Tongguan capsule derived-herb ameliorates remodeling at infarcted border zone and reduces ventricular arrhythmias in rats after myocardial infarction.

OBJECTIVE: Tongguan Capsule, a traditional Chinese medicine, is safe to use and is efficient in treating ischemic heart diseases. The present study aimed to investigate whether Tongguan capsule derived-herb (TGD) can mitigate left ventricular remodeling and dysfunction in post myocardial infarction (MI) rats as well as reduce arrhythmias. DESIGN AND METHODS: MI was induced by a ligation of the left anterior descending coronary artery. TGD was administered to the post-MI rats over a period of 4 weeks. TGD treatment significantly attenuated tachyarrhythmia inducibility and cardiac dysfunction in post-MI heart. Echocardiogram showed that TGD significantly reduced the development of ventricular remodeling. Histological study revealed that TGD significantly reduced myocardial interstitial collagen deposition, myocyte area and α-smooth muscle actin (α-SMA) expression, and increased connexin 43 expression in the infarcted border zone (IBZ). Western blotting results revealed that TGD treatment significantly down-regulated the protein expression levels of type I and III collagen, α-SMA, and up-regulated connexin 43. RT-qPCR results showed that TGD decreased the levels of ANP and BNP. CONCLUSIONS: These findings provided strong evidences that TGD intervention ameliorated interstitial fibrosis, myocyte hypertrophy and gap junction expression in the IBZ, attenuated left ventricular remodeling and dysfunction, and reduced vulnerability to tachyarrhythmia. TGD inhibited IBZ remodeling by its inhibition effect on myofibroblasts differentiation.

Carotid baroreceptor stimulation suppresses ventricular fibrillation in canines with chronic heart failure.

Carotid baroreceptor stimulation (CBS) has been shown to improve cardiac dysfunction and pathological structure remodelling. This study aimed to investigate the effects of CBS on the ventricular electrophysiological properties in canines with chronic heart failure (CHF). Thirty-eight beagles were randomized into control (CON), CHF, low-level CBS (LL-CBS), and moderate-level CBS (ML-CBS) groups. The CHF model was established with 6 weeks of rapid right ventricular pacing (RVP), and concomitant LL-CBS and ML-CBS were applied in the LL-CBS and ML-CBS groups, respectively. After 6 weeks of RVP, ventricular electrophysiological parameters and left stellate ganglion (LSG) neural activity and function were measured. Autonomic neural remodelling in the LSG and left ventricle (LV) and ionic remodelling in the LV were detected. Compared with the CHF group, both LL-CBS and ML-CBS decreased spatial dispersion of action potential duration (APD), suppressed APD alternans, reduced ventricular fibrillation (VF) inducibility, and inhibited enhanced LSG neural discharge and function. Only ML-CBS significantly inhibited ventricular repolarization prolongation and increased the VF threshold. Moreover, ML-CBS inhibited the increase in growth-associated protein-43 and tyrosine hydroxylase-positive nerve fibre densities in LV, increased acetylcholinesterase protein expression in LSG, and decreased nerve growth factor protein expression in LSG and LV. Chronic RVP resulted in a remarkable reduction in protein expression encoding both potassium and L-type calcium currents; these changes were partly amended by ML-CBS and LL-CBS. In conclusion, CBS suppresses VF in CHF canines, potentially by modulating autonomic nerve and ion channels. In addition, the effects of ML-CBS on ventricular electrophysiological properties, autonomic remodelling, and ionic remodelling were superior to those of LL-CBS.

Elimination of Purkinje Fibers by Electroporation Reduces Ventricular Fibrillation Vulnerability.

Background The Purkinje network appears to play a pivotal role in the triggering as well as maintenance of ventricular fibrillation. Irreversible electroporation ( IRE ) using direct current has shown promise as a nonthermal ablation modality in the heart, but its ability to target and ablate the Purkinje tissue is undefined. Our aim was to investigate the potential for selective ablation of Purkinje/fascicular fibers using IRE . Methods and Results In an ex vivo Langendorff model of canine heart (n=8), direct current was delivered in a unipolar manner at various dosages from 750 to 2500 V, in 10 pulses with a 90-µs duration at a frequency of 1 Hz. The window of ventricular fibrillation vulnerability was assessed before and after delivery of electroporation energy using a shock on T-wave method. IRE consistently eradicated all Purkinje potentials at voltages between 750 and 2500 V (minimum field strength of 250-833 V/cm). The ventricular electrogram amplitude was only minimally reduced by ablation: 0.6±2.3 mV ( P=0.03). In 4 hearts after IRE delivery, ventricular fibrillation could not be reinduced. At baseline, the lower limit of vulnerability to ventricular fibrillation was 1.8±0.4 J, and the upper limit of vulnerability was 19.5±3.0 J. The window of vulnerability was 17.8±2.9 J. Delivery of electroporation energy significantly reduced the window of vulnerability to 5.7±2.9 J ( P=0.0003), with a postablation lower limit of vulnerability=7.3±2.63 J, and the upper limit of vulnerability=18.8±5.2 J. Conclusions Our study highlights that Purkinje tissue can be ablated with IRE without any evidence of underlying myocardial damage.

Localized Structural Alterations Underlying a Subset of Unexplained Sudden Cardiac Death.

BACKGROUND: Sudden cardiac death because of ventricular fibrillation (VF) is commonly unexplained in younger victims. Detailed electrophysiological mapping in such patients has not been reported. METHODS: We evaluated 24 patients (29±13 years) who survived idiopathic VF. First, we used multielectrode body surface recordings to identify the drivers maintaining VF. Then, we analyzed electrograms in the driver regions using endocardial and epicardial catheter mapping during sinus rhythm. Established electrogram criteria were used to identify the presence of structural alterations. RESULTS: VF occurred spontaneously in 3 patients and was induced in 16, whereas VF was noninducible in 5. VF mapping demonstrated reentrant and focal activities (87% versus 13%, respectively) in all. The activities were dominant in one ventricle in 9 patients, whereas they had biventricular distribution in others. During sinus rhythm areas of abnormal electrograms were identified in 15/24 patients (62.5%) revealing localized structural alterations: in the right ventricle in 11, the left ventricle in 1, and both in 3. They covered a limited surface (13±6 cm2) representing 5±3% of the total surface and were recorded predominantly on the epicardium. Seventy-six percent of these areas were colocated with VF drivers (P<0.001). In the 9 patients without structural alteration, we observed a high incidence of Purkinje triggers (7/9 versus 4/15, P=0.033). Catheter ablation resulted in arrhythmia-free outcome in 15/18 patients at 17±11 months follow-up. CONCLUSIONS: This study shows that localized structural alterations underlie a significant subset of previously unexplained sudden cardiac death. In the other subset, Purkinje electrical pathology seems as a dominant mechanism.

Epicardial ablation utilizing remote magnetic navigation in a patient with Brugada syndrome and inferior early repolarization.

We report a case of epicardial ablation in a combined Brugada and inferior early repolarization syndrome patient with recurrent defibrillator therapy for spontaneous ventricular fibrillation. Electroanatomic mapping and ablation were achieved with remote magnetic navigation. Highly fractionated electrograms were seen epicardially in the anterior right ventricular outflow tract (RVOT) and at the anterior-inferior right ventricle. Ablation of the RVOT region resulted in resolution Brugada pattern electrocardiogram. The inferior early repolarization persisted despite ablation of the inferior right ventricular epicardium. Our patient remained event free at 12-months follow-up.

Electrical Substrate Elimination in 135 Consecutive Patients With Brugada Syndrome.

BACKGROUND: There is emerging evidence that localization and elimination of abnormal electric activity in the epicardial right ventricular outflow tract may be beneficial in patients with Brugada syndrome. METHODS AND RESULTS: A total of 135 symptomatic Brugada syndrome patients having implantable cardiac defibrillator were enrolled: 63 (group 1) having documented ventricular tachycardia (VT)/ventricular fibrillation (VF) and Brugada syndrome-related symptoms, and 72 (group 2) having inducible VT/VF without ECG documentation at the time of symptoms. About 27 patients of group 1 experienced multiple implantable cardiac defibrillator shocks for recurrent VT/VF episodes. Three-dimensional maps before and after ajmaline determined the arrhythmogenic electrophysiological substrate (AES) as characterized by prolonged fragmented ventricular potentials. Primary end point was identification and elimination of AES leading to ECG pattern normalization and VT/VF noninducibility. Extensive areas of AES were found in the right ventricle epicardium, which were wider in group 1 (P=0.007). AES increased after ajmaline in both groups (P<0.001) and was larger in men (P=0.008). The increase of type-1 ST-segment elevation correlated with AES expansion (r=0.682, P<0.001). Radiofrequency ablation eliminated AES leading to ECG normalization and VT/VF noninducibility in all patients. During a median follow-up of 10 months, the ECG remained normal even after ajmaline in all except 2 patients who underwent a repeated effective procedure for recurrent VF. CONCLUSIONS: In Brugada syndrome, AES is commonly located in the right ventricle epicardium and ajmaline exposes its extent and distribution, which is correlated with the degree of coved ST-elevation. AES elimination by radiofrequency ablation results in ECG normalization and VT/VF noninducibility. Substrate-based ablation is effective in potentially eliminating the arrhythmic consequences of this genetic disease. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02641431.

Prolonged Ventricular Conduction and Repolarization During Right Ventricular Stimulation Predicts Ventricular Arrhythmias and Death in Patients With Cardiomyopathy.

OBJECTIVES: The goal of this study was to evaluate whether prolonged ventricular conduction (paced QRS) and repolarization (paced QTc) times observed during ventricular stimulation predict ventricular arrhythmic events and death. BACKGROUND: Abnormal ventricular conduction and repolarization can predispose patients to ventricular arrhythmias. METHODS: Consecutive patients with left ventricular dysfunction (ejection fraction <50%) undergoing electrophysiology studies from January 2002 until May 2014 were identified at Mayo Clinic (Rochester, Minnesota). Patients were followed up until December 2014 for occurrence of ventricular arrhythmias and death. RESULTS: Among the 501 patients included (mean age 65 years; mean left ventricular ejection fraction 33.1%), longer paced ventricular conduction was associated with longer baseline QRS duration, longer QT interval, and lower ejection fraction. On multivariable analysis, longer paced QRS duration was associated with higher risk of ventricular arrhythmia (hazard ratio [HR]: 1.11 per 10-ms increase; 95% confidence interval [CI]: 1.07 to 1.16; p < 0.001) and all-cause death or arrhythmia (HR: 1.09; 95% CI: 1.09 to 1.13; p < 0.001). A paced QRS duration >190 ms was associated with a 3.6 times higher risk of ventricular arrhythmia (HR: 3.6; 95% CI: 2.35 to 5.53; p < 0.001) and a 2.1 times higher risk of death or arrhythmia (HR: 2.12; 95% CI: 1.53 to 2.95; p < 0.001), independent of left ventricular function or baseline QRS duration. Longer QTc interval during ventricular pacing was associated with a higher risk of ventricular arrhythmia (HR: 1.03 per 10-ms increase; 95% CI: 1.02 to 1.12; p < 0.001) independent of paced QRS duration. CONCLUSIONS: Longer paced QRS duration and paced QTc interval predict ventricular arrhythmias in patients with cardiomyopathy. Ventricular conduction and repolarization prolongation during right ventricular pacing can determine the risk of ventricular arrhythmias.

Characterization of the epicardial substrate for catheter ablation of Brugada syndrome.

BACKGROUND: Catheter ablation in the right ventricular outflow tract (RVOT) may modify the electrophysiologic substrate for recurrent ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with Brugada syndrome (BrS). OBJECTIVE: The purpose of this study was to investigate the mechanism and arrhythmogenic substrate of VT/VF and to evaluate the long-term outcomes of catheter ablation in patients with BrS. METHODS: Eleven consecutive patients with BrS referred to 2 academic medical centers underwent combined epicardial-endocardial electroanatomic mapping. Catheter ablation was performed in regions of localized conduction slowing. Transmural dispersion of late activation was calculated as the difference between the latest activation between epicardium and endocardium, and low-voltage areas were analyzed. RESULTS: Eleven patients met diagnostic criteria for BrS (spontaneous type 1, n = 9; Na channel provocation = 2). All patients were found to have a localized region in the anterior epicardial RVOT with conduction slowing evidenced by prolonged electrogram duration (78.79 ± 19.87 ms vs 58.93 ± 10.11 ms in epicardial right ventricle, and 59.87 ± 12.61 ms in endocardial RVOT, P <.005, respectively) with variable low voltage (0.97 ± 0.48 mV; median scar area 19.8 ± 25.9 cm2). Epicardial ablation resulted in normalization of spontaneous type 1 Brugada ECG pattern in all patients, and 73% were free from VT/VF at 25 ± 11 months. CONCLUSION: Prolonged electrograms localized to epicardial RVOT with variable low voltage were identified in all patients with BrS. J-point and ST-segment elevation correlated with greater transmural dispersion of late activation and was independent of total low-voltage area. Despite normalization of spontaneous type 1 pattern in all patients after ablation, recurrence was still observed, suggesting the implantable cardioverter-defibrillator as the cornerstone therapy for BrS.

An Automatic Algorithm Based on Morphological Stability During Fast Ventricular Arrhythmias Predicts Successful Antitachycardia Pacing in ICD Patients: A Multicenter Study.

BACKGROUND: Different types of ventricular arrhythmias (monomorphic ventricular tachycardia [VT], polymorphic VT, or ventricular fibrillation) can be detected by implantable cardiac defibrillators (ICDs) in fast VT zone. The efficacy of antitachycardia pacing (ATP) depends on the type of the treated arrhythmia. We hypothesized that an automatic algorithm based on morphological affinity of ICD far-field electrograms during tachycardia can predict ATP success and the need of shock. METHODS: The algorithm was evaluated on ventricular arrhythmias recorded in CareLink ICD remote monitoring system (Medtronic Inc., Minneapolis, MN, USA). Patients were selected if first ATP programmed was a burst of eight pulses at 88% coupling interval and if a far-field electrogram was available. The algorithm calculated a stability coefficient (SC) for all their stored ATP-treated fast ventricular arrhythmia (VA) episodes (LC 200-300 ms), analyzing the morphology homogeneity of the last eight recorded far-field electrograms before ventricular arrhythmias detection. RESULTS: Inclusion criteria were fulfilled by 717 patients from 29 centers. Three hundred and twenty fast VA were recorded in 103 patients. A higher SC was observed in episodes terminated with the first-ATP (0.78 [0.72-0.84] vs 0.74 [0.60-0.84]; P = 0.006). These differences were especially marked among the 62 episodes of very fast VA (CL ≤250 ms) (0.77 [0.74-0.85] vs 0.64 [0.51-0.8]; P = 0.006). In the multivariate analysis, a SC > 70% was independently associated with a higher likelihood of first-ATP success (odds ratio [OR] = 2.5; [95% confidence interval (CI) = 1.4-4.5], P = 0.001) and a lower need of shock (OR = 0.37; [95% CI = 0.2-0.7], P = 0.002). CONCLUSION: This automatic algorithm (stability coefficient) shows that ATP therapy response can be predicted in fast ventricular arrhythmias through morphology evaluation.

Reduction of inappropriate anti-tachycardia pacing therapies and shocks by a novel suite of detection algorithms in heart failure patients with cardiac resynchronization therapy defibrillators: a historical comparison of a prospective database.

AIMS: Implantable cardioverter defibrillators improve survival of patients at risk for ventricular arrhythmias, but inappropriate shocks occur in up to 30% of patients and have been associated with worse quality of life and prognosis. In heart failure patients with cardiac resynchronization therapy defibrillators (CRT-Ds), we evaluated whether a new generation of detection and discrimination algorithms reduces inappropriate shocks. METHODS AND RESULTS: We analysed 1983 Medtronic CRT-D patients (80% male, 67 ± 10 years), 1368 with standard devices (Control CRT-D) and 615 with new generation devices (New CRT-D). Expert electrophysiologists reviewed and classified the electrograms of all device-detected ventricular tachycardia/fibrillation episodes. Total follow-up was 3751 patients-years. Incidence of inappropriate shocks at 1 year was 2.8% [95% confidence interval (CI) = 2.0-3.5] in Control CRT-D and 0.9% (CI = 0.4-2.2) in New CRT-D (hazard ratio = 0.37, CI = 0.21-0.66, P < 0.001). In New CRT-D, inappropriate shocks were reduced by 77% [incidence rate ratio (IRR) = 0.23, CI = 0.16-0.35, P < 0.001] and inappropriate anti-tachycardia pacing by 81% (IRR = 0.19, CI = 0.11-0.335, P < 0.001). Annual rate per 100 patient-years for appropriate VF detections was 3.0 (CI = 2.1-4.2) in New CRT-D and 3.2 (CI = 2.1-5.0) in Control CRT-D (P = 0.68), for syncope was 0.4 (CI = 0.2-0.9) in New CRT-D and 0.7 (CI = 0.5-1.0) in Control CRT-D (P = 0.266), and for death was 1.0 (CI = 0.6-1.6) in New CRT-D and 3.5 (CI = 3.0-4.1) in Control CRT-D (P < 0.001). CONCLUSION: Detection and discrimination algorithms used in new generation CRT-D significantly reduced inappropriate shocks when compared with standard CRT-D. This result, with no compromise on VF sensitivity or risk of syncope, has important implications for patients' quality of life and prognosis.

Rise in DPA Following SDA-Rich Dietary Echium Oil Less Effective in Affording Anti-Arrhythmic Actions Compared to High DHA Levels Achieved with Fish Oil in Sprague-Dawley Rats.

Stearidonic acid (SDA; C18:4n-3) has been suggested as an alternative to fish oil (FO) for delivering health benefits of C ≥ 20 long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA). Echium oil (EO) represents a non-genetically-modified source of SDA available commercially. This study compared EO and FO in relation to alterations in plasma and tissue fatty acids, and for their ability to afford protection against ischemia-induced cardiac arrhythmia and ventricular fibrillation (VF). Rats were fed (12 weeks) diets supplemented with either EO or FO at three dose levels (1, 3 and 5% w/w; n = 18 per group). EO failed to influence C22:6n-3 (DHA) but increased C22:5n-3 (DPA) in tissues dose-dependently, especially in heart tissue. Conversely, DHA in hearts of FO rats showed dose-related elevation; 14.8%-24.1% of total fatty acids. Kidney showed resistance for incorporation of LC n-3 PUFA. Overall, FO provided greater cardioprotection than EO. At the highest dose level, FO rats displayed lower (p < 0.05) episodes of VF% (29% vs. 73%) and duration (22.7 ± 12.0 vs. 75.8 ± 17.1 s) than the EO group but at 3% EO was comparable to FO. We conclude that there is no endogenous conversion of SDA to DHA, and that DPA may be associated with limited cardiac benefit.

Risk stratification in Brugada syndrome: Clinical characteristics, electrocardiographic parameters, and auxiliary testing.

Risk stratification in Brugada syndrome remains a clinical challenge because the event rate is low but the presenting symptom is often cardiac arrest (CA). We review the data on risk stratification. A history of CA or malignant syncope is a strong predictor of spontaneous ventricular fibrillation (VF), whereas the prognostic value of a history of familial sudden death and the presence of a SCN5A mutation are less well defined. On the electrocardiogram, the presence of spontaneous type I electrocardiogram increases the risk for VF in all studies, whereas the presence of fragmented QRS complexes and early repolarization correlates with increased risk in several studies. Signal-averaged techniques using late potentials and microscopic T-wave alternans show some promising results in small studies that need to be confirmed. The value of electrophysiologic studies for predicting spontaneous VF remains controversial, and this includes programmed stimulation protocols that avoid a third extrastimuli or stimulation from the right ventricular outflow. Risk prediction is particularly challenging in children and women.

MG132 proteasome inhibitor upregulates the expression of connexin 43 in rats with adriamycin-induced heart failure.

The connexin 43 (Cx43) gap junction protein is important in the synchronization of contraction of cardiac myocytes. Abnormal expression of Cx43 contributes to ventricular arrhythmia, which is the major cause of sudden death in heart failure (HF). Cx43 is known to interact with zonula occludens (ZO)­1, and the proteasome is involved in the regulation of Cx43 degradation. Although Cx43 is downregulated in heart failure, the underlying mechanisms remain to be elucidated. The present study aimed to investigate the effect of the MG132 proteasome inhibitor on the expression levels of Cx43, ZO­1, 20S proteasome and ubiquitin in a rat model of HF, induced by adriamycin. MG132 reduced adriamycin­induced injury in the failing heart. In addition, MG132 inhibited the expression of 20S proteasome and ubiquitin, accompanied by an upregulation in the expression of Cx43 and ZO­1. These findings suggested that inhibition of the ubiquitin­proteasome system upregulated the expression of Cx43. Therefore, the proteasome inhibitor may be used to prevent degradation of Cx43 in HF, and thus may prevent Cx43-mediated arrhythmia in HF.

High atrioventricular phase index on near-field intracardiac electrogram is associated with risk of ventricular arrhythmia.

The purposes of this study were to characterize and quantify concordance between consecutive atrial and ventricular activation time points through analysis of phases and to explore its association with outcomes in patients with implantable cardioverter-defibrillator (ICD). Patients with structural heart disease and dual-chamber ICDs underwent 5min baseline right ventricular (V) near-field and atrial (A) electrogram (EGM) recording. The cross-dependencies of phase dynamics of the changes in consecutive A (AA') and V (VV') were quantified and the AV phase dependency index was determined. In Cox regression analysis, a high AV phase index (in the highest quartile, >0.259) was significantly associated with higher risk of ventricular tachyarrhythmias (HR 2.84; 95% CI 1.05-7.67; P=0.04). In conclusion, in ICD patients with structural heart disease, high sinus AV phase dependency index on EGM is associated with the risk of ventricular arrhythmia.

Brugada Syndrome Phenotype Elimination by Epicardial Substrate Ablation.

BACKGROUND: Whether Brugada syndrome (BrS) depends on functional epicardial substrates, which may be definitively eliminated by radiofrequency ablation, remains unknown. METHODS AND RESULTS: Patients with BrS underwent epicardial mapping to identify areas of abnormal electrograms as target for radiofrequency ablation. Substrate identification consisted in mapping right ventricle epicardial surface before and after flecainide (2 mg/kg per 10 minutes). After radiofrequency ablation, flecainide and remap confirmed elimination of abnormal substrate, BrS ECG pattern, and ventricular tachycardia/ventricular fibrillation inducibility. Flecainide testing was performed at each follow-up visits ≤6 months. Fourteen patients with BrS, median age 39 years (30.3-42.3) with implantable cardioverter-defibrillator were enrolled. Low-voltage areas (<1.5 mV) were commonly identified on the anterior right free wall and right ventricular outflow tract, which increased after flecainide from 17.6 cm(2) (12.1-24.2) to 28.5 cm(2) (21.6-30.2; P=0.001). Similarly, areas with abnormal electrograms increased after flecainide from 19.0 (17.5-23.6) to 27.3 cm(2) (24.0-31.2; P=0.001). After 23.8 minutes (18.1-28.5) of radiofrequency ablation, abnormal electrograms disappeared, whereas low-voltage areas were replaced by scar areas (<0.5 mV) of 25.9 cm(2) (19.6-31.0). Substrate elimination resulted in BrS ECG pattern disappearance and no ventricular tachycardia/ventricular fibrillation inducibility without complications. After a median follow-up of 5 months (3.8-5.3), ECG remained normal despite flecainide. CONCLUSIONS: In patients with BrS, there is a relationship between abnormal ECG pattern, the extent of abnormal epicardial substrate, and ventricular tachycardia/ventricular fibrillation inducibility. Ablation of the substrate identified in the presence of flecainide can eliminate the BrS phenotype and warrants further study.

The Effect of Direct Current Stimulation versus T-Wave Shock on Defibrillation Threshold Testing.

INTRODUCTION: There are several methods to induce ventricular fibrillation (VF) during defibrillation threshold (DFT) testing. Delivering a shock at a critical time during the T wave (T-shock) is the conventional approach, while delivering a constant direct current voltage (DC stim) from the implantable cardioverter defibrillator is an alternative method. Only a few reports compare VF induction methods. The purpose of this study was to evaluate the effects and safety of DC stim versus T-shock. METHODS: We retrospectively investigated 414 consecutive patients undergoing DFT testing. We compared the two groups (DC stim and T-shock) with respect to clinical characteristics, electrocardiogram (ECG) changes, and complications. RESULTS: Ventricular arrhythmia, including ventricular tachycardia (VT) and VF, was induced by DC stim in 93 patients or T-shock in 321 patients. No more than three attempts were performed during one procedure. There was no significant difference in the baseline ECG, induced tachycardia cycle length (TCL), or complications between the two groups. However, the induced TCL was significantly shorter than the clinical TCL regardless of induction method (P = 0.001). Five patients suffered major complications (i.e., electromechanical dissociation or incessant VT). A history of atrial fibrillation was significantly greater in patients with major complications than the others (80% vs 24%, P = 0.004), and was an independent predictor on multivariate analysis. CONCLUSIONS: There is no significant difference in induced TCL or complications between the DC stim and T-shock. The induced TCL is significantly shorter than clinical TCL regardless of induction method.

Spinal cord stimulation protects against ventricular arrhythmias by suppressing left stellate ganglion neural activity in an acute myocardial infarction canine model.

BACKGROUND: Previous studies have shown that spinal cord stimulation (SCS) may reduce ventricular arrhythmias (VAs) induced by acute myocardial infarction (AMI). Furthermore, activation of left stellate ganglion (LSG) appears to facilitate VAs after AMI. OBJECTIVE: The purpose of this study was to investigate whether pretreatment with SCS could protect against VAs by reducing LSG neural activity in an AMI canine model. METHODS: Thirty dogs were anesthetized and randomly divided into SCS group (with SCS, n = 15) and sham group (sham operation without SCS, n = 15). SCS was performed for 1 hour before AMI. Heart rate variability (HRV), ventricular effective refractory period (ERP), serum norepinephrine level, LSG function measured by blood pressure increases in response to LSG stimulation, and LSG neural activity were measured for 1 minute at baseline and 1 hour after SCS. AMI was induced by left anterior descending coronary artery ligation, and then HRV, LSG neural activity, and VAs were measured. RESULTS: Compared to baseline, SCS for 1 hour significantly prolonged ventricular ERP, increased HRV, and attenuated LSG function and LSG activity in the SCS group, whereas no significant change was shown in the sham group. AMI resulted in a significant decrease in HRV and increase in LSG neural activity in the sham group, which were attenuated in the SCS group (frequency: 99 ± 34 impulses/min vs 62 ± 22 impulses/min; amplitude: 0.41 ± 0.12 mV vs 0.18 ± 0.05 mV; both P <.05). The incidence of VAs was significantly lower in the SCS group than in the sham group. CONCLUSION: SCS may prevent AMI-induced VAs, possibly by suppressing LSG activity.

Multicentre comparison Of shock efficacy using single-vs. Dual-coil lead systems and Anodal vs. cathodaL polarITY defibrillation in patients undergoing transvenous cardioverter-defibrillator implantation. The MODALITY study.

PURPOSE: An optimal active-can lead configuration during implantable cardioverter defibrillator (ICD) placement is important to obtain an adequate defibrillation safety margin. The purpose of this multicenter study was to evaluate the rate of the first shock success at defibrillation testing according to the type of lead implant (single vs. dual coil) and shock polarity (cathodal and anodal) in a large series of consecutive patients who received transvenous ICDs. METHODS: This was a multicenter study enrolling 469 consecutive patients. Single- versus dual-coil leads and cathodal versus anodal polarity were evaluated at defibrillation testing. In all cases, the value of the energy for the first shock was set to 20 J less than the maximum energy deliverable from the device. RESULTS: A total of 469 patients underwent defibrillation testing: 158 (34 %) had dual-coil and 311 (66 %) had single-coil lead systems configuration, 254 (54 %) received anodal shock and 215 (46 %) received cathodal shock. In 35 (7.4 %) patients, the shock was unsuccessful. No significant differences in the outcome of defibrillation testing using single- versus dual-coil lead were observed but the multivariate analysis showed an increased risk of shock failure using cathodal shock polarity (OR 2.37, 95 % CI 1.12-5.03). CONCLUSIONS: Both single- and dual-coil transvenous ICD lead systems were associated with high rates of successful ICD implantation, and we found no significant differences in ventricular arrhythmias interruption between the two ICD lead systems configuration. Instead, anodal defibrillation was more likely to be successful than cathodal defibrillation.

Ventricular tachyarrhythmia recurrence in primary versus secondary implantable cardioverter-defibrillator patients and role of electrophysiology study.

PURPOSE: In recent years, there has been a shift away from performing electrophysiologic study (EPS) to guide implantable cardioverter-defibrillator (ICD) implantation with a reliance on left ventricular ejection fraction (LVEF) alone. METHODS: ICD patients were prospectively recruited from the multicentre COMFORT (Concept of Optimal Management of ventricular Fibrillation Or Very fast ventricular Tachycardia) trial. Primary prevention ICD patients (n = 260, groups 1 and 2) were compared to secondary prevention ICD patients (n = 210, group 3). Primary prevention ICDs were implanted in patients with ischemic cardiomyopathy based on LVEF ≤ 40 % and inducible ventricular tachycardia (VT) at EPS (n = 123, group 1) or impaired LVEF alone (LVEF ≤ 30 % or LVEF ≤ 35 % with NYHA class II or III; n = 137, group 2). EPS was performed in 61 % of secondary prevention ICD patients (n = 129). Patients were followed up for >12 months with a primary endpoint of spontaneous VT/ventricular fibrillation (VF). RESULTS: A significantly higher rate of spontaneous VT/VF occurred in secondary versus primary prevention ICD patients (P < 0.001) and in EPS-guided versus LVEF-guided primary prevention ICD patients (P = 0.029). At 2 years, the proportion of patients with ≥1 VT/VF episode was 24.6 ± 4.2 %, 19.9 ± 4.6 % and 37.1 ± 3.9 % for groups 1, 2 and 3, respectively. In the secondary prevention, patients who underwent EPS, VT/VF occurred in 44.4 ± 5.9 % and 14.1 ± 6.6 % with a positive versus negative result, respectively (P = 0.02). CONCLUSIONS: Secondary prevention ICD patients have more spontaneous VT/VF than primary prevention ICD patients. Secondary and primary prevention ICD patients with inducible VT at EPS have more VT/VF than patients without inducible VT or impaired LVEF alone.

Carotid baroreceptor stimulation prevents arrhythmias induced by acute myocardial infarction through autonomic modulation.

: Electrical carotid baroreceptor stimulation (CBS) has shown therapeutic potential for resistant hypertension and heart failure by resetting autonomic nervous system, but the impacts on arrhythmias remains unclear. This study evaluated the effects of CBS on ventricular electrophysiological properties in normal dog heart and arrhythmias after acute myocardial infarction (AMI). In the acute protocol, anesthetized open chest dogs were exposed to 1 hour left anterior descending coronary occlusion as AMI model. Dogs were received either sham treatment (Control group, n = 8) or CBS (CBS group, n = 8), started 1 hour before AMI. CBS resulted in pronounced prolongation of ventricular effective refractory period and reduction of the maximum action potential duration restitution slope (from 0.85 ± 0.15 in the baseline state to 0.67 ± 0.09 at the end of 1 hour, P < 0.05) before AMI. Number of premature ventricular contractions (277 ± 168 in the Control group vs. 103 ± 84 in the CBS group, P < 0.05) and episodes of ventricular tachycardia/ventricular fibrillation (7 ± 3 in the Control group vs. 3 ± 2 in the CBS group, P < 0.05) was decreased compared with the control group during AMI. CBS buffered low-frequency/high-frequency ratio raise during AMI. Ischemic size was not affected by CBS. CBS may have a beneficial impact on ventricular arrhythmias induced by AMI through modulation of autonomic tone.