8 ± 2.2, respectively. MACE occurred in a total of 9 subjects (14.1%) (7 males, mean age 50 ± 21 years) (cardiovascular death 1, critical ventricular arrhythmia 5, and hospitalization due to heart failure 3). According to the receiver operating characteristic (ROC) curve analysis, the best cutoff value for the number of morphological types of all VPBs to distinguish between the subjects with andwithoutMACEwas 12with sensitivity 66.7%, specificity 92.7% and are under the curve (AUC) 0.783 (Fig. 2). ByKaplan–Meier analysis, therewas a significant difference in the occurrence of MACE between the subjects with morphological types of all VPBs≥ 12 and b 12 (P b 0.001) during the follow-up period (Fig. 3). According to another ROC curve analysis, the best cutoff value for the number of morphological types of fragmented VPBs to distinguish between the subjects with and without MACE was 2 with sensitivity 100%, specificity 41.8% and AUC 0.762 (Fig. 4). By Kaplan–Meier

Early experience with the subcutaneous ICD.

The Subcutaneous Internal Cardiac Defibrillator (S-ICD) represents a major advance in the care of patients who have an indication for an internal cardiac defibrillator without pacing indications. Its main advantage is that it can deliver a shock to cardiovert ventricular arrhythmias utilising a tunnelled subcutaneous lead, negating the risks associated with conventional transvenous systems. Initial studies have shown comparable efficacy in cardioversion of induced and spontaneous ventricular tachycardia (VT) and ventricular fibrillation (VF) when compared to conventional transvenous systems. In addition, inappropriate shocks occurred in a similar percentage of patients to conventional ICD studies. Complication rates are low and relate largely to localised wound infections, treated successfully with antibiotics. The long term efficacy of the device is yet to be ascertained, however, a randomised trial & prospective registries are currently in progress to enable direct comparison with transvenous ICDs. This article summarises the early clinical experience and trials in the implantation of the S-ICD.

Apamin-sensitive potassium current and the Mechanisms of ventricular arrhythmia: Perspectives in heart failure treatment

In patients with advanced heart failure (HF), recurrent spontaneous ventricular fibrillation (SVF)/electrical storm (ES) is a frequent complication requiring multiple defibrillation shocks within a short space of time. The mechanism underlying initiation of SVF/ES, spontaneously or immediately after defibrillation shocks, remains unclear. In 2009, Ogawa et al. developed a pacing-induced HF model, in which SVF occurred frequently in failing rabbit ventricles [1]. In that model, acute but reversible post-shock action potential duration (APD) shortening could induce recurrent SVF (Fig. 1, panel A) [1]. The induction of SVF was associated with persistent intracellular calcium (Cai) elevation during late phase 3 and/or phase 4 of the action potential (AP), indicating that APD shortening, in conjunction with persistent post-shock Cai elevation, is a novel mechanism of post-shock SVF/ ES [1]. However, the mechanisms underlying acute APD shortening after fibrillation/defibrillation episodes in HF ventricles remains to be determined. HF is associated with the down-regulation of multiple potassium (K) currents (i.e., Ito, IKs, IKr, IK1, and IKATP). The only K channel that is upregulated in HF is the small conductance Ca-activated K (SK) channel. The SK channel was originally found in most neurons. The increase in Cai evoked by the AP allows the SK channel to become activated, and generates a long-lasting afterhyperpolarization (AHP). Physiologically, the AHP can inhibit repetitive firing, and prevent deleterious tetanic activity in the nervous system. Previous studies show that the SK current is abundantly present in cardiac atrial cells, but not in normal ventricular cells. Because ventricular fibrillation (VF) is associated with Cai accumulation, especially in HF ventricles, Chua et al. hypothesized that SK channels might exist in HF ventricles and contribute to the post-shock APD shortening observed in Ogawa's study [1,2]. To test this hypothesis, they used apamin, a selective SK channel blocker that specifically inhibits apamin-sensitive K current (IKAS), to explore the roles of the SK channel in mediating ventricular arrhythmia of failing ventricles. Chua et al. found that apamin administration effectively prevented post-shock APD shortening, late phase 3 early after-depolarizations (EAD), and triggered activity and recurrent SVF in failing rabbit ventricles (see Fig. 1, panel B) [2]. Using a voltage-clamp technique, they reported that the IKAS current density was significantly larger in failing ventricular cardiomyocytes than in normal ones [2]. The IKAS sensitivity to Cai was increased in cardiomyocytes isolated from failing ventricles compared to those from normal ventricles [2]. Similar findings were reproduced in failing human ventricles by Chang et al. [3]. They also showed that the IKAS current density was lower in the mid-myocardial cells than in the epicardial and endocardial cells [3]. The subtype 2 of SK (SK2) protein expression was 3-fold higher in HF than in non-HF human ventricles [3]. These findings indicated for the first time that HF heterogeneously increases the sensitivity of IKAS to Cai, leading to the up-regulation of IKAS, post-shock APD shortening, late phase 3 EAD, triggered activity, and recurrent SVF in both animal models and failing human ventricles.

Analysis on the risk factors for occurrence of electrical storm in percutaneous coronary intervention and its treatment

Objective To investigate the risk factors for occurrence of electrical storm in the patients with acute ST segment elevation myocardial infarction (STEMI) when treat them by percutaneous coronary intervention (PCI) and provide evidence for prospective treatment.Methods Collected the clinical data of 280 patients with STEMI and treated by PCI from January 2008 to December 2011,the patients with no less than twice spontaneous ventricular tachycardia (VT) or ventricular fibrillation (VF) were classified to the electrical storm group and others were classified to control group.Results The number of patients with electrical storm is nineteen and the incidence rate is 6.8％.In early group (from January 2008 to December 2009),the number of patients with electrical storm is sixteen.In late group (from January 2010 to December 2011),the number of patients with electrical storm is three.The electrical storm group:The value of creatine kinase isoenzyme MB (CK-MB),the value of troponin I (TNI),right coronary artery being the infarction related artery (IRA),TIMI level,bradycardia and sustained hypotension in the electrical group are significantly higher than those of control group (P ＜ 0.05).Multiple logistic regression analysis showed that the independent predictors of VAS were the value of troponin I (TNI),TIMI level and sustained hypotension.Conclusions The value of creatine kinase isoenzyme MB (CK-MB),the value of troponin I (TNI),right coronary artery being the infarction related artery (IRA),TIMI level,bradycardia and sustained hypotension are the risk factors for occurrence of electrical storm.the value of troponin I (TNI),TIMI level and sustained hypotension were stronger predictors of electrical storm.Early treatment to the risk factors can reduce the incidence of VAS,and improve the prognosis. Key words: Myocardial infarction; Percutaneous coronary angioplasty; Ventricular arrhythmia storms ; Risk factors; Treatment

Hypokalemia promotes late phase 3 early afterdepolarization and recurrent ventricular fibrillation during isoproterenol infusion in Langendorff perfused rabbit ventricles

Hypokalemia and sympathetic activation are commonly associated with electrical storm (ES) in normal and diseased hearts. The mechanisms remain unclear. The purpose of this study was to test the hypothesis that late phase 3 early afterdepolarization (EAD) induced by IKATP activation underlies the mechanisms of ES during isoproterenol infusion and hypokalemia. Intracellular calcium (Cai) and membrane voltage were optically mapped in 32 Langendorff-perfused normal rabbit hearts. Repeated episodes of electrically induced ventricular fibrillation (VF) at baseline did not result in spontaneous VF (SVF). During isoproterenol infusion, SVF occurred in 1 of 15 hearts (7%) studied in normal extracellular potassium ([K(+)]o, 4.5 mmol/L), 3 of 8 hearts (38%) in 2.0 mmol/L [K(+)]o, 9 of 10 hearts (90%) in 1.5 mmol/L [K(+)]o, and 7 of 7 hearts (100%) in 1.0 mmol/L [K(+)]o (P <.001). Optical mapping showed that isoproterenol and hypokalemia enhanced Cai transient duration (CaiTD) and heterogeneously shortened action potential duration (APD) after defibrillation, leading to late phase 3 EAD and SVF. IKATP blocker (glibenclamide, 5 μmol/L) reversed the post-defibrillation APD shortening and suppressed recurrent SVF in all hearts studied despite no evidence of ischemia. Nifedipine reliably prevented recurrent VF when given before, but not after, the development of VF. IKr blocker (E-4031) and small-conductance calcium-activated potassium channel blocker (apamin) failed to prevent recurrent SVF. Beta-adrenergic stimulation and concomitant hypokalemia could cause nonischemic activation of IKATP, heterogeneous APD shortening, and prolongation of CaiTD to provoke late phase 3 EAD, triggered activity, and recurrent SVF. IKATP inhibition may be useful in managing ES during resistant hypokalemia.

Is there a role of MMA T wave alternans test for risk assessment in Brugada syndrome?

We read with interest the scientific letter by Drs. Yalin et al. (1) in The Anatolian Journal of Cardiology on the null outcome of their T-wave alternans (TWA) analysis by the Modified Moving Average method in patients with the Brugada syndrome. To date, TWA has been found in only two studies (2, 3) to predict lethal arrhythmias in Brugada syndrome patients, despite the fact that it is a prominent feature in their ambulatory ECG (AECG) recordings (4). Tada and colleagues (2) reported in a case series of 77 Brugada syndrome patients that overt TWA provoked by pilsicainide predicted spontaneous ventricular fibrillation with odds of 22.2 (95% CI: 3.3-149.9, p<0.001) after multivariate analysis. Most recently, Uchimura-Makita and coworkers (3) used MMA-based TWA in a case series of 42 Brugada syndrome patients and reported that the incidence of VF events was significantly higher among those with TWA ≥60μV than in those with lower TWA levels in lead V2 (p=0.0026). Dr. Yalin et al. (1) indicated that TWA testing was performed at the time of diagnosis of Brugada syndrome but did not state whether the patients were undergoing an exercise stress test or were at rest. While no studies have been undertaken to examine the optimum recording conditions for TWA analysis, it is reasonable to expect that TWA testing should be performed in conjunction with a diagnostic stressor such as the sodium channel blocking agents ajmaline, flecainide, procainamide, pilsicainide (2, 5), which unmask the Brugada syndrome (6), or during spontaneous appearance of the diagnostic Brugada ECG during daily activity at more normal heart rates (7), as is captured on AECG recordings. Indeed, the presence of TWA is considered to support the diagnosis of Brugada syndrome in asymptomatic patients with ST-segment elevation in at least one right precordial lead (6). Nighttime may be a particularly suitable period for AECG recording for TWA analysis, as the majority of ventricular fibrillation episodes in Brugada syndrome patients occur during sleep (8). The finding that TWA level is greatly reduced when heart rate is increased to 80-110 beats/min (7), such as is reached during exercise, may be the key to the failure of TWA testing by the spectral method (9, 10). If TWA had been analyzed from AECGs recorded during daily activity or sleep, it is likely that many if not all of the Brugada syndrome patients enrolled in this study may have shown significant levels of TWA. Determining the most appropriate setting for TWA testing in Brugada Syndrome patients will be an important contribution to stratification of their risk for lethal arrhythmias and ICD discharge. We compliment Dr. Yalin and colleagues on the valuable contributions of their study. With best regards,

Dantrolene Suppresses Ventricular Ectopy and Arrhythmogenicity with Acute Myocardial Infarction in a Langendorff‐Perfused Pacing‐Induced Heart Failure Rabbit Model

Dantrolene prevents arrhythmogenic Ca(2+) release during heart failure (HF). However, direct evidence to support its antiarrhythmic effects in failing hearts with acute myocardial infarction (AMI) is lacking. HF was induced by right ventricular pacing (312 beats/min, 4 weeks) in 19 rabbits. AMI was induced by coronary artery ligation in rabbits surviving chronic pacing (n = 17). The hearts were quickly excised and Langendorff-perfused for simultaneous membrane potential and intracellular Ca(2+) (Cai ) optical mapping when ventricular fibrillation (VF) occurred or 4 hours after AMI. The VF inducibility was defined as the ability to provoke sustained VF (>2 minutes) by pacing. Dantrolene (10 μM) was administered after baseline studies. Spontaneous VF occurred in 5 rabbits (SVF group). The ventricular premature beat (VPB) burden was significantly higher in the SVF group than the non-SVF group (P < 0.05). Dantrolene suppressed VPB burden (P = 0.03) and prolonged action potential duration (APD; P < 0.05) to reduce VF inducibility (P < 0.05). However, dantrolene shortened immediate postshock APD50 even if VF storm was suppressed. In failing hearts with AMI, VPB burden plays a pivotal role in SVF occurrence. Dantrolene suppresses VPBs and/or prolongs repolarization to inhibit spontaneous VF and reduce VF inducibility.

Abstract 85: Development of a Readily Translatable Model of Resuscitation From Ischemic Cardiac Arrest to Assess Regional and Global Arrhythmia Substrates and Outcomes

Background: Little is known about the effect of therapeutic hypothermia (TH) on arrhythmias in the resuscitated heart. TH has a beneficial effect on defibrillation thresholds and ROSC. However, there are no studies investigating why TH might be anti-arrhythmic during resuscitation from ischemia-induced cardiac arrest, the most common clinical scenario. Our goal was to develop a novel translational porcine model of resuscitation from regional ischemia-induced VF with the ability to identify differences in both regional and global arrhythmia substrates in order to determine mechanisms of the antiarrhythmic effect of TH and improve outcomes. Methods: Pigs underwent anesthesia and thoracotomy, and a large LAD occlusion was made. VF was induced after 30 min if spontaneous VF did not occur. CPR was started after 8 min with defibrillation and cardiac massage to achieve ROSC. Infarct was continued for a total of 60 min then reperfusion was continued for 60 min. Electrograms (EG) were recorded from multipolar needle (transmural) plunge electrodes at multiple sites and monophasic action potential (MAP) recordings were used to determine transmural and regional heterogeneities of repolarization and conduction. All spontaneous arrhythmias were recorded. Outcomes were compared between control (temp 37oC, CT), Pre-ischemia TH (TH 33oC), and post-infarct TH (TH-infarct). Cooling was induced using a cooling blanket, cold saline IV infusion, and ice packs. Results: Hemodynamic parameters were recorded during ischemia, during CPR, and reperfusion. Appropriate CPR was verified by BP and CO2 monitoring. 2/4 animals survived to the end of protocol in the CT group, 4/5 in the TH group, and 0/2 in the TH-infarct group. Total ROSC time was 9.8±7 for CT vs 37.5±6 (p&lt;.04) for TH group (no ROSC for TH-infarct). EG’s were used to assess activation recovery intervals at transmural sites in the infarct, noninfarct, and border zones. Regional VF waveforms were obtained. Conclusions: We developed a translatable model of resuscitation from ischemic cardiac arrest using regional and global electrophysiologic monitoring to assess arrhythmia substrates. These data suggest improved outcomes during resuscitation with TH.

Letter to the editor: “The role of short QT interval and elevated LV end-diastolic pressure in the genesis of ventricular tachycardia and fibrillation”

to the editor: We read with great interest the article by Pizzuto and associates ([4][1]) in the American Journal of Physiology-Heart and Circulatory Physiology , entitled: “Dissociation of hemodynamic and electrocardiographic indexes of myocardial ischemia in pigs with hibernating myocardium and

Remote monitoring of a high-risk patient with Brugada syndrome: association of different arrhythmic manifestations

We report on the remote arrhythmia monitoring of a 34-year-old man with highly symptomatic Brugada syndrome, who initially presented with syncope, paroxysmal atrial fibrillation, and spontaneous coved-type electrocardiogram. The patient received a dual-chamber implantable cardioverter-defibrillator (ICD) with Home Monitoring™ facilities and experienced recurrent ICD shocks for spontaneous ventricular fibrillation (VF) episodes during the first year after ICD implantation. Remote monitoring revealed an increased burden of premature ventricular complexes and atrial arrhythmias each time VF spontaneously occurred. Atrial and ventricular arrhythmias were effectively suppressed by low-dose quinidine without severe side effects.

Bisoprolol reversed small conductance calcium-activated potassium channel (SK) remodeling in a volume-overload rat model

A recent study indicated that apamin-sensitive current (I KAS, mediated by apamin-sensitive small conductance calcium-activated potassium channels subunits) density significantly increased in heart failure and led to recurrent spontaneous ventricular fibrillation. While the underlying molecular correlation with SK channels is still undetermined, we hypothesized that they are remodeled in HF and that bisoprolol could reverse the remodeling. Volume-overload models were created on male Sprague-Dawley rats by producing an abdominal arteriovenous fistula. Confocal microscopy, quantitative real-time PCR, and western blot were performed to investigate the expression of SK channels and observe the influence of β-blocker bisoprolol on the expression of SK channels I KAS, and the effect of bisoprolol on I KAS and the sensitivity of I KAS to [Ca(2+)]i at single isolated cells were also explored using whole-cell patch clamp techniques. SK channels were remodeled in HF rats, displaying the significant increase of SK1 and SK3 channel expression. After the treatment of HF rats with bisoprolol, the expression of SK1 and SK3 channels was significantly downregulated, and bisoprolol effectively downregulated I KAS density as well as the sensitivity of I KAS to [Ca(2+)]i. Our data indicated that the expression of SK1 and SK3 increased in HF. Bisoprolol effectively attenuated the change and downregulated I KAS density as well as the sensitivity of I KAS to [Ca(2+)]i.

Shock efficacy of the entirely subcutaneous defibrillator for termination of spontaneous ventricular fibrillation in Brugada syndrome

Shock efficacy of the entirely subcutaneous defibrillator for termination of spontaneous ventricular fibrillation in Brugada syndrome

Amiodarone inhibits apamin-sensitive potassium currents.

BackgroundApamin sensitive potassium current (I KAS), carried by the type 2 small conductance Ca2+-activated potassium (SK2) channels, plays an important role in post-shock action potential duration (APD) shortening and recurrent spontaneous ventricular fibrillation (VF) in failing ventricles.ObjectiveTo test the hypothesis that amiodarone inhibits I KAS in human embryonic kidney 293 (HEK-293) cells.MethodsWe used the patch-clamp technique to study I KAS in HEK-293 cells transiently expressing human SK2 before and after amiodarone administration.ResultsAmiodarone inhibited IKAS in a dose-dependent manner (IC50, 2.67±0.25 µM with 1 µM intrapipette Ca2+). Maximal inhibition was observed with 50 µM amiodarone which inhibited 85.6±3.1% of IKAS induced with 1 µM intrapipette Ca2+ (n = 3). IKAS inhibition by amiodarone was not voltage-dependent, but was Ca2+-dependent: 30 µM amiodarone inhibited 81.5±1.9% of I KAS induced with 1 µM Ca2+ (n = 4), and 16.4±4.9% with 250 nM Ca2+ (n = 5). Desethylamiodarone, a major metabolite of amiodarone, also exerts voltage-independent but Ca2+ dependent inhibition of I KAS.ConclusionBoth amiodarone and desethylamiodarone inhibit I KAS at therapeutic concentrations. The inhibition is independent of time and voltage, but is dependent on the intracellular Ca2+ concentration. SK2 current inhibition may in part underlie amiodarone's effects in preventing electrical storm in failing ventricles.

Significance of Non-Type 1 Anterior Early Repolarization in Patients With Inferolateral Early Repolarization Syndrome

The aim of this study was to investigate the significance of non-type 1 anterior early repolarization (NT1-AER) combined with inferolateral early repolarization syndrome (ERS). Inferolateral ERS might be a heterogeneous entity, although it excludes type 1 Brugada syndrome (BS). Of 84 patients with spontaneous ventricular fibrillation, 31 ERS patients were divided into 2 groups. The ERS(A)-group consisted of inferolateral ER and NT1-AER--that is, notching or slurring with J-wave ≥ 1 mm at the end of QRS to early ST segment in any of V1 to V3 leads, in which the ST-T segment did not change to a coved pattern in the standard and high costal (second and third) electrocardiographic recordings even after drug provocation tests (n = 12). The other, ERS(B)-group, showed only inferolateral ER (n = 19). Clinical characteristics and outcomes were compared between the ERS groups, 40 patients with type-1 BS (BS-group), and 13 patients with idiopathic ventricular fibrillation lacking J-wave (IVF-group). Ventricular fibrillation occurred during sleep or near sleep in 10 of 12 patients in ERS(A)-group and in 22 of 40 patients in BS-group but in 2 of 19 patients in ERS(B)-group and in 1 of 13 patients in IVF-group (ERS[A] vs. ERS[B], p < 0.0001). Ventricular fibrillation recurrence was significantly higher in ERS(A)-group (58%), particularly in patients with J waves in the high lateral lead, and BS-group (55%), compared with ERS(B)-group (11%) and IVF-group (15%) (ERS[A] vs. ERS[B], p = 0.012). Inferolateral ERS comprises heterogeneous ER subtypes with and without NT1-AER. Coexistence of NT1-AER was a key predictor of poor outcome in patients with ERS.

A Randomized Study of Cardiac Resynchronization Therapy Defibrillator Versus Dual-Chamber Implantable Cardioverter-Defibrillator in Ischemic Cardiomyopathy With Narrow QRS

Background— Current recommendations require a QRS duration of ≥120 ms as a condition for prescribing cardiac resynchronization therapy (CRT). This study was designed to test the hypothesis that patients with heart failure (HF) of ischemic origin, current indications for defibrillator implantation, and QRS &lt;120 ms may benefit from CRT in the presence of marked mechanical dyssynchrony. Methods and Results— Patients with intraventricular dyssynchrony on echocardiography were randomly assigned to CRT or dual-chamber defibrillator implantation (CRT defibrillator and dual-chamber implantable cardioverter-defibrillator arm, respectively). The primary end point was the HF clinical composite response, which scores patients as improved, unchanged, or worsened. The secondary end point was the cumulative survival from HF hospitalization and HF death. An additional secondary end point was the composite of HF hospitalization, HF death, and spontaneous ventricular fibrillation. Twenty-three of 56 patients with CRT defibrillator showed an improvement in their clinical composite response at 1 year, compared with 9 of 55 patients with dual-chamber implantable cardioverter-defibrillator (41% versus 16%; P =0.004). After a median follow-up of 16 months, the CRT defibrillator arm showed a nonsignificant higher survival from HF hospitalization and HF death ( P =0.077), and a significantly higher survival from the combined end point of HF hospitalization, HF death, and spontaneous ventricular fibrillation ( P =0.028). Conclusions— In this comparison of CRT defibrillator and dual-chamber implantable cardioverter-defibrillator, CRT improved clinical status in some patients with ischemic cardiomyopathy, mild-to-moderate symptoms, narrow QRS duration, and mechanical dyssynchrony on echocardiography. Clinical Trial Registration— URL: http://clinicaltrials.gov . Unique identifier: NCT01577446.

Administration of Amiodarone During Resuscitation Is Associated with Higher Tumor Necrosis Factor-α Levels in the Early Postarrest Period in the Swine Model of Ischemic Ventricular Fibrillation

To compare the early postarrest inflammatory cytokine response between animals administered amiodarone (AMIO) and lidocaine (LIDO) intra-arrest during resuscitation from ventricular fibrillation (VF). Domestic swine (n=32) were placed under general anesthesia and instrumented before spontaneous VF was induced by balloon occlusion of the left anterior descending coronary artery. After 7 min of VF, standard ACLS resuscitation was performed and animals were randomized to either bolus AMIO (5 mg/kg, n=13) or LIDO (1 mg/kg, n=14) for recurrent or refractory VF. A non-antiarrhythmic (n=5) was also used for comparison. Following return of spontaneous circulation (ROSC), tumor necrosis factor (TNF)-α levels were drawn at 30 and 60 min. Groups were comparable with respect to prearrest hemodynamics and resuscitation variables. In the postarrest period, the LIDO and non-antiarrhythmic group demonstrated virtually identical TNF-α response trajectories. However, TNF-α levels were significantly higher in AMIO- than LIDO-treated animals at 30 min (geometric mean 539 versus 240 pg/mL, 2.2-fold higher, 95% confidence interval [CI] 1.3-3.8-fold higher, P=0.003) and at 60 min (geometric mean 570 versus 204 pg/mL, 2.8-fold higher, 95% CI 1.1-7.0-fold higher, P=0.03). Significant differences in the postarrest TNF-α levels were observed between animals treated with AMIO as compared to those treated with LIDO. Improved rates of ROSC seen with AMIO may come at the expense of a heightened proinflammatory state in the postcardiac arrest period.

Brugada burden in Brugada syndrome: The way to go in risk stratification?

Better means for risk stratification of patients with asymptomatic Brugada syndrome are urgently needed. To begin with, the majority of Brugada syndrome patients encountered nowadays consistently belong to this category (63% of Brugada syndrome patients in Japan and 64% of those in Europe are asymptomatic when diagnosed). Moreover, in contrast to patients with long QT syndrome, who often have warning symptoms in the form of recurrent syncope before they develop cardiac arrest, arrhythmias in the Brugada syndrome often are lethal when they first occur. On the other hand, the absolute risk of developing spontaneous ventricular fibrillation (VF) among asymptomatic patients is lower than previously estimated. Until recently, electrophysiologic studies (EPS) were proposed to virtually all patients with asymptomatic Brugada syndrome based on the premise that patients with inducible VF are more likely to develop similar spontaneous arrhythmias. Unfortunately, original encouraging reports were not confirmed. Combined analysis of the largest studies suggests that the risk for spontaneous VFwithin 4 to 5 years is 2.6% for inducible patients and 1.8% for noninducible patients, not much of a difference. In the recent, prospective PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) study, the risk was actually higher (albeit without reaching statistical significance) for patientswithout inducible VF: 4.9% of noninducible patients, but only 3.9% of those inducible, had spontaneous VF within 3 years. Importantly, limiting the definition of “positive EPS” to VF induction with≤ double ventricular extrastimulation, or to VF induced from the right ventricular apex (S. Priori, Personal Communication, March 16, 2013), does not improve the predictive accuracy of EPS. Therefore, it is time to seek alternative means of risk stratification.

Refractory ventricular fibrillation during bi-ventricular implantable cardioverter defibrillator implantation: a case report of successful cardioversion only with a left ventricular defibrillator lead

A 63-year-old male with ischaemic cardiomyopathy, New York Heart Association III and an ejection fraction of 25% had a bi-ventricular implantable cardioverter defibrillator (CRT-D) implant. The procedure was performed under general anaesthesia and during the placement of the defibrillator lead he went into spontaneous ventricular fibrillation …